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Dementia is defined as a acquired syndrome of declining memory and at least in one of a number of other cognitive functions and is. In addition to amnesia we have apraxia, aphasia and agnosia that should be easy for you to remember as you related it to dementia. But this is not just a memory problem. One should see difficulty overall in comprehension, with the ability to do a variety of motor functions as well. It should be sufficient to affect daily life in somebody who is otherwise alert. That notion of alertness is to differentiate this from delirium, which is acute onset and always affects consciousness and tension in Alzheimer's Disease.
The most common causes of dementia is dementia of the Alzheimer’s type. Now if you look at a variety of studies of dementia in late life in the United States, you will see that overall if you look at populations that are over the age of 65, what you will find is that usually somewhere between 5-10% of people who are over the age of 65 are affected. You can see that as age increases, prevalence rates increase as well. What’s important here is that 10% of the population over the age of 65 is suffering with significant dementia. That means that somewhere around 90% are not. Those prevalence rates increase dramatically with age. By the time one reaches the age of 85, according to that study, one sees that as many as 49% of people over the age of 85 have significant dementia. But again, in the younger old population.
You can see that the most important of the dementias is the dementia of the Alzheimer’s type. About two-thirds of all dementias are caused by Alzheimer’s disease. About 15% by vascular dementia, multi-infarct dementia, small strokes. What used to be ascribed to so-called hardening of the arteries. What we do know is that vascular changes in late life do increase the probability of dementia. In that other category then, probably the Alzheimer’s category is a group of people with mixed disease. Just because you have Alzheimer’s disease doesn’t prevent you from having essentially atherosclerotic, cardiovascular, cerebrovascular disease and it doesn’t reduce the risk factors that might co-exist, like diabetes, hypertension.
Essentially the DSM IV criteria for dementia of the Alzheimer’s type includes the symptoms that I mentioned before - the four A’s; amnesia, apraxia, aphasia and agnosia - and I’ve seen a substantial number of people who present first with the same kind of horrifying, frustrating language disturbance that one sees in a left parietal capital lesion from stroke. Having the same kind of language difficulties and associated behavioral disorder and the more profound memory impairments seem to follow. So that this is a somewhat idiosyncratic disease in that it doesn’t progress in everybody in exactly the same way. Some difficulty in executive functioning and some focal level problems; difficulty with abstraction, organization, often behavioral disinhibition and remember that there is a gradual, insidious onset.
Diagnostically, be comprehensive here. Remember, we don’t have a gold standard diagnosis of this disease. However, if one does a great workup consistent with the guidelines that I’ll present to you, that are consistent with the NIH consensus criteria or with the criteria that were established by the Alzheimer’s Disease Related Disorders Association somewhere around the middle of the 1980’s. The correlation between the diagnosis clinically and postmortem findings in good centers approaches 90%. If one thinks about it, what that means in regard to false negative and false positive rates that you’ve heard about in these patients, that certainly is probably as good as decline.
Additionally, a comprehensive laboratory assessment that is looking at trying to eliminate other potential etiologies for dementia or other etiologies for reversible declining cognitive function. What’s interesting about this set of studies is not that necessarily one will find a substantial number of people, for example, with hypothyroidism who have fully reversible cognitive decline. But it is likelier in a large group that one will find a substantial number of people who have excess disability, that in addition to a baseline dementia will have a incremental cognitive decline on the basis of the medical finding. However, it is possible, for example, to not have a full-blown evidence of B-12 macrocytic anemia that has a subclinical B-12 deficiency and if essentially treated with B-12 appropriately will in fact fully
Dementia with Lewy bodies is also critically important, obviously the evidence of kidney disorder. All these things, parkinsonism. Very detailed visual hallucinations are often associated with the Lewy body dementias. And substantial fluctuations over the course of time. Again, this is a very difficult diagnosis to make clinically. If one sees somebody who has these parkinsonian symptoms very early in the
There are a number of risk factors that have become increasingly associated with Alzheimer’s disease and let’s just touch upon them. Specifically and directly I will try to identify the more important ones for you. Obviously the most important one is age. There is evidence that people over the age of 85, as close to half of them suffered what was considered to be symptoms consistent with dementia of the Alzheimer’s type. Mostly that the prevalence rate is between 35-40% in that age group is probably more realistic in the company of more recent immunologic data in some of the older studies. But you can see that the longer one lives, given the overall higher risk for
There has been substantial focus on trying to look for gene locus that is associated with either late onset Alzheimer’s disease - that is, after the age of 60 or 65 - early onset Alzheimer’s disease and the other risk factors that seem to be associated with the disorder. I mentioned a few of them before. In addition to late onset, particularly associated with one of the apo protein B, which I’ll talk about in a second, has been identified on chromosome 19 in addition to the other three that I mentioned to you before. There’s been much attention over the course of the last four years or five years in the protein Apo E-4. The gene for Apo E-4 is found on chromosome 19. There are three locus on this gene, number 2, 3 and 4. What is interesting is that there is an association specifically increased risk of late onset familial and sporadic Alzheimer’s disease in people who have evidence of having Apo E-4 and that raises substantial questions as to whether the marker might be on that locus. Also the Ape E-2 and its presence seems to decrease the risk. So understand essentially the association of E-4, increased risk and also its association with late onset disorder, but that Ape E-2 may in fact appear to be
There is an interesting relationship between depression in late life and Alzheimer’s disease. Clearly, any of us who have taken care of people in the earlier stages of dementia have seen that there seems to be an increased risk, particularly with depressive symptoms, particularly among people who continue the ability to examine themselves and to be able to appreciate the loss of their functioning that is apparent to them over time with the also related psychological factors from changing or transmitters that we know Alzheimer’s disease also affects is unclear. However, if one looks at a group of people - we used to pay a lot of attention to try and discern this so-called
Additionally, an interesting look that is studied extensively by John Hall between Down’s syndrome and Alzheimer’s disease and that is that most people, by the time they are 40-years-old with Down’s syndrome will develop dementia and the plaques and tangles that are associated with Alzheimer’s disease. And it is quite interesting to look at this population, even those in studies after the age of 40 who don’t have behavioral symptoms seem to almost universally have plaques and tangles. Additionally, there seems to be an association
About 40% of people with Alzheimer’s disease will suffer clinically significant behavioral disorders, such as agitation or symptoms of psychosis at sometime over the course of the illness. There is no evidence whatsoever that a preexisting personality or other psychiatric illness except that the person has a concomitant psychotic disorder are significant risk factors. So some people will become psychotic because before, unless of course they have a recurrence of the disorder. The psychosis, agitation, aggression associated with Alzheimer’s disease are entirely unpredictable and are associated with substantial debility. They are the most important risk factors for institutionalization. So these behavioral disorders and their difficulty in management are the most important predictors of whether people
On the pharmacologic side, in terms of the cognitive disorder associated with Alzheimer’s disease. It’s just important to say that the first two drugs ever approved to treat the cognitive decline associated with dementia were approved within the last six or seven years. They are tacrine and donepezil. The effects are seen most cognitively in people’s mind. Moderate disorders. What it appears they do is they slow the progression of the disease over time. The best studies would indicate that if you look at a whole population of people, you treat
Additionally, we are working in a variety of other areas. You’ve heard about for example the Washington Heights study which demonstrated that postmenopausal women who are taking estrogen appear to reduce their risk of developing Alzheimer’s disease and those that did develop it, developed it at a later stage. Additionally, at least one study of people with arthritis who were treated with
Clearly understand that is an ongoing disorder and it is your role essentially to try to moderate excess disability, to support that family, to make the diagnosis, obviously, appropriately, to get people to come to support groups and other kinds of specific aids that they can use in the community, and in terms of behavioral disorder to focus very hard and try to palliate what is excess disability. Clearly there is an interaction between dementia and depression. The affective symptoms of depression, particularly much later in life, as I said before can
The other thing that is critically important is to understand that this finding and particularly a depressive syndrome that meets some but not all of these symptoms, will be categorized as clinically depressed, clinically significant depressive symptoms and probably will respond to treatment. Increasing studies indicate that they will respond to psychotropic and psychotherapeutic interventions, and may in fact reduce the disability that is associated with this current disorder. There has been some evidence of structural brain lesions with differences associated with depression that occurs in late life. These are not recurrent depressives who had their first episode when they were 35 or 40. These are people who became depressed in late life. More white men are hyperintense, vascular lesions are associated. So essentially, as I mentioned before, there are a substantial number of risk factors that one can identify. It’s also critical to try to discern
Obviously there are a variety of drugs that we use in this population that can cause significant evidence of apathy, difficulty in concentration, sleep changes, etc. I think that the real issue here is that one constantly has to weigh a toxic intervention and the hopeful outcome with what the average events that are associated with treatment might be. In general, the notion is to try to be aggressive. There’s no question. And the notion is to try to help people adapt to the losses that they are focusing on, prior to intervening, particularly with somatic interventions. But the real outcomes that we try to achieve relate really to life quality. Most people attribute most aspects of life quality as they rate it in late life, is to function at capacity. So if you treat somebody and we essentially make them severely orthostatic and they can’t get up, but their mood is better, we are not really achieving an improvement in life quality and functional capacity and that scale continues to be involved. Essentially there are three modalities, the same as there are in the remainder of psychiatry, and very frankly among the tricyclic antidepressants, these are still mainstay treatments. Most often at the present time people are not using these as the first interventions. In general, when one uses these drugs, stay away only from the tertiary new tricyclics which are severely anticholinergic and have severe side alpha effects. Really, secondary to these are nortriptyline and desipramine are the mainstays. There is some discussion about this in your notes. But start low, go slow, constantly be on the phone with patient populations and essentially do your best to monitor blood levels where that is feasible in that population. MAOI’s remain an important drug in this population and are well tolerated by most people except those with cognitive impairment can do okay with maintaining the diet. Essentially the thing you need to worry about here is that these drugs are great antihypertensives. They are super-antihypertensives, so you may have to discern if somebody is on an antihypertensive drug, reducing the probability of some other atherosclerotic plaques and kill two birds with one stone. I have found that all three sets of these drugs, SSRI’s, MAOI’s and secondary main tricyclics, I see it to be a principal cause of SIADH. The number of people I have given hyponatremia to with these drugs is just remarkable. Whether this is purely a CNS effect is unclear. But I would carefully monitor sodium in these patient populations. These are adverse effects that were reported in a number of studies, or reported considerably more frequently particularly in people with any evidence of renal artery disease.
Essentially, the SSRI’s were a wonder, from the perspective of the older adult populations because they are very well tolerated, very little anticholinergic effects. Some studies indicate, and these are reported in the literature and worthy of note, that it may take, in the