The final sample of 4,108 participants included those experiencing early maternal death at age 0-4 years (n=87), 5-10 years (n=99), 11-17 years (n=108), while early paternal death included participants who experienced paternal death at age 0-4 years (n=69), 5-10 years (n=122), 11-17 years (n=174; ). Subject’s education, mother’s and father’s age at subject’s birth, and AD diagnosis in late life were associated with early maternal death and early paternal death, with subject’s age at baseline interview associated with early maternal death ().
Descriptive Summary of Subjects Who Were Exposed and Unexposed to Early Maternal and Early Paternal Death
In an initial model, older age, female gender, and one or two copies of the APOE e4 allele were associated with greater risk for AD, while education was non-significant (). After covariate adjustments, the overall association between early paternal death and AD diagnosis in late life was marginal, with paternal death before subject age 5 linked to a doubling in prevalence of AD. Mother’s death during adolescence was likewise associated with more than double the prevalence of AD. The final model adjusted for (categorical) Nam-Powers SES, which was not significantly associated with AD. Further, after SES adjustment, associations for both mother’s death and father’s death were virtually identical (similar results for SES adjustment using mean imputation, not shown). Additional models (not shown) adjusted for number of siblings, where associations for both mother death and father death were likewise virtually unchanged.
Logistic regression analysis of early paternal and early maternal death on offspring risk for Alzheimer’s disease (Odds ratios and p-values; N=4108)
In separate models (not shown), participant gender was tested as potential moderator of mother’s death and father’s death associations with late-life diagnosis of AD. Gender did not moderate either association (Wald=4.22, df=3, p=.239; Wald=2.651, df=3, p=.449, gender interactions, respectively). Similarly, presence of the e4 allele did not moderate these associations (Wald=1.98, df=5, p=.851; Wald=8.06, df=6, p=.234, respectively). In models including only incident cases, and then only prevalent cases (not shown), results were essentially unchanged. Mother’s death and father’s death were not associated with non-AD dementia risk (models not shown; Wald=3.01, df=3, p=.391; Wald=3.97, df=3, p=.264, respectively, full model). Thus, associations between early parental loss and dementia were specific to AD.
We explored lifetime history of major depression as partial evidence that childhood bereavement may generate stress with lasting emotional, developmental and physiologic impacts. Subjects with maternal death during adolescence had lifetime prevalence of major depression of 30%, while those exposed at ages younger than 11 years and those with maternal death in adulthood each had major depression prevalence of 23%. This association did not reach statistical significance (χ2=2.645, df=2, p=.266).
Separate models (not shown) were computed to examine older parental age at subject’s birth, potentially resulting in heightened risk for chronic diseases such as AD later in life. In simple bivariate models, both maternal age (OR=1.02, Wald=5.71, df=1, p=.017) and paternal age (OR=1.01, Wald=5.46, df=1, p=.019) at subject’s birth were associated with higher rates of AD. However, when tested for their association with AD net of maternal and paternal death, both maternal age (OR=1.01, Wald=.699, df=1, p=.403) and paternal age (OR=1.00, Wald=.00, df=1, p=.966) at subject’s birth were no longer associated with AD. However, the associations between mother death during subject’s adolescence (OR=2.27, Wald=10.218, df=1, p=.001) and father’s death before subject age 5 (OR=2.10, Wald=5.32, df=1, p=.021) with AD remained robust after adjustment for parental ages at subject’s birth.
In additional models, we tested the seven-category exposure variable (paternal death and maternal death with/without remarriage of widowed parent during remaining years of subject’s childhood). In the final model with this expanded exposure variable, paternal death was no longer associated with AD (). However, maternal death during subject’s adolescence was associated with a higher rate of AD when the widowed father did not remarry.
Logistic regression analysis of early paternal and early maternal death on offspring risk for Alzheimer’s disease, when widowed parent does or does not remarry during offspring’s childhood (Odds ratios and p-values; N=4108)
Our sample included a small number (n=27) of subjects whose mother and father both died during subject’s childhood. In exploratory analyses, orphanhood was not associated with higher rate of AD (OR=1.59, Wald=0.78, df=1, p=.378).