The Many Roads to Senile Dementia

When I was much younger, and just beginning graduate work, I was relatively convinced that intelligence was a young person's domain. I was keenly aware of the cross sectional studies that appeared to show that intellectual processes began to deteriorate at the same time that we reached the magical age at which we were no longer growing, physically, about the age of nineteen or so. I was 21 and felt my intelligence slipping on a daily basis. A few years later, pursuing another degree, I chanced to work with the very distinguished professor who was head of the brain institute at UCLA. I confided my fears to him and he threw out the off hand remark that we lost 105 brain cells a day (that's 100,000) from the age of maturity (19 or so) on. My fears were confirmed! Even after I realized that this was a small number and didn't necessarily imply what it seemed, I could feel my head growing emptier by the minute.

As an aside, the distinguished scientist in question notwithstanding, in the subsequent forty-five years, I have never been able to verify (or contradict) that number. I have come to question its accuracy. At the time, though, this was the most authoritative person I knew and, arguably, the leading scientist in the world on this issue. I didn't doubt him. So, if senility was inevitable, and dementia the necessary end of a long life, I thought that I had better get in my contributions to the world in a great hurry, before I drooled on my lab coat.

I have not only learned a great deal since that time, I have, also, experienced many years of that cell loss. After a while, I was able to stop checking my number span, forward and backward, on a regular basis, and stop looking for the feared signs of deterioration. Besides, I always drooled on my lab coat. I continued various graduate degrees until well into middle age, and found it easier every time. I searched the literature again and came to a conclusion markedly different from the one previously feared. The early studies were very flawed and, it seemed, some abilities continued to improve for many years after maturity. Not all; there is a process of loss. As one ages, the ability to deal with multiple streams of sensory input reduces; speed of calculations diminishes, concentration narrows some. But, in normal aging, we grow slower, not stupid.

The early research that seemed to show less achievement and intellectual prowess with advancing years suffered from a number of flaws. One thing that does diminish with age is drive, motivation, the need to succeed. Couple this with the ever-changing technology that favors the recently educated and the relatively minor losses that do occur, and you have the illusion of deterioration, particularly when you compare groups of different ages at the same time (cross sectional research) as opposed to following changes in the same group over time (longitudinal research). Yes, some alacrity is lost, but, at the same time, the continued learning over a lifetime contributes a major advantage. The more we learn, the more we can understand new facts, fitting them into what I like to call an "apperceptive mass"; that is, the sum total of all you know. If this mass is organized, as in people who are intelligent and keep using their intelligence, new facts are not isolated but rather fit into the understanding of everything else. It is, therefore, important to continue to be intellectually active in order to maximize this benefit of learning.

So what's the point of all this? Obviously, some people, in fact a significant fraction, do show signs of markedly deteriorated mental processes with age. There is a phenomenon lurking in the advancing years, called dementia. My point is that this is not a normal aging process, but rather the result of a number of different pathologies. If the deterioration reaches a stage in which it interferes with "normal functioning" it warrants the label of dementia. If it occurs in people over the age of 65, it is called, senile dementia. Under the age of 65, not too surprisingly, it is called, pre-senile dementia. True dementia afflicts approximately six to eight percent of the population over the age of 65, although there is an unknown number of less severe manifestations that, nevertheless, contribute to mental loss in aging.

However, the five to seven percent is an overall figure. It is much higher in the older age ranges until nearly half of people over the age of eighty manifest significant signs of dementia. That fact inflates the appearance of deterioration as a function of age, and age is certainly a major risk factor. But age, alone, does not cause major loss of mental powers; mild forgetfulness, yes, deterioration of comprehension and major loss of mentation, no. It does, though, increase the probability of suffering from the disorders that do.

The word, dementia refers to cognitive impairment that manifests primarily as a form of memory disorder. In the early stages, the primary loss is in recent memory but that is a little misleading in that the underlying impairment is predominantly in the process of forming the memory, that is, the attentional process is impaired more than the retention of facts that have been allocated into permanent memory. Thus, the people so afflicted often have better recall of long ago experiences than very recent ones. The cause of this is that the recent ones never make it into the permanent memory storage processes. When they are gone, they're gone. There is nothing that has been processed by the brain. There is nothing to recall. Older memories are still there. Sometimes they cannot be easily accessed, but they are there, somewhere in the brain. This accounts for the appearance of 'good days' and 'bad days' that demented people exhibit. On good days, they are in situations in which they can access the old memories more easily than on bad days. However, they still exhibit attentional difficulties for recent events, even on the 'good' days. In the most common types of dementia, as the disease progresses, all memory processes become involved and even well rehearsed daily tasks of self care can be lost.

As there are many different causes of the symptoms of dementia, some of which are treatable, accurate diagnosis is extremely important so that those who can benefit from treatment might get it. Assuming all dementia that occurs in the elderly is irreversible and untreatable can lead to much unnecessary pain. A quick review of the major syndromes might result in saving some of that pain.

Causes of Dementia

Alzheimer's:

Ninety to ninety-five percent of diagnosed dementias are senile. Somewhat over half (50 to 60%) are caused by Alzheimer's disease. Dr. Alois Alzheimer, in 1906, described neuroanatomical changes in the brain of a patient who had died after exhibiting unusual mental symptoms. These changes are now diagnostic of the disease that bears his name. The disorder interferes with the brain's ability to communicate among its own cells, eventually killing the cells. It is a progressive disorder, usually beginning after the age of 60 and continuing until it causes a premature death. It begins as mild forgetfulness that can be overlooked and progresses until the afflicted becomes helpless for any self care, continuing until the basic homeostatic processes for living are stricken. Undoubtedly, this is not one disease, but several. The causes are still unknown, but one form that begins very early (sometimes as early as 30) has a strong hereditary component. Senile forms apparently are less genetically loaded, although there is still some weaker family effect.

Alzheimer's is incurable at this time. However, there has been recent progress in finding factors that slow its onset and its progress, including drugs that increase the available amount of a particular neurotransmitter, acetylcholine. The benefits, though, are temporary, and no treatment known can cure or even arrest the disorder more than partially and temporarily. There are several vitamins and 'supplements' (generally antioxidents) that have been tested because of some indication or theoretical relation with the changes wrought by the disease. However, these have generally shown little or no effect when tested experimentally. (Nevertheless, personally, I still take a high dose of coenzyme Q10 because it has other, proven effects on gums and heart, and might have some small protective effect on Alzheimer's.)

Vascular Dementia:

The word, "vascular" refers to the blood vessels. If the flow of blood is reduced, in any way, obviously the brain function suffers. There are many different ways in which the blood flow to the brain can be restricted. Cardiovascular diseases are among the most common problems. Arteries can occlude in the brain and the vessels feeding into the brain just as they can occlude in the heart and the vessels supplying the heart. In the extreme instance, this can cause cerebrovascular accidents, strokes, (post stroke dementia) or more transient effects that are potentially reversible. However, vascular problems can manifest in more subtle ways, particularly if numerous small vessels are involved, reducing blood flow to large areas of the brain (multi-infarct dementia). In such instances, a type of dementia can result that is somewhat different in character from that caused by Alzheimer's disease.

The symptoms are more likely to involve physical disturbances, such as balance, gait, weaknesses, or sensory losses in the early stages than Alzheimer's. Confusion, particularly at night might be a more prominent feature than memory loss. The symptoms often develop in discrete steps as opposed to the slow and gradual deterioration in Alzheimer's. Nevertheless, the differences can be subtle or essentially non existent, although modern brain imaging techniques can usually provide the diagnosis.

If you consider all circumstances of impaired function, including the relatively mild problems that don't reach the level of full blown dementia, it can be said that vascular problems are the most frequent cause. However, they are more preventable than other causes because they are related to the variables that cause cardiac problems, weight, blood pressure, glucose control, and lipids. Personal habits such as smoking and excess alcohol intake are also risk factors that are under the control of the individual. However, once the dementia develops, there is no more current treatment than for Alzheimer's. Some of the same pharmacologic agents that help or slow the progress of Alzheimer's disease are helpful in maintaining function. However, there is some evidence that at least some of these drugs pose risks of increasing potentially fatal cardiac events in this population.

Mixed Dementia:

A fair number of people suffer from both Alzheimer's and vascular dementias at the same time. In fact, it is now thought that nearly half of the victims of one of the disorders also show signs of the other. Symptoms are, as you might expect, typical of either or both of the causes. Treatment is also similar to the treatments above, with an emphasis on prevention of the risk factors for vascular dementia. The outcome and progression (prognosis) is worse, however, than for either syndrome alone.

Lewy Body Dementia:

Another group of disorders resembling the losses in Alzheimer's are brain diseases that display abnormal inclusions in the brain cells called Lewy Bodies. Many of the symptoms are similar to those in Alzheimer's or vascular dementias, but there are some significant differences, too. There is more likely to be a particular type of shuffling gait change with a physical 'stiffness' and characteristic blank facial expressions. Unfortunately this can be similar to some reactions to drugs used to treat psychoses, and the possible confusion is worsened by the fact that Lewy Body dementias can manifest psychotic signs, such as hallucinations. However, treatment with antipsychotic drugs actually worsens the condition. The symptoms can also be similar to those in another category that will be discussed below, Parkinson's Disorder, although they are distinctly different entities. About half the time, characteristic disturbances in REM (rapid eye movement) sleep are associated with Lewy Bodies.

There are several apparently different causes of Lewy Body inclusions. It is unclear how many different disorders are included in this category. As a whole, though, the symptoms respond to the drugs used to treat Alzheimer's, mentioned above. As in other disorders, the drug treatment, at best, slows the progress of the disease and maintains function for at least a few months longer. At the outset of treatment, they can, sometimes, temporarily restore some of the function that has been lost.

Frontotemporal Dementia:

Not too many years ago, a form of rapidly deteriorating dementia was described that, at first, was confused with Alzheimer's. However, the symptom pattern was significantly different, manifesting a more rapid development than the typical Alzheimer's patient and marked more by loss of emotional controls and, particularly judgment. In fact, it resembled some of the changes found in frontal lobe brain injuries, but was not associated with trauma and steadily worsened. Symptoms can include mood shifts that often progress to almost total apathy. Sometimes control over eating is affected and rapid weight gain can be a symptom of this disorder.

Ultimately, postmortem examination of brain tissue showed an inclusion (named Pick Bodies; guess why) in cells of the frontal lobes and, in lengthier histories, cases, the temporal lobes as well. When Dr.Pick discovered these inclusions, they were noted to correlate very well with this particular symptom pattern. Nearly all patients who had these inclusions, and the usually concomitant atrophy of the lobes, displayed a deteriorating mental picture. On the other hand, by no means did everyone who displayed similar symptoms also have the Pick Bodies or the clear atrophy. So, what was known as Pick's disease is now considered but one subtype of frontotemporal dementia.

What are the other types? How many are there? I don't know, and I don't know anyone who does. Fortunately, all of them combined are relatively rare; very fortunately because there is not only no known cure, there is nothing known to affect its course. It can usually, but not always, be diagnosed by brain imaging that identifies the excessive shrinkage in the frontal and, possibly temporal lobes. However, confirming the diagnosis only has the benefit of planning for the deterioration as there is nothing you can do about it, anyway.

Don't ask what causes this group of disorders unless you are willing to fund some very costly research.

Normal Pressure Hydrocephalus (adult)

There are several possible etiologies that lead to the final common pathway labeled, normal pressure hydrocephalus. This describes the fact that there is a blockage in the system that drains the fluid in which the brain and spinal cord rest (cerebrospinal fluid). When this happens, the fluid accumulates in the ventricles (spaces) in the brain and expands them, impairing the function of the surrounding brain cells. The name derives from the difficulty in diagnosing this disorder by using a spinal tap to measure the pressure of the cerebrospinal fluid. Although it is obvious that it must be an increase in pressure from the blockage that causes the swelling of the ventricles, the measurement of fluid pressure from the spine remains within or near normal levels. Therefore, measuring cerebrospinal fluid pressure is not a definitive (or even good) diagnostic technique; hence the name, which serves as a warning to not rule out hydrocephalus simply because the pressure is within normal limits.

In the instance of this disorder, arriving at the proper diagnosis matters, possibly a lot. This is usually a treatable condition. Once the blockage is identified and relieved, some or most of the deterioration can be reversed, depending, of course on its length and severity. And, more often than not, there will be some technique available to reduce the pressure. If the blockage cannot be cured, a shunt that drains the fluid into some safe place in the body cavity is often helpful. So, unlike the other causes of dementia previously discussed, this one can be usefully and effectively treated.

Can it be recognized from the presentation, the pattern of symptoms? Maybe. The presentation is somewhat different from any of the other causes of dementia. The early prominent symptoms tend to be threefold, difficulty in ambulation (walking can be seriously impaired), loss of bladder control, and a general slowing of mental processes. That last, the slowing of mentation, can often be discriminated from the loss of mental abilities in other dementias because it is a true slowing, not an incapacity. Problems of any sort can still be solved, accurately, but more slowly than the person could before.

So diagnosis is important. With modern brain imaging techniques that can show the functioning of the tissue as well as its general shape and size (morphology), the enlarged ventricles and their effects on the surrounding cells can usually (unfortunately not always -- of course) be seen and lead to the diagnosis. Although this is considered a relatively rare disorder, it just may be that accurate diagnosis will identify a few more than were previously suspected and at least a few of the people who had been written off as hopelessly senile, can be brought back to normal living. This is unusual among the dementias and, along with a couple other causes discussed below, should be ruled out before anyone is labeled hopelessly "senile."

The next few disorders are included simply to be thorough because they do, technically, cause dementia, but they are nearly never confused with any of the other causes, at least not for very long, anyway.

Huntington's Disease (alternatively, Huntington's chorea)

Huntington's disease is a hereditary disorder that is a function of a genetic defect, involving a single, dominant gene which was identified in 1993. It strikes in people who had developed perfectly normally up to the onset of symptoms, most often in early to middle adulthood. The age at which it becomes apparent varies, but it is usually by the age of 35 to 40. It was called Huntington's chorea because the early symptoms tend to produce typical movement changes (choreiform) involving twitches, spasms, balance, and gait problems. Also early in the development, confusion, mood changes, and the typical group of concentration, memory, and judgment difficulties of dementia.

Huntington's disease is terminal, that is, invariably leads to death from the disorder itself (massive destruction of brain tissue), or from the difficulties in care that it creates. The speed at which it develops varies from one person to another, the clinical symptoms sometimes lasting fifteen to twenty years. There is no known cure or treatment of much use. The movements and anxiety can be ameliorated but the underlying process continues. The identification of the errant gene has spurred research recently, and I would expect a possible cure in the near future. As 98 to 99% of all cases occur in individuals with known family histories, it is rarely missed or misdiagnosed.

Creutzfeldt-Jakob Disease

Another group of disorders that result in symptom of dementia is collectively called Cruetzfeldt-Jakob Disease. These are marked by the appearance of abnormally shaped proteins in a previously normal adult brain. It usually appears in adults over 60 and is marked by confusion, memory problems, and other dementia symptoms making it possible to mistake it for Alzheimer's. However, agitation and movement disorders are also generally present at the outset of the disease. It progresses rapidly and usually leads to death within a year. It is, however, relatively rare with a prevalence of approximately one case per million population.
Evidence that this represents more than one syndrome comes from various sources, most notably a variant that appears to be related to the ingestion of meat from animals afflicted with mad cow's disease. This variation can start in much younger people, even as early as the teen age years. There are fairly laboratory tests that can, sometimes, identify the disorder. Although in the early stages, C-J Disease can be mistaken for the more common types of senile dementia. The major problem with that possibility is simply the fact that neither the person nor the caregivers can prepare for the rapid decline and useless (or worse) treatments that help in Alzheimer's or vascular dementias might be mistakenly implemented.

Parkinson's Disease

Parkinson's disease is listed here for two reasons; one of which is the fact that it is historically found in most lists of causes of dementia. The other is that it bears a relation to other causes in that it often manifests Lewy Bodies (above). However, Parkinson Disease, as so many of the other syndromes, represents a description of symptoms with a similar clinical presentation, relatively similar outcomes (prognosis), but probably varied causes (etiologies).

Parkinson's describes a disorder that is primarily of movement. Its predominant symptoms are tremors (shakiness), stiffness, loss of muscle control that affects gait, balance, facial expressions, and, often, speech. In the late stages, some, but not all develop dementia to some degree. It tends to worsen over a period of years and is life shortening when it does. While there is no treatment for the dementia, if and when it develops, there are effective treatments that slow its progress through the stages.
Multiple traumas to the head can produce a similar picture, as in professional boxers who are exposed to head blows, repeatedly, over a period of years. Also, some of the drugs that were recently popular in treating schizophrenia can produce movement disorders that appear Parkinsonian. Therein lies the only diagnostic issue, that is, distinguishing between a primary Parkinson's Disease and tremors secondary to drugs or trauma. They are treated somewhat differently and have somewhat different outcomes.

Wernicke-Korsakoff Syndrome

I am describing this last among the standard causes of dementia because it provides a segue into the last part of this article. Technically, Wernicke-Korsakoff Syndrome is a nutritional disorder, a vitamin deficiency. The culprit is Vitamin B1, or thiamine. Thiamine is a substance that helps brain cells turn sugar into energy. There are several causes for thiamine deficiency; a lack of thiamine in the diet is rarely one of them.

Historically, this syndrome has been associated with alcoholism and, indeed, excessive alcohol interferes with the absorption of thiamine and has been one of the major contributors to this syndrome. It is not, however, the only one. Aids and disseminated cancers can cause thiamine deficiencies but in that case, the patient has more to worry about than thiamine. However, a number of other, more treatable disorders can also produce this condition (for example, severe hyperthyroidism) and should be investigated if the cause is not clear.

Wernicke-Korsakoff Syndrome is a two stage disorder. The first stage, Wernicke encephalopathy is acute. That is, among other things, it is potentially reversible. However, with continued deprivation of B1¬¬¬, the disease progresses to Korsakoff psychosis, an interesting form of dementia and only partially reversible, at best. Why is it interesting? Because it is marked by a phenomenon known as ¬¬ confabulation. First, the general symptoms will sound familiar, confusion, memory gaps, and coordination problems progressing to weakness. The confabulation is a tendency to invent memories to replace the ones that are lost, sometimes in detail. It actually seems as though the individual believes the invention. Not all Korsakoff psychoses manifest confabulation, and it is not quite unique to Korsakoff's. However, it is a pretty good diagnostic sign.

Consistent with long clinical observation that some people seem more sensitive to the effects of alcohol than others, a genetic variant has been recently identified that appears to be associated with a greater vulnerability to Wernicke-Korsakoff than others. Adding to the significance of this observation is the fact that it is also found more frequently in people who exhibit Alzheimer's than those who do not.
In the Wernicke stage, stopping the insult (alcohol or whatever) and providing good nutritional support can reverse some, often most of the damage. Later, however, by the time Korsakoff's psychosis has developed, very little can be done to improve the condition, but deterioration can be slowed by supportive care and proper nutrition.

Why did I say that this was a segue into the last part of this article? The reason I made that statement is because the early stage of the deterioration is related to drugs and nutritional issues and it illustrates the possible importance of these factors.
I promised you a point. I promised that if you would stick with this long article, I would eventually provide something of practical importance. Here it is:

When is a dementia, not a dementia?

The above is an overview of the medical disorders associated with dementia. Of course, physical trauma can also result in dementia, but, interestingly, it generally does not mimic the disorders above because it rarely involves very large areas of the brain if the person survives. However, as these pose no diagnostic problem, there is no need to discuss trauma in this article. But there is a need, a very important need, to discuss two other issues: drugs, and depression, both of which are often confused with physical dementias. Both of which need to be distinguished from the physical syndromes and dealt with in a proper manner.
I think that in clinical practice, more than half of the old folks I have seen who were marginalized and virtually discarded because they were "senile," weren't senile at all. Oh, they were old; they weren't active; they didn't respond too well; they might not have known what day it was, but they weren't demented. So how come they looked so demented? There are several possible reasons for this. The two major ones are depression and drugs. No, I don't mean that Grandma was out behind the garage shooting heroin or smoking crack. I mean that Dr. Givermore (and don't bother me) hasn't been paying attention to how much she has been getting from everyone.

As a rule of thumb, the dose of most psychiatric drugs is cut in half for people over 65.Of course there is no magical event that happens at midnight of your 65th birthday. (It really happens at noon - just kidding.) It's not rigid, but it is an arbitrary recommendation to remind the clinician that older people do not metabolize or tolerate drugs as well as younger people. Many people are overmedicated, particularly if they see different physicians for different problems. Many people are prescribed multiple drugs in the same class and no one, least of all the patient, is aware that these are having additive effects. And when the patient has more ailments, more physicians, and more age, all of which tend to increase together, there can come a point at which the drugs are causing severe symptoms, sometimes to the point of being obtunded and unresponsive. At this juncture, they don't tend to take care of themselves very well, nutrition suffers and the problem is compounded. If you had a chronic overdose of tranquilizers and were undernourished, you might look a little demented, too.

Before committing Uncle Charlie, or even making him a comfortable little nest in your basement. have one competent physician assess the entire picture of illnesses, drugs, nutrition, sleep, and exercise, and if that assessment does not yield any useful information, then turn to the next most likely issue, depression, before you go off the deep end and order the whole pantheon of tests and brain imaging.
Depression is even more often mistaken for dementia than overmedication. The elderly often lose the support of loved ones around them, through both death and departure of the younger people into their own lives and away from the older elderly. It is not hard to understand a withdrawal into severe depression that resembles dementia. This is sometimes called a pseudo-dementia and is eminently treatable, returning a significant amount of normal life that might otherwise have been wasted by being marginalized and discarded because the individual is considered senile and demented.

The point is this. All of the syndromes of illnesses above, and more, represent physical causes for dementia. All of them are difficult to treat or even control. They have fatalism in common that is based on a poor prognosis that complicates simple age. When they are present, it is important to obtain an accurate diagnosis in order to predict the future and provide optimum treatment or support. Toward that end, I have summarized some diagnostic features of the most likely syndromes. However, it is even more important to recognize the treatable causes of what appears to be dementia, but is either a drug response or the pseudo-dementia of depression.