Patterns of compensation and vulnerability in normal subjects at risk of Alzheimer's disease

Alzheimer's disease (AD) is the most frequent form of dementia in elderly individuals and its incidence and prevalence increases with age. This risk of AD is increased in the presence of genetic and demographic factors including apolipoprotein E 4 allele, lower education, and family history of AD. There are medical risk modifiers including systemic hypertension, diabetes mellitus, cardiovascular disease, and cerebrovascular disease that increase the vulnerability for AD. By contrast, there are lifestyle risk modifiers that reduce the effects of AD risk factors include diet and physical and cognitive activity. Our research has consistently shown that it is the interactions among these risk factors with the pathobiological cascade of AD that determine the likelihood of a clinical expression of AD-either as dementia or mild cognitive impairment. However, the association between "vulnerability" and "protective" factors varies with age, since the effects of these factors on the risk for AD may differ in younger (age < 80) versus older (age > 80) individuals. The understanding of the dynamic of these factors at different age periods will be essential for the implementation of primary prevention treatments for AD.