Familial or sporadic clusters of presenile Alzheimer's disease in Scotland: II. Case kinship

Clusters of high incidence areas of presenile Alzheimer's disease were found in Scotland between 1974 and 1988. We present a novel index of case kinship based on the number of observed common ancestors of cases compared with the number expected in order to evaluate whether these cluster are attributable to familial cases. One county with high incidence was Lanarkshire, with 69 of the 451 national presenile Alzheimer's disease cases and 185 of the 1794 any-cause dementia cases. None of the 69 presenile Alzheimer's disease cases shared a common great-grandmother and there was no instance where an individual case's great-grandmother was another case's grandmother. Five pairs of dementia cases shared a great-grandmother; for two pairs, one case's great-grandmother was another's grandmother. We estimated the 'at-risk' ancestral population as 46 000 for the midpoint census of 1861 for the cross-sectional estimate, 155 812 for the cumulative estimate between 1831 and 1891, and 90 282 for the cumulative estimate between 1841 and 1871. Hence, we expected a maximum of 0.29 shared great-grandmothers for presenile Alzheimer's disease cases, and 2.13 shared great-grandmothers for dementia cases. Case-kinship is 2.35 more than expected (estimated range 1.84-3.18). We conclude that familial factors contribute to the incidence of dementia in Lanarkshire.