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OBJECTIVE: In this study, we examined the association of non-insulin-dependent diabetes mellitus (NIDDM) and impaired glucose tolerance (IGT) with cognitive function in a population-based sample of older individuals. RESEARCH DESIGN AND METHODS: Subjects were 1509 healthy, community-dwelling men and women aged 55 years and older who were participants in the Rancho Bernardo Study and attended clinic visits in 1984–87 and in 1988–91. An oral glucose tolerance test was administered during the 1984–87 visits. Based on World Health Organization criteria, participants were classified into those with NIDDM, IGT, or normal glucose tolerance. During the 1988–91 clinic visits, 12 tests of cognitive function were administered. RESULTS: Of the participants, 14.3% of the men and 9.9% of the women had NIDDM, and 21.0% of the men and 28.0% of the women had IGT. Multiple regression analysis was used to compare the cognitive function of individuals with NIDDM and IGT with individuals with normal glucose tolerance after adjustment for age, education, obesity, depression, blood pressure, and current estrogen use. In men, there were no statistically significant differences in any of the 12 cognitive function tests by glucose tolerance category. Compared with those with normal glucose tolerance, women with IGT had lower scores on almost every cognitive function test, whereas women with NIDDM had higher scores, but none of these differences were statistically significant after adjustment for multiple comparisons. Futhermore, observed differences by NIDDM or IGT status were small and accounted for

Frontotemporal dementia with parkinsonism, chromosome 17 type (FTDP-17), a recently defined disease entity, is clinically characterized by personality changes sometimes associated with psychosis, hyperorality, and diminished speech output, disturbed executive function and nonfluent aphasia, bradykinesia, and rigidity. Neuropathological changes include frontotemporal atrophy often associated with atrophy of the basal ganglia, substantia nigra, and amygdala. Neurofibrillary tangles (NFTs) are seen in some but not all families. Inheritance is autosomal dominant and the gene has been regionally localized to 17q21-22 in a 2- to 4-centimorgan (cM) region flanked by markers D17S800 and D17S791. The gene for tau, the primary component of NFTs, is located in the same region of chromosome 17. Tau was evaluated as a candidate gene. Physical mapping studies place tau within 2 megabases or less of D17S791, but it is probably outside the D17S800-D17S791 FTDP-17 interval. DNA sequence analysis of tau coding regions in affected subjects from two FTDP-17 families revealed nine DNA sequence variants, eight of which were also identified in controls and are thus polymorphisms. A ninth variant (Val279Met) was found in one FTDP-17 family but not in the second FTDP-17 family. Three lines of evidence indicate that the Val279Met change is an FTDP-17 causative mutation. First, the mutation site is highly conserved, and a normal valine is found at this position in all three tau interrepeat sequences and in other microtubule associated protein tau homologues. Second, the mutation co-segregates with the disease in family A. Third, the mutation is not found in normal controls.

A dinucleotide repeat polymorphism in a tau intron was identified and used in a case-control study to analyze the genetic association of tau with several neurodegenerative diseases with tau pathology. Subjects with the homozygous tau AO alleles were excessively represented in the progressive supranuclear palsy (PSP) group, compared with the age-matched healthy control group. Consequently, this allele is more frequently found in PSP than in a group of healthy subjects. This trend was not found in Alzheimer's disease or parkinsonism-dementia complex of Guam, both of which are accompanied by major tau pathology. The result suggests a possible involvement of tau in the pathogenesis of PSP.

OBJECTIVE: To determine whether the weight loss associated with Alzheimer's disease precedes or follows the dementia. DESIGN: Older community-dwelling men (n = 134) and women (n = 165) were followed for 20 years before they were diagnosed as cognitively intact or demented. A repeated measures analysis was used to compare weight change in those who developed Alzheimer's Disease (AD) with those who remained cognitively intact. MEASUREMENTS: Weight was measured at three clinic visits between 1972-74, 1984-87, and 1990-93. Participants were classified as having probable or possible AD or being cognitively intact at the 1990-93 evaluation. Diagnoses were made by two neurologists and a neuropsychometrist, based on neuropsychological tests and physical examination, using NINCDS-ADRDA criteria. RESULTS: There were 36 men and 24 women diagnosed with probable or possible AD; they were considered to have mild to moderate dementia based on their test scores and community-dwelling status. Those who developed dementia were older than those diagnosed as cognitively intact. In age-adjusted analyses, both men and women who were later diagnosed with AD had a significant decrease in weight after the baseline visit (P < .001 and P < .003, respectively), but there was no significant weight loss in the men and women who remained cognitively intact. These differences were not explained by lifestyle, depression, or other illness. CONCLUSION: Weight loss precedes mild to moderate dementia; early weight loss is, therefore, unlikely to be a consequence of AD patients being unable or unwilling to eat.

Objective: To establish population-based data, with special emphasis on the effects of age, gender, and education, for eight, widely used neuropsychological tests in a community-dwelling cohort of normal and cognitively impaired older adults. Design: A population-based observational study. Setting: Examinations were performed in a research clinic by specially trained staff during a 1988–1992 evaluation for osteoporosis. Participants: 1,692 community-dwelling subjects, aged 55 to 94 years, who were members of the Rancho Bernardo Heart and Chronic Disease Study initiated in 1972. The mean age for men was 73.9 years (SD 9.3) and for women, 73.5 (SD 9.1). Outcome measures: Eight neuropsychological tests were used to measure cognitive functions. Analysis of variance and post hoc contrasts were performed to determine the effects of age, gender, education, and their interactions on performance on these tests. Results: Performance on all tests decreased progressively, without leveling off, from the youngest, age 55, to the oldest, age 94. Women performed better on verbal tasks and men on tests of visuospatial, visuoconceptual, and mental control functions. Performances of men on several tests declined more rapidly with advancing age than those of women. Both men and women with some college education performed better on most tests than men and women with high school educations, and the rate of decline with age was sometimes slower in the college-educated group. Only the savings score from the Visual Reproduction Test, which is a measure of rate of forgetting, and the scores of short-term recall derived from the Selective Reminding Test (Buschke-Fuld) were unaffected by educational attainment. Conclusions: In a community-dwelling cohort, including normal and cognitively impaired elderly men and women, advancing age is accompanied by decline in cognitive functions as measured by neuropsychological tests. This decline is slower in women and in college-educated subjects. Two cognitive indices were unaffected by education, and these may be especially useful in cross-cultural studies.

Longitudinal studies of subjects with autopsy-proven Alzheimer's disease in one skilled nursing home and of clinically diagnosed cases (NINCDS/ADRDA criteria) in three community cohorts are compared with regard to the annual rate of change in the error score of the Blessed information-memory-concentration test (IMC) in which the maximum number of errors possible is 33. The four cohorts differed significantly from each other in regard to age, education, sex, and the degree of dementia as measured by the initial IMC score. Subjects spanned the age range of 52 to 96 years and had 2 to 20 years of education. The rate of change in error score per year was similar whether the initial error score was 0 to 7, 8 to 15, or 16 to 23; however, the rate was reduced when the initial error score was 24 or above, due to a ceiling effect of the test. Among subjects with initial IMC scores less than 24, the annual rate of change varied considerably. However, the mean annual rate of change, 4.4 errors (SD 3.6, SEM 0.3) per year, was independent of residence in a nursing home, location of the study site, and of the patient's sex or education. Of particular importance was the finding that the rate of change in mental test score was independent of age. It can be concluded that the rate of cognitive deterioration in patients with Alzheimer's disease is quite variable among individuals and is independent of the patient's age and whether the patient resides in the community or in a nursing home. More importantly, the rate of change of the IMC test provides no evidence for a difference between early-onset and late-onset Alzheimer's disease. The average rate of change on the IMC and its variance can be used as the basis for designing studies of drugs or procedures that might alter the course of Alzheimer's disease.