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Alzheimer's disease and mild cognitive impairment
Rates of mild cognitive impairment (MCI) vary widely. Using the cohort in Washington Heights, we developed diagnostic criteria for MCI to examine its frequency in our ethnically and linguistically diverse elders of northern Manhattan. The frequency of amnestic MCI, the form thought to represent early Alzheimer's disease, was 5.0 percent. MCI was frequent among older individuals and those with nine years of schooling or less. As in Alzheimer's disease, the APOE-e4 allele was also more frequent among those with amnestic MCI. In a related clinical study from the Memory Disorders Center, we found that APOE-e4 was one of the most consistent predictors of conversion to Alzheimer's disease in older outpatients.
We also studied several risk factors for cognitive decline among nondemented elderly. For example, we found that smoking among elderly below the age of 75 years was related to poor performance on cognitive tests and to a decline in memory over time. However, contrary to other studies, we observed that elevated plasma triglycerides or low-density lipoprotein were not associated with decline in cognitive performance over time and that the use of lipid-lowering agents, such as Lipitor, did not improve cognitive performance.
Our studies of risk factors related to Alzheimer's disease focused primarily on cardio-vascular and cerebrovascular risk factors. Diabetes and current smoking were the strongest risk factors, but clusters including hypertension and heart disease also increased the risk of this disease. We also led a large multicenter study examining the association between cerebrovascular disease and the pathologic manifestations of Alzheimer's disease using data from the United States National Alzheimer's Coordinating Center database. We studied data from 1,054 individuals and found that neuritic plaques and neurofibrillary tangles were associated with amyloid angiopathy. The most surprising finding was that the presence of large-vessel cerebrovascular disease, or atherosclerosis, was strongly associated with an increased frequency of neuritic plaques, which are a hallmark of the illness.
Led by Nicole Schupf, we investigated the relation between rate of decline in cognitive and both functional and physical abilities and risk of death in nondemented elderly using data from the Washington Heights and Inwood cohort. We observed that the rate of decline in cognitive and functional skills predicted higher mortality rates for normal elderly. We also investigated the relationship between the lipid profile and mortality. Surprisingly, low cholesterol was the most robust predictor of mortality among the elderly, indicating that it may represent a marker of frailty.
Richard Mayeux edited a series in the Journal of Clinical Investigation on Genetic Epidemiology. With a working draft of the human genome now in hand, the availability of high-throughput genotyping, a plethora of genetic markers, and the development of new analytical methods, he posits that scientists are now turning their attention to common complex disorders such as diabetes, obesity, hypertension, and Alzheimer's disease (see figure).