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Risk factors and early signs of Alzheimer's disease in a family study sample. Risk of AD.

OBJECTIVE
Several predictors of Alzheimer's disease (AD) have been identified. However, the relevance and independent contribution of risk factors and of possible early signs such as mild cognitive impairment and subjective memory impairment on the development of AD has not been investigated prospectively in a cohort of non-demented elderly including first-degree relatives of AD subjects.


METHOD
The development of AD was investigated in 757 non-demented elderly. Initial diagnoses were made from personal interviews. Information on 633 subjects after 4.7 +/- 1.2 years (mean +/- SD) was obtained either from personal or family history interviews. Using forward logistic regression analysis, predictors were identified by comparing their presence in 38 subjects who developed AD and 577 subjects who remained non-demented.


RESULTS
The most important predictors of later Alzheimer's disease were increased age (Odds ratio OR = 1.086/additional year, p < 0.001), initial subjective memory complaints (OR = 2.68, p = 0.019), initial mild cognitive impairment (OR = 2.51, p = 0.032) and female gender (OR = 2.84, p = 0.069). Exploratory analysis revealed that previous depression after the age of 60 years (OR = 2.37, p = 0.033) and the presence of the apolipoprotein E4 allele (OR = 2.49, p = 0.043) individually predicted new AD during follow-up. A positive family history of AD (i. e. being a first degree relative of a subject suffering from AD) did not significantly influence the development of AD (p > 0.2).


CONCLUSIONS
Increased age, the presence of mild cognitive impairment, subjective memory impairment and gender are the most relevant independent predictors of later Alzheimer's disease that may be used in combination for clinical prediction of AD.