Specificity of the fivefold increase in AD in mothers of adults with Down syndrome

Background: In a previous study, the authors found that the risk of AD among mothers who were 35 years or younger when their children with Down syndrome (DS) were born was five times that of mothers of children with other forms of mental retardation. The current study investigated the specificity of the familial aggregation of DS and AD by examining whether mothers who gave birth to children with DS before age 35 are also at increased risk of other age-related neurologic or medical disorders. Methods: The authors used survival methods to compare cumulative incidence and relative risk of AD, other dementias, and common age-related disorders in parents of 200 adults with DS and parents of 252 adults with other forms of mental retardation. Results: Mothers who were : less than or equal to 35 years of age when their children with DS were born were four to five times as likely to develop AD as control mothers (rate ratio = 4.8, 95% GI 2.1, 11.2), whereas risk of AD among mothers who were > 35 years when their children with DS were born was not significantly increased (rate ratio = 1.8, 95% CI 0.6, 5.1). Risk of AD among fathers of probands with DS was similar to that of control fathers, and did not vary by age at proband birth. Risk of other dementias and of other age-related medical condition was similar among mothers and fathers of probands with DS and control parents, regardless of age at proband birth. Conclusion: These findings suggest that the increased risk of AD among mothers who gave birth to children with DS before age 35 appears to represent a specific vulnerability to AD, as opposed to other age-related degenerative disorders.