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Abstract

The primary objective of this thesis was to determine if patients with early onset ( 65 years) non-autosomal dominant AD. Secondary aims were: (i) to examine the effect(s) of the gender of the index case on the risk of AD to first degree relatives (ii) to examine the effect(s) of the gender of the first degree relative on their AD risk (iii) to examine the effect(s) of the relationship between the index case and the first degree relative (parent or sib) on the relative's risk of AD (iv) to compare the risk estimates for first degree relatives of non-autosomal dominant AD cases with those for first degree relatives of controls to determine genetic loading, and (v) if certain subgroups of first degree relatives of AD cases were at an increased risk, to determine whether this was reflected in the general population. Kaplan-Meier age-specific risk estimates were calculated for the 2519 first degree relatives of the 453 early and late onset non-autosomal dominant AD cases seen at the Clinic for Alzheimer Disease and Related Disorders -UBC Site from 1985 to 1995. Kaplan-Meier risk estimates were also calculated for 4324 first degree relatives of 796 controls taken from the Canadian Study of Health and Aging (CSHA). The cumulative lifetime risk estimate to age 88 for first degree relatives of early onset cases was 7.9± 2.1% compared to 8.0± 1.5% for first degree relatives of late onset cases, and 4.1 ± 0.6% for first degree relatives of controls. The difference between the cumulative lifetime risk estimates for first degree relatives of early and late onset cases was not significant (Z=0.04, p=0.48). The cumulative lifetime risk estimate for first degree relatives of late onset cases was significantly different from the cumulative lifetime risk estimate for first degree relatives of controls (Z=2.41, p