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Early parental death and remarriage of widowed parents as risk factors for Alzheimer disease: the Cache County study.

OBJECTIVES
Early parental death is associated with lifelong tendencies toward depression and chronic stress. We tested the hypothesis that early parental death is associated with higher risk for Alzheimer disease (AD) in offspring.


DESIGN
A population-based epidemiological study of dementia with detailed clinical evaluations, linked to one of the world's richest sources of objective genealogical and vital statistics data.


SETTING
Home visits with residents of a rural county in northern Utah.


PARTICIPANTS
4,108 subjects, aged 65-105.


MEASUREMENTS
Multistage dementia ascertainment protocol implemented in four triennial waves, yielding expert consensus diagnoses of 570 participants with AD and 3,538 without dementia. Parental death dates, socioeconomic status, and parental remarriage after widowhood were obtained from the Utah Population Database, a large genealogical database linked to statewide birth and death records.


RESULTS
Mother's death during subject's adolescence was significantly associated with higher rate of AD in regression models that included age, gender, education, APOE genotype, and socioeconomic status. Father's death before subject age 5 showed a weaker association. In stratified analyses, associations were significant only when the widowed parent did not remarry. Parental death associations were not moderated by gender or APOE genotype. Findings were specific to AD and not found for non-AD dementia.


CONCLUSIONS
Parental death during childhood is associated with higher prevalence of AD, with different critical periods for father's versus mother's death, with strength of these associations attenuated by remarriage of the widowed parent.