One source of variance in familial aggregation studies in Alzheimer''s disease (AD) is proband diagnosis. In this study, the morbid risk of primary progressive dementia (PPD) was assessed in first degree relatives of 32 patients with clinically diagnosed AD (mean onset = 59.9 ± 7.2 years) whose diagnoses were confirmed at autopsy. The Alzheimer''s Disease Risk Questionnaire and the Dementia Questionnaire were administered to multiple family informants by trained raters blind to the probands'' clinical and neuropathologic diagnoses. Morbid risk for PPD was analyzed using the Kaplan-Meier life-table method. The estimated cumulative risk of PPD in first degree relatives (n = 159; age ≧: 45) was estimated to be 48.8 ± 11.3% by age 86. The risk estimate for affected siblings (n = 96; age ≧ 45) reached 54.9 ± 20.7 % by age 78. These figures are consistent with those calculated for most cohorts of relatives of clinically selected AD probands lacking autopsy confirmation of diagnosis. Although based on a relatively small sample, this series is the first morbid risk analysis to employ clinically diagnosed probands with neuropathologic confirmation of AD.

Keywords:
Alzheimer's disease, Family history, Genetics
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© 1992 S. Karger AG, Basel
1992
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