A family-genetic study of dementia of Alzheimer type.

A family study of 22 rigorously diagnosed subjects with dementia of Alzheimer type (DAT) and 24 nondemented controls revealed a morbid risk of DAT to first-degree relatives of probands of 41% by age 83 years compared with a risk of 23% by age 85 years in control relatives. Senescent forgetfulness, defined as consistent but not incapacitating memory deficit, may have represented early DAT in some instances. When such cases were included as secondary cases, the morbid risk to first-degree relatives of probands was 67% by age 86 years while risk to comparable control relatives remained 23%. No cases of Down's syndrome were observed. A significant excess of hematologic malignant neoplasms was found among first-degree relatives of probands, supporting an association with DAT. Overall, the findings add further evidence of the action of familial-genetic factors in the etiology of DAT. The magnitude of the effect is consistent with an autosomal dominant mode of inheritance, with penetrance nearly complete by age 85 years. The probands were not selected on the basis of factors posited by some to indicate a familial form of DAT, suggesting that such a genetic mechanism may be involved in the occurrence of DAT in general.