Paula Altman Fuld

A 6-item Orientation-Memory-Concentration Test has been validated as a measure of cognitive impairment. This test predicted the scores on a validated 26-item mental status questionnaire of two patient groups in a skilled nursing home, patients in a health-related facility, and in a senior citizens' center. There was a positive correlation between scores on the 6-item test and plaque counts obtained from the cerebral cortex of 38 subjects at autopsy. This test, which is easily administered by a nonphysician, has been shown to discriminate among mild, moderate, and severe cognitive deficits.

Two simple methods that are clinically useful for analyzing impaired memory and learning are selective reminding or restricted reminding. These new methods provide simultaneous analysis of storage, retention, and retrieval during verbal learning because they let the patient show learning by spontaneous retrieval without csnfounding by continual presentation. Because selective reminding and restricted reminding let the patient show consistent retrieval without any further presentation, they also distinguish list learning from item learning, so that impaired memory and learning can be analyzed further in terms of two stages of learning (item and list).

Fourteen case histories of persons who had a histological diagnosis of either senile dementia of the Alzheimer type, multiinfarct dementia, or a mixed dementia composed of these two types and who showed evidence of a moderate to severe dementia on psychological testing were rated for the presence of thirteen clinical features comprising Hachinski's Ischemic Score. These features are frequently considered primarily characteristic of vascular dementia. Persons with senile dementia of the Alzheimer type were clearly differentiable from persons with multiinfarct dementia and mixed dementia, while the latter two groups were indistinguishable from one another. In our sample, eight features were found to characterize those persons with vascular dementia. These data verify the usefulness of the Ischemic Score in differentiating between senile dementia of the Alzheimer type and vascular dementia.

Postmortem examination was performed on 137 residents (average age 85.5 years) of a skilled nursing facility whose mental status, memory, and functional status had been evaluated during life. Seventy-eight percent were demented using conservative criteria; 55% had characteristic Alzheimer's disease. Choline acetyltransferase and somatostatin were significantly reduced in the brains of patients with Alzheimer's disease as compared with age-matched nursing home control subjects, although the degree of the reduction was less severe than found in subjects less than 80 years of age. Ten subjects whose functional and cognitive performance was in the upper quintile of the nursing home residents, as good as or better than the performance of the upper quintile of residents without brain pathology (control subjects), showed the pathological features of mild Alzheimer's disease, with many neocortical plaques. Plaque counts were 80% of those of demented patients with Alzheimer's disease. Choline acetyltransferase and somatostatin levels were intermediate between controls and demented patients with Alzheimer's disease. The unexpected findings in these subjects were higher brain weights and greater number of neurons (greater than 90 micron 2 in a cross-sectional area in cerebral cortex) as compared to age-matched nursing home control subjects. These people may have had incipient Alzheimer's disease but escaped loss of large neurons, or alternatively, started with larger brains and more large neurons and thus might be said to have had a greater reserve.

We compared neuropsychological findings in 28 longitudinally evaluated elderly subjects with their postmortem neuropathology, including senile plaque and neurofibrillary tangle counts from standardized sections. Nine of the subjects were not demented when evaluated just prior to their death. Numerous cortical senile plaques and other changes of Alzheimer's disease (AD) occurred in six of nine nondemented old-old subjects. Five of these six subjects had shown decline on yearly neuropsychological tests but their cognitive impairment was too mild to meet clinical criteria for dementia. Whereas cortical senile plaque count did not distinguish well between demented and nondemented subjects, every subject with numerous cortical neurofibrillary tangles was demented. The nondemented subjects with Alzheimer pathology may have had "preclinical" AD, or numerous cortical plaques may occur in some elderly subjects who would never develop clinical dementia.