Jacob H. Fox

Natural history of mild cognitive impairment in older persons

Background Cognitive abilities of older persons range from normal, to mild cognitive impairment, to dementia. Few large longitudinal studies have compared the natural history of mild cognitive impairment with similar persons without cognitive impairment. Methods Participants were older Catholic clergy without dementia, 211 with mild cognitive impairment and 587 without cognitive impairment, who underwent annual clinical evaluation for AD and an assessment of different cognitive abilities. Cognitive performance tests were summarized to yield a composite measure of global cognitive function and separate summary measures of episodic memory, semantic memory, working memory, perceptual speed, and visuospatial ability. The authors compared the risk of death, risk of incident AD, and rates of change in global cognition and different cognitive domains among persons with mild cognitive impairment to those without cognitive impairment. All models controlled for age, sex, and education. Results On average, persons with mild cognitive impairment had significantly lower scores at baseline in all cognitive domains. Over an average of 4.5 years of follow-up, 30% of persons with mild cognitive impairment died, a rate 1.7 times higher than those without cognitive impairment (95% CI, 1.2 to 2.5). In addition, 64 (34%) persons with mild cognitive impairment developed AD, a rate 3.1 times higher than those without cognitive impairment (95% CI, 2.1 to 4.5). Finally, persons with mild cognitive impairment declined significantly faster on measures of episodic memory, semantic memory, and perceptual speed, but not on measures of working memory or visuospatial ability, as compared with persons without cognitive impairment. Conclusions Mild cognitive impairment is associated with an increased risk of death and incident AD, and a greater rate of decline in selected cognitive abilities.

The validity of criteria for the evaluation of cerebral atrophy by computed tomography.

Computed tomography of the brain was used in evaluating demented and nondemented elderly people. The incidence of convulutional atrophy and ventricular enlargement correlated well with pathologic and pneumoencephalographic examination of a similar population. Computed tomography also showed certain instances of dementia without atrophy and evidence of atrophy without dementia. The absence of brain atrophy in a demented patient should prompt a search for a potentially treatable cause of the dementia. The authors discuss criteria for diagnosing atrophy by computed tomography and conclude that, because of its noninvasive nature, it is a valuable aid in screening demented patients for treatable diseases.

Decision rules guiding the clinical diagnosis of Alzheimer's disease in two community-based cohort studies compared to standard practice in a clinic-based cohort study

We developed prediction rules to guide the clinical diagnosis of Alzheimer’s disease (AD) in two community-based cohort studies (the Religious Orders Study and the Rush Memory and Aging Project). The rules were implemented without informant interviews, neuroimaging, blood work or routine case conferencing. Autopsies were performed at death and the pathologic diagnosis of AD made with a modified version of the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) criteria. We compared the positive predictive value of the clinical diagnosis in the two community-based studies to the positive predictive value of the clinical diagnosis of AD made by standard clinical practice in a clinic-based cohort study using AD pathology as the gold standard. Of 306 clinic cases with probable AD, 286 (93.5%) met CERAD neuropathologic criteria for AD; the results were comparable for those with possible AD (51 of 54, 94.4%). Of 141 study subjects with probable AD, 130 (92.2%) met CERAD neuropathologic criteria for AD; the results were lower but acceptable for those with possible AD (26 of 37, 70.3%). The results were similar in secondary analyses using alternate neuropathologic criteria for AD. The clinical diagnosis of AD can be made in community-based studies without the use of informant interviews, neuroimaging, blood work or routine case conferencing. This approach holds promise for reducing the operational costs of epidemiologic studies of aging and AD.

Remote Memory in Senile Dementia

This study was designed to examine Ribots hypothesis that the probability of forgetting an event is inversely related to the time since the occurrence of that event. Patients with senile dementia (N = 20; mean age = 67.3) and normal controls (N = 24; mean age = 69.4) were given two tests of memory for persons and events that became famous between 1930 and 1975. The results indicate that patients with senile dementia do have significant (p less than .001) difficulty recalling information from remote memory. The results do not support Ribots hypothesis, however. The dementia patients show a relatively consistent recall deficit over the time period examined. There appears to be a trend for poorer recall of material from the 1960s and 1970s, possibly reflecting anterograde learning deficits early in the course of senile dementia.

Cerebral atrophy, EEG slowing, age, education, and cognitive functioning in suspected dementia

Seventy-eight hospital patients, 50 years of age or older, were selected for suspected changes in mentation and for the absence of focal or other organic brain disease. They were studied in relation to education, age, cerebral atrophy (by computerized tomography), electroencephalographic (EEG) slowing, and performance in several neuropsychologic tests. Adequate test-retest reliability of the cognitive measures and interjudge reliability of the cerebral atrophy and EEG measures were demonstrated. Stepwise multiple regression analyses suggested the following: (1) EEG slowing is the strongest and most general pathologic influence on cognition in elderly persons without overt brain disease. (2) Cerebral atrophy independently affects primarily the verbal recall of recent and remote information. (3) Age independently affects primarily recent memory for both verbal and nonverbal material. (4) Formal education is a powerful influence that must be accounted for in all studies of the effects of age on cognition.

Cortical biopsy results in Alzheimer's disease Correlation with cognitive deficits

Neuropsychologic and pathologic data are presented for a group of 11 patients with a clinical diagnosis of probable Alzheimers disease (AD) according to recently proposed criteria. In all cases, the diagnosis was verified by cortical biopsy. In addition, increased cortical plaque counts were associated with greater deficits in language production and comprehension and poorer performance on an index of global mental status. These results suggest that a clinical diagnosis of AD is very accurate when patient selection is restricted to typical cases and that language deficits may provide a useful indicator of severity of disease in AD patients.

Cerebellar atrophy demonstrated by computed tomography

We studied 55 cases of cerebellar atrophy identified by computerized tomography. Atrophy was determined by subjective assessment and objective measurements (superior cerebellar cistern, fourth ventricle, and brainstem). Different patterns of cerebellar atrophy were related to clinical diagnoses. A high incidence of vermal atrophy was observed in primary cerebellar degeneration and chronic alcoholism. More than half the patients with alcoholism had hemispheral atrophy. Vermal atrophy and enlargement of superior cerebellar cisterns (but not hemispheral atrophy) were associated with carcinomatous cerebellar degeneration. Atrophy caused by chronic phenytoin usage showed a specific pattern of enlargement of the cisterna magna, cerebellopontine angle, and superior cerebellar cisterns. Supratentorial atrophy was increased significantly only in the alcoholics. In general, limb ataxia, dysarthria, and nystagmus were related to hemispheral but not to vermal atrophy.

Facial Recognition Memory in Dementia

Previous investigations of memory in senile dementia of the Alzheimers type (SDAT) have focused on verbal learning and memory. The aim of the present study was to determine whether the amnesia of SDAT is limited to verbal material. Patients with SDAT (N = 29; mean age = 69.3) and healthy normal controls (N = 41; mean age = 69.3) were given a test of facial perception and two recognition memory tasks, one for words and one for faces. The results indicate that dementia patients show a deficit in the retention of facial information. This deficit cannot be attributed to faculty initial perception or to a response bias. The verbal and facial memory deficits in SDAT appear to differ: performance on tests of verbal and facial memory is relatively independent, and substantial encoding and linguistic defects contribute to the verbal, but not the facial, memory disorder resulting in more severe impairment on tests of verbal memory. The implications of these findings for research on the neuropharmacology and pathophysiology of SDAT are discussed.

Word frequency effect and recognition memory in dementia of the alzheimer type

Normal persons show better recognition memory for rare than for common words. In the first experiment, we examined this word frequency effect in 17 patients with dementia of the Alzheimer type (DAT) and 20 normal controls of equivalent age and education. The DAT patients showed a normal tendency to false alarm to common words but failed to show the normal rare word advantage in their hit rate. In a second experiment, we examined normal memory immediately and after a delay of 1 week when it is approximately equivalent to that of DAT patients. There was no attenuation of the usual rare word advantage. These findings suggest that DAT patients fail to encode the featural and intrastructural elements of to-be-remembered verbal information and that this processing deficit may contribute to their impaired recognition memory performance.

Use of the national adult reading test to estimate premorbid iq in dementia

Two methods for estimating premorbid IQ were employed in a sample of 199 dementia patients and 26 control subjects: (1) the National Adult Reading Test (NART), a present ability measure, and (2) an age, sex, race, education and occupation regression formula-a demographically based estimate. The dementia sample consisted of probable Alzheimers disease, multi-inf arct dementia and a mixture of the two. Controls consisted of the spouses of the patient sample. The patient sample was divided into three levels of dementia severity equated for age and level of education. The NART estimates in the mild and moderate/severe dementia groups differed significantly from those for the very mildly demented patients and controls. The results suggest that the applicability of the NART in estimating premorbid IQ in dementia may be limited.