Online newspaper of professor Yasser Metwally

The author: Professor Yasser Metwally

http://yassermetwally.com

INTRODUCTION

April 21, 2008 — Changes in cognition are among the most frequent and the most important (in terms of morbidity, mortality, and impact on family members and society in general) age-related medical conditions.

I . Alzheimer’s disease

Cognitive changes in normal aging and in progressive Alzheimer’s disease occur in a continuum. Barry Reisberg and associates describe seven major clinically distinguishable stages from normality to most severe Alzheimer’s disease in the Global Deterio- ration Scale. These stages and their implications are summarized below.

Stage 1: Normal-no objective or subjective evidence of cognitive decrement.

Current epidemiological data indicate that only a minority of elderly persons fall within this category, perhaps 20% of persons over age 65.

Stage 2: Normal for age-subjective complaints of cognitive decrement.

Most persons over age 65 have subjective symptoms of not remembering the names and locations of objects as well as they did in the previous 5-10 years.

These symptoms can be troubling to aged persons. In Europe, such symptoms appear to be the leading reason why persons take medications of all forms. In the United States, elderly persons commonly take lecithin. multivitamins, and various nostrums for these complaints.

Present prognostic data do not indicate that these symptoms of age- associated memory impairment are the precursor of further decline in most elderly persons. Although medications and nostrums are frequently taken, there remains no convincing evidence of their efficacy.

Stage 3: Compatible with incipient Alzheimer’s disease-subtle evidence of objective decrement in complex occupational or social tasks.

Subtle deficits may become evident in various ways. For example, the patient may become hopelessly lost when traveling to an unfamiliar location; decreased performance in a demanding occupation may be noted by coworkers; patients may display overt word- and name-finding deficits; concentration deficits may be evident to family members or on clinical testing; and an overt tendency to forget what has just been said and to repeat oneself may be manifest.

The prognosis associated with these subtle, but identifiable, symptoms varies. In some cases, these symptoms are the result of brain insults, such as small strokes, which may not be evident from the clinical history neurological examination, or neuroimaging findings. In other cases, symptoms are due to subtle, and perhaps not clearly identifiable, psychiatric, medical, and neurological disorders of diverse causes. In other cases, the symptoms represent the earliest symptoms of Alzheimer’s disease and may last as long as 7 years. The diagnosis of Alzheimer’s disease in this stage, however, can be made with confidence only in retrospect.

Anxiety is a frequent psychiatric concomitant of the cognitive losses at stage 3. Given the frequently benign prognosis, the inability to diagnose with confidence at this stage, and the prolonged duration of these symptoms when they do represent the earliest signs of Alzheimer’s disease, the most effective treatment for the anxiety is that the patient withdraw from anxiety-provoking activities. For example, withdrawal from a job that is beyond the patient’s cognitive capacities can eliminate daily stress and humiliation. It can also eliminate, at least temporarily, the patient’s problems, since patients at this stage do not have difficulty with routine tasks of daily living.

Stage 4: Mild Alzheimer’s disease-clearly manifested deficits on a careful clinical interview.

Deficits manifest in concentration, memory, orientation, or functional capacity. Concentration deficit may be large enough that not only does the patient display a deficit on the standard subtraction of serial 7s task, but he or she has difficulty subtracting serial 4s from 40. Recent memory may suffer such that some major events of the previous week are not recalled. Detailed questioning may reveal that the spouse’s knowledge of the patient’s past is superior to the patient’s own recall of his or her personal history. The patient may mistake the date by 10 days or more. The spouse (or other family members) may note that the patient no longer is able to balance a checkbook, no longer remembers to pay the rent or other bills properly, has difficulty preparing meals, or displays similar deficits in the ability to manage complex occupational and social tasks.

Alzheimer’s disease can be diagnosed with confidence in this stage. It is possible to follow patients through the course of this stage, the mean duration of which has been estimated to be 2 years. Symptoms may plateau in this stage, and some patients may not manifest a further overt decline for 4 years or longer.

The most prominent psychiatric features of stage 4 are the patient’s decreased interest in personal and social activities, accompanied by a flattening of affect. Depressive symptoms also may be noted, but are generally mild enough that no specific treatment is indicated. Depressive symptoms sometimes are severe enough to warrant treatment, frequently with a low dose of an antidepressant. Patients are still capable of living alone if assistance is provided with such complex, but essential, activities as paying the rent and managing the patient’s bank account.

Stage 5: Moderate Alzheimer’s disease-deficits large enough to prevent patients from surviving without assistance.

Patients at this stage can no longer recall major relevant aspects of their lives, e.g., they may not recall the name of the president, their correct current address, or the name of the school they attended. Patients at this stage frequently do not recall the current year and have enough difficulty in concentration and calculation as to err in subtracting serial 2s from 20. In addition to their inability to manage complex activities of daily living, patients generally have difficulty choosing the proper clothing to wear for the season and the occasion.

The duration of this stage is approximately 11/2 years, although, as with the previous stage, some patients may plateau with these symptoms for many years.

Although generally more overt, the psychiatric symptoms at stage 5 are in many ways similar to those noted in stage 4. Consequently, the patient’s denial and flattening of affect tend to be more evident. Depressive symptoms may occur. Anger and some of the more overt behavioral symptoms of Alzheimer’s disease also are common. Depending on the nature and magnitude of the psychiatric symptoms, treatment with an antidepressant or an antipsychotic medication may be indicated. When the latter is used, the dictum previously stated for the treatment of psychosis in the elderly applies: “start low and go slow.”

Patients who are living alone at this stage require at least part-time assistance for continued community survival. When additional community assistance is not feasible or available, institutionalization may be required. Patients who are residing with a spouse frequently resist additional assistance as an invasion of their home.

Stage 6: Moderately severe Alzheimer’s disease-deficits large enough to necessitate assistance with basic activities of daily living.

Patients at this stage may occasionally forget the name of the spouse on whom they depend for survival. They frequently do not know their address but can generally recall some important aspects of their domicile, such as the street or the town. Patients have generally forgotten the schools they attended but recall some aspects of their early lives, such as their birthplace, former occupation, or one or both of their parents’ names. Patients generally still can state their correct personal name. They may have difficulty counting backward from 10 by Is.

Over the course of stage 6, which lasts approximately 21/2 years, deficits in dressing and bathing increase progressively. In the latter part of this stage, toileting and continence become compromised.

Emotional and behavioral problems become most manifest and disturbing. Agitation, anger, sleep disturbances, physical violence, and negativity are examples of symptoms that commonly require treatment at this point in the illness. Although low doses of antipsychotics may be useful, high doses are frequently necessary for many patients, and a satisfactory response is sometimes difficult to obtain.

Patients require full-time assistance in community settings. If the patient lives with his or her spouse, the spouse will generally require at least part-time additional management assistance.

Stage 7: Severe Alzheimer’s disease-deficits that necessitate continuous assistance with activities of daily living.

Speech activity is severely circumscribed early in this stage and is eventually lost. Ambulation and other motor capacities are also lost. Most patients survive until this stage, when they commonly succumb at approximately the time ambulatory ability is lost. Although some patients survive in this stage for 6 years or longer, most patients succumb approximately 2-3 years after stage 7 begins. Pneumonia appears to be the most common proximate cause of death.

Although agitation can be a problem for some patients, psychotropic medication can frequently be discontinued successfully. Nursing homes may be better equipped than spouses for the management of patients. Many devoted spouses, however, prefer to continue to care for their partner, in which case, round-the-clock home health care assistance may be a necessary adjunct as management of incontinence and other basic life activities, such as bathing and feeding, become major concerns. Psychiatrists should be prepared to counsel family members regarding such issues as institutionalization and the continued meaning of life.

2. Vascular dementia. This is the second major cause of dementia in the elderly. It occurs most frequently in conjunction with Alzheimer’s disease. Classic pathological studies have indicated that approximately 50% of dementia cases coming to autopsy are associated with Alzheimer’s disease alone, 25% with Alzheimer’s disease in association with cerebrovascular factors, and 15% with vascular dementia in the absence of neuropathological evidence of Alzheimer’s disease.

Vascular dementia is believed to be the result of cerebral infarctions of varying size in multiple brain regions. Conditions associated with cerebral infarction, such as cardiac arrhythmias and hypertension, predispose to vascular dementia.

Clinically, vascular dementia is believed to follow a more stepwise course than the relatively gradual course of Alzheimer’s disease. The time course of decline of vascular dementia is at least as rapid as that of Alzheimer’s disease. In mixed cases, the presence of cerebral infarction appears to increase morbidity. Consequently, the rate of dementia and the time of death are relatively rapid in vascular dementia and in mixed dementia compared with Alzheimer’s disease.

The clinical presentation of vascular dementia is more diverse than that of Alzheimer’s disease. Speech disturbance or gait disturbance, for example, may occur at varying points in the evolution of vascular dementia pathology, whereas in Alzheimer’s disease these deficits tend to occur at a specific point in the evolution of the dementia process.

Psychiatric disturbances occurring in vascular dementia include general dementia-related psychiatric conditions, such as the affective, psychotic, and agitation disturbances described at each stage of Alzheimer’s disease. Emotional changes characteristic of stroke-related dementia also occur, e.g., emotional incontinence and other sudden, labile mood changes. Emotional incontinence generally is not treated with medication. The guidelines for the treatment of dementia-related psychiatric disturbances previously outlined for Alzheimer’s disease apply for the treatment of affective, psychiatric, and other behavioral disturbances in vascular dementia.

The treatment for the underlying cause of vascular dementia is stroke prevention. These include the treatment of hypertension and cardiac arrhythmias and the use of platelet-deaggregating agents for the prevention of stroke. Among the latter, salicylates, such as aspirin, are perhaps the most effective.

3. Other dementing disorders and differential diagnosis of dementia. Other causes of dementia include Pick’s disease, Creutzfeldt-Jakob disease, Huntington’s disease, alcohol abuse, normal pressure hydrocephalus, and dementias secondary to diverse physiological disturbances.

1. Pick’s disease-a degenerative dementia that is difficult to distinguish clinically from Alzheimer’s disease. Neuropathologically, Pick’s disease differs in that autopsy;brain examination reveals so- called Pick bodies and not the characteristic neurofibrillary tangles, senile plaques, or granulovacuolar degeneration of Alzheimer’s dis- ease. Pick’s disease also tends to affect the frontal region of the brain, whereas Alzheimer’s disease is a much more diffuse cerebral process. Pick’s disease has a somewhat younger age distribution than Alzheimer’s disease, accounting for a significant percentage of dementia patients in the sixth decade of life. Clinically, Pick’s disease appears to be marked by more frontal lobe features than Alzheimer’s disease. Pick’s disease has no known treatment.

2. Creutzfeldt-Jakob disease-a rare condition, occurring in approximately one person per million. Onset and course are variable and acute; subacute and chronic forms have been described. Frequently, Creutzfeldt-Jakob disease is distinguished from Alzheimer’s disease by its course, which may be more rapid, or by the occurrence of focal and localized neural pathology. The latter includes cranial nerve signs, such as auditory deficits associated with 8th nerve involvement, and gait disturbance, associated with cerebellar involvement. Occasionally, Creutzfeldt-Jakob disease closely mimics the course of Alzheimer’s disease.

3. Huntington’s disease-may present with a dementia disturbance prior to the appearance of choreiform pathology and should be considered in the differential diagnosis of dementia.

4. Alcohol-induced persisting dementia or amnestic disorder-frequently distinguished from Alzheimer’s disease by the presence of confabulation and by a memory deficit out of proportion to cognitive and functional disturbances in other areas.

5. Normal pressure hydrocephalus-marked by gait disturbance, urinary incontinence, and dilated cerebral ventricles out of proportion to the magnitude of cortical atrophy and dementia. Urinary incontinence, neuroradiological findings, and the relatively early appearance of gait disturbance assist in distinguishing this condition from Alzheimer’s disease.

6. Dementias secondary to diverse physiological disturbances-the diagnosis of dementia, which may be secondary to more than 50 possible primary etiologies, and the differentiation of these conditions from the major cause of dementia, Alzheimer’s disease, is based on laboratory investigations and knowledge of the clinical course of Alzheimer’s disease. The basic laboratory workup for dementia includes a complete blood count and differential, serum electrolytes and serum enzyme studies, serum B 12 and serum folate levels, thyroid levels, urine analysis, and a cerebral neuroimaging study. Positive findings from any of these studies must be interpreted by the clinician. They may indicate a primary etiology of dementia, which may be treatable; they may indicate added insult in the context of degenerative dementia; or they may be incidental. A knowledge of the clinical course of Alzheimer’s disease can help the clinician in distinguishing these possibilities.

References

1. Metwally, MYM: Textbook of neuroimaging, A CD-ROM publication, (Metwally, MYM editor) WEB-CD agency for electronic publication, version 9.2a April 2008 [Click to have a look at the home page]