Increased risk of Alzheimer's disease in mothers of adults with Down's syndrome.

Most adults with Down's syndrome (DS) develop neuropathology characteristic of Alzheimer's disease (AD) by the age of 40. Most of the non-dysjunction events in DS are of maternal origin. We postulated therefore that a shared genetic susceptibility to DS and AD would be associated with an increased frequency of AD among mothers, but not fathers, of individuals with DS. We further hypothesised that the shared susceptibility could involve an accelerated ageing process, leading to the birth of a child with DS to a relatively young mother and to an increased risk of dementia in the mother and her relatives. Families of 96 adults with DS and of 80 adults with other forms of mental retardation were ascertained through the New York State Developmental Disabilities services network. A semi-structured interview was used to obtain information on the presence or absence of non-stroke-related dementia and other disorders in parents. There was an increase in risk of dementia among mothers of DS probands compared with control mothers (risk ratio 2.6 [95% CI 0.9-7.3]). The risk of dementia among mothers who were 35 or younger when their DS children were born was 5 times that of control mothers (4.9 [1.6-15.4]). There was no increase in risk of dementia among mothers who were older (> 35 years) at the proband's birth (0.8 [0.2-3.4]). There was no difference in risk of dementia between fathers of DS cases and fathers of controls (1.2 [0.4-3.9]) and no discernible influence of age on this risk. Familial aggregation of dementia among mothers of adults with DS supports the hypothesis of a shared genetic susceptibility to DS and AD.