Genes and recent developments in the epidemiology of Alzheimer's disease and related dementia.

In the search for cause or prevention of Alzheimer's disease, the traditional aims of analytic epidemiology have been hindered by several technical difficulties. The heterogeneous genetic influences on Alzheimer's disease have probably contributed substantially to difficulties in the detection of host or environmental factors associated with modified disease risk. We have discussed five areas of improved technical or theoretical approach, each of which has materially improved the prospects for future success in this endeavor. Improved methods of diagnosis have yielded purer samples of "cases" and have made it more practical to undertake population-based studies. Genetic determinants of Alzheimer's disease risk are being understood with increasing sophistication. A growing recognition of the time-dependent nature of the Alzheimer process has led to new and heuristically valuable ways of thinking about the disease, its causes (genetic and otherwise), and its prevention. While there is a growing consensus that Alzheimer's disease is probably not one disease but several, the limited success of efforts to identify distinguishable phenotypes has largely given way to the identification of those with various measures of disease risk and (probably) mechanisms on the basis of identifiable genotypic variation. Thus, several forms of this disease may soon be segregated for separate analysis. Two of the predisposing genes have apparent implications for disease pathogenesis; others remain identified only as anonymous "loci" implicated by linkage analyses. The greater understanding of genetic mechanisms serves to enable not only studies of gene effects in pathogenesis, but also the influence of various environmental factors that may modify the effects.(ABSTRACT TRUNCATED AT 250 WORDS)