Continue reading »]]> 1. WHAT IS CONFABULATION?

We are all wrong. Philosophers, scientists, writers, poets, even mathematicians make huge, sometime devastating errors. We make errors in our daily life — errors of judgement, of planning, of memory, among others. Much of the time, we are not aware of our errors, we feel that we are right and we keep maintaining our position regardless of any evidence in contrast with it. In some cases, however, our mistakes in judging and remembering are so evident that we need other names to distinguish them from ‘‘normal’’ errors. Delusion and confabulation are the names we use to indicate ‘‘abnormal’’ errors in judgement and remembering.

So starts a recent paper (Dalla Barba and Boisse 2010) on a study on confabulation.

The term “confabulation” has been used to denote a wide range of errors in memory as well as distortions in other cognitive domains. Despite confabulation having been studied for well over a century, there is very little on which researchers agree, even when it comes to the most basic question of how confabulating should be defined, or how many types of confabulation there are.

At its simplest, people who confabulate provide information, or act based on information, that is obviously false. These people are genuinely unaware that the information is wrong.

A number of disorders can cause confabulations, including Korsakoff’s syndrome, ruptured aneurisms of the anterior or posterior communicating artery, subarachnoid hemorrhage, encephalitis, traumatic brain injuries, brain tumors, Binswanger’s encephalopathy, multiple sclerosis, and psychotic disorders. Confabulation is often seen in dementia patients, although it has not been extensively studied in this particular group; and to my knowledge, the studies that have been done have focused exclusively on early-stage dementia.

Studies on all disorders are typically lumped together when trying to develop clues on what causes confabulation and how it is expressed. However, there may be distinct differences in the ways and frequencies with which patients with different disorders, with damage to different parts of the brain, or with different types of damage to the same part(s) of the brain, confabulate. And it is quite possible that the results from studies done on early-stage dementia may result in a skewed concept of when and why and how moderately- and severely-demented patients confabulate.

1.1. Different types of confabulations

The most recent papers I found generally agree on the core characteristics of all forms of confabulation, i.e.:

(i) Confabulation is an account based in memory that is false with respect to the context (e.g., time, place, etc) in which the event is placed, and may contain false or grossly inaccurate details within its own context.

(ii) Patients typically exhibit anosognosia for their memory problems and are unaware of the fact that they are confabulating. Thus, confabulations are not intentionally produced and are probably not the result of compensatory mechanisms. However, the content of a confabulation may be emotionally biased, e.g., may reflect unintentional motivations and drives.

(iii) Patients may act upon their confabulation, reflecting their genuine belief in the false memory.

(iv) Confabulations are most frequent in the autobiographical domain (e.g., personal past experiences or plans for the future), and autobiographical confabulations are usually associated with the strongest confidence in their veracity.

Various attempts have been made to distinguish among the different kinds of confabulation. One common distinction is between “semantic” and “episodic” confabulations. Semantic memory refers to a person’s store of conceptual and factual knowledge that is not related to any specific memory, such as the color of broccoli or what a fork is used for.  Episodic memory involves the ability to learn, store, and retrieve information about unique personal experiences that occur in daily life, such as the details of a recent office meeting or a special holiday gathering that took place several years earlier. Episodic memories typically include information about the time and place of an event, as well as detailed information about the event itself. These memories may be drawn upon to envision future events. Planning and anticipation are similar to recalling personal memories and use similar areas of the brain. Semantic confabulations, then, are false statements associated with knowledge of generally known facts. Episodic confabulations are false statements associated with memories of personal past episodes or experiences, or personal plans for the future.

Another very common distinction is between “provoked” and “spontaneous” confabulations. Provoked confabulations are typically described as plausible minor memory distortions in response to direct questioning — reflecting the need to fill a memory gap when questioned or in a test situation — whereas spontaneous confabulations are unprovoked, often implausible, memories. Provoked confabulation resembles errors produced by healthy persons on tests of memory following prolonged retention intervals, and may reflect a normal strategy to compensate for memory deficits. Spontaneous confabulation, on the other hand, is thought to be due to impaired source memory (i.e., a deficit in remembering contextual information about an event) and temporal confusion (i.e., the difficulty in distinguishing irrelevant and old memory traces from relevant and new traces referring to the ongoing reality).

However, it can be difficult to draw the line between provoked and spontaneous confabulations. Moreover, several researchers have noted cases in which spontaneous confabulations were plausible and provoked confabulations were bizarre and implausible. In fact, a recent study (Dalla Barba and Boisse 2010) concluded that the great majority of confabulations do not clearly fall in either category. Instead, they consisted of “general memories, habits, and misplacements”, i.e., either true episodes misplaced in time and place, or personal habits and routines that the patient “remembers” as specific events. When asked what they did today or what they will do tomorrow, for example, confabulating patients may reply with well-established memories from their pasts, however irrelevant these memories may be to their present situations.

Accordingly, Dalla Barba and Boisse also suggested distinguishing between semantically anomalous and semantically appropriate confabulations. A confabulation that is semantically anomalous is one that is inconsistent with knowledge and information shared by the members of society. However, it may be made of autobiographical elements put together in an inappropriate semantic structure. An example of this is a statement made by a patient suffering from traumatic brain injury. He said that he had won a running race the previous day and was awarded with a piece of meat that was placed on his right knee. It is unlikely that anyone would have such an experience (semantically anomalous). However, elements of the statement were autobiographical: the patient had spent much of his free time running races earlier in his life, and he fell during a race, incurring severe head trauma and an open wound on his right knee. A semantically appropriate confabulation, on the other hand, might sound perfectly plausible to someone who does not know the patient. An example might be asking a dementia patient how she celebrated Christmas last year, and the patient responding with a description of family traditions even though the previous Christmas was spent doing something entirely new and different. Unless the questioner actually knew what the patient had done that year, her answer would have sounded factual. An example of a semantically appropriate personal plan for the future might be asking a dementia patient what he intends to do tomorrow, and the dementia patient responding that he intends to give a piano lesson. This would sound perfectly reasonable to anyone who did not know that the patient had stopped playing the piano or giving piano lessons two years earlier.

1.2. Confabulation versus delusions

Patients with confabulation will sometimes cling to their false memories even when confronted with the truth or despite being aware of contradictory evidence. Accordingly, confabulation needs to be distinguished from other types of false ideas, most notably delusions.

There are at least superficial similarities between confabulation and delusions; e.g., both involve the production of unintentional false statements, both are resistant to contradictory evidence, and both have been shown to be influenced by emotion and motivation. Some researchers hold that confabulation is a form of delusion, when delusions are more broadly defined.

Others contend that a distinction can be made based on the context in which the two disorders occur (neurological vs. psychiatric) and the fact that confabulation is a memory-related phenomenon whereas delusion is a belief formation disorder. Several clinical characteristics distinguish the two, most notably that delusions tend to be more systematic and pervasive, whereas confabulations are more isolated, polythematic, and fleeting in nature. Recent papers have suggested that, if delusions have a memory component at all, it appears to be related to biased input, encoding, and integration of novel information.

Alzheimer’s patients can exhibit delusions as well as confabulations. The delusions that are frequently observed in Alzheimer’s patients include beliefs about theft, the patient’s house not being his home, Capgras syndrome (someone close to the patient, such as a spouse, is an impostor), belief an intruder is in the house, abandonment, spousal infidelity, and paranoia.

An Alzheimer’s patient who spontaneously confabulates forms a “memory” for an event that did not occur, but is merely consistent with current information. For example, the patient may not remember that she has rearranged the furniture in the living room. Upon seeing the furniture in locations that do not match her memory, she may create a new “memory” that involves someone breaking into the house and moving the items. This confabulation fades with time. A patient with delusions of theft, on the other hand, may become convinced that a particular individual has repeatedly robbed him, even in the absence of readily understood triggers such as a lost billfold.

2. WHAT CAUSES CONFABULATION?

To discuss what causes confabulation, one must first understand memory — at least, to the extent that memory is currently “understood” — and the ways in which Alzheimer’s affects memory.

2.1. Memory in Alzheimer’s

There are thought to be a number of different memory systems, including episodic memory, semantic memory, autonomic simple classical conditioning, motoric simple classical conditioning, procedural memory, perceptual priming, conceptual priming, and working memory. Each of these depends on different parts of the brain. Some of these memory systems are severely impaired in Alzheimer’s patients, while others, such as procedural memory (cognitive and behavioral skills that operate at an automatic and unconscious level, such as learning to ride a bicycle or to play the piano) are relatively preserved — at least, in the earlier stages.

Here, the focus will be on episodic and semantic memory, since they are thought to be the most relevant to confabulating.

The medial temporal lobes (including the hippocampus, parahippocampus, presubiculum, subiculum, and amydala) constitute the core of the episodic memory system. The medial temporal lobes interact extensively with other brain regions (e.g., the anterior thalamus nucleus, mammillary bodies, fornix, and prefrontal cortex), some of which are associated with “Papez’s circuit”. A lesion in any one of these structures may cause the pattern of impairment that is characteristic of episodic memory dysfunction, i.e., the greatest disruption is in the ability to learn new information, moderate disruption is seen in the ability to recall recently learned information, and the ability to recall remotely learned information is generally intact.

How the medial temporal lobes store memories is not yet understood, but is thought to involve collecting and combining information from multiple cortical streams, such as the sights, sounds, smells, tastes, emotions, and thoughts during a given episode (e.g., eating a special holiday meal.) This information is transferred first to the parahippocampal region, then to the hippocampus proper, and then to the entorhinal cortex. It is processed in the dentate gyrus, and then transferred to the CA3 region of the hippocampus, where the critically important hippocampal index is assigned, allowing the memory to be stored in a unique way so that it can later be recalled.

Typically, memories are retrieved when a cue from the environment matches a part of the stored memory. For example, years later, the individual bites into a little cake that tastes remarkably like the one he had previously eaten at that special holiday meal. This sensory cue is transferred from the cortex to the parahippocampal region, the hippocampus, and then the entorhinal cortex. From there, it goes directly to the CA3 region where the original hippocampal index is found. The cue activates the hippocampal index associated with the index of the original stored memory — not the memory itself — in the CA3 region. This activation leads to the reinstatement of much of the neural pattern of activity associated with the original event in the CA1 region of the hippocampus, the subiculum and various cortical regions — leading to the experience of ‘remembering’ all of the sights, sounds, smells, tastes, emotions, and thoughts of the original holiday meal.

The hippocampus remains critical for memory retrieval until a process known as consolidation occurs. This process is still not understood, but it is thought that once a memory is consolidated, the distributed pattern of cortical neural activity is directly linked together, such that when a cue is encountered, the memory may be retrieved directly from cortical-cortical connections, without the need for the hippocampus.

In addition to the medial temporal lobes and Papez’s circuit, the frontal lobes are also important for episodic memory. Whereas the medial temporal lobes are critical for the retention of information, the frontal lobes play key roles in the acquisition and encoding of information; retrieval of information without contextual and other cues; recollection of the source of information; and assessment of the temporal sequence and recency of events. One important reason why the frontal lobes are important for encoding episodic memory is that they enable the individual to focus his attention on the information to be remembered and to engage the medial temporal lobes. Dysfunction of the frontal lobes may cause a variety of memory problems, including distortions of episodic memory and false memories, such as when information becomes associated with the wrong context or incorrect specific details.

A simple analogy has been used to help conceptualize the differences between deficits in episodic memory that occur because of damage to the medial temporal lobes (and the Papez circuit) and those that occur because of damage to the frontal lobes. The frontal lobes are analogous to the “file clerk” of the episodic memory system, the medial temporal lobes to the “recent memory file cabinet,” and other cortical regions to the “remote memory file cabinet”. Thus, if the frontal lobes are impaired, it is difficult — but not impossible — to get information in and out of storage. However, the information may be distorted due to “improper filing” that leads to an inaccurate source, context, or sequence. Getting information into storage may require stronger encoding, and getting information out of storage may require stronger cues from the environment.

If, on the other hand, the medial temporal lobes are impaired, it may be impossible for recent information to be stored. This will often lead to the impaired person asking for the same information again and again and again. Older information that has been consolidated over months to years is likely stored in other cortical regions — the “remote memory file cabinet” — and will therefore be available for retrieval even when the medial temporal lobes or Papez’s circuit are damaged.

Of the six major memory systems, episodic memory is the most clinically relevant for Alzheimer’s patients. Very early in the course of the disease, there is prominent medial temporal lobe pathology and pathologic involvement of the lateral temporoparietal and medial parietal cortex, as well as a lesser (and more variable) degree of pathology in lateral and medial prefrontal cortex. These cause disruptions to the episodic memory system that are among the earliest signs and symptoms of Alzheimer’s. Initially, they result in minor memory lapses such as misplaced keys, missed appointments and late bills that are brushed off as forgetfulness due to fatigue, distraction or “senior moments”. More critical lapses, such as failing to remember whether the stove has been turned off or medications have been taken, often precipitate the initial visit to a doctor to diagnose the problem. Episodic memory deficits continue to represent one of the most significant functional problems as a patient progresses through the mild and moderate stages of Alzheimer’s.

As mentioned above, damage to structures associated with episodic memory results in a characteristic pattern in which recent memories are more vulnerable to decay than remote memories. Accordingly, as episodic memory abilities continue to decline, events from the distant past are better remembered than events that occurred after or shortly before the onset of the disease. Vivid remote memories may sometimes be confused with psychotic delusions or hallucinations, such as claims to have recently seen and interacted with a long-dead friend or family member. Inevitably, the inability to remember recent events or learn new information leads to functional deficits that are devastating.

One common assumption is that episodic memory is primarily or entirely concerned with the past. However, a growing number of investigators have begun to approach episodic memory in a broader context, one that emphasizes both the ability of individuals to re-experience episodes from the past and also imagine or pre-experience episodes that may occur in the future — e.g., planning and anticipation. Evidence for this close linkage of past and future events comes from studies of patients with episodic memory deficits. For example, studies on amnesia patients have found that they not only cannot consciously remember their pasts, but also cannot imagine their personal futures.

Neuroimaging has provided supportive evidence that the same regions of the brain are involved. For example, a recent neuroimaging study was designed to examine the neural regions involved in the construction (i.e., the search and reconstruction of a past event or the creation of a future event) and subsequent elaboration (i.e., retrieving or imagining supplementary details) of past and future events. The results showed that the left hippocampus and posterior visuospatial regions were involved in both past and future event construction. Elaboration was characterized by a remarkable overlap of activity in regions comprising the autobiographical memory retrieval network, including self-referential processing, contextual and episodic imagery. This striking neural overlap is consistent with findings that amnesic patients exhibit deficits in both past and future thinking, and confirms that the episodic system contributes importantly to imagining the future.

However, remembering the past and imagining the future differ, at least with respect to temporal orientation, and some unique cognitive processes and neural regions should therefore be associated with each. And indeed, this same study found that, during the construction phase, future events recruited regions involved in prospective thinking and generation processes, i.e., right frontopolar cortex and left ventrolateral prefrontal cortex, respectively; and also uniquely engaged the right hippocampus, possibly as a response to the novelty of these events. Unexpectedly, there was no evidence of any regions of the brain engaged uniquely by past events. Every region engaged by the construction and elaboration of past events was also engaged by future events either to a similar or significantly higher level.

Accordingly, it has been suggested that these results raise questions about the adaptive significance of the episodic system. Although the function of the episodic system is typically conceived of as retrieval of past events, it is possible that the primary role of this system is not reminiscence, but rather, future thinking. As such, the ability to retrieve episodic information would exist primarily for the purpose of simulating possible future scenarios and outcomes, and anticipating future needs. And, although I have not seen this suggested in any of the papers I’ve read so far, it also goes a long way toward explaining why so many of our loved ones seem so unafraid of the future … and also why they often see no need to consult doctors, take medicines, or take other steps to try to slow down the progression of their dementia.

From this viewpoint, damage to the episodic “memory” system is even more clinically relevant for Alzheimer’s patients.

Semantic memory involves memory for factual knowledge that has been learned, but for which specific “time and place” information about the source of the original experience is typically not known. Encyclopedic knowledge of information such as the features of objects (e.g., apples are usually red), categories (e.g., oranges and bananas are both types of fruit), historical events, mathematical tables, and similar types of information are considered to be stored in semantic memory systems of the brain. Semantic memories may also include “autobiographical” information, i.e., personal facts, such as one’s place and date of birth, or the names of family members. Evidence that the semantic memory system is different from episodic memory comes from neuroimaging studies, and the fact that previously acquired semantic memory is spared in patients who have severe impairment of the episodic memory system, such as with disruption of the Papez circuit (e.g., in Korsakoff’s syndrome) or surgical removal of the medial temporal lobes.

The anterior and inferolateral temporal lobes are important in the naming and categorization tasks by which semantic memory is usually assessed. However, in the broadest sense, semantic memory includes all of the person’s knowledge of the world not related to any specific episodic memory. It could therefore be argued that semantic memory resides in multiple cortical areas throughout the brain. For example, there is evidence that visual images are stored in nearby visual association areas.

Alzheimer’s is the most common clinical disorder that disrupts semantic memory. This disruption may be due to pathology in the anterior and inferolateral temporal lobes, and/or to pathology in the frontal cortex leading to poor activation and retrieval of semantic information.

In Alzheimer’s disease, episodic and semantic memory decline independently of each other, supporting the idea that two separate memory systems are impaired in this disorder.

Interestingly, the content of autobiographical memories shifts from episodic to semantic with aging in healthy adults. Alzheimer’s disease enhances this pattern. Very recent neuroimaging studies showed that, as hippocampal volume decreased in Alzheimer’s patients, the left inferior frontal gyrus and the ventromedial prefrontal cortex (vmPFC) were activated. The linking function of the hippocampus is related to vivid, episodic retrieval and the linking function of the vmPFC is related to semantic retrieval. The researchers speculated that the linking function of the degraded hippocampus is taken over by the vmPFC, resulting in the shift to semantisation.

Not all dementias are alike in the memory systems that are affected. For example, patients with semantic dementia (the temporal variant of frontotemporal dementia) exhibit deficits in all functions of semantic memory, such as naming, single-word comprehension, and impaired general knowledge (such as the color of common items) early in the course of the disease. Other aspects of cognition, however, are relatively preserved, including components of speech, perceptual and nonverbal problem-solving skills, and episodic memory.

2.2. Brain damage associated with confabulation in dementia patients

There is a general consensus of opinion that confabulation is the result of damage to the brain … but questions still remain as to what types of damage, and where, are needed for confabulation to occur. I get the distinct impression that one possible reason for the controversy is that the data on all types of brain damage, producing all types of confabulation, tend to be lumped together, which may confuse more than clarify. In particular, I wonder how much confabulation in Alzheimer’s patients has in common with confabulation in patients who have sharply-localized damage to a single site in the brain. Alzheimer’s is a multidomain disorder, including not only memory loss, but also executive dysfunction (e.g., impaired ability to plan ahead, prioritize, stop and start activities, shift from one activity to another activity, and to monitor one’s own behavior) and varying degrees of visuospatial and language deficits.

Accordingly, I have done my best to focus on studies specifically done on Alzheimer’s and related dementias — although it is often difficult to determine whether researchers derived some of their conclusions about Alzheimer’s patients from studies on non-demented persons. Moreover, please note that a 2006 paper commented, “Previous studies that have investigated confabulation in AD have failed to take into account the characteristics of the disease…”

Studies that couple brain imaging techniques (e.g., MRI, PET, and SPECT) with tests on cognitive function (e.g., the MMSE and CASI*) have found that, in early-stage Alzheimer’s patients tested about autobiographical memory (personal semantic and episodic information):

- Alzheimer’s patients produce more confabulations in response to episodic than to personal semantic memory questions, probably reflecting the much more marked impairment of episodic memory characteristic of early-stage Alzheimer’s.

- There is a correlation between the degree of cognitive impairment (defined by MMSE and CASI scores) and personal semantic confabulation, but not between cognitive impairment and episodic confabulation, or between cognitive impairment and temporality. (Remember, this is in early-stage Alzheimer’s. Remote memory, including personal semantic memory, is relatively preserved in early-stage Alzheimer’s.)

- Semantic confabulation (and MMSE and CASI scores) correlates with atrophy in the anterior cingulate, bilateral medial temporal, and right middle temporal gyrus.

- Confabulation scores for remembering the past and planning the future (i.e., confabulations involving the episodic memory system) are strongly correlated, and are higher in patients who also exhibit delusion and/or aggression.

- Lower blood flow (“hypoperfusion”) in the frontal and/or temporal regions of the brain, including Brodmann’s area 9 which plays a role in episodic memory retrieval, is associated with delusion in Alzheimer’s patients. Lower metabolism (“hypometabolism”) has also been reported in frontal or temporal regions of the brain in delusional Alzheimer’s patients.

- Delusional Alzheimer’s patients exhibit more episodic confabulations and have lower blood flow in the prefrontal cortex than nondelusional Alzheimer’s patients.

From these studies, the following conclusions were drawn:

- Different mechanisms are involved in personal semantic and episodic confabulations in Alzheimer’s patients.

- Episodic confabulation is affected by delusions related to prefrontal hypoperfusion.

- Semantic confabulation (at least, personal semantic confabulation) is associated with cognitive impairment.

[*The Cognitive Abilities Screening Instrument (CASI) includes subscales related to frontal lobe function -- i.e., attention and list-generating fluency -- as well as subscales related to concentration and mental manipulation, orientation, short-term memory, long-term memory, language, visual construction, and abstraction and judgment.]

Progressive neurodegenerative disorders such as Alzheimer’s inevitably go on to develop damage in more and more regions of the brain; and so the characteristics of confabulation seen in early-stage dementia may be considerably different from those seen in later-stage patients. However, confabulation in later stage patients has rarely, if ever, been studied.

2.3. Possible mechanisms associated with confabulation

Researchers have come up with a number of hypotheses to explain why confabulators “remember” a past that is different from the “real” past. One of the earliest hypotheses was that confabulations occurred as a compensatory mechanism for memory loss (i.e., the patient produces confabulations to fill in memory gaps and avoid embarrassment). However, this hypothesis has been vigorously challenged and is no longer in favor. Current hypotheses fall into two main classes, i.e., temporality/source confusion, and strategic retrieval. (These hypotheses have been developed to cover all types of confabulations associated with all types of brain damage, even though it is becoming apparent that different types of confabulations are associated with different mechanisms. The majority of the studies have focused on provoked confabulations, for the very simple reason that they are much easier to study. Personal experience leads me to believe that spontaneous confabulating may play a much more important role in the later stages of Alzheimer’s, which apparently has never been studied.)

Temporality/source confusion hypotheses posit that confabulations are true memories displaced in time, caused by impaired search processes of the long-term memory storage system. Cues that are necessary for the retrieval of memories might match and activate stored experiences other than the episode that is sought. In the “temporality and consciousness” model, the three dimensions of temporality — past, present, and future — map onto three types of confabulation that are expressed in the context of past episodic memory, current time-place disorientation, and future plans, respectively. The model distinguishes a “knowing” consciousness (expressed in the form of habits and semantics) and a “temporal” consciousness (related to unique personal events, specified in time.) Studies have shown that dementia patients tend to retrieve habitual, generic, well-learned information and to mistake it for specific events. The model proposes that this tendency reflects a disruption in temporal consciousness, leading the patient to rely on “knowing” consciousness instead.

Strategic retrieval hypotheses suggest a general retrieval failure of which temporal confusion is a common symptom. They note that since confabulation can concern experiences encoded and stored before the onset of brain damage, it seems to be associated more with memory retrieval rather than memory encoding or storage difficulties. According to these models, when memories are not elicited directly or automatically by a cue, the target memory needs to be recovered through strategic search processes akin to problem solving. Strategic retrieval processes operate at input to frame the memory problem and initiate a search, to constrain the search, and to guide it toward local, proximal cues that can activate associative memory processes. Then, once a memory is recovered, strategic processes operate at output to monitor whether the recovered memory is consistent with the goals of the memory task and whether it is consistent with other knowledge, thereby verifying whether the recovered memory is likely true or false. Memory-related confabulation represents a failure of one or more of these strategic processes.

Proponents of strategic retrieval have suggested a pair of mental systems that can help explain the process of the acceptance or rejection of an experience or a memory as true. The first is an intuitive “feeling of rightness” (FOR) that allows healthy individuals to reject memories that simply do not make sense. FOR is impenetrable to rational influences, suggesting it is formed outside of conscious awareness and may be affectively (emotionally) laden. FOR is thought to be defective in people who confabulate. It precedes the second system, which is a more advanced system that cross references FOR-validated material with the body of previously accumulated knowledge. Because confabulators do not have good memory retrieval, this second system will not filter out incorrect statements. All the confabulators are left with is the feeling of rightness response. FOR is hypothesized to be one function of the ventromedial PFC (vmPFC). Recall that neuroimaging studies showed that, as hippocampal volume decreased in Alzheimer’s patients, the vmPFC was increasingly activated, resulting in a shift to semantisation.

Although some models favor a disruption of frontal/executive functions involved in the control of retrieval from long-term memory, this involvement is controversial. Several studies on Alzheimer’s patients did not find any correlation between confabulation and performance on executive tasks, the ability to discriminate the origin of information, and/or working memory. Temporality models were developed, in part, in response to such findings. Similarly, studies comparing Alzheimer’s and FTD patients failed to provide any evidence of a correlation between the performance on frontal/executive tasks and the tendency to confabulate. Patients with FTD were found to confabulate more on both episodic memory and personal future planning tasks than patients with Alzheimer’s. It was suggested that “frontal executive” tasks are not able to discriminate between patients with primary frontal pathology (FTD patients) and patients with secondary frontal dysfunction (Alzheimer’s patients); and that the reason FTD patients are more prone to confabulate may be due to a more severe disruption of personal temporality in FTD.

Another area of controversy surrounds whether and/or how emotional mechanisms influence the presence or the content of confabulations. Initial evidence that confabulations may reflect unintentional motivations and drives that are positively biased led some researchers to coin the terms “motivated” or “self-enhancing” confabulation. This was not seen as an exaggeration of psychological motivation per se. Instead, it was conceptualized as the direct outcome of reduced executive control over memory. When irrelevant memory representations are not inhibited and memories are not retrieved in an appropriate manner, motivational factors may acquire a greater role in determining which memories are selected for retrieval and accepted as true. One study concluded that confabulations about current circumstances showed the positive bias, whereas confabulations about the past did not. More recent studies have found that, while an emotional bias may exist, it is not necessarily a positive one. Patients with various memory disorders had an enhanced tendency to produce confabulations with affective content (pleasant and unpleasant), and the affective content appeared to relate, at least in part, to the patient’s current mood-state.

The proposal that emotions might play a key role in the affective content of confabulations has received very little attention, even though it is consistent with what is now known about the anatomical basis of confabulating, notably its association with damage to key emotion-related structures in the medial frontal and anterior limbic areas. Memories with affective content (pleasant or unpleasant) are better remembered than neutral events. Emotional enhancement of episodic memory has been linked to the amygdala, a group of nuclei located in the medial temporal lobe. One hypothesis is that emotional arousal activates the amygdala and that such activation results in the modulation of memory storage or consolidation occurring in other brain regions, regulating the strength of memories in relation to their emotional significance. The amygdala is important in the creation of biases and in decision making. There is extensive evidence that the amygdala is crucially involved in regulating stress effects on memory. Stress hormones and stress-activated neurotransmitters enhance the consolidation of memory for emotionally arousing experiences through actions involving the amygdala. Such amygdala activation strengthens the storage of different kinds of information through the amygdala’s widespread network of efferent projections to other brain regions.

It is unlikely that regions of the brain that remain structurally intact are functionally insulated from the effects of damage elsewhere in the brain. In neurodegenerative diseases, such as Alzheimer’s, disruption of the functional integrity within individual regions, such as the hippocampus and amygdala, as well as connections between these regions, influences the functional milieu of the remaining network. One consequence of this breakdown is a decline in performance, such as the changes seen on tests of short-term episodic memory. At the same time, there is the possibility of compensatory changes that allow performance to remain above what would be expected given the extent of structural damage to the hippocampus and related regions. For example, the amygdala is not normally recruited in healthy older adults to any greater extent during memory tasks. A recent PET study of Alzheimer’s patients engaged in a delayed match-to-sample face recognition task, however, revealed that increased activity within the amygdala was found to be associated with better task performance during longer memory delays. Memory networks may be redirected towards the more primitive circuitry involving the amygdala and its connectivity with related brain structures as a buffer for episodic memory decline following degeneration of other medial temporal lobe regions, even though the amygdala as well as the hippocampus frequently undergo significant pathological changes in the early stages of Alzheimer’s.

3. HOW COMMON IS CONFABULATION IN DEMENTIA PATIENTS?

Several papers written by researchers who study confabulation commented that confabulation is “often” seen in dementia patients, but I did not find any papers which specifically studied the prevalence of confabulation in Alzheimer’s. What I did find was a handful of studies which compared the frequency with which various types of confabulations were observed in different dementias.

For example, one study compared Alzheimer’s and FTD patients using questions about temporality (personal past, orientation, and future planning). Patients in both groups had mild dementia, and were equally impaired on tests of executive function. Both groups confabulated across all three categories of confabulation, and produced significantly more confabulations in episodic memory than in semantic memory or personal future. However, FTD patients confabulated significantly more than Alzheimer’s patients on both episodic memory and personal future. The dementia groups produced fewer correct responses on the confabulation battery in comparison with normal controls, confirming that both a memory impairment and a deficit in personal future planning tasks are a part of the clinical picture of both Alzheimer’s and FTD. Interestingly, although FTD patients confabulated more frequently than Alzheimer’s patients on episodic memory and personal future, there was no evidence that there were any qualitative differences (i.e., differences in the content of the confabulations) between the two groups. Both patient groups produced the same type of “semantically appropriate confabulation”.

A case history suggested that at least some patients with behavioral variant frontotemporal dementia (bvFTD) may actually be demonstrating “fantastic thinking” (vividly experienced imagination) rather than delusions or spontaneous confabulations, and actually be aware that the false statements are imaginary.

One study compared Alzheimer’s with Lewy body dementia (LBD). The Alzheimer’s and LBD groups of patients were matched for age, illness duration, nature and severity of cognitive deficits, and regional blood flow distribution on SPECT. Confabulatory responses (as well as inattention, visual distractibility, impairments in establishing and shifting mental set, incoherence, perseveration, and intrusions) were significantly more common in LBD than in Alzheimer’s. However, it appears that the LBD group included patients who actually had Parkinson’s disease dementia (PDD) rather than LBD per se. When the data from these PDD patients were removed from the comparisons, the pattern of findings remained essentially unchanged, except that the differences in confabulation and memory interference no longer reached significance.

Another reported that confabulation is rare in patients who have MCI. (Note, please, that MCI is not a dementia per se, although about a third of patients with MCI do go on to develop a dementia.) There did not appear to be any differences in the prevalence of confabulating among patients diagnosed with amnestic MCI (deficits in memory), non-amnestic MCI (cognitive impairment is restricted to non-memory domains) and multiple MCI (both memory and non-memory domains of cognition are impaired).

What I found increasingly bizarre, the more I read, is that researchers who study confabulation don’t seem to be aware that dementia patients exhibit spontaneous confabulation. Confabulation is often described as an “infrequent disorder”. Spontaneous confabulation is repeatedly described as “rare”, in comparison with provoked confabulation. And yet, Alzheimer’s is now the sixth leading cause of death in the United States … and surely all of those who die from Alzheimer’s had exhibited spontaneous confabulation for quite some time before they died.

Statements by researchers who study confabulation that seem wildly incongruous to an Alzheimer’s caregiver:

“Most patients with spontaneous confabulation eventually stop confabulating.”

“Confabulators may occasionally act upon their confabulation.” (“Occasionally”? Later-stage Alzheimer’s patients persistently and repeatedly act upon the belief their childhood memories are relevant to their present circumstances.)

“Confabulations are usually limited in time; they relate to the recent past, the present, and the future.”

In sharp contrast, a recent study conducted by dementia experts to identify patterns of symptoms that can be used to diagnose dementias — i.e., a study involving patients who are still in the early stages of dementia –found that spontaneous confabulation was a symptom in roughly a third of patients with Alzheimer’s or mixed dementia, and a quarter of patients with vascular dementia. Earlier studies had found that spontaneous confabulation is significantly more common in FTD than other dementias, although this particular study only observed it in ~15% of FTD patients.

4. WHAT CAN BE DONE TO TREAT OR MINIMIZE CONFABULATION?

There is very little mention in the scientific literature of attempting to “treat” or minimize confabulations, even for patients with non-degenerative disorders. One recent paper commented, “Few reports of rehabilitation or management of confabulation exist in the literature, possibly because it is so difficult. Asking the patient to use a stricter criterion at retrieval, or to reason through a series of logical steps to see that his confabulation cannot be true, may do little to convince him, especially in the long run.”

Some researchers have had modest success asking the (non-neurodegenerative) patient to keep a “memory book” in which all activities are recorded, with date and time, and used as an aid in temporal and spatial reorientation. This may, in fact, be helpful in minimizing spontaneous confabulations on which early-stage Alzheimer’s patients act, since members of discussion forums have reported relying on similar types of memory devices to help them maintain their independence. Other measures to help the Alzheimer’s loved one remain oriented with respect to time include, e.g., clocks that show the day and date as well as the time, with a face large enough that all information is readily seen; a calendar to keep track of time and to remember important dates, kept it where it will be seen often; a newspaper delivered daily, and develop the habit of comparing its date with the calendar. Note, please, that orientation is not something to be forced on the loved one but, rather, something to be offered, to the extent the loved one can understand and appreciate it.

One study on early-stage Alzheimer’s patients confirmed that poor encoding can play a significant role in provoked confabulations. My take-away lesson is that distractions must be eliminated, to the greatest extent possible, when attempting to communicate with an Alzheimer’s patient. Turn off the TV and radio, make sure the loved one is focused on you, and do not expect (or allow) the loved one to try to do anything else while the two of you are talking. This may help minimize provoked confabulations … in the earlier stages.

While struggling to find hints helpful for the Alzheimer’s caregiver, I was struck by the discussion in one paper (Schnider 2003) that began, “Spontaneous confabulation is a pervasive disorder that represents a great challenge to any rehabilitation team.” The patients under consideration had suffered non-degenerative brain damage of some sort, and the general approach was to hope that the symptom would eventually resolve itself, and to support the patient in the meantime. The authors went on to say, “Early clinicians proposed avoiding memory training — such as repeated questions about orientation — with patients and engaging them in common everyday activities, accepting their false interpretation of reality as much as possible. Our studies support such an approach. Knowing that any cue can activate a memory and provoke a presently inappropriate action, patients should receive information about their hospitalization, but their false ideas about current reality should not constantly be corrected.”

This is, of course, advice that Alzheimer’s caregivers frequently share with each other.

In fact, the more I read this paper — one of the very few that exist on spontaneous confabulation — the more I thought I recognized my husband (stage 6 Alzheimer’s), as well as the loved ones of many caregivers who frequent discussion forums.

And so, I finally decided that, although I don’t recall having read any discussion of spontaneous confabulation in the Alzheimer’s patient … that is exactly what our loved ones do, more and more, as the disease progresses and they live more and more in the past. And while provoked confabulations are a major annoyance in the early stages — when friends, family, and the medical community take everything our loved ones say at face value, no matter how false we know their statements to be — spontaneous confabulations become a far greater concern in the later stages, because spontaneous confabulations are much more likely to be acted upon by the loved one.

Approaches that can be used to cope with spontaneous confabulation, and ease the confusion, frustration, and fear for the loved one, can be found in resources such as:

Jennifer Ghent-Fuller’s paper “Understanding the Dementia Experience”

Jolene Brackey’s book, Creating Moments of Joy

Naomi Feil’s “validation therapy”

The Savvy Caregiver training program

___

Alzheimer’s

Layers of memories separated in time
Photographic double exposures

~ Anonymous Caregiver

FURTHER READING AND REFERENCES

- Gilboa A, Verfaellie M. Telling it like it isn’t: the cognitive neuroscience of confabulation. J Int Neuropsychol Soc. 2010 Nov;16(6):961-6.

http://www.bu.edu/mdrc/PDFs/2010_Gilboa_JINS.pdf

- Dickerson BC, Eichenbaum H. The episodic memory system: neurocircuitry and disorders. Neuropsychopharmacology 2010 Jan;35(1):86-104.

http://www.nature.com/npp/journal/v35/n1/full/npp2009126a.html

- Budson AE. Understanding memory dysfunction. The Neurologist 2009;15: 71-79.

http://people.bu.edu/abudson/ctcn/Publications/2009%20Neurologist.pdf

- Lee E, Kinomura S, Meguro K, Akanuma K, Meguro M, Fukuda H. Confabulations on episodic and semantic memory questions are associated with different neurologic backgrounds in Alzheimer disease. Cogn Behav Neurol. 2009 Jun;22(2):81-8.

http://www.ncbi.nlm.nih.gov/pubmed/19506423

- Attali E, De Anna F, Dubois B, Dalla Barba G. Confabulation in Alzheimer’s disease: poor encoding and retrieval of over-learned information. Brain. 2009 Jan;132(Pt 1):204-12. Epub 2008 Oct 1.

http://brain.oxfordjournals.org/content/132/1/204.long

- Schnider A. Spontaneous confabulation and the adaptation of thought to ongoing reality. Nat Rev Neurosci. 2003 Aug;4(8):662-71. Note: there is little in this paper that is specific to Alzheimer’s patients, but this is one of the very few papers that focused on spontaneous confabulation. What was said rang true to me regarding the later stages of Alzheimer’s.

http://www.psychology.iastate.edu/~almorris/519%20readings/Schnider.2003.pdf

- Dalla Barba G, Boisse MF. Temporal consciousness and confabulation: is the medial temporal lobe “temporal”? Cogn Neuropsychiatry. 2010 Jan;15(1):95-117.

http://cogimage.dsi.cnrs.fr/hmtc/references/files/mctt/09_cnp2.pdf

- Addis DR, Wong AT, Schacter DL. Remembering the past and imagining the future: common and distinct neural substrates during event construction and elaboration. Neuropsychologia. 2007 April 8; 45(7): 1363-1377. This paper proposes a very interesting, and possibly highly relevant, hypothesis about the adaptive significance of the episodic memory system.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1894691/

- Rosenbaum RS, Furey ML, Horwitz B, Grady CL. Altered connectivity among emotion-related brain regions during short-term memory in Alzheimer’s disease. Neurobiol Aging. 2010 May;31(5):780-6. Epub 2008 Jul 17.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2842478

- Roozendaal B, McEwen BS, Chattarji S. Stress, memory and the amygdala. Nat Rev Neurosci. 2009 Jun;10(6):423-33. Note: this paper does not discuss confabulation or dementia per se; but much of what is said about affective disorders appears relevant to Alzheimer’s from a caregiver’s perspective.

http://anatomy.neurosciencegroningen.nl/txt/publications/roozendaal2009c.pdf

- Meulenbroek O, Rijpkema M, Kessels RP, Rikkert MG, Fernández G. Autobiographical memory retrieval in patients with Alzheimer’s disease. Neuroimage. 2010 Oct 15;53(1):331-40.

http://www2.ru.nl/vox/Meulenbroek-Proefschrift-spreads.pdf#page=42

- Reuter-Lorenz PA, Lustig C. Brain aging: reorganizing discoveries about the aging mind. Curr Opin Neurobiol 2005; 15:245-51.

http://www.rcgd.isr.umich.edu/life/Readings2007/Reuter-Lorenz%20reading%201.pdf

Continue reading »]]> Appleton

Alzheimer’s Center of Excellence
ThedaCare Behavioral Health
444 N. Westhill Boulevard
Appleton, WI 54914
920/720-2300 or 800/501-8247
Website

Beaver Dam

Memory Care Clinic
Beaver Dam Community Hospital
3rd Floor Hospital
707 S University Ave
Beaver Dam, WI 53916
920-887-4321
Website

Beloit

Stateline Area Memory Clinic
Beloit Clinic
1905 E. Huebbe Parkway
Beloit, Wisconsin 53511
608-364-1427
Website

Chippewa Falls

Marshfield Clinic
Chippewa Center
2655 County Highway I
Chippewa Falls, WI 54729
715-726-4200
Website

Eau Claire

Marshfield Clinic
Eau Claire Center
2116 Craig Rd.
Eau Claire, WI 54701
715-858-4500
Website

Luther Midelfort-Mayo Health System
Memory Care Clinic
Physicians: Donn Dexter, MD and Rae Hanson, MD
1400 Bellinger Street
5th Floor Neurosciences
Eau Claire, WI 54703
715-838-1900
Website

UW Health Eau Claire Family Medicine Clinic*
617 W. Clairemont Avenue
Eau Claire, Wisconsin 54701
715-839-5175
Website

Friendship

Memory Assessment Clinic
Moundview Memorial Hospital and Clinics
402 West Lake St
Friendship, WI 53934
608-339-8360
Website

Fort Atkinson

Fort Healthcare Memory Center
Outpatient Clinic
611 Sherman Ave East
Fort Atkinson, WI 53538
920-568-5334
Website

Hartford

Memory Assessment Center
Froedtert Health Hartford Clinic – West
402 W. Sumner Street
Hartford, WI 53027
(262) 670-4824
Website

Janesville

Janesville Geriatric Assessment Center
Mercy Clinic South
849 Kellogg Avenue
Janesville, WI 53546
608-755-7960
Website

Kenosha

Senior Services
Aurora Medical Center (Kenosha)
10400 75th St.
Kenosha, WI 53142
262-948-6648
Website

La Crosse

The Memory Center
Gundersen Lutheran Health System
1900 South Avenue
La Crosse, WI 54601-5496
(608) 775-9000
Website

Franciscan Skemp Healthcare
Dementia Care Program
800 West Ave S
La Crosse, WI 54601
608-392-9505
Website
Website

Madison

Memory Assessment Clinic
University of Wisconsin-Madison
2880 University Ave
Madison, WI 53705
608-263-7740
Website

UW-Health Clinics Geriatric Assessment Clinic (East)
5249 E. Terrace Dr.
Madison,WI 53718
608-265-1210 or 1-800-323-8942
Website

Geriatric Research & Education Center
William S. Middleton Veterans Hospital
2500 Overlook Terrace
Madison, WI 53705
608/280-7000 or 608/280-7061
Website

Dean Health System
Memory Assessment Program
Dean & St Marys Outpatient Center
700 S. Park St.
Madison, WI 53715
608-260-3425
Website

Manitowoc

Memory Assessment Clinic
Park Medical Center
601 North 8th Street
Manitowoc, WI 54220
920-682-4646
Website

Holy Family Memorial
Memory Assessment Clinic
2300 Western Ave
Manitowoc, WI 54220
920-320-3880
Website

Marquette

Memory Diagnostic Center of Upper Michigan
580 West College Avenue
Marquette, MI 49855
906-225-3993 or 888-886-4644
Website

Marshfield

Memory Disorders Clinic
Marshfield Clinic
1000 N. Oak Ave.
Marshfield, WI 54449-5777
715-387-5350 or 800-782-8581
Website
Website

Mauston

Mile Bluff Medical Center
Memory Assessment Clinic
1040 Division St.
Mauston, WI 53948
608-847-5000
Website
Website

Menomonee Falls

Senior Health Memory and Mood Disorders Clinic
Community Memorial Medical Commons (CMMC)
W129 N7055 Northfield Dr
Building A, Suite 302
Menomonee Falls, WI 53051
262-253-2450
Website
Website

Milwaukee

Memory Disorders Program
Froedtert Neurosciences Center
Froedtert Memorial Lutheran Hospital
9200 W Wisconsin Ave
Milwaukee, WI 53226-3596, Milwaukee County
414-805-8710
Website

Center for Senior Health and Longevity
Aurora Sinai Medical Center
945 N 12th St
Milwaukee, WI 53233
414-219-7300
Website

Aurora Health Center – Midtown
Memory Disorder, Dementia Evaluation & Treatment Clinic
5818 W. Capitol Dr
Milwaukee, WI 53216
414-449-2114
Website

United Community Center*
Latino Geriatric Center Memory Clinic
1028 S. 9th Street
Milwaukee, Wisconsin 53204
414-649-2855
Website

Milwaukee Health Services
MLK Heritage Health Center
2555 N. Dr. Martin Luther King Jr. Drive
Milwaukee WI 53212
414-372-8080
Website

Wheaton Franciscan Healthcare
Alexian Village Retirement Community
9255 N. 76th Street
Milwaukee, WI 53223
414-357-5233
Website

Neenah

Neuroscience Group of Northeast Wisconsin
1305 W. American Drive
Neenah, WI 54956
920-725-9373
Website

Platteville

Southwest Health Center
Memory Diagnostic Clinic
1185 N. Elm Street
Platteville, Wisconsin 53818
608-348-3656
Website

Racine

Senior Services
Aurora Medical Center (Racine)
8348 Washington Ave.
Racine, WI 53406
262-884-4138
Website

Wheaton Franciscan Healthcare
Memory Disorder Services
3805B Spring Street, Suite 320
Racine, WI 53405
262-687-8322
Website
Website

Rice Lake

Marshfield Clinic
Rice Lake Center
1700 West Stout Street
Rice Lake, WI 54868
715-236-8100
Website

Richland Center

Richland Medical Center
Geriatric Assessment Clinic
Center Creek Professional Building
1313 West Seminary Street
Richland Center, WI 53581
608-647-6161
Website

Rhinelander

Marshfield Clinic
Rhinelander Center
3716 Country Drive
Suite 6
Rhinelander, WI 54501
715-369-5051
Website
Website

Northern Wisconsin Memory Diagnostic Center
Ministry Medical Group — Riverside Clinic
1020 Kabel Avenue
Rhinelander, Wisconsin 54501
715-361-4880
Website

Spooner

Spooner Health System Memory Clinic
819 Ash Street
Spooner, WI 54801, Washburn County
715-635-1442
Website

Sturgeon Bay

Ministry Memory Clinic Door County
Ministry Door County Medical Center
323 S. 18th St.
Sturgeon Bay, WI 54235
800-864-6179
Website

Summit

Center for Senior Health and Longevity at Summit
Aurora Summit Medical Clinic
4th Floor Internal Medicine Clinic
36500 Aurora Dr.
Village of Summit, WI 53066
262-434-1000
Website

Waukesha

Senior Health Center
Waukesha Memorial Hospital
Professional Office Building
721 American Avenue, Suite 508
Waukesha, WI 53188
262-928-7898
Website

Wausau

Aspirus Memory Clinic
Aspirus Wausau Hospital
2720 Plaza Drive, Suite 1400B
Wausau, WI 54401
715-847-2004
Website

Marshfield Clinic
Wausau Center
2727 Plaza Dr.
Wausau, WI 54401
715-847-3000
Website

Wauwatosa

Wheaton Franciscan Geriatric Medicine
10100 W. Bluemond Rd.
Wauwatosa, WI  53226
414-874-1201
Website

Weston

Marshfield Clinic
Weston Center
3501 Cranberry Boulevard
Weston, WI 54476
715-393-1000
Website

Continue reading »]]> Asheville

Mountain Memory Assessment
56 College St., Ste 204
Asheville, NC 28801
(828) 545-7776?
Website

Memory Assessment Clinic
MemoryCare™
100 Far Horizons Lane
Asheville, North Carolina 28803
(828) 771-2219?
Website

Chapel Hill

UNC School of Medicine
Geriatric Specialty Clinic
6013 Farrington Road, Bldg 200 Ste 301
Chapel Hill, NC 27514
919-957-6599
Website

Charlotte

The Alzheimer’s Memory Center
485 N. Wendover Road
Charlotte, NC 28211
704-364-4000
Website

The Neurological Institute
2219 East 7th Street
Charlotte NC, 28204
888-898-0963
704-372-3714
Website

Columbus

St. Luke’s Hospital
Center of Behavioral Medicine
101 Hospital Drive
Columbus, NC 28722
(828) 894-3311 ?
Website

Durham

Joseph and Kathleen Bryan Alzheimer’s Disease Research Center
Memory Disorders Clinic
Duke Health Center
932 Morreene Road
Durham, NC 27705
(919) 668-7600
Website
Greensboro

Guilford Neurologic Associates
912 Third Street, Suite 101
Greensboro, NC  27405
(336) 273-2511
Website

High Point

High Point Regional Health System
Neuroscience Center
601 North Elm Street
High Point, NC 27262-4331
(336) 878-6888
Website

Cornerstone Neurology
1814 Westchester Drive, Suite 401
High Point, NC 27262
336 802-2080
Website

Statesville

Piedmont HealthCare
- Neurology
341 Brookdale Drive
Statesville, NC 28677
(704) 873-1100
Website

Wilmington

Memory Assessment & Research
1241A Military Cutoff Road
Wilmington, NC 28405-3637
(910) 962-7898
Website

Winston-Salem

Kulynych Memory Assessment Clinic
J. Paul Sticht Center on Aging and Rehabilitation
Wake Forest Baptist Medical Center
Medical Center Boulevard
Winston-Salem, North Carolina 27157
336-713-8963
Website

Triad Neurological Associates
145 Kimel Park Drive, Suite 100
Winston-Salem, NC 27103
336 768-6347
Website

Continue reading »]]> 1. WHAT IS SUNDOWNING?

Surprisingly, that’s not an easy question to answer. Sundowning is a descriptive term rather than a diagnosis. Different researchers have different definitions — which has complicated attempts to study the symptom, determine what causes it, and find ways to treat it.

Broadly speaking, sundowning is a cyclical increase in agitation (which may include restlessness, confusion, disorientation, wandering, searching, escape behaviors, tapping or banging, vocalization, combativeness, and/or hallucinations) that takes place at roughly the same time every day. Despite its name, and the wide-spread belief that sundowning occurs in the late afternoon and early evening, studies have found that the peak of sundowning activity is more likely to occur in the early- to mid-afternoon (e.g., around 1:00pm), while in some patients, it may occur late at night. It may even peak in the early morning in a fairly high percentage of patients.

For those of you struggling to cope with sundowning — whenever it peaks — take heart:  many researchers have reported that it tends to occur in the middle stages of dementia, and to disappear as the dementia progresses.

2. WHAT CAUSES SUNDOWNING?

Many researchers consider sundowning to be a type of agitation, called “spontaneous agitation”, that is caused by two factors, i.e.:
(1) Confusion, over-stimulation, and fatigue during the day, which results in increased disorientation, restlessness, and insecurity at night.  And
(2) Fear of the dark, perhaps because of the lack of familiar daytime noises and activity and the lack of visual cues. The loved one may not be able to see as well in the gathering dusk, and/or be disturbed by strange shadows or reflections in window glass.

Others consider it to be a type of sleep disturbance that is “characterized by nocturnal wandering and confusion”. Sundowning and sleep disturbance may appear to be related to each other since a sleep disorder, such as sleep disordered breathing, can be associated with a daytime behavior disorder.

However, more recent studies have concluded that sundowning is a chronobiological phenomenon that is unrelated to sleep disturbances.  It is thought to be caused by a disturbance in the normal circadian rhythms, i.e., the “internal clock”.  Human circadian rhythms are biological cycles of ~24 hours that include sleep/wake, body temperature, and melatonin secretion cycles. They are regulated, in large part, by the suprachiasmatic nucleus (SCN), a cluster of neurons in the anterior hypothalamus. The SCN deteriorates significantly in Alzheimer’s disease, contributing to disruption of circadian rhythms.

Decreased exposure to bright light has been suggested as a factor that contributes to the disruption of the circadian clock in dementia patients. Bright light (>2,000 lux) is one of the most powerful synchronizers of circadian rhythms and directly influences secretion of melatonin, sleep/wake patterns, and body temperature cycles. Young adults and healthy older people are, on average, exposed to one hour of bright light a day, whereas Alzheimer’s patients living at home are exposed to only 30 minutes a day, and Alzheimer’s patients living in nursing homes are typically exposed to little or no bright light above 2,000 lux and only 10-20 minutes a day to light above 1,000 lux.  However, it should be noted that the circadian rhythm disturbances in frontotemporal dementia (FTD) patients differ significantly from those in Alzheimer’s patients. For example, in one study, Alzheimer’s patients showed increased nocturnal activity and a significant phase-delay in their rhythms of core-body temperature and activity compared with FTD patients (and controls); whereas the activity rhythm of FTD patients was highly fragmented and phase-advanced in comparison with controls and apparently uncoupled from the rhythm of core-body temperature. The implication is that environmental factors such as exposure to bright light could not have caused differences between the two groups of dementia patients, suggesting a neurobiological basis for the time-dependent changes in activity.

Some studies have found no clinical evidence for the existence of sundowning per se. Studies that monitored agitated behaviors throughout the 24-hour day have repeatedly found that roughly the same number of patients exhibited cyclical agitated behavior in the early morning as those exhibiting it in the late afternoon/early evening. One conclusion was that disruptive behaviors which occur in the evening simply are noticed and reported much more frequently because they have a greater impact on caregivers. By the end of the day, the caregivers (whether at home or in a nursing facility) are too tired and irritated to cope with the loved one’s behaviors as easily and effectively as they could when they were fresh and rested, and are also likely to be distracted by shift changes, family returning home from work/school, and evening chores such as preparing/serving dinner. Although often noticed, the “sunrising” phenomenon has rarely been studied, in and of itself, since cyclical early morning agitation has been dismissed as a symptom of depression, which is often worse in the early morning. However, a study designed specifically to determine whether there is a correlation between “sunrising” and depression did not find one.

3. HOW COMMON IS SUNDOWNING?

Reports of sundowning in Alzheimer’s patients are typically in the 10 – 25% range, but have been as low as 2.4% and as high as 66%. Not surprisingly, the prevalence that is reported depends on the definition of “sundowning” that is used, and the type of population involved in the study (e.g., the type and level of dementia and the environment in which the patients live).

4. WHAT CAN BE DONE TO MINIMIZE SUNDOWNING?

Conventional recommendations for treating sundowning behavior revolve around trying to establish “good sleep hygiene”, a reflection of the widely-held belief that sundowning is a sleep disorder.  However, there are a number of other approaches to consider, as well.

4.1. Is it really sundowning?

First, be sure that what you are observing actually is “sundowning”.  Is the behavior new and did it appear suddenly?  Have the doctor check for infections (especially urinary tract infections, UTIs) and dehydration. Perhaps your loved one recently had a new stroke or was hurt in a fall. Flare-ups of chronic diseases such as diabetes or heart, liver, or kidney disease can also cause agitation or delirium.

Pain is undiagnosed or undertreated in a staggeringly high percentage of dementia patients, and is a major cause of agitation and sleeplessness. Could your loved one be suffering from arthritis, constipation, gastroesophageal reflux, or sitting all day in an uncomfortable position? Tools to help you evaluate whether your loved one is in pain can be found at the University of Alberta and AlzBrain websites.

Perhaps your loved one takes a medicine that would control some source of discomfort, and that is wearing off at the time when the “sundowning” behavior appears.

Conversely, a medicine might be causing the symptoms you’re seeing. Medicines that are commonly prescribed for dementia patients often have side effects that negatively affect sleep and wakefulness, or cause agitation or discomfort. Aricept, for example, can cause dream disturbances and/or insomnia.  Antidepressants (especially SSRIs) can induce or exacerbate periodic limb movements in sleep (PLMS).  Atypical antipsychotics increase daytime fatigue and somnolence, and may induce restlessness or akathisia. Check any medicines that your loved one takes — even those he has been taking for a long time — for possible adverse effects. Also, consider the possibility of drug interactions that can exacerbate adverse effects or make one or both of the drugs less effective.  Talk with the doctor or pharmacist about the possibility that your loved one is on the wrong dose, possibly due to kidney or liver problems, or weight loss or gain.

Your loved one may be getting tired and irritable due to a sleep disorder. There are many different sleep disorders that may develop in dementia patients, such as sleep-disordered breathing, PLMS, restless legs syndrome (RLS), obstructive sleep apnea, nocturnal myoclonus, and parasomnias (e.g., REM sleep behavior disorder, RBD.) The treatments that are most likely to be helpful depend on the specific type(s) of sleep disturbances involved. For example, patients suffering from sleep apnea have difficulty breathing; depending on the cause of the apnea, treatment may be, e.g., a change in diet, simple devices to encourage sleeping in a different position, an oral appliance which prevents airway blockage, or a CPAP (continuous positive airway pressure) machine. RLS is caused by a functional disturbance in the dopaminergic system, and so the treatment of choice consists of dopaminergic drugs or dopamine agonists such as pergolide or pramipexole.

Depression is very common in dementia patients. Diurnal mood variation, a pattern of mood variability in which a person’s worst and best moods vary in a predictable fashion, is a symptom of major depression. Mood is most commonly worse in the morning and better in the early evening, but the opposite pattern occurs as well. As noted elsewhere, variability in mood associated with depression is not sundowning (or “sunrising”), and may be responsive to an antidepressant.

Specific interactions with other people might be the culprit. For example, dementia patients in nursing homes might become upset by visitors they don’t recognize or don’t like, or by strangers who are visiting other residents of the facility. Because visiting hours are time-regulated, this reactive agitation might appear to have a temporal association.

Your loved one’s behavior might even be due to something as simple as hunger and/or thirst. Try serving dinner earlier, or offering a snack or something to drink until dinner is ready.

4.2. Good sleep hygiene

Conventional wisdom for treating sundowning has been to try to help re-establish a “normal” sleeping pattern, coupled with taking steps to minimize factors that might trigger fear or confusion:

• Increase your loved one’s daytime activities, particularly physical exercise, and discourage inactivity and napping during the day. If fatigue is exacerbating the sundowning, try a brief (one hour) nap, early afternoon or just before the usual sundowning time. If the loved one won’t nap, an hour of quiet time — sitting quietly and talking together, for example, or listening to soothing music — may help.
• Since an Alzheimer’s patient is usually better able to tolerate outings, activities and increased stimulus during the earlier part of the day, plan trips to the grocery store, involvement with kids, visits to day care and so forth during the morning.
• Even during the earlier part of the day, an Alzheimer’s patient can tolerate only so much stimulation and commotion. Take steps to eliminate over-stimulation such as noisy television or radio, boisterous children, quick movements, and many things going on at one time.
• Sometimes excessive stimulation cannot be avoided. Make sure that there is a private “time out” place where your loved one can retreat for peace and quiet. Make it off-limits to children and general traffic; even the caregiver should try not to intrude unless absolutely necessary.
• Don’t physically restrain the loved one. Let him pace where he is safe. A supervised walk outdoors can help reduce restlessness. Indoors, clear all clutter and obstacles (e.g., low coffee tables and foot stools) from your loved one’s walking paths. Keep knickknacks to a minimum and the tops of tables, shelves, and other surfaces as clear as possible. Mirrors and pictures may be interpreted as unfriendly visitors; complicated, noisy appliances can be frustrating. Avoid making changes once you have things simplified.
• Give diuretics and laxatives early in day.
• Plan for the afternoon hours to be quiet and calm, to allow your loved one to unwind and relax. However, structured, quiet activity is important. Perhaps take a stroll outdoors, play a simple card game, or sing favorite songs together.
• Early evening activities that are familiar from an earlier time in the person’s life may be helpful, for example, walking the dog, a pre-dinner drink, or assisting with preparing dinner or setting the table.
• Physical discomfort — hunger, being wet or soiled, or feeling cold/hot — can play a part in sundowning. Light snacking during the day can be helpful. Apples and other fruits can help replace lost energy; even a loved one who is pacing back and forth does not have an endless supply of energy.
• Turning on lights well before sunset and closing the curtains at dusk will minimize shadows and may help diminish confusion.
• Discourage drinking stimulants (e.g., caffeine) or smoking near bedtime.
• Set a quiet, peaceful mood in the evening to help the loved one relax. Keep the lights low, and try to reduce the noise levels, e.g., from television and radios. Some loved ones are comforted by soft toy animals, pets, hearing familiar tunes, or an opportunity to engage in a favorite pastime.
• Have a bedtime routine. Try to have the loved one go to bed at the same time each night. Have a routine for getting ready for bed, such as taking a bath and having some warm milk, a back rub, or perhaps reading out loud.
• Make sure the loved one gets enough rest at night. Provide a comfortable bed. Create a calm atmosphere for sleeping. Reduce noise and light. Stuffed animals or a pet may soothe the loved one and allow them to sleep. Soothing music may help, or a recording of ocean waves or a mountain stream, or even “white noise” from, e.g., a fan.
• Have the loved one use the toilet right before bedtime, to minimize the need for nighttime toileting. Place a commode next to the bed for nighttime urination. Walking to the bathroom in the middle of the night may wake the loved one up too much, making it difficult to get back to sleep.
• Close the curtains and leave night lights on in the bedroom, hall, and bathroom if the darkness is frightening or disorienting.

Most of these recommendations appear (to me) to be based on common sense. A few, however, might be somewhat controversial, as will be discussed later.

Such recommendations have rarely been studied in clinical trials. I did find one, called “NITE-AD” (McCurry et al 2005), which was focused primarily on sleep disturbances. At the end of six months, loved ones whose caregivers were trained in a combination of sleep hygiene, daily walking, and light exposure interventions were found to have fewer nighttime awakenings, less total time awake at night, and less depression. The researchers noted that, given the design of the study, it was impossible to determine whether an individual intervention or some combination of interventions had the greatest effect on the outcomes.

I found it curious that the paper did not present any data on “secondary outcomes” other than depression, such as disruptive behaviors — even though the data was collected — and ignored the worrisome (to me) observation that NITE-AD patients exhibited a trend toward more-rapid cognitive decline over time. Granted, the trial was very small and the data might have been skewed … but that is true of all the data, not just the rates of cognitive decline.

4.3. Support a “normal” circadian rhythm

As sundowning is being established more firmly as a chronobiological phenomenon, measures intended to help re-establish a “normal” circadian rhythm are being suggested more often for treating it.  These include:

- Designing ChEI therapy to support, rather than disrupt, the circadian rhythm

Deterioration of the brain’s cholinergic system is a hallmark of Alzheimer’s, with degeneration of cholinergic neurons in the basal forebrain being one of the first biochemical changes that is seen. The cholinergic system comprises the neurotransmitter acetylcholine, the enzyme cholinesterase (whose function is to destroy excess acetylcholine), and cholinergic receptors. The Alzheimer’s brain does not produce adequate acetylcholine for optimum neurotransmission. Drugs such as Aricept/donepezil, Razadyne/galantamine, and Exelon/rivastigmine are cholinesterase inhibitors (ChEIs), i.e., they prevent the enzyme from destroying as much of the acetylcholine as usual, thereby effectively increasing its levels in the brain and increasing cholinergic activity.

The cholinergic system has a pronounced circadian rhythm upon which sleep, waking, and fundamental aspects of learning depend. For example, in general, the healthy brain has low levels of acetylcholine during slow-wave sleep, and high levels during wakefulness. ChEIs have the potential to either mitigate disease-induced disturbances of the cholinergic rhythm by raising acetylcholine levels (increasing cholinergic activity) during the day, or to exacerbate sleeplessness and agitation by preventing the normal fall in acetylcholine levels (and thereby interfering with the normally reduced cholinergic transmission) at night.

The ChEI drug that is used and the time of day at which it is given can determine whether the normal cholinergic transmission and rest-activity cycles are supported or undermined. For example, Aricept/donepezil has a very long half-life (70 hours) in the body. Since its concentration in the blood doesn’t vary much over the course of a 24-hour day (once the loved one has reached steady state, i.e., has been taking a given dose of the drug for a couple of weeks), it maintains high levels of acetylcholine in the brain at night, even if the drug is given in the morning. Aricept therefore has the potential to disrupt sleep and trigger insomnia. Razadyne/galantamine, on the other hand, has a much shorter half-life (7 hours). The extended-release formulation administered in the morning, in particular, helps support the normal circadian cholinergic rhythm, maintaining higher levels of the drug in the blood (and thereby higher levels of acetylcholine in the brain) during the day and lower levels at night.

- Bright light therapy

Since exposure to light plays a major role in regulating the phase relationships among core body temperature, melatonin rhythm, and the circadian rest-activity cycle, bright light therapy is frequently suggested as one simple way to help treat sundowning.

There is evidence that bright light can be used to change the timing of circadian rhythms (the circadian “phase”) or, when administered at certain times of the day, may increase the amplitude of circadian rhythms without necessarily affecting the phase. Some — but not all — studies have found that circadian rhythms in older adults are phase-advanced, that is, the rhythms are shifted to an abnormally early time, resulting in the adults falling asleep and waking up earlier than usual. Conversely, some Alzheimer’s patients have phase-delayed activity, that is, sleep onset and morning rising are shifted to abnormally late times. Evening bright light has been shown to delay circadian rhythms, whereas early morning light has been shown to advance circadian rhythms. As a result, advanced rhythms, such as those seen in healthy older adults, might be beneficially delayed with exposure to evening light, whereas a phase delay such as that seen in Alzheimer’s may be beneficially advanced with exposure to morning light.

Results from clinical studies on dementia patients, however, have been inconsistent — quite possibly due to differences in the type of light that was used, the length of exposure, and the time of day the therapy was implemented.  Some researchers have suggested that more consistent results might be obtained if only one type of dementia were included in a study, or if the studies did not focus on severely impaired institutionalized patients who are likely to have incurred more marked SCN degeneration. Women show different patterns of sleep and circadian physiology during aging than men, so perhaps the genders should be studied separately. Some researchers suspect that other factors are likely to have been involved, that were not detected due to lack of appropriate controls. One wonders whether more consistent results might have been seen if subjects were screened to eliminate dementia patients who suffer from sleep disorders and other common causes of agitation (e.g., pain), for example.

In any event, some of the largest and best-designed studies found no improvement in nighttime sleep or daytime alertness from bright light therapy, and/or no improvement in agitated behavior, and one study actually reported an increase in behavioral problems. (Note: bright light can contribute to eyestrain and headaches, and can cause glare and reflection off polished surfaces which, in turn, can cause confusion, agitation, and anger.)

- Melatonin supplements, alone and in combination with bright light therapy

As noted above, circadian rhythm disturbances have been linked to abnormalities in the SCN. Rhythmic nocturnal melatonin secretion from the pineal gland is directly generated by the circadian clock located in the SCN. Because several studies suggest that melatonin levels are either low or dysregulated in Alzheimer’s, oral melatonin supplements have been proposed as a treatment for sundowning.

However, clinical trials on the use of melatonin for treating sundowning or sleep disorders have failed to show that the approach will be broadly beneficial for dementia patients.  A recent multicenter, placebo-controlled trial of melatonin for sleep disturbance in Alzheimer’s disease found, on average, no significant improvement in objective measures of sleep. Some patients showed improved sleep quality (less interrupted sleep and reduced daytime sleepiness and agitation), some showed no effects on sleep, and some patients became more aggressive. Three double-blind, placebo-controlled studies with objective assessment criteria for measuring sundowning behavior itself — not sleep per se — produced conflicting results. Two concluded that there was a small but statistically significant improvement in sundowning/agitated behavior, although one of these noted that melatonin was less effective than morning bright light therapy. The third controlled study concluded there was no improvement.

The stage of dementia may affect the potential benefit of melatonin. For melatonin to have an effect, it must be able to bind to melatonin receptors. Since the numbers of melatonin MT1 receptors in the SCN are extremely low in late-stage Alzheimer’s patients (i.e., only 10% of those found in age-matched controls), supplementary melatonin in the late stages may not have a discernible effect on circadian rhythm disorders. Moreover, the sleep/circadian timing systems are the product of complex interactions among multiple brain regions, neurotransmitter systems and modulatory hormones. The rhythmic levels of many other hormones besides melatonin (e.g., cortisol, vasopressin, pulsatile luteinizing hormone, testosterone secretion, dehydroepiandrosterone, beta-endorphine) may be affected in Alzheimer’s patients. Since abnormalities in any key neurotransmitter system will impinge on the sleep/circadian timing systems at multiple levels, oral supplements of a single hormone are unlikely to readjust the entire, complex sleep/circadian timing systems as the dementia progresses and more of these neurotransmitter systems are damaged.

Studies on bright light therapy in combination with melatonin supplements have also produced conflicting results. Haffmans et al (2001), for example, found that bright light therapy has a positive effect on sundowning, whereas bright light therapy plus melatonin does not. They hypothesized that the treatment, as designed, “overshot” the chronobiological synchronization of the melatonin supplement. (In healthy people, the density and the sensitivity of melatonin receptors are elevated during the daytime, when endogeneous melatonin levels are low. Hence, a melatonin dose given at a time when melatonin receptor density and sensitivity are lowest may show no effect compared with the same dose given when receptor density and sensitivity are highest.) Others found that the combination reduced agitation and improved several sleep parameters, although some adverse side effects were reported (dysphoric mood, irritability, dizziness, and headache.)

One recent study concluded that melatonin should only be used in combination with bright light therapy. Melatonin by itself shortened sleep onset latency and increased total sleep time; however, it also decreased affect ratings and increased withdrawn behavior, which were counteracted by light therapy. (“Affect” refers to the experience of feeling or emotion.)

All of these were relatively short-term studies. It should be noted that the safety of long-term use of melatonin supplements has never been established.  Melatonin can cause a number of serious side effects — including confusion and depression — which become more likely as the patient continues to receive it. Supplemental melatonin may exacerbate seizure disorders, which is a concern for Alzheimer’s patients since they can develop seizure disorders at any stage. Since melatonin shrinks arteries, it may be contraindicated in loved ones with cardiovascular disease (including vascular dementia). It may also aggravate autoimmune disorders (which can cause dementia symptoms) such as arthritis and severe allergies.

Daily administration of melatonin, even of a low dose (e.g., < 3 mg) can cause the loved one to build up a tolerance, and can eventually disrupt, rather than improve, sleep in some people. Also, melatonin can have serious interactions with a number of medicines, including the antidepressants that are often prescribed for Alzheimer’s patients,  blood thinners (e.g., warfarin, heparin), blood pressure medications (especially nifedipine), drugs that may affect the immune system (e.g., azathioprine, cyclosporine, prednisone), and fluvoxamine. Anyone considering starting a loved one on melatonin should first discuss it with the doctor and the pharmacist.

- Physical activity

Numerous studies have concluded that exercise can help minimize or eliminate agitated behavior in dementia patients. Exercise also has been linked to phase shifting of circadian rhythms as well as promotion of more restful sleep in older adults, and is considered to be likely to do the same for dementia patients, although no controlled trials that looked at the isolated effects of exercise on sleep in dementia have been done, to my knowledge. Regular exercise also builds muscle mass, improves strength, reduces falls, and improves mood. There do not appear to be any down sides to physical activity, as long as the exercise program is designed for the capabilities and interests of the loved one, whereas there are many potential benefits.

4.4. Let them eat chocolate

Over the past dozen or so years, Alzheimer’s care has been undergoing a major paradigm shift, toward “person-centered care”. Person-centered care is based on the premise that the personality of the loved one is increasingly concealed rather than lost, and therefore seeks to personalize the loved one’s care and environment, to honor who he is and what brings him joy.

This has led to recognition of the fact that the loved ones’ behaviors may often be understood as expressions of their individual desires and needs, rather than simply as symptoms of the disease process. As the loved ones’ dementia advances, they experience increasing deficits in all aspects of their lives, but most especially and importantly, they lose the ability to verbally communicate their needs — physiological, psychological, spiritual, social, and comfort needs — to others. Their behaviors become the conduit for expressing their needs, pleasures, and frustrations. Stress, from fatigue, changes in routine, caregiver, or environment, demands that exceed the loved one’s ability to function, multiple and competing stimuli, perceptions of loss, and physiologic factors such as illness, pain, discomfort, and adverse effects of medications, can result in anxiety and increasingly dysfunctional behaviors. In this context, behavioral “symptoms” — both verbal manifestations such as repetitive questioning or vocalizations and non-verbal ones including withdrawal or physical violence — can be interpreted as communications meant to convey specific messages and to achieve particular goals relating to unmet needs. Comfortable people do not hit, scream, pound on tables, or call out.

If the loved one’s needs remain unmet while the caregivers’ energies are directed toward curtailing the behaviors themselves, the likely outcome of this miscommunication is a vicious cycle of further withdrawal and isolation due to perceived inability of the loved one to interact effectively with others, leading to increased depression and anxiety, leading to more dysfunctional behaviors.

Here we get to the crux of it:  If the loved one’s circadian rhythm is out of whack, and we struggle mightily to force the loved one into wake-sleep patterns that fit our own circadian rhythms instead of his, won’t we be in danger of increasing his agitation, as an expression of his stress, fears, and discomfort?  And to my way of thinking, this concern is supported by the rash of studies, both recent and not so recent, which have shown that allowing dementia patients to be active when they choose to be active, and sleep when they choose to sleep, may decrease, or even eliminate, serious behavioral problems.

For example, in a study of more than 50 nursing homes (Sloane et al 1998), the proportion of residents who exhibited an agitated behavior varied from “none” in several homes to 38% in one home. Lower rates of agitation were seen in homes that had higher proportions of residents in bed during the day.

More recently, the Parker Jewish Institute in New Hyde Park, NY, implemented a “midnight snack” program, giving wanderers access to food and beverages at will in the middle of the night, instead of insisting that they go back to bed. They report that the program resulted not only in far less agitation among their residents, but also in a sharp decrease in falls and related injuries, and even a huge decrease in pressure sores.

The Hebrew Home at Riverdale in New York established “ElderServe at Night”, an “Adult Night Care” program that offers activities and socialization, meals and showers, and even evening trips to the circus or nearby restaurants, for loved ones who are active at night and sleep during the day.  Both the patients and their caregivers are enthusiastic about the program.  The patients are more alert and happy, and exhibit far fewer behavioral problems, while their families can sleep soundly through the night.

Beatitudes nursing home in Phoenix has gone even further, setting up a person-centered care facility in which residents are allowed to sleep, be bathed, and dine whenever they choose, and eat and drink whatever appeals to them — even a little alcoholic “nip” now and then. There is a 24-hour restaurant which functions as the primary dining room and snack area. There is an around-the-clock activity program, that offers a balance of sensory-calming and sensory-stimulating activities individualized to each resident. Instead of group activities such as bingo, in which few residents could actually participate, they conduct one-on-one activities — block-building, coloring, simply conversing — and use art, music, and exercise to “generate positive emotions”, and the outdoors to create connections with the wind, bird song, and sunshine.  They have eliminated anything that might be considered restraining, from deep-seated wheelchairs that hinder standing up to bedrails (although some beds are lowered and protected by mats). Bathing is a pleasurable experience and the towel bath method is an option for those who no longer enjoy a shower. Instead of using antipsychotics to treat serious behavioral issues, emphasis is on adequate pain medication and antidepressants. There is no sundowning — even though the facility is specifically for patients with moderate to severe dementias (of all sorts, including frontotemporal dementia and dementia with Lewy bodies), and accepts those who previously exhibited serious behavioral problems; and even though residents are allowed to stay until they die.

In 2005, Beatitudes instituted a training program for qualified and interested nursing facilities to learn best practices in person-centered dementia care. Those facilities similarly report a reduction in the use of antipsychotic, antidepressant,  and sedative medications, decreased use of physical restraints, decreased weight loss, and less hospitalization and emergency department use.

In short, it seems prudent to adjust “conventional wisdom” recommendations to take personal preferences of the loved one into account, including preferences for wake/sleep cycles and napping, to the greatest extent practicable. One caregiver on a discussion forum noted that her loved one was very resistant to staying in bed at night, and was developing behavioral problems. The situation was resolved simply by offering a midnight snack. Beatitudes emphasizes that it is much easier and more effective to anticipate needs rather than wait for a behavior to occur. Caregivers need to be sure to identify discomfort (such as pain, constipation, skin deterioration, malnutrition, physical exhaustion, and adverse drug effects) and manage it effectively. Offer food and drink frequently; anticipate bowel and bladder needs by regularly escorting the loved one to the bathroom (on the loved one’s schedule); and assure other comfort needs are met such as comfortable clothing, room temperatures, and lighting and noise levels. Activities need to be meaningful to the loved one, with the opportunity to make connections to the people and the environment around him; and should be offered to the loved one, not forced on him. Remember that too much stimulation can be just as harmful (if not more so) as too little.

It is one thing for a well-staffed facility to cater to its residents’ unique needs, but it may not be practical for the at-home caregiver to adjust the entire household to the rhythms of the loved one.  If your loved one simply must be active in the middle of the night, one thing that might be considered is setting up a “safe room” where your loved one can safely pace, which allows you to sleep more soundly.  Beverly Bigtree Murphy (if you’re not familiar with her website, you should be) describes the “safe room” she set up for her husband — who paced at night for two years.

5. When all else fails

Learning person-centered care techniques sounds like a lot of hard work and effort. Actually, the sooner the caregiver begins learning “how to speak Alzheimer’s”, the better off everyone will be, and the less likely that behavioral problems will crop up. Studies have repeatedly shown that caregivers trained in non-drug interventions can not only reduce the frequency and severity of behavioral symptoms and produce higher quality of care for their loved ones, but also reduce their own depression and burden.

Are there medicines that may help?  There is some evidence that antipsychotics may help reduce agitation in select patients, but little evidence to support the use of other drugs that are sometimes suggested, such as benzodiazepines, antihistaminics, anticonvulsants, monoamine oxidase inhibitors, or SSRIs. To date, there is no published Class I evidence that any of these drugs are useful for treating sundowning per se. Moreover, there is an increasing reluctance on the part of educated doctors to prescribe medicines for “treating” sundowning because (a) evidence indicates that non-drug interventions are more likely to be beneficial, (b) antipsychotics and benzodiazepines further weaken the already unstable sleep-wake rhythms and further decrease neuronal metabolic activity, and (c) each class of drugs carries considerable risk, ranging from increased likelihood of falls and hip fractures, confusion, psychoses, weight loss, stroke, and/or heart attacks, to increased likelihood of sudden death. Concomitant use of cholinesterase inhibitors (Aricept/donepezil, Razadyne/galantamine, and Exelon/rivastigmine) and antipsychotics may increase the risk of extrapyramidal symptoms by disrupting the acetylcholine/dopamine balance in the striatum. In addition, some drugs are contraindicated for loved ones with some types of dementia, such as the antipsychotics to which Lewy body dementia patients are typically extremely sensitive.

However, each loved one is different. If all else fails, yours might be helped by a drug that is not generally beneficial. Given the risks associated with the candidate drugs, plus possible interactions with other medicines your loved one may be taking, it would be prudent to seek the help of a highly qualified and experienced neuro or geripsych to manage the treatment for your loved one.  Be sure to discuss the risks with the doctor, and ask what adverse effects to watch for.

If you are willing to consider trying something outside-the-box, there have been two successful (albeit tiny) clinical trials on using prazosin to treat agitation and aggression in Alzheimer’s patients.  Two larger trials are now recruiting. Prazosin is a mild antihypertensive with a good safety profile, is inexpensive, and is becoming more and more widely used to treat sleep disruption and agitation associated with PTSD. Given an hour before bedtime, low doses of prazosin reduce light sleep, normalize REM sleep, and increase total sleep time. An additional daytime dose was found to reduce residual daytime agitation symptoms of civilian trauma victims.

Further reading and references

General overviews on sundowning, circadian rhythms, and sleep disturbances

- Volicer L, Harper DG, Manning BC, Goldstein R, Satlin A. Sundowning and circadian rhythms in Alzheimer’s disease. Am J Psychiatry 2001;158 (5): 704–11.

http://ajp.psychiatryonline.org/cgi/content/full/158/5/704

- Bachman D, Rabins P. “Sundowning” and other temporally associated agitation states in dementia patients. Annu Rev Med. 2006;57:499-511.

http://cursa.ihmc.us/rid%3D1GM097FD0-1SFSKL8-1FVH/sundowning.pdf

- Kim P, Louis C, Muralee S, Tampi RR. Sundowning Syndrome in the Older Patient. Clinical Geriatrics 2005; 13(4):32-36.

http://www.clinicalgeriatrics.com/article/4013

- Klaffke S, Staedt J. Sundowning and circadian rhythm disorders in dementia. Acta Neurol Belg 2006; 106:168-175

http://www.actaneurologica.be/acta/download/2006-4/03-Klaffke%20et%20al.pdf

- Theison AK, Geisthoff UW, Förstl H, Schröder SG. Agitation in the morning: symptom of depression in dementia? Int J Geriatr Psychiatry 2009 Apr;24(4):335-40.

http://www.gnmhealthcare.com/pdf/09-2008/09/1638914_Agitationinthemorningsymp.pdf

- Wulff K, Gatti S, Wettstein JG, Foster RG. Sleep and circadian rhythm disruption in psychiatric and neurodegenerative disease. Nat Rev Neurosci. 2010 Aug;11(8):589-99.

http://www.ncbi.nlm.nih.gov/pubmed/20631712

- Ancoli-Israel S, Ayalon L. Diagnosis and Treatment of Sleep Disorders in Older Adults.  American Journal of Geriatric Psychiatry 2006; 14:95–103

http://www.focus.psychiatryonline.org/cgi/content/full/7/1/98

- Harper DG, Stopa EG, McKee AC, Satlin A, Harlan PC, Goldstein R, Volicer L. Differential circadian rhythm disturbances in men with Alzheimer disease and frontotemporal degeneration. Arch Gen Psychiatry 2001;58:353-360

http://archpsyc.ama-assn.org/cgi/content/full/58/4/353

- Weldemichael DA, Grossberg GT. Circadian Rhythm Disturbances in Patients with Alzheimer’s Disease: A Review. Int J Alz Disease 2010; Article ID 716453.

http://www.sage-hindawi.com/journals/ijad/2010/716453/

- Huybrechts KF, Rothman KJ, Silliman RA, Brookhart A, Schneeweiss S. Risk of death and hospital admission for major medical events after initiation of psychotropic medications in older adults admitted to nursing homes.CMAJ 10.1503/cmaj.101406

http://www.eurekalert.org/pub_releases/2011-03/cmaj-omh032311.php

http://www.cmaj.ca/cgi/rapidpdf/cmaj.101406v1.pdf

Nondrug interventions

- Kolanowski AM, Litaker M, Buettner L. Efficacy of theory-based activities for behavioral symptoms of dementia. Nurs Res 2005 Jul-Aug;54(4):219-28.

http://www.nursing-research-editor.com/authors/OMR/5/OMRManuscript.pdf

Note that the patients engaged in the activities for “up to 20 minutes per day”, and the authors referenced Kovach and Wells (2002) who found that the daily activity schedule had to be balanced, since over-stimulation as well as under-stimulation can contribute to agitation.
- Teri L, Logsdon RG, McCurry SM. Exercise interventions for dementia and cognitive impairment: the Seattle Protocols. J Nutr Health Aging. 2008;12:391–394.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2518041/

- Baehr EK, Eastman CI, Revelle W, Olson SH, Wolfe LF, Zee PC. Circadian phase-shifting effects of nocturnal exercise in older compared with young adults. Am J Physiol Regul Integr Comp Physiol. 2003;284:R1542–R1550.

http://ajpregu.physiology.org/content/284/6/R1542.long

- McCurry SM, Gibbons LE, Logsdon RG, Vitiello MV, Teri L. Nighttime Insomnia Treatment and Education for Alzheimer’s Disease: A Randomized, Controlled Trial. J Am Geriatr Soc. 2005;53(5):793-802.

http://www.medscape.com/viewarticle/504709

Person-centered care

- Long CO, Alonzo TA. (2008). Palliative care for advanced dementia: A model teaching unit. Practical approaches and results. Arizona Geriatrics Society Journal, 13(2), 14-17.

http://www.nccdp.org/resources/PalliativeCare.pdf

- Long CO. Palliative care for advanced dementia. J Gerontol Nurs. 2009 Nov;35(11):19-24.

http://www.ncbi.nlm.nih.gov/pubmed/19904852

- Belluck P. Giving Alzheimer’s Patients Their Way, Even Chocolate. New York Times Dec 31, 2010.

http://www.nytimes.com/2011/01/01/health/01care.html

- Buckley C, Estrin J. All-Night Care for Dementia’s Restless Minds. New York Times June 12, 2009.

http://www.nytimes.com/2009/06/14/nyregion/14cover.html

- Girshman P. Midnight Munchies Keep Elderly Safer In NY Nursing Home. Kaiser Health News Mar 16, 2010.

http://www.kaiserhealthnews.org/stories/2010/march/16/midnight-munchies-keep-elderly-safer-in-ny-nursing-home.aspx

- Sloane PD, Mitchell CM, Preisser JS, Phillips C, Commander C, Burker E. Environmental correlates of resident agitation in Alzheimer’s disease special care units. J Am Geriatr Soc 1998; 46:862-869.

http://www.ncbi.nlm.nih.gov/pubmed/9670873

http://psycnet.apa.org/?fa=main.doiLanding&uid=1998-04923-004

- Gauthier S, Cummings J, Ballard C, Brodaty H, Grossberg G, Robert P, Lyketsos C. Management of behavioral problems in Alzheimer’s disease. International Psychogeriatrics 2010

http://www.cmrr-nice.fr/doc/IP2010.pdf

- Smith M, Buckwalter K. Behaviors associated with dementia. AJN 2005; 105(7):40-52.

http://journals.lww.com/ajnonline/Fulltext/2005/07000/BEHAVIORS_ASSOCIATED_WITH_DEMENTIA__Whether.28.aspx

- Rader J, Barrick AL, Hoeffer B, Sloane PD, McKenzie D, Talerico KA, et al. (2006). The bathing of older adults with dementia. American Journal of Nursing 106(4), 40-48.

http://www.nursingcenter.com/library/JournalArticle.asp?Article_ID=637530

- Whall AL. Changing the care provided persons with dementia — The role of experiential knowledge and philosophy of science.

http://www2.oakland.edu/oujournal/files/15_changing_the_care.pdf

- McGeorge, S. (2008) Acute Mental Health Issues, in Older People and Mental Health Nursing: A Handbook of Care (eds R. Neno, B. Aveyard and H. Heath), Blackwell Publishing Ltd, Oxford, UK.

http://faculty.ksu.edu.sa/73408/documents/older_people_and_mental_health_nursing.pdf#page=171

Person-centered care at home

- Brackey J. Creating Moments of Joy: A Journal for Caregivers, Fourth Edition. Purdue University Press; (September 1, 2008)

http://www.enhancedmoments.com/

- The Savvy Caregiver training program

http://www.caresprogram.com

(You may be able to get a 20% discount with code AADVD20 .)
- Feil N.  The Validation Breakthrough: Simple Techniques for Communicating with People with ‘Alzheimer’s-Type Dementia, Second edition. Health Professions Press (January 15, 2002).

http://www.vfvalidation.org

Bright light therapy

- Forbes D, Culum I, Lischka AR, Morgan DG, Peacock S, Forbes J, Forbes S. Light therapy for managing cognitive, sleep, functional, behavioural, or psychiatric disturbances in dementia. Cochrane Database Syst Rev. 2009 Oct 7;(4):CD003946.

http://www2.cochrane.org/reviews/en/ab003946.html

- Skjerve A, Bjorvatn B, Holsten F. Light therapy for behavioural and psychological symptoms of dementia. Int J Geriatr Psychiatry. 2004 Jun;19(6):516-22.

http://ot.creighton.edu/community/EBLP/Question4/Skjerve%202004%20Light%20Therapy%20for%20behavioral.pdf

- Ancoli-Israel S, Martin JL, Gehrman P, et al: Effect of light on agitation in institutionalized patients with severe Alzheimer disease. Am J Geriatr Psychiatry 2003;11:194-203.

http://luminoterapia.blogdiario.com/img/Luminoterapia-Alzheimer.pdf

- Barrick AL, Sloane PD, Williams CS, Mitchell CM, Connell BR, Wood W, Hickman SE, Preisser JS, Zimmerman S.  Impact of ambient bright light on agitation in dementia. Int J Geriatr Psychiatry. 2010 Oct;25(10):1013-21.

http://www.ncbi.nlm.nih.gov/pubmed/20104513

Melatonin

- Melatonin. Alzheimer Research Forum.

http://www.alzforum.org/dis/tre/drc/detail.asp?id=52

- Gehrman PR, Connor DJ, Martin JL, Shochat T, Corey-Bloom J, Ancoli-Israel S. Melatonin Fails To Improve Sleep Or Agitation In A Double-Blind Randomized Placebo-Controlled Trial Of Institutionalized Patients With Alzheimer’s Disease. Am J Geriatr Psychiatry. 2009 February; 17(2): 166–169.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2630117/

- Asayama K, Yamadera H, Ito T, Suzuki H, Kudo Y, Endo S. Double blind study of melatonin effects on the sleep-wake rhythm, cognitive and non-cognitive functions in Alzheimer type dementia. J Nippon Med Sch. 2003 Aug;70(4):334-41.

http://www.ncbi.nlm.nih.gov/pubmed/12928714

- Singer C, Tractenberg RE, Kaye J, Schafer K, Gamst A, Grundman M, Thomas R, Thal LJ. 2003. A multicenter, placebo-controlled trial of melatonin for sleep disturbance in Alzheimer’s disease. Sleep 26(7): 893–901.

http://www.chalmersresearch.com/bmg/docs/t2a3.pdf

- Serfaty M, Kennell-Webb S, Warner J, Blizard R, Raven P. 2002. Double blind randomised placebo controlled trial of low dose melatonin for sleep disorders in dementia. Int J Geriatr Psychiatry 17(12): 1120–1127.

http://www.chalmersresearch.com/bmg/docs/t2a2.pdf

Bright light and melatonin

- Haffmans PM, Sival RC, Lucius SA, Cats Q, Van Gelder L. Bright light therapy and melatonin in motor restless behaviour in dementia: A placebo-controlled study. Int J Geriatric Psych 2001; 16[1]:106-10

http://ot.creighton.edu/community/EBLP/Question4/Haffmanns%202001%20Bright%20light%20therapy%20and%20melatonin.pdf

- Dowling A, Burr Robert L, Van Someren Eus JW, Hubbard Erin M, Luxenberg JS, Mastick J, Cooper BA. Melatonin and bright-light treatment for rest-activity disruption in institutionalized patients with Alzheimer’s disease. J Am Geriatr Soc 2008; 56(2): 239-246.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2642966/

- Riemersma-van der Lek RF, Swaab DF, Tiwsk J, Hol EM, Hoogendijk WJ, Van Someren EJ. Effect of bright light and melatonin on cognitive and noncognitive function in elderly residents of group care facilities: a randomized controlled trial. JAMA. 2008;299:2642–2655.

http://jama.ama-assn.org/content/299/22/2642.long

Cholinesterase inhibitors (ChEIs)

- Nieoullon A, Bentué-Ferrer D, Bordet R, Tsolaki M, Förstl H. Importance of circadian rhythmicity in the cholinergic treatment of Alzheimer’s disease: focus on galantamine*. Curr Med Res Opin. 2008 Dec;24(12):3357-67.

http://www.ncbi.nlm.nih.gov/pubmed/19032118

- Davis B, Sadik K. Circadian cholinergic rhythms: implications for cholinesterase inhibitor therapy. Dement Geriatr Cogn Disord. 2006;21(2):120-9.

http://www.ncbi.nlm.nih.gov/pubmed/16391473

- Robert P. Understanding and Managing Behavioral Symptoms in Alzheimer’s Disease and Related Dementias: Focus on Rivastigmine. Curr Med Res Opin. 2002;18(3).

http://www.medscape.com/viewarticle/439728

Prazosin

- Wang LY, Shofer JB, Rohde K, Hart KL, Hoff DJ, McFall YH, Raskind MA, Peskind ER. Prazosin for the treatment of behavioral symptoms in patients with Alzheimer disease with agitation and aggression. Am J Geriatr Psychiatry. 2009 Sep;17(9):744-51.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2842091

- Wang LY, Petrie EC, Rohde K, Hart KL, Hoff DJ, Shofer JB, Rasking MA, Peskind ER. P2-277: Prazosin for treatment of disruptive agitation in Alzheimer’s disease. Alz & Dementia 2008;4(4):T453

http://www.alzheimersanddementia.com/article/PIIS1552526008015136/fulltext

- Two larger trials are now recruiting.

http://clinicaltrial.gov/ct2/show/NCT01126099

http://clinicaltrial.gov/ct2/show/NCT00161473

- Taylor FB, Martin P, Thompson C, et al. (2008) Prazosin effects on objective sleep measures and clinical symptoms in civilian trauma posttraumatic stress disorder: a placebo-controlled study. Biol Psychiatry 63:629–632.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2350188

- Raskind MA, Peskind ER, Hoff DJ, et al. (2007) A parallel group placebo controlled study of prazosin for trauma nightmares and sleep disturbance in combat veterans with post-traumatic stress disorder. Biol Psychiatry 61:928–934.

http://axon.psyc.memphis.edu/~charlesblaha/7705/Papers_10/Aycock%20Rebecca%20-%20Prazosin%20and%20PTSD.pdf

- Raskind MA, Peskind ER, Kanter ED, Petrie EC, Radant A, Thompson C, et al. Reduction of Nightmares and Other PTSD Symptoms in Combat Veterans by Prazosin: A Placebo-Controlled Study. Am J Psychiatry. 2003;160:371–373.

http://ajp.psychiatryonline.org/cgi/content/full/160/2/371

- Taylor F, Raskind MA. The alpha1-adrenergic antagonist prazosin improves sleep and nightmares in civilian trauma posttraumatic stress disorder. J Clin Psychopharmacol. 2002;22:82–85.

http://www.ncbi.nlm.nih.gov/pubmed/11799347

- Taylor F, Lowe K, Thompson C, McFall MM, Peskind ER, Kanter ED, et al. Daytime prazosin reduces psychological distress to trauma specific cues in civilian trauma posttraumatic stress disorder. Biol Psychiatry. 2006;59:577–581

http://www.ncbi.nlm.nih.gov/pubmed/16460691

Continue reading »]]> Alabama

University of Alabama at Birmingham
Alzheimer’s Disease Research Center
Sparks Research Center
1720 7th Avenue South, Ste. 650K
BIRMINGHAM, AL 35233-7340
205-934-3847
Website

Arizona

Arizona Alzheimer’s Disease Center/Sun Health Research Institute
Banner Alzheimer’s Institute
901 E. Willeta Street
PHOENIX, AZ 85006
602-239-650
Website

California

University of California, Irvine
Alzheimer’s Disease Research Center
Gillespie Neuroscience Research Facility, Rm. 1113
IRVINE, CA 92697-4540
949-824-5847
Website

Alzheimer’s Disease Cooperative Study (ADCS)
University of California, San Diego
9500 Gilman Drive, P.O. BOX 0949
LA JOLLA, CA 92093-0949
858-622-5880
Website

University of California, San Diego
Perlman Neurology Outpatient Clinic
LA JOLLA, CA 92037
858-657-8540
Website

UCLA Alzheimer’s Disease Center
10911 Weyburn Ave., 2nd Floor
LOS ANGELES, CA 90095-7226
310-794-3231
Website

University of Southern California Memory and Aging Center
USC Alzheimer’s Disease Research Center
University of Southern California Keck School of Medicine
1510 San Pablo St., HCC 600
LOS ANGELES, CA 90033
323-442-7600
Website

University of Southern California
Alzheimer’s Disease Research Center
Health Consultation Center
1510 San Pablo Street, HCC643
LOS ANGELES, CA 90033
323-442-7600
Website

University of California, Davis Alzheimer’s Disease Center
University of California, Davis Medical Center
4860 Y Street, Suite 3700
SACRAMENTO, CA 95817-4540
916-734-5496
Website

UCSF Memory & Aging Center
350 Parnassus Avenue, Suite 706
SAN FRANCISCO, CA 94143-1207
415-476-6880
Website

The Stanford Center for Memory and Behavioral Disorders
Department of Psychiatry, 5550
401 Quarry Road, C305
STANFORD, CA 94305-5717
650-725-5792
Website

Olive View-UCLA Medical Center
Memory Disorders Diagnostic and Treatment Clinic
SYLMAR, CA 91342-1437
(818) 212-4597
Website

District of Columbia

Georgetown University School of Medicine
Memory Disorders Program
WASHINGTON, DC
202-687-7337
Website

Florida

Johnnie B. Byrd, Sr. Alzheimer’s Center & Research Institute
4001 E Fletcher Avenue
TAMPA, FL 33613
813-866-1600
Website

Mayo Clinic Memory Disorders Clinic
4500 San Pablo Road
JACKSONVILLE, FL 32224
904-953-0853
Website

Georgia

Emory Alzheimer’s Disease Research Center
Department of Neurology
Emory University
1841 Clifton Rd, 3rd Floor
ATLANTA, GA 30329
404-728-4956
Website

Illinois

Cognitive Neurology & Alzheimer’s Disease Center
Northwestern University Feinberg School of Medicine
320 E. Superior, #11-453B
CHICAGO, IL 60611
312-695-9627
Website

Rush University Medical Center
Alzheimer’s Disease Center
Armour Academic Center
600 South Paulina Street, Suite 1028
CHICAGO, IL 60612
312-942-3333
Website

Indiana

Indiana Alzheimer Disease Center
Indiana University School of Medicine
541 Clinical Drive, Room 291
INDIANAPOLIS, IN, 46202
317-278-3968
Website

Kentucky

University of Kentucky Alzheimer’s Disease Center
Sanders-Brown Center on Aging, Rm. 101
800 South Limestone St.
LEXINGTON, KY 40536-0230
859-323-6040
Website

Maine

Houlton Regional Hospital
Specialty Clinics, Neurology
20 Hartford Street
HOULTON, ME 04730
207-532-2900
Website

Maryland

The Johns Hopkins University Medical Institutions
Alzheimer’s Disease Research Center
Division of Neuropathology
558 Ross Research Building
720 Rutland Avenue
BALTIMORE, MD 21205-2196
410-502-5164
Website

Frontotemporal Dementia and Young-Onset Dementia Clinic
Johns Hopkins Hospital
550 North Broadway, Suite 308
BALTIMORE, MD 21287
410-502-2981
Website

Massachusetts

Memory Diagnostic Clinic
ENRM Bedford Veterans Administration Medical Center
200 Springs Road
BEDFORD, MA 01730
781-687-2701
Website

Boston University Alzheimer’s Disease Center
Boston University School of Medicine
715 Albany Street, B-7800
BOSTON, MA 02118
617-414-1195
Website

Boston University
Alzheimer’s Disease Center
VA Boston Healthcare System
Neurology Service (127)
150 South Huntington Avenue
BOSTON, MA 02130
888-458-2823
Website

Massachusetts General Hospital/Harvard Medical School
Memory Disorders Unit
114 16th Street, Room 2009
CHARLESTOWN, MA 02129
617-726-1728
Website

University of Massachusetts Medical Center
55 Lake Avenue North
WORCESTER, MA 01655
508-426-0893
Website

Michigan

University of Michigan
Alzheimer’s Disease Research Center
Department of Neurology
2101 Commonwealth, Suite D
ANN ARBOR, MI 48105
734-936-8281
Website

Minnesota

Mayo Clinic
Alzheimer’s Disease Research Center
4111 Highway 52 North
ROCHESTER, MN 55901
507-284-1324
Website

Missouri

Washington University School of Medicine Familial Adult Children Study
4488 Forest Park Avenue, Suite 101
St. Louis, MO 63108
314-747-7066
Website

New York

Litwin-Zucker Research Center for the Study of Alzheimer’s Disease and Memory Disorders
350 Community Drive
MANHASSET, Long Island, NY 11030
516-487-3492
Website

Columbia University
Columbia University Alzheimer’s Disease Center
630 West 168th Street, P&S 15-402
NEW YORK, NY 10032
212-305-2077
Website

Mount Sinai School of Medicine
Alzheimer’s Disease Research Center
Department of Psychiatry
Mount Sinai School of Medicine
One Gustave Levy Place, Box 1230
NEW YORK, NY 10029-6574
212-241-8329
Website

New York University
Alzheimer’s Disease Center
ADRC, Millhauser Labs
560 First Avenue
NEW YORK, NY 10016
212-263-8088
Website

Sergievsky Center
Columbia University
630 W. 168th St.
NEW YORK, NY 10032
212-305-7382
Website

North Carolina

Duke University Medical Center
Joseph and Kathleen Bryan Alzheimer’s Disease Research Center
2200 West Main Street
Suite A-200
DURHAM, NC 27705
866-444-2372
Website

Oregon

Memory Assessment Clinic
Oregon Health & Science University
3181 SW Sam Jackson Park Road
PORTLAND, OR 97239-3098
503-494-6695
Website

Pennsylvania

University of Pennsylvania
Alzheimer’s Disease Center
Department of Pathology and Laboratory Medicine
University of Pennsylvania School of Medicine
HUP, Maloney 3rd Floor
36th and Spruce Streets
PHILADELPHIA, PA 19104-4283
215-662-7810
Website

University of Pittsburgh
Alzheimer’s Disease Research Center
3471 Fifth Avenue, Suite 811
PITTSBURGH, PA 15213
412-692-4622
Website

Texas

University of Texas, Southwestern Medical Center
Alzheimer’s Disease Research Center
Department of Neurology
5323 Harry Hines Boulevard
DALLAS, TX 75390-9129
214-648-9376
Website

Utah

University of Utah School of Medicine Center for Alzheimer’s Care, Imaging and Research
Outpatient Clinic
729 Arapeen Drive
Research Park
SALT LAKE CITY, UT 84108
801-585-6387
Website
Website

Washington

Alzheimer’s Disease Center/Veterans Affairs Puget Sound Health Care System
Mental Health Services, S-116
1660 South Columbian Way
SEATTLE, WA 98108
206-764-2713
206-764-2069
Website

Wisconsin

University of Wisconsin Alzheimer’s Disease Center
2500 Overlook Terrace
GRECC 11G
MADISON, WI 53705
866-636-7764
Website

Continue reading »]]> Albany

Neurosciences Institute
Alzheimer’s Center
Albany Medical Center Hospital
43 New Scotland Ave.
Albany, NY 12208
518-262-0800
Website

Binghamton

Memory Clinic
Decker School of Nursing’s Elder Services Center
Binghamton University
4400 Vestal Pkwy
Binghamton, NY 13850
(607) 777-6636
Website
Primary Care Associates
276-280 Robinson Street
Binghamton, NY
607-722-2769
Website

Bronx

Montefiore Medical Center
Aging and Dementia Program
Department of Neurology
111 East 210th St
Bronx, NY 10467
718-920-4656
Website

Montefiore Medical Center
Division of Geriatric Medicine
Harry and Jeanette Weinberg Geriatric Ambulatory Practice
3400 Bainbridge Avenue, 2nd Floor
Bronx, NY 10467
(866) 633-8255 then press “3”
Website

Mount Sinai/James J. Peters VA Medical Center
Alzheimer’s Disease Research Center
Memory and Aging Center
130 West Kingsbridge Road
Bronx, NY 10468
718-584-9000, ext 5199
Website

MMC Medical Park
Department of Neurology- Private Practice
Memory Disorders Clinic
1515 Blondell Ave, Suite 220
Bronx, NY 10461
(718) 405-8140
Website

Brooklyn

SUNY Downstate Medical Center
Brooklyn Alzheimer’s Disease Assistance Center (BADAC)
370 Lenox Road
Brooklyn, NY 11226
718-287-4806
Website

UHB Alzheimer’s Disease and Memory Disorders Center
SUNY Downstate Medical Center
450 Clarkson Ave
Brooklyn, NY 11203
718-270-6388
Website

Maimonides Medical Center
Neurosciences Memory Disorder Center
883 65th Street
Brooklyn, NY 11220
(718) 283-7470
Website

New York Methodist Hospital
Memory and Attention Center
Neurosciences Institute
506 Sixth Street
Brooklyn, NY 11215-3609
(718) 246-8590
Website

The Brooklyn Hospital Center
Geriatrics
Main Hospital, 8th Floor
121 DeKalb Ave
Brooklyn, NY 11201
718-250-6100
Website

Buffalo

ADAC of Western New York
Millard Fillmore Gates Circle Hospital
3 Gates Circle
Buffalo, NY 14209
(716) 887-4021
Website
Website

Cohoes

ADAC of the Capital Region
Eddy Alzheimer’s Services
Marjorie Doyle Rockwell Center
421 West Columbia St
Cohoes, NY 12047
(518) 238-4164
Website
Website

Fresh Meadows

Neuroscience Institute
New York Hospital Queens
59-16 174th Street
Fresh Meadows, New York 11365
718-670-1777
Website

Glen Oaks

Zucker Hillside Hospital
North Shore Long Island Jewish Medical Center
Neuwirth Memory Disorders Program
74th Ave and 263rd Str
Glen Oaks, New York 11004
(718/516) 470-8030
Website

Latham
Latham

Alzheimer’s Disease Assistance Center Clinic
Capital Region Health Park
713 Troy Schenectady Road, Suite 124
Latham, NY
(518) 238-4164
(518) 238-4163
Website
Website

Manhasset

North Shore – Long Island Jewish Health System
Harvey Cushing Institutes of Neuroscience
300 Community Drive
9 Tower
Manhasset, NY 11030
(516) 562-3822
Website

Manhattan

Columbia Presbyterian Medical Center
Lucy G. Moses Center for Memory and Behavioral Disorders
Neurological Institute
710 West 168th Street
(212) 305-6939
Website

Columbia University
Memory Disorders Center
New York State Psychiatric Institute
1051 Riverside Drive
New York, NY 10032
(212) 543-5853
Website

Weill Cornell Medical Center
Memory Disorders Program
428 East 72nd Street, Suite 500
New York, NY 10021
212-746-2441
Website

Memory Disorders Center
Harlem Hospital Center
Samuel L. Kountz Pavilion
9th Floor, Room 913
15 West 136th St.
New York, NY 10037
(212) 939-3021
Website

Mount Sinai School of Medicine
Alzheimer’s Disease Research Center
Memory and Aging Center
One Gustave L. Levy Place  (100th Street and Madison Avenue)
New York, NY 10029
212-241-8329
Website

Alzheimer’s Disease Center
Center of Excellence on Brain Aging
New York University Langone Medical Center
145 East 32nd Street (2nd Floor)
New York, NY 10016
212-263-8088
Website
>> Pearl Barlow Center for Memory Evaluation and Treatment
Silberstein Alzheimer’s Institute
212-263-3210
Website
>> Lewy Body Disease Specialty Center
212-263-0731
Website

Beth Israel Medical Center
Department of Psychiatry and Behavioral Sciences
Betty and Morton Yarmon Neurobehavior and Alzheimer’s Disease Center
1st Avenue at 16th Street
Bernstein Pavillion, 2nd Floor
New York, N.Y. 10003
(212) 420-4111
Website

Bellevue Hospital Center
Geriatric Outpatient Clinic
462 1st Avenue (27th Street and 1st Avenue)
New York, NY 10016
(212) 562-1683
(212) 562-7272
Website

Beth Israel Senior Health
Division of Geriatrics, Dept of Medicine
275 Eighth Ave at 24th St
New York, NY 10001
212-463-0101
House calls: 212-206-1299
An integral part of Penn South, a naturally occurring retirement community (NORC)

St. Luke’s Hospital
Department of Neurology
1111 Amsterdam Ave. (at 114th St.)
New York, NY 10025
(212) 523-6521
Website
?

New York

Memory Disorder Center
Columbia Presbyterian Eastside
Neurology
16 East 60th Street, Suite 440
New York, NY 10022
(212) 305-6939
(212) 326-8455
Website
Website

Mount Sinai Faculty Practice Associates
Neurology
5 East 98th Street, 7th floor
The Mount Sinai Medical Center
New York, NY 10029
212-241-7076
Website

Memory Disorders Program
Cornell University Irving S Wright Center on Aging
1484 First Avenue
(between 77th and 78th Streets)
New York City, NY
(212) 746-7000
Website
Website

NY Memory Services
65 East 76th Street
New York, NY 10021
(212) 517 6881
Website

Plattsburgh

SUNY Plattsburgh
Alzheimer’s Disease Assistance Center (ADAC)
Sibley Hall, Room 227
101 Broad St
Plattsburgh, NY 12901
518-564-3377
Website
Website

Rochester

Memory Disorders Clinic
University of Rochester Medical Center
Monroe Community Hospital
435 East Henrietta Road
Rochester, NY 14620
(585) 760-6221
Website

Highland Neurology
Memory Care Program
919 Westfall Rd
Clinton Crossings Building C
Suite 220
Rochester, NY 14618
585-273-5454
Website
Website

Staten Island

Staten Island University Hospital
Geriatric Consultation Center
500 Seaview Ave
Staten Island, NY 10305
718-351-8100
718-351-3319
Website

Stony Brook

Alzheimer’s Disease Assistance Center of Long Island
Stony Brook University Hospital
Department of Psychiatry
Health Science Center T10
Stony Brook, New York 11794-8101
516-444-1365
Website
Website

Syracuse

ADAC of Central New York
SUNY Upstate Medical University
750 East Adams Street, Syracuse, NY 13210
(315) 464-5678
Website
Website

White Plains

The Burke Rehabilitation Hospital
Memory Evaluation and Treatment Service
785 Mamaroneck Ave
White Plains, NY 10605
(914) 597-2307
Website
Website

Continue reading »]]> There are two main categories of drugs for treating Alzheimer’s, i.e.:

(1) Cholinesterase inhibitors
These include the prescription drugs Aricept/donepezil, Razadyne/galantamine, and Exelon/rivastigmine, and the over-the-counter “supplement” huperzine A.

(2) NMDA antagonists
So far, there is only one drug in this category, i.e., Namenda/memantine.

These drugs do not cure Alzheimer’s, and there is scant evidence that they slow down the damage that is being done. What they can do, however, is help the damaged regions of the brain function better, which in turn slows down the emergence of symptoms and improves your loved one’s quality of life.

Some doctors believe that Alzheimer’s drugs provide little or no benefit. It is true that some patients do not appear to be affected by them; however, some of these may actually be stabilized, and for a long time. Others show a marked improvement. And some, sadly, are not helped much if at all, or may develop adverse effects. Because the benefits differ from patient to patient, the results from clinical trials indicate that average improvements in mental function are modest. The only way to find out how well your loved one will respond is to try them.

Some people believe that the drugs only help improve memory. This is not true, either. Clinical trial tests showed they can improve cognitive, social, and motor impairments, and participation in activities of daily living. They can help delay or prevent the onset of serious behavioral problems (anger, aggression, agitation, wandering, etc), and reduce or eliminate the need for antipsychotics, antidepressants, and anxiolytics.

And yet … the majority of Alzheimer’s patients are never given Alzheimer’s drugs, and even those for whom they are prescribed often receive them for less than three months.

Cholinesterase Inhibitors (ChEIs)

Aricept, Razadyne, and Exelon are the cholinesterase inhibitors (ChEIs) most commonly recommended by doctors. Another ChEI, Cognex (tacrine), was prescribed in the past but is no longer recommended because it can cause liver damage.

How they work: Alzheimer’s disease changes the brain in many ways. One of the changes results in a decrease in the levels of acetylcholine, a chemical messenger believed to be important for alertness, memory, thought and judgment. In the healthy brain, the enzyme cholinesterase destroys excess acetylcholine. Cholinesterase inhibitors (ChEIs) slow the activity of cholinesterase, making more acetylcholine available for communication between cells.

What they can do: Aricept has been approved for all stages of Alzheimer’s — mild, moderate, and severe. Razadyne and Exelon have only gone through the extensive clinical trials needed for FDA approval for treating mild to moderate Alzheimer’s and so have only been approved for the earlier stages. That does not mean that they are not beneficial for the later stages. In fact, there is reason to think that Exelon may be better than Aricept for loved ones with moderate to severe Alzheimer’s (see below).

ChEIs can alleviate apathy and anxiety, improve alertness and motivation, and improve memory. Some patients were able to perform tasks which they had forgotten how to do, such as going shopping.

Roughly 40 to 50 % of patients improve when prescribed these drugs. Most will experience a delay in the progression of the illness. However, it may take some months of treatment for there to be a noticeable improvement or slowing down of memory loss. Unfortunately, not everyone benefits from them, and sometimes the side effects are intolerable.

Which ChEI should be used: Doctors tend to be more familiar with Aricept, since it has been on the market longer and has been approved for treating all stages of Alzheimer’s, and therefore prescribe it much more often. In clinical studies involving large numbers of subjects with mild to moderate Alzheimer’s, on average, all cholinesterase inhibitors appeared to work equally well. These drugs all have the same, basic mechanism of action; that is, they all inhibit the enzyme acetylcholinesterase (AChE).

However, there are some significant differences among the three drugs. For example, the elimination pathway is through the kidney for Exelon, through the kidney and liver for Razadyne, and through the liver for Aricept. This should be taken into account when selecting the ChEI and dosage for patients with liver or kidney disease, or elderly patients with reduced kidney or liver function.

In addition, Aricept and Razadyne only inhibit AChE, while Exelon targets butyrylcholinesterase (BuChE) as well as AChE. Razadyne also modulates nicotinic receptors. Researchers don’t yet know the full impact that these differences may have, when it comes to the individual patient.

While these three drugs appeared to work equally well when the results from large clinical trials are averaged, it is well established that one ChEI may work better or produce fewer acute (near-term) side effects in a given individual than another.  If your loved one is started on one ChEI and either does not appear to be improving or at least stabilized, and/or is suffering side effects that do not go away after a few weeks or are intolerable, consider asking your doctor to prescribe a different ChEI.

The chronic (long-term) side effects of the three drugs are different, too. Some researchers have reported that Aricept is more likely to cause sleep disturbances, cardiovascular problems such as bradycardia, extrapyramidal symptoms (EPS), and behavioral disturbances; and Razadyne is more likely to cause syncope (fainting). Again, if your loved one does not appear to be responding to a given ChEI any longer, or is developing one of these chronic side effects, don’t simply give up on ChEI therapy — switch to a different drug.

Switching drugs is commonly done for antidepressants and medicines for congestive heart failure and epilepsy, so it’s strange that so few doctors consider trying it with ChEIs. And there is even experimental evidence from several clinical trials that switching can often help, by providing superior efficacy, reducing side effects, or both.

If the reason for changing to a different ChEI is adverse effects, some doctors recommend a “wash out” period of one week before beginning treatment with another, to allow the adverse effects time to resolve. No wash out period is needed for patients who tolerated a ChEI well but are switching because they failed to respond or did not respond as well as expected.

Sleep disturbances: Caregivers often report that a loved one who is on Aricept is distressed by vivid dreams. If that happens to your loved one, suspect the Aricept. This is a very common side effect of this ChEI, and one that is often resolved by simply giving the drug to your loved one in the morning rather than the evening. There is no reason to give the drug in the evening that I’ve been able to discover, other than, perhaps, the hope that the gastrointestinal side effects won’t be as bothersome when the patient is asleep.

However, you might want to consider not only giving your loved one’s medicine in the morning, but also switching to one of the other ChEIs as well. Both Razadyne and Exelon have been shown to be less likely to trigger sleep disturbances than Aricept, and any caregiver who has had to cope with sleep disturbances will tell you they are to be feared and avoided if at all possible. Acetylcholine — the chemical messenger whose levels are increased by ChEIs — plays an active role in maintaining a normal sleep pattern. The healthy brain has low levels of acetylcholine during slow-wave sleep, and high levels during wakefulness. High levels of ChEIs in the bloodstream at night, which result in high levels of acetylcholine in the Alzheimer’s brain, can sometimes trigger sleep disorders. (Since a normal sleep pattern is important for memory consolidation, disruption of the circadian rhythm can add to memory problems as well.) ChEIs that have short half-lives in the blood and are given in the morning will support the normal circadian cholinergic rhythm. Aricept has a very long half-life (70 hours) in comparison with Razadyne (7 hours) and Exelon (1.5 hours) (and huperzine A, 4.5 hours).

Why do different patients have different responses to ChEIs: The reasons why some patients respond well to a given drug and others develop intolerable side effects are not yet fully known. However, recent studies on Aricept indicate that the therapeutic responses to this drug may be due to subtle differences in certain genes. Aricept is metabolized via CYP-related enzymes in the liver, especially CYP2D6, CYP3A4, and CYP1A2. Approximately 15-20% of Alzheimer’s patients may exhibit an abnormal metabolism of Aricept. Of these, ~50% show an ultrarapid metabolism, requiring higher doses of the drug to reach a therapeutic threshold, whereas the other 50% show a poor metabolism, exhibiting adverse side effects at low doses.  Pharmacogenetic and pharmacogenomic factors may account for 75-85% of the therapeutic response to ChEIs that are metabolized via liver enzymes of the CYP family.

What about moderate to severe Alzheimer’s: As noted above, Aricept is the only ChEI that has been formally approved for treating the later stages of Alzheimer’s.  The fact that Aricept was found to be helpful in the later stages tends to indicate that ChEIs, in general, might be beneficial in the later stages. Just because all three ChEIs showed equal benefits in the earlier stages, however, does not mean that they will all perform equally well in the later stages.

In fact, there is some reason to believe that Exelon might be more beneficial for loved ones with moderate to severe Alzheimer’s. As noted above, Exelon has dual activity against AChE and BuChE, whereas the other ChEIs are specific for AChE. This dual capability may become more important as the disease progresses, since the activity of AChE decreases in the Alzheimer’s brain, while that of BuChE increases, particularly in the cortex and hippocampus. BuChE-positive neurons are thought to have roles in attention, executive function, emotional memory and behaviour. Therefore, inhibition of BuChE may provide additional benefits as time goes by. (Note: Oral Exelon is reported to be more likely to cause acute gastrointestinal side effects than the other ChEIs. However, many researchers believe that the drug would be just as readily tolerated as the others if the dose were ramped up more slowly than recommended. Also, using the Exelon patch rather than the oral pill is likely to cause fewer adverse events while the body is adjusting to the drug. With the patch, the Exelon enters the blood stream through the skin/muscle, rather than through the stomach and intestines. Ergo, the patch tends to have fewer gastrointestinal side effects.)

Until recently, all comparisons of these three ChEIs were done in patients who had mild to moderate Alzheimer’s. However, there has now been one head-to-head comparison of oral Exelon and Aricept, in nearly one thousand patients with moderate to moderately-severe Alzheimer’s. Adverse events were more frequent in the Exelon group during the titration phase, but similar in the maintenance phase. Centrally mediated adverse events such as nausea and vomiting tended to be higher in Exelon-treated patients (remember, this was the oral formulation, and the patients were titrated fairly quickly, as is “officially” recommended), whereas brainstem and peripherally mediated adverse events such as insomnia, muscle cramps and urinary incontinence had a low incidence overall, but tended to be higher in Aricept-treated patients. Results indicated that ChEI treatment was beneficial throughout the 2 years of the study. Although both drugs performed similarly on cognition and behavior, Exelon appeared to provide greater benefit in activities of daily living and global functioning. Alzheimer’s patients who had genotypes that encoded for full expression of the BuChE enzyme, who were < 75 years of age, or who had symptoms suggestive of concomitant Lewy body dementia showed significantly greater benefits from Exelon treatment.

What about generics: Razadyne has been available as the generic galantamine in the US, and Aricept very recently became available as the generic donepezil. While generic products have the same active ingredients as the brand name drugs, they are not entirely identical. Historically, physicians have noted a variety of differences in individual responses — both positive and negative — to generic drugs for other health conditions. Therefore, a caregiver whose loved one has been receiving Razadyne or Aricept may notice a difference in effectiveness when switching to the generic product. If the generic does not appear to be as effective as the brand name, talk with the doctor about prescribing the brand name product instead.  Patients who are trying a ChEI for the first time may choose a generic due to its lower cost. Those who do not appear to benefit from it may want to consider switching to Exelon.

What about the new 23 mg Aricept: A new, high-dose formulation of Aricept recently came on the market.  There have been a number of misconceptions about this product.

First and foremost, the new 23mg Aricept is an extended release formulation. This means that you should not break it in half, crush it, or dissolve it to administer it.

It also means that the maximum levels of the drug in the blood are significantly lower than the levels you would achieve by taking two 10mg pills. So do not try doubling up on the 10mg pills instead!

Patients should be on a steady dose of one 10mg tablet for at least four to six weeks — and tolerating it well — before switching to the 23mg pill. Do not try to titrate up to 23mg using 5 and 10mg pills.

The overall benefits from switching to this new pill are, in my opinion, questionable. There was a 24-week, double-blind, placebo-controlled clinical trial of 1,467 patients with moderate-to-severe AD who had been on 10mg Aricept once daily for at least 3 months. Half were given the higher dose, the other half continued to take the 10mg. Tests used to evaluate efficacy were cognition (SIB) and global function (CIBIC+). It is interesting that they did not use the ADAS-Cog, which is the “gold standard” in clinical trials for treating dementia … and which Aricept has not been shown to affect in some of the earlier trials.

The SIB (Severe Impairment Battery) is similar to the MMSE but designed for use with severely demented patients (MMSE below 1-12 points). The MMSE cannot discriminate among patients in this severe AD range … and the SIB cannot discriminate among patients who have mild to moderate AD. The SIB takes only 20-30 minutes to administer, and consists of one-step questions and commands that are presented with gestural cues and can be repeated as needed by the patient. There was a statistically significant improvement in SIB scores on the higher dose.

The Clinician’s Interview-Based Impression of Change plus caregiver input (CIBIC+) is a much more extensive test, and involves detailed interviews of the caregiver regarding the loved one’s abilities, behavior, and mood, etc, as well as direct assessments of the AD patient. There was no difference in CIBIC+ results between patients on the 23mg ER formulation and those who continued taking 10mg.

These results mean that, as far as the caregivers were concerned, on average, there were no detectable benefits from switching to the higher dose.

However, as might be expected, there were distinct disadvantages: i.e., switching to the higher dose caused more adverse side effects. So if you decide to try the higher-dose formulation to see whether your loved one might do better on it, be aware of this possibility and keep track of your loved one’s behaviors to see if new symptoms crop up or old symptoms are exacerbated.

Huperzine A: Huperzine A is an inexpensive alternative to the prescription ChEIs. It is an over-the-counter supplement that has been used to treat Alzheimer’s (and vascular dementia) in China for many years, and reportedly is well tolerated. It was recently evaluated in a double-blind, placebo-controlled Phase II clinical trial in the US, and found to be beneficial at the higher dose that was tested (i.e., 400 mcg 2x per day) over the six months of the blinded trial. As far as I’ve been able to tell, only the results from the initial six months have been released. The trial went into a series of open-label stages which purportedly were going so well, they continued to increase the length of the study in six-month increments for two additional years. All told, interested patients were in the trial for two and a half years. My husband was in the trial for the entire time, in the cohort that received the lower dose (200 mcg x2).  He responded well and, if given the drug after a full meal, did not have any noticeable side effects from it. Several years later, as his symptoms began to progress, his neuro recommended that we ramp up to the higher dose, which is what he is taking now. Huperzine A can be found at some online health food stores. If you and your doctor decide to try huperzine A instead of one of the prescription ChEIs, choose a formulation that does not contain any other supplements. Several trials are currently recruiting or preparing to recruit for a sustained-release tablet formulation.

Drug interactions: A number of drugs which are often prescribed for elderly people, such as those for treating urinary incontinence, have anticholinergic activity, i.e., they decrease the amount or activity of acetylcholine. Anticholinergics, in essence, have the opposite effect of ChEIs. The simultaneous use of both types of drugs is likely to lead to reduced effectiveness of one or both drugs. Many doctors are unaware of the potential problem, and as many as one-third of dementia patients are given both. Be sure to ask your pharmacist about the compatibility of any new drug or over-the-counter medicine or supplement before giving it to your loved one.

Should ChEIs be used to treat other dementias: In addition to Alzheimer’s, ChEIs may be effective for use in the treatment of Lewy body dementias (Parkinson’s dementia and dementia with Lewy bodies), especially for neuropsychiatric symptoms.

ChEIs are sometimes prescribed for vascular dementia (VaD), but the drugs have not been officially “blessed” by the FDA for this application. In fact, their use is discouraged since there is no consistent evidence that ChEIs are beneficial for “pure” VaD, and since at least one trial raised safety concerns, including the potential for a slightly higher death rate in this patient population. However, ChEIs are believed to be helpful to loved ones with “mixed dementia”, i.e., Alzheimer’s and VaD, which is very common and often misdiagnosed as “pure” VaD.

ChEIs are rarely, if ever, beneficial for patients with frontotemporal dementia (FTD) and may cause adverse effects, especially agitation. ChEIs are therefore not recommended for treating FTD. ChEIs have not been shown to be helpful in progressive supranuclear palsy.

Several meta-analyses of the studies conducted to date have concluded that ChEIs will not delay the conversion of mild cognitive impairment (MCI) to Alzheimer’s. However, these studies would have included many MCI patients who would not have converted to Alzheimer’s in any event. (See the Compendium article on MCI conversion rates.) There might be benefits to select individuals. The problem is discerning which individuals would be helped, and which would needlessly suffer adverse effects.

Namenda

How Namenda works: Namenda was the first drug approved by the FDA to treat the symptoms of moderate to severe Alzheimer’s. It is also the first of this new class of uncompetitive NMDA receptor antagonists that alter the brain’s response to glutamate, a messenger chemical involved in all brain function, including learning and memory. Excessive stimulation of the N-methyl-D-aspartate (NMDA) receptor by high levels of glutamate leads to increased flow of calcium cations into the cell through the receptor’s ion channel, resulting in excitotoxicity, a pathological process causing neuron injury or death. Namenda works by preferentially binding to the NMDA receptor-operated cation channels, thereby decreasing the effects of glutamate.  Interestingly, there is also evidence that the drug may be able to improve cerebral glucose metabolism.

What it can do: Randomized clinical trial data indicate that Namenda can improve cognition, global assessment, and quality of life in patients with moderate to severe Alzheimer’s. Specific cognition sub-items that appear to respond most significantly to Namenda include memory, language, orientation, praxis and visuospatial ability. For example, a U.S. study found that outpatients with Alzheimer’s who were using Namenda were better able to use the phone, pay attention to conversation, get around outside the home, and perform daily tasks such as clearing the dishes after eating. There is also evidence that the drug helps in very advanced cases of Alzheimer’s. A European study that focused on nursing-home patients with severe dementia found that those who took the drug were more likely to be able to stand up, move, eat and drink, dress themselves, and use the toilet. Namenda has also been shown to reduce agitation/aggression and irritability/lability, on average. Clinical trial results are further supported by results from open-label extension studies and studies investigating combination therapy with ChEIs.

Namenda tends to be better tolerated and with fewer side effects than the ChEIs, based on several clinical trials and on use in Europe since 1989 — although, as with any drug, some individuals may experience significant side effects. It undergoes very little metabolism and is excreted mainly through the kidneys.

What about mild to moderate Alzheimer’s: There is evidence that Namenda may be beneficial to some patients in the earlier stages of Alzheimer’s, although the drug is not specifically approved for that application. Two clinical trials showed 60-70% therapy response rate, with minimal side effects, in mild-to-moderate Alzheimer’s.  More recent studies with the new extended-release formulation concluded that patients with mild to moderate Alzheimer’s had modest improvements in their memory and thinking skills. It is my understanding that the American Academy of Neurology (AAN) Management of Dementia Guidelines were recently revised to suggest that Namenda be prescribed for early-stage Alzheimer’s patients who cannot tolerate ChEIs.

What about generics: Namenda is still under patent protection in the U.S.

Drug interactions: The combined use of Namenda with other NMDA antagonists (amantadine, ketamine, and dextromethorphan) has not been systematically evaluated and any such use should be approached with caution.

Since Namenda clearance is reduced by about 80% under alkaline urine conditions at pH 8, anything that alters urine pH toward the alkaline condition may lead to an accumulation of the drug with a possible increase in adverse effects. Urine pH is altered by diet, drugs (e.g. carbonic anhydrase inhibitors, sodium bicarbonate) and clinical state of the patient (e.g. renal tubular acidosis or severe infections of the urinary tract). Namenda should be used with caution under these conditions.

Should Namenda be used to treat other dementias: Several clinical trials indicated that Namenda is beneficial for patients with mild to moderate vascular dementia, including benefits associated with behavioral symptoms.

A recent study on Lewy-body-related dementias found that patients who have dementia with Lewy bodies who received Namenda showed significantly greater improvement in global clinical status and behavioral symptoms than those taking placebo. Interestingly, no significant differences were found between the two treatments in patients with Parkinson’s disease dementia in this particular study, even though earlier studies have shown a benefit for this dementia.

There is some evidence that Namenda may be beneficial for alcohol-related dementia, AIDS-related dementia, and Huntington disease.

There is anecdotal evidence that Namenda may be helpful to loved ones with FTD. However, the results from a very small, open-label study were not particularly promising. Larger clinical trials are now under way to help determine whether the drug may be broadly beneficial to FTD patients.

Combination Therapy

Studies have shown that, in general, Alzheimer’s patients do better on a combination of a ChEI and Namenda than they do on either one alone, even in the long term (five years or more). For example, in one of the first clinical trials on combination therapy, more than 400 patients with moderate to severe Alzheimer’s who were on stable doses of Aricept were randomly assigned to receive either Namenda or a placebo as well. Those who received Namenda had significantly better outcomes on measures of cognition, activities of daily living, global outcome, and behavior.

In a more recent study, 382 patients were given one of three treatments, i.e., standard care without either type of Alzheimer’s drug; ChEI monotherapy; or ChEI plus Namenda combination therapy. They were evaluated every six months for up to 4 years. The combination therapy group had significantly lower rates of deterioration than the monotherapy or no therapy groups, and the differences between combination therapy and the other groups increased with treatment duration over the course of the study.

An observational study published in 2009 found that Alzheimer’s patients who used cholinesterase inhibitors and Namenda were able to postpone nursing home admission significantly longer than those who only took cholinesterase inhibitors.

Since Namenda was originally tested for efficacy in the later stages of Alzheimer’s, doctors tend to start a patient on a ChEI, and then, once the patient is stabilized on that drug, introduce Namenda. However, there is no medical reason for starting patients in that order of which I’m aware. In fact, my husband started on Namenda — while he still had only moderate Alzheimer’s — and responded very well. It was only later that we added the huperzine A.

How Long Do They Work?

Some doctors are under the misapprehension that because the clinical trials that were used to obtain FDA approval were only designed to last for three to six months, Alzheimer’s drugs are only effective for a maximum of six months.  This is not true.

In fact, every long-term study of which I am aware, whether conducted on a single Alzheimer’s drug or on combination therapy, and whether prospective or retrospective, concluded that the drugs were still beneficial — on average — for the full length of the study, i.e., up to ten years (the longest time that has been studied to date). However, results may be different for a given individual. Some respond better to the drugs than others; some develop serious adverse effects that others do not.

When Should Alzheimer’s Drugs be Discontinued?

It can sometimes be difficult to tell if Alzheimer’s drugs are providing any benefit, especially after they have been used for several years, because no one knows how quickly the disease would have progressed without them. Sometimes, caregivers believe the drugs are not doing any good and decide to discontinue them. Studies have found that some patients may decline rapidly once the drugs are discontinued; and even if the drugs are restarted, these patients may be stabilized at their new level of cognitive function but will not regain their former level of function. However, other patients show no discernible effects when the drugs are stopped; and some may actually improve when taken off one or both drugs if they have developed adverse effects from them.

If you decide to stop giving your loved one these drugs, it is always a good idea to slowly wean your loved one off the drugs, one drug at a time.  That way, if the loved one experiences a sudden decline in abilities, the drug can be restarted before significant damage is done.

What about when the loved one is in the advanced stages of Alzheimer’s? There is no substantive evidence that these drugs prolong life. As far as is known, they simply help the damaged brain function better than it would without them. But sooner or later, there comes a time when it seems senseless to keep on administering these drugs.

When to discontinue Alzheimer’s drugs due to progression of the disease has not been studied per se, and many healthcare guidelines don’t even address the subject. The ISOA guidelines recommend that physicians discontinue Alzheimer’s drugs if patients reach “profound” stages of dementia, when the patients has no cognitive or functional skills left to preserve. Note that there is a distinction between “severe” and “profound” dementia. The guidelines from the American College of Physicians and the American Academy of Family Physicians indicate that “if slowing decline is no longer a goal, treatment with [Alzheimer's drugs] is no longer appropriate.” Others have stated that treatment should be withdrawn at the point were a patient is entirely dependent in all basic ADLs, and the family and physician believe that “meaningful social interactions and quality of life benefits are no longer possible.”
_______

Further reading:

“Official” Medical Guidelines
- O’Brien JT, Burns A. Clinical practice with anti-dementia drugs: a revised (second) consensus statement from the British Association for Psychopharmacology. J Psychopharmacol. 2010 Nov 18.

http://www.bap.org.uk/pdfs/Anti-dementia_2010_BAP.pdf

- Doody RS. Cholinesterase Inhibitors and Memantine: Best Practices. CNS Spectr. 2008;13:10(Suppl 16):34-35.

http://www.cnsspectrums.com/aspx/articledetail.aspx?articleid=1854

- VHA Pharmacy Benefits Management Service and the Medical Advisory Panel. Updated Criteria for Use: Cholinesterase Inhibitors to Treat Dementia.

http://www.pbm.va.gov/Clinical%20Guidance/Criteria%20For%20Use/Cholinesterase%20Inhibitors%20Criteria%20for%20Use%20Updated%207.31.08.doc

Cholinesterase Inhibitors
- Potkin S. The Management of Alzheimer’s Disease and Related Dementias: Part 2 — The Role of Cholinesterase Inhibitors in the Treatment of Alzheimer’s Disease and Related Dementias. Postgraduate Institute for Medicine CME 2004.

http://cme.medscape.com/viewarticle/467554_1

- Hitti M. Trio of Drugs May Improve Alzheimer’s. WebMD 2006.

http://www.webmd.com/alzheimers/news/20060125/trio-drugs-may-improve-alzheimers

- Lane RM, Potkin SG, Enz A. Targeting acetylcholinesterase and butyrylcholinesterase in dementia. Int J Neuropsychopharmacol. 2006 Feb;9(1):101-24.
- Bullock R, Touchon J, Bergman H, Gambina G, He Y, Rapatz G, Nagel J, Lane R. Rivastigmine and Donepezil Treatment in Moderate to Moderately- Severe Alzheimer’s Disease Over a 2-Year Period. Curr Med Res Opin. 2005 Aug;21(8):1317-27.

http://www.redorbit.com/news/health/267067/rivastigmine_and_donepezil_treatment_in_moderate_to_moderately_severe_alzheimers/

- Winblad B, Cummings J, Andreasen N, Grossberg G, Onofrj M, Sadowsky C, et al. A six-month double-blind, randomized, placebo-controlled study of a transdermal patch in Alzheimer’s Disease — rivastigmine patch versus capsule. Int J Geriatric Psychiatry 2007; 22:456-467.

http://www.ncbi.nlm.nih.gov/pubmed/17380489

Switching ChEIs
- Gauthier S, Emre M, Farlow MR, Bullock R, Grossberg GT, Potkin SG. Strategies for continued successful treatment of Alzheimer’s disease: switching cholinesterase inhibitors. Curr Med Res Opin. 2003;19:707–14.

http://www.medscape.com/viewarticle/466047

- Dantoine T, Auriacombe S, Sarazin M, et al. Rivastigmine monotherapy and combination therapy with memantine in patients with moderately severe Alzheimer’s disease who failed to benefit from previous cholinesterase inhibitor treatment. Int J Clin Pract. 2006;60:110–18.

http://www.medscape.com/viewarticle/521100

- Bartorelli L, Giraldi C, Saccardo M, et al. Effects of switching from an AChE inhibitor to a dual AChE-BuChE inhibitor in patients with Alzheimer’s disease. Curr Med Res Opin. 2005;21:1809–18. [

http://www.ncbi.nlm.nih.gov/pubmed/16307702

ChEI-Caused Sleep Disturbances
- Nieoullon A, Bentué-Ferrer D, Bordet R, Tsolaki M, Förstl H. Importance of circadian rhythmicity in the cholinergic treatment of Alzheimer’s disease: focus on galantamine*. Curr Med Res Opin. 2008 Dec;24(12):3357-67.

http://www.ncbi.nlm.nih.gov/pubmed/19032118

- Davis B, Sadik K. Circadian cholinergic rhythms: implications for cholinesterase inhibitor therapy. Dement Geriatr Cogn Disord. 2006;21(2):120-9.

http://www.ncbi.nlm.nih.gov/pubmed/16391473

- Robert P. Understanding and Managing Behavioral Symptoms in Alzheimer’s Disease and Related Dementias: Focus on Rivastigmine. Curr Med Res Opin. 2002;18(3).

http://www.medscape.com/viewarticle/439728

ChEIs for Mild Cognitive Impairment (MCI)
- Feldman HH, Ferris S, Winblad B, Sfikas N, Mancione L, He Y, Tekin S, Burns A, Cummings J, del Ser T, Inzitari D, Orgogozo JM, Sauer H, Scheltens P, Scarpini E, Herrmann N, Farlow M, Potkin S, Charles HC, Fox NC, Lane R. Effect of rivastigmine on delay to diagnosis of Alzheimer’s disease from mild cognitive impairment: the InDDEx study. Lancet Neurol. 2007 Jun;6(6):501-12.

http://industry.biomed.cas.cz/kamil/clanky/feldman%20et%20al%202007%20lancet%20neurology.pdf

Genes Affect ChEI Efficacy and Adverse Effects
- Cacabelos R. Donepezil in Alzheimer’s disease: From conventional trials to pharmacogenetics. Neuropsychiatr Dis Treat. 2007 June; 3(3): 303–333.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2654795/

Huperzine A
- Wang BS, Wang H, Wei ZH, Song YY, Zhang L, Chen HZ. Efficacy and safety of natural acetylcholinesterase inhibitor huperzine A in the treatment of Alzheimer’s disease: an updated meta-analysis. J Neural Transm. 2009 Apr;116(4):457-65.

http://www.ncbi.nlm.nih.gov/pubmed/19221692

- Sabbagh MN. Drug development for Alzheimer’s disease: where are we now and where are we headed? Am J Geriatr Pharmacother. 2009 Jun;7(3):167-85.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2948028/

- Alzheimer Research Forum

http://www.alzforum.org/drg/drc/detail.asp?id=53

Anticholinergic Drugs
- Sink KM, Thomas J, Xu H, Craig B, Kritchevsky S, Sands LP. Dual Use of Bladder Anticholinergics and Cholinesterase Inhibitors: Long-Term Functional and Cognitive Outcomes. J Am Geriatr Soc.  2008;56(5):847-853.

http://www.medscape.com/viewarticle/578206

Namenda
- Blesa Rafael. Clinical experience of memantine in Alzheimer’s disease. European Neurology 2009; 3(2)

http://www.touchneurology.com/files/article_pdfs/blesa.pdf

- Jancin B. Memantine effective in mild to moderate Alzheimer’s. Internal Medicine News, June 15, 2004.

http://findarticles.com/p/articles/mi_hb4365/is_12_37/ai_n29133473/

- Just S. Namenda™ (Memantine) for Moderate-to-Severe Alzheimer’s Disease. Pharmacotherapy Update 2004; 8(3).

http://www.clevelandclinicmeded.com/medicalpubs/pharmacy/mayjune2004/namenda.htm

Combination Therapy
- Trial of Memantine/Donepezil Paves the Way for Combination Therapy

http://www.alzforum.org/new/detail.asp?id=950

- McGreevey S. Study confirms benefit of combination therapy for Alzheimer’s disease. 2008.

http://www.eurekalert.org/pub_releases/2008-09/mgh-scb092208.php

- Lopez OL, Becker JT, Wahed AS, Saxton J, Sweet RA, Wolk DA, Klunk W, Dekosky ST. Long-term effects of the concomitant use of memantine with cholinesterase inhibition in Alzheimer disease. J Neurol Neurosurg Psychiatry. 2009 Jun;80(6):600-7.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2823571

Long-Term Benefits
- Cassels C, Lie D. Long-Term Combination Alzheimer’s Therapy Slows Decline CME. Medscape 2008.

http://www.medscape.com/viewarticle/581273

- Rountree SD, Chan W, Pavlik VN, Darby EJ, Siddiqui S, Doody RS. Persistent treatment with cholinesterase inhibitors and/or memantine slows clinical progression of Alzheimer’s disease (AD). Alzheimer’s Research & Therapy 2009, 1:7

http://alzres.com/content/1/2/7

- Donepezil — Relief for Patients with Severe AD?  (Be sure to read Dr Schneider’s comments as well as the article)

http://www.alzforum.org/new/detail.asp?id=1364

- Seltzer B. Is long-term treatment of Alzheimer’s disease with cholinesterase inhibitor therapy justified? Drugs Aging. 2007;24(11):881-90.

http://www.ncbi.nlm.nih.gov/pubmed/17953456

- Bullock R, Dengiz A. Cognitive performance in patients with Alzheimer’s disease receiving cholinesterase inhibitors for up to 5 years.  Int J Clin Pract. 2005 Jul;59(7):817-22.

http://www.ncbi.nlm.nih.gov/pubmed/15963209

Treating Behavioral Problems
- Cholinesterase Inhibitors Reduce Aggression, Wandering And Paranoia In Alzheimer’s Disease. Medical News Today 2008.

http://www.medicalnewstoday.com/articles/132476.php

- Beier MT. Treatment Strategies for the Behavioral Symptoms of Alzheimer’s Disease: Focus on Early Pharmacologic Intervention. Pharmacotherapy. 2007;27(3):399-411.

http://www.medscape.com/viewarticle/555408

- Masterman DL. Role of Cholinesterase Inhibitors in Managing Behavioral Problems in Alzheimer’s Disease. Prim Care Companion J Clin Psychiatry. 2004; 6(3): 126-131.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=474736

- Gauthier S, Loft H, Cummings J. Improvement in behavioural symptoms in patients with moderate to severe Alzheimer’s disease by memantine: a pooled data analysis. Int J Geriatr Psychiatry 2008; 23: 537–545.

http://www.legemiddelsiden.no/Lundbeck/microsite/Gauthier_pooled_data.pdf

- Birks J. Cholinesterase inhibitors for Alzheimer’s disease. Cochrane Database of Systematic Reviews 2006, Issue 1. Art. No.: CD005593. DOI: 10.1002/14651858.CD005593.

http://www.cochrane.org/reviews/en/ab005593.html

- Grossberg GT, Pejovi? V, Miller ML, Graham SM. Memantine therapy of behavioral symptoms in community-dwelling patients with moderate to severe Alzheimer’s disease. Dement Geriatr Cogn Disord. 2009;27(2):164-72.

http://www.ncbi.nlm.nih.gov/pubmed/19194105

Discontinuing Alzheimer’s Drugs
- Fillit HM, Hofbauer RK, Setyawan J, et al. Memantine Discontinuation and the Health Status of Nursing Home Residents With Alzheimer’s Disease. Journal of the American Medical Directors Association, 2010; 11 (November) 636-644.e1

http://www.jamda.com/article/S1525-8610%2809%2900522-2/abstract

- Doody RS, Geldmacher DS, Gordon B, et al. Open-label, multicenter, phase 3 extension study of the safety and efficacy of donepezil in patients with Alzheimer’s disease. Arch Neurol. 2001;58:427-33.

http://archneur.ama-assn.org/cgi/content/full/58/3/427

Continue reading »]]> The National Institute on Aging currently funds more than 30 Alzheimer’s Disease Centers (ADC’s) at major medical institutions across the nation. Researchers at these centers are working to translate research advances into improved care and diagnosis for Alzheimer’s disease (AD) patients while, at the same time, focusing on the program’s long-term goal — finding a way to cure and possibly prevent AD.

Areas of investigation range from the basic mechanisms of AD to managing the symptoms and helping families cope with the effects of the disease. Center staff conduct basic, clinical, and behavioral research, and train scientists and health care providers new to AD research. Although each center has its own unique area of emphasis, a common goal of the ADC’s is to enhance research on AD by providing a network for sharing new ideas as well as research results.

Collaborative studies draw upon the expertise of scientists from many different disciplines. The National Alzheimer’s Coordinating Center coordinates data collection and fosters collaborative research among the ADC’s. Many ADC’s have satellite facilities, which offer diagnostic and treatment services and collect research data in underserved, rural, and minority communities.

For patients and families affected by AD, many ADC’s offer:

* Diagnosis and medical management (costs may vary — centers may accept Medicare, Medicaid, and private insurance).
* Information about the disease, services, and resources.
* Opportunities for volunteers to participate in drug trials, support groups, clinical research projects, and other special programs for volunteers and their families.

>> ALABAMA

University of Alabama at Birmingham

Alzheimer’s Disease Research Center
University of Alabama at Birmingham
Sparks Research Center
1720 7th Avenue South, Ste. 650K
Birmingham, AL 35233-7340
Website
205-934-3847

>> ARIZONA

Sun Health Research Institute/Arizona Consortium

Arizona Alzheimer’s Disease Center
Banner Alzheimer’s Institute
901 E. Willeta Street
Phoenix, AZ 85006
Website
602-239-6525

>> ARKANSAS

University of Arkansas for Medical Sciences

Alzheimer’s Disease Center
Donald W. Reynolds Department of Geriatrics
University of Arkansas for Medical Sciences
4301 W. Markham, Slot 811
Little Rock, AR 72205-7199
Website
501-603-1294

>> CALIFORNIA

University of California, Irvine

Alzheimer’s Disease Research Center
University of California, Irvine
Gillespie Neuroscience Research Facility, Rm. 1113
Irvine, CA 92697-4540
Website
949-824-5847

University of California, Los Angeles

Alzheimer’s Disease Center
10911 Weyburn Avenue, Ste. 200
Los Angeles, CA 90095-1769
Website
310-794-6039

University of Southern California

Alzheimer’s Disease Research Center
University of Southern California
Health Consultation Center
1510 San Pablo Street, HCC643
Los Angeles, CA 90033
Website
323-442-7600

Stanford University

Stanford/VA Alzheimer’s Disease Center
Department of Psychiatry
3801 Miranda Avenue (151Y)
Palo Alto, CA 94304
Website
650-852-3287

University of California, Davis

Alzheimer’s Disease Center
Department of Neurology
University of California, Davis
4860 Y Street, Suite 3900
Sacramento, CA 95817
Website
916-734-5496

University of California, San Diego

Alzheimer’s Disease Research Center
Department of Neurosciences
UCSD School of Medicine
9500 Gilman Drive (0948)
La Jolla, CA 92093-0948
Website
858-622-5800

University of California, San Francisco

Alzheimer’s Disease Research Center
University of California, San Francisco, Box 1207
350 Parnassus Avenue, Suite 905
San Francisco, CA 94143-1207
Website
415-476-6880

>> FLORIDA

Florida Alzheimer’s Disease Research Center/Byrd Alzheimer’s Institute

Florida Alzheimer’s Disease Research Center
Byrd Alzheimer’s Institute
4001 East Fletcher Avenue
Tampa, FL 33613
Website
866-700-7773 (toll free)

>> GEORGIA

Emory University

Alzheimer’s Disease Center
Wesley Woods Health Center, 3rd Floor
1841 Clifton Road
Atlanta, GA 30329
Website
404-728-6950

>> ILLINOIS

Northwestern University

Cognitive Neurology and Alzheimer’s Disease Center
Feinberg School of Medicine
Northwestern University
675 N St. Claire, Galter 20-100
Chicago, IL 60611
Website
312-908-9339

Rush-Presbyterian-St. Lukes Medical Center

Alzheimer’s Disease Center
Rush University Medical Center
Armour Academic Center
600 South Paulina Street, Suite 1028
Chicago, IL 60612
Website
312-942-3333

>> INDIANA

Indiana University

Indiana Alzheimer Disease Center
Department of Pathology and Lab Medicine
Indiana University School of Medicine
635 Barnhill Drive, MS-A-138
Indianapolis, IN 46202-5120
Website
317-274-1590

>> KENTUCKY

University of Kentucky

University of Kentucky Alzheimer’s Disease Center
Sanders-Brown Center on Aging, Rm. 101
800 South Limestone St.
Lexington, KY 40536-0230
Website
859-323-6040

>> MARYLAND

The Johns Hopkins Medical Institutions

Alzheimer’s Disease Research Center
Division of Neuropathology
The Johns Hopkins University Medical Institutions
558 Ross Research Building
720 Rutland Avenue
Baltimore, MD 21205-2196
Website
410-502-5164

>> MASSACHUSETTS

Boston University

Boston University Medical Center
Alzheimer’s Disease Clinical & Research Program
72 East Concord Street, B-7800
Boston, MA 02118
Website
888-458-2823 (toll free)

Harvard Medical School/Massachusetts General Hospital

Alzheimer’s Disease Research Center
Massachusetts General Hospital
114 16th Street, Room 2009
Charlestown, MA 02129
Website
617-726-3987

>> MICHIGAN

University of Michigan

Alzheimer’s Disease Research Center
Department of Neurology
300 North Ingalls, Room 3D15
Ann Arbor, MI 48109-0489
Website
734-764-6831

>> MINNESOTA

Mayo Clinic

Alzheimer’s Disease Research Center
4111 Highway 52 North
Rochester, MN 55901
Website
507-284-1324

>> MISSOURI

Washington University

Alzheimer’s Disease Research Center
Washington University School of Medicine
Department of Neurology
4488 Forest Park Avenue, Suite 130
St. Louis, MO 63108-2293
Website
314-286-2881

>> NEW YORK

Columbia University

Columbia University Alzheimer’s Disease Center
630 West 168th Street, P&S 15-402
New York, NY 10032
Website
212-305-1818

Mount Sinai School of Medicine/Bronx VA Medical Center

Alzheimer’s Disease Research Center
Department of Psychiatry
Mount Sinai School of Medicine
One Gustave Levy Place, Box 1230
New York, NY 10029-6574
Website
212-241-8329

New York University

NYU Langone Medical Center
Center of Excellence on Brain Aging
145 E 32nd St, 5th Floor
New York, NY 10016
Website
212-263-8088

>> NORTH CAROLINA

Duke University

Joseph and Kathleen Bryan Alzheimer’s Disease Research Center
2200 West Main Street
Suite A-200
Durham, NC 27705
Website
866-444-2372 (toll free)

>> OHIO

Case Western Reserve University

University Memory and Aging Center
University Hospitals of Cleveland
Case Western Reserve University
12200 Fairhill Road
Cleveland, OH 44120-1013
Website
800-252-5048

>> OREGON

Oregon Health and Science University

Layton Aging and Alzheimer’s Disease Center
Center for Health and Healing
3303 SW Bond Avenue
Portland, Oregon 97239
Website
503-494-7772

>> PENNSYLVANIA

University of Pennsylvania

Alzheimer’s Disease Center
Department of Pathology and Laboratory Medicine
University of Pennsylvania School of Medicine
HUP, Maloney 3rd Floor
36th and Spruce Streets
Philadelphia, PA 19104-4283
Website
215-662-7810

University of Pittsburgh

Alzheimer’s Disease Research Center
University of Pittsburgh
UPMC Montefiore, 4th floor, suite 421
200 Lothrop Street
Pittsburgh, PA 15213-2582
Website
412-692-2700

>> TEXAS

University of Texas, Southwestern Medical Center

Alzheimer’s Disease Research Center
Department of Neurology
University of Texas SW Medical Center
5323 Harry Hines Boulevard
Dallas, TX 75390-9036
Website
214-645-8800

>> WASHINGTON

University of Washington

Alzheimer’s Disease Center
VA Puget Sound Health Care System
Mental Health Services, S-116 6 East
1660 South Columbian Way
Seattle, WA 98108
Website
800-317-5382

Continue reading »]]> Many Alzheimer’s patients scratch themselves bloody — my mother did that.  Sometimes it’s an obsessive/compulsive behavior that’s almost impossible to stop. Other times, though, there is another cause. Among the many tips I’ve seen for trying to help the patient:

>> FIND THE CAUSE

First, evaluate the Alzheimer’s patient thoroughly to see whether something may be causing itching.
– Perhaps the patient has developed an allergy to the bath soap s/he uses.  Try different soaps, or perhaps substitute shampoo, instead of soap, to cleanse the skin.  Liquid soaps may be very harsh to delicate skin, so avoid those.
– S/he may also have developed a reaction to a laundry detergent or fabric softener.  Try different ones, preferably without scents or perfumes.
– If a woman’s face itches, it may be due to the makeup she wears.  Try switching to a non-allergenic makeup, or see if she’ll stop wearing makeup altogether.
– Also consider whether face creams or cleansers, perhaps a man’s shaving cream or lotion, might be causing the problem.
– The culprit could be bed bugs, lice, or scabies, all of which are on the rise all across the country; or (if you have pets) fleas.

The problem could be dehydration.  Be sure your Alzheimer’s loved one drinks plenty of fluids, preferably 2 liters of water a day.

Many of the drugs prescribed for dementia patients – for behavioral problems, sleep aids, slowing down memory loss, and depression – can cause severe itching as a side effect.  Other drugs commonly prescribed for older people, for blood pressure, prostate issues and many others, also can cause intense itching.  Look up the potential side effects of each medicine your loved one is taking.  This side effect may be listed either as itching or urticaria. You may find it listed under “Integumentary System.”  One of the best sites for researching side effects is RxList.

If you identify a medicine that can cause this side effect, talk to the doctor about the possibility of discontinuing it for a while, to see if it’s the culprit, and/or switching to a different drug.

An Alzheimer’s patient may develop obsessive-compulsive disorder (OCD) symptoms, although it is fairly rare.  Certain selective serotonin reuptake inhibitors (SSRIs), such as escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline, have been found to be helpful for treating OCD patients, and OCD symptoms in frontotemporal dementia (FTD) patients.  Talk with the doctor about the advisability of trying one of these drugs.

>> SOOTHE THE ITCHING

Keep any scabs soft with ointment, such as Mupirocin. (Dry scabs invite more scratching.)  Treat open sores with an antibiotic such as neosporin.  Sometimes Alzheimer’s patients will leave bandaids alone, so cover healing scabs with bandaids.  (NOTE:  keep an eye out for allergic reactions to bandaids with latex in them!  Allergic reactions can develop very quickly, and itch like crazy.  All bandage boxes are required to have warning labels if the bandages contain latex, but the warnings can sometimes be very hard to find.  Keep looking until you find something that indicates latex is not in the bandage.)

Tea Tree Oil can help scabs heal and stop the itching.  But be careful when first starting to use this product — it can sometimes be painful.  Watch for signs that the skin is turning red.

Some caregivers have reported success with Pure Aloe Vera Gel.  Be sure to get pure gel, without any lotions or other ingredients.  (If you try using sap from an aloe plant, be forewarned that the sap may stain linens.  Some caregivers have warned that it can also stain the skin a yellow-brown color.)

If the itching is caused by the Exelon patch, remember to put the patch on a different place every day.  Don’t “re-use” the same place for 12 days.  Clean the site well and moisturize the area.  If the itching/light rash persist, some doctors recommend applying Flonase to the skin after removing the patch.  A light coating of a cortisone ointment may also help, but be sure to talk with the doctor before trying this.  Cortisone is absorbed, and it might interfere with some other medicine the patient is taking.  Consult a doctor if the rash persists or spreads, or if the patient develops a rash in any place other than the site where the patch was applied.

Older patients often have very fragile skin.  Frequent bathing may not be advisable.  Switch from a bath to a shower, warm water rather than hot, and only twice a week.  If that doesn’t help, try sponge baths with a no-rinse product.

Keep the skin moisturized. Slather on lotion (people have recommended Eucerin, Aveeno or Cetaphil or other non-allergenic lotions) after each shower while the skin is still moist. Also put lotion on before the Alzheimer’s patient goes to bed. (Accompany this with a massage of the back and shoulders, to make the patient feel loved and pampered.)  Some doctors prescribe a Kenalog/Lubriderm lotion, to soothe the itching and keep the skin soft.

Over-the-counter cortisone cream may ease the itching, but use it only for small areas and only for short periods of time.  If it helps in the short-term but does not break the itching cycle, consult the doctor to see whether continued use is advisable.

Just as tylenol relieves minor pain, it will also reduce the sensation of itching. This can be helpful to break a cycle of itch/scratch or help to determine if there is an actual itch sensation that is causing the scratching. (Be sure to ask the doctor whether it’s okay to give the patient tylenol.)

Make an appointment with a good dermatologist if there’s any rash or redness or any other skin changes.

>> STOP THE SCRATCHING

If no cause for itching can be identified, and nothing you try seems to soothe it, then try other methods to stop the scratching:

Keep the patient occupied; and when s/he is just sitting, keep the hands busy.  Give the person something to hold – small, soft objects to “finger and fiddle” with.  This lessens the picking and gives the skin time to heal.  Some patients like a doll or plush animal.  “Stress balls” come in different colors and shapes, and won’t do any harm if the patient decides to throw it.  “Worry beads” may also work well.

Keep fingernails cut short.  For a woman, get her acrylic nails done, and tell the manicurist to make them very short and very thick – that can make it a bit more difficult for her to “gain purchase” under a scab or loose piece of skin.

See if you can get the patient to wear soft cotton gloves.  Tell a woman they are part of a “spa” treatment – if she thinks she’s being pampered, she may be more cooperative.

If the patient scratches his arms, dress him in long-sleeved shirts, or use “wristies” — elbow length sleeves with elastic at the top and bottom.  The patient may still pick, but at the fabric rather than his skin.  These are sold at websites such as Buck & Buck.

If all else fails, “posey mitts” can be used to give the skin time to heal.  These are sold by many companies … google to find the best bargain.  However, posey mitts are considered to be “constraints”, and may be frustrating and distressful for your loved one.  Only use them as a last resort; and try using just one, on the loved one’s dominant hand, and only during times when your loved one is agitated enough to pick or scratch his/her skin.