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We evaluated age at onset and lifetime risk for Alzheimer's disease(AD)in 70 kindreds with familial AD(designated FAD)composed of 541 affected and 1,066 unaffected offspring of demented parents who were identified retrospectively.Using a survival analysis method which takes into account affected persons with unknown onset ages and unaffected persons with unknown censoring ages,we found lifetime risk of AD among at-risk offspring by age 87 to be 64%.Analysis of age at onset among kindreds showed evidence for a bimodal distribution:in this sample,families with a mean onset age of less than 58 years were designated as having early- onset,while late-onset families had a mean onset age greater than 58 years.At-risk offspring in early-onset families had an estimated lifetime risk for dementia of 53%,which is significantly less than the risk of 86% that was estimated for offspring in late-onset families.Men and women in early-onset families had equivalent risk of dementia.In late-onset families,the risk to female offspring was somewhat higher than to male offspring but this difference was marginally significant.Lifetime risk of dementia in early-onset FAD kindreds is consistent with an autosomal dominant inheritance model.Our results may suggest that late-onset FAD has at least 2 etiologies;AD in some families may be transmitted as a dominant trait,whereas a proportion of cases in these and other late-onset families may be caused by other genetic or shared environmental factors. |
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Alzheimer's disease
Alzheimer's disease,early onset
Alzheimer's disease,familial
Alzheimer's disease,heterogeneity of
familial
genetic neurologic disorders
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