Nongenetic Factors as Modifiers of the Age of Onset of Familial Alzheimer's Disease

Abstract

Objective: The purpose of this research was to identify environmental and personal factors that could be related to the variability in the age of onset of familial Alzheimer's disease (FAD) (36–62 years). Methods: A sample was taken of 49 subjects with FAD and with the mutation E280A in the presenilin-1 gene on chromosome 14; the sample was divided into two subgroups: 27 individuals with age of onset of the disease between 36 and 46 years (early onset) and 22 individuals whose disease began between 47 and 62 years (late onset). Information on environmental and personal factors was collected by means of a questionnaire answered by the patients if their clinical condition allowed it, or by their relatives; such information was organized in a categorical way. Comparisons between the two groups for each categorical variable were done by means of the chi-square test. Noncollinear variables that showed statistical significance were included as independent variables in a logistic regression analysis to predict their association with early onset of the disease. Results: Only 5 of the 140 studied variables were different between the two groups in univariate analysis: education, surgical history, type of stressful event, depression, and affective losses. The logistic regression model was constituted by education, depression, and affective losses. High-level education had approximately 15 times more probability of association with an early onset of the disease; both the history of affective losses and depressive symptoms had 4 times more probability of a similar association. Conclusions: The association of high-level education and early onset of the disease could be related to an earlier detection of symptoms, in turn determined by greater intellectual and environmental demands. The occurrence of depression and affective losses has been considered a prodromic manifestation of the disease. Our findings are evidence of high clinical heterogeneity even in a genetically homogeneous group.