Clinical Manifestations and Diagnosis

Clinical Manifestations

Alzheimer-type senile dementia is associated with behavioral signs and symptoms that divide into corre­sponding stages. In the early stage, subjective mem­ory deficit may be difficult to differentiate from be­nign senile forgetfulness.

Typically, patients with Alzheimer’s disease forget where things are placed, become lost easily, and have difficulty remembering appointments. Both re­cent and remote memory are affected, which may be documented by neuropsychological testing. When pa­tients recognize their cognitive and social losses, many develop feelings of hopelessness and despon­dency. As Alzheimer-type senile dementia pro­gresses, the patient enters a Confusional phase with more global impairment of cognitive functioning (Schenk, Reisberg, and Ferris 1982). Changes in higher cortical functions, such as language, spatial relationships, and problem solving, become more ap­parent.

During the Confusional phase, obvious denial be­gins to replace anxiety, and cognitive deficits are noticeable to family and friends. In the final phase, the patient becomes aimless and may hallucinate or be restless and agitated. Language disorders such as aphasia occur in late stages. Abnormal neurological reflexes, indicative of loss of higher neural inhibi­tion, are common. Not all patients with Alzheimer- type senile dementia demonstrate the classic evolu­tion of symptoms. Although almost all patients have some memory impairment, other focal cortical defi­cits may predominate initially. Spatial relationship impairment is common early. The patient may also complain of word-finding difficulty or demonstrate mild problems in speaking and understanding.

Diagnosis

Diagnosis of Alzheimer’s disease remains a diagno­sis of exclusion. In the absence of biological markers for the illness, it is not surprising that clinical diag­nosis may be less than accurate and, in fact, may be correct in as few as one-half of Alzheimer-type senile dementia cases (Alafuzoff et al. 1987). Not only do cognitive changes associated with normal aging over­lap those found in the early stages of dementia, but also a wide spectrum of conditions may produce de­mentia. In any given patient, several conditions lead­ing to progressive cognitive decline may occur simul­taneously. Even neuropathologists may encounter diagnostic difficulty and may be reluctant to make the diagnosis without the proper Clinicopathological correlation (Khachaturian 1985).

The clinical diagnosis of Alzheimer-type senile de­mentia always requires documentation of progres­sion (McKhann et al. 1984). Reports from family and friends provide the most valid measures of cognitive decline in elderly persons and support the clinician’s judgment that global intellectual deterioration has occurred.

Clinical Staging and Evaluation

Progression is usually gradual but with fluctuation of symptom severity. The patient may react very dramatically to changes in the living situation, to losses of friends or relatives, or even to admission to the hospital for evaluation. These acute changes probably represent withdrawal of orienting stimuli and emotional distress rather than progression of the disease process.

A number of clinical staging strategies have been developed, but there is no entirely satisfactory tech­nique as yet. Simplified rating scales (such as the Folstein Mini-Mental) may be efficiently adminis­tered, but only identify the presence or absence of cognitive impairment. Other cognitive scales are more accurate, but they are also more complex and may take an hour to administer.

Psychometric tests may be useful in delineating patterns of cognitive deficit at various stages of se­verity and in identifying the qualitative aspects of performance deficit. Although laboratory tests are sometimes used to support the diagnosis of Alz­heimer’s disease, the laboratory is actually more useful in excluding other causes of cognitive deterio­ration. Atrophy of the cerebral cortex is often seen on computed tomography, but it is frequently overinterpreted. There is a poor correlation between size of the brain ventricles, widened cerebral sulci, and severity of dementia (Fox, Topel, and Huckman 1975). Attempts have been made to correlate demen­tia with brain density (Albert et al. 1984). Unfortu­nately, results have been inconsistent, and there is a pressing need for quantitative computed tomo­graphic studies that correlate the scanning images with clinical and pathological findings.

Differential Diagnosis

Alzheimer’s disease may be difficult to distinguish from other Untreatable progressive dementias, which include Pick’s disease, demyelinating diseases, slowly progressive brain tumors, inflammatory diseases, ar­teriosclerotic vascular diseases, toxic exposures, re­peated metabolic insults, deficiency diseases, late se­quelae of head trauma, Creutzfeldt-Jakob disease, and viral and fungal infections. Dementia is common in patients with terminal cancer and may result from a variety of causes.

The evaluation of a patient presenting with de­mentia often reveals Untreatable causes, but treat­able dementia is discovered in 20 to 25 percent of such patients (Wells 1977).

Treatable causes of dementia include pernicious anemia, thyroid disorders, chronic central nervous system infections, toxic exposures, surgically correct­able mass lesions, inflammatory vascular disease, certain forms of arteriosclerotic vascular disease, and normal-pressure hydrocephalus. Occasionally, iatrogenic dementia, related to the inappropriate use of medication or to idiosyncratic drug effects, is identified. Multi-infarct dementia may be the most difficult progressive dementia to differentiate from Alzheimer’s disease despite the fact that specific di­agnostic criteria for each have been promulgated in the official nomenclature. There is an obvious need for a valid and reliable set of clinical criteria to distinguish the two conditions. Nonetheless, risk fac­tors for stroke should be evaluated and controlled when possible in every patient with early dementia.

J. L. Cummings and D. F. Benson (1983) suggest that all forms of dementia other than Alzheimer’s and Pick’s disease show signs of subcortical dysfunc­tion in addition to more obvious cortical signs. This is especially true of dementia associated with basal ganglia disease, which regularly produces the char­acteristic subcortical pattern of slowed thinking, at­tention deficit, memory impairment, and apathy. Subcortical dementia occurs in 20 to 40 percent of patients with Parkinson’s disease (Marttila and Rinne 1976) and is also observed in progressive su­pranuclear palsy, Huntington’s chorea, and Wilson’s disease. Symptomatic treatment of basal ganglia dis­ease occasionally improves the associated dementia. Antidepressants may improve cognition as well as any associated depression (Albert, Feldman, and Wil­lis 1974).

Depression is the most common treatable illness that may masquerade as Alzheimer-type senile de­mentia. Cognitive abilities return to baseline levels when depression is treated. Because some patients with early dementia have secondary depression, de­mentia and pseudodementia may be difficult to dif­ferentiate. The depression that occurs in the early stages of Alzheimer-type senile dementia tends to resolve as the disease progresses. Pseudodemented, depressed patients are apt to have poor attention, inconsistent cognitive changes, absence of cortical signs, weight loss, sleep disturbance, guilt, poor self­esteem, a past personal family psychiatric history, and a more rapid onset.

In contrast, patients with cortical dementia of Alzheimer-type often show insidious onset, slow pro­gression, early loss of insight, amnesia for remote and recent events, spatial disorientation, reduction in spontaneous speech, and occasionally aphasia. Agnosia, apraxia, increased muscular tension, and abnormal neurological reflexes may also be present (Gustafson and Nilsson 1982).