Predictive value of APOE genotyping in incipient Alzheimer's disease.

The Mayo Alzheimer's Disease Center/Alzheimer's Disease Patient Registry is a prospective, longitudinal project of aging and dementia in a community setting. Over 400 pairs of individuals have been studied through this project, and extensive data on clinical, radiological, neuropathological, and biological variables have been gathered. Previous case-control studies on this group of subjects have documented the role of the apolipoprotein E (APOE) epsilon 4 as a risk factor for dementia. Subsequent analyses between APOE and the age of the patients with dementia have shown that most of the epsilon 4 effect is manifest in subjects under 75 years of age. We have also used this patient resource to study a group of individuals who are at risk for dementia by virtue of having a significant memory impairment. We have designated these patients as having a mild cognitive impairment because they have abnormal memory function but do not reach criteria for dementia. Over the course of several years of follow-up, these subjects evolve to dementia at a rate of approximately 15% per year. The presence of an APOE epsilon 4 carrier status is the best predictor of subsequent development of dementia in these individuals. These studies indicate that APOE is an important risk factor for AD, and in patients with a mild cognitive impairment, APOE may be useful in predicting who is likely to progress to dementia.