Christine Hannigan

Insulin in combination with other diabetes medication is associated with less Alzheimer neuropathology

Objective: To examine the association between treatment for diabetes and Alzheimer disease (AD) neuropathology. Methods: This postmortem study matched 124 subjects with diabetes to 124 without diabetes from the Mount Sinai School of Medicine Brain Bank, on age (mean = 81.2 + 9.3), sex (57.3% F), and severity of dementia (Clinical Dementia Rating [CDR] 2.4 + 1.7). Densities of neuritic plaques (NPs) and of neurofibrillary tangles (NFTs) were assessed in several neocortical regions and in the hippocampus, entorhinal cortex, and amygdala. Diabetic subjects were classified according to their recorded lifetime antidiabetic medications: none (n = 29), insulin only (n = 49), diabetes medications other than insulin only (n = 28), or concomitant use of both insulin and any oral antidiabetic medications (n = 18). For each dependent variable, analysis of covariance controlling for age at death, sex, and CDR distinguished among the nondiabetic patients and four diabetic subgroups. Results: There were differences among the five groups for NP ratings in the entorhinal cortex (p = 0.003), amygdala (p = 0.009), and overall NP (p = 0.014) as well as counts of NPs in all regions examined (p values ranging from 0.009 to 0.04). NP ratings in the hippocampus (p = 0.057) and the combined neocortical measure (p = 0.052) approached significance. In each analysis, the concomitant medication group had significantly fewer NPs (∼20%) than any of the other groups, which were relatively similar. No significant NFT differences were found. Conclusion: The results of this study suggest that the combination of insulin with other diabetes medication is associated with substantially lower neuritic plaque density consistent with the effects of both on the neurobiology of insulin.

Better memory functioning associated with higher total and low-density lipoprotein cholesterol levels in very elderly subjects without the apolipoprotein e4 allele.

OBJECTIVE To examine the association of cholesterol with cognitive functioning in oldest old community dwelling individuals with and without the apolipoprotein e4 (APOE4) allele. METHOD One hundred eighty-five nondemented, community dwelling individuals (>or=85) were assessed with a broad neuropsychological battery. Bloods were drawn to assess total, low-density lipoprotein (LDL), and high-density lipoprotein cholesterol, as well as for APOE genotyping. RESULTS In contrast to our expectations, high total cholesterol and high LDL cholesterol were associated with higher memory scores for noncarriers of the APOE4 allele. No significant associations between cognitive performance and lipid profile were found for carriers of the APOE4 allele. CONCLUSIONS In oldest old nondemented noncarriers of the APOE4 allele, high cholesterol is associated with better memory function. Further examination of the role of APOE genotype on the association between cholesterol and cognitive performance, especially in the oldest old is warranted.

P-177: Leisure activities are associated with cognition in community dwelling very elderly

Background: Recent findings suggest that socially or mentally stimulating activity may protect against dementia. Objective: To examine, cross sectionally, the association of several leisure activities with cognitive functioning in a non-demented community dwelling very elderly sample from an ongoing longitudinal study on risk and protective factors for Alzheimer’s disease. Methods: Factor analyses of the neuropsychological variables yielded two rotated varimax factors: memory (primarily immediate and delayed recall, recognition, and Savings) and executive functioning (primarily Trail Making Tests A and B, and Shipley Vocabulary Test). The 10 leisure activities (watching news on TV, listening to radio, games, theater, courses, social gatherings, travel, gardening, art with hands, and writing) were not strongly inter-correlated. Multiple partial correlation assessed the association of the leisure activities with the neuropsychological factors, controlling for age, sex, and education. Results: 148 subjects (61% women, mean age 87.3 5.8 and mean education 15.1 3.2) had complete data. For memory, the multiple partial correlation did not reach statistical significance (R .32; F(10,134) 1.56; p .13). The only significant partial correlation for individual leisure activities was for art with hands (r .21; p .01). For executive functioning, the significant association (R .39; F(10,134) 2.33; p .02) reflected writing (r .23; p .005), (not) watching news on TV (r -.18; p .03), listening to radio (r .17; p .04), and travel (r .16; p .05). Partial correlations with writing of the Shipley Vocabulary Test (r .24; p .003) was stronger than with the Trails A (r -.15; p .07) and B (r -.16; p .06) suggesting that the association with the executive functioning factor reflected cognition rather than simple motor ability. Conclusions: In this interim sample, cognition was associated with increasing frequency of several leisure activities, after adjusting for age, sex, and years of education, in non-demented community dwelling subjects who are very old and thus at high risk for dementia. Leisure activities are a modifiable life style characteristic that might contribute to prevention of dementia.