Familial Alzheimer Dementia: a prevalent disorder with specific clinical features

Abstract

Synopsis: The early literature on Alzheimer Dementia (AD) describes the clinical features aphasia, apraxia and agraphia as characteristic. We investigated the hypothesis that these features would specifically identify the familial form of AD (FAD). Since pedigree studies had suggested that FAD is an autosomal dominant genetic disorder, we hypothesized that the first-degree relatives of language-disordered or apractic AD probands would show at least 50% lifetime risks of dementia. Using standardized methods, we screened 3500 nursing home beds for stringently defined AD cases and controls, tested for agraphia, and obtained probands' clinical and family histories from multiple informants. Language disorder and apraxia were found in 78% of AD cases. They strongly predicted familial aggregation of dementia, with a 90-year lifetime incidence among relatives exceeding 50%, or 7 times the control values. The results suggest that language disorder and apraxia specifically identify a distinct clinical entity, Familial Alzheimer Dementia, that is among the commonest forms of senile dementia.