Early Parental Death and Remarriage of Widowed Parents as Risk Factors for Alzheimer Disease: The Cache County Study

Department of Family Consumer and Human Development (MCN), Utah State University, Logan, UT 84322-2905, USA.
The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry (Impact Factor: 4.24). 09/2011; 19(9):814-24. DOI: 10.1097/JGP.0b013e3182011b38
Source: PubMed


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.
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.
Home visits with residents of a rural county in northern Utah.
4,108 subjects, aged 65-105.
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.
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.
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.

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    • "A stepparent might not simply " replace " a biological parent, as step-parental relationships are often of poorer quality (Daly and Wilson, 2005). But, since RWP is beneficial for other health outcomes (Andersson et al., 1996; Norton et al., 2011), it likely also attenuates any increased suicide risk. Examining multiple outcomes in the same study has been enjoined as another approach for clarifying stress-related mechanisms (Thoits, 1995). "
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    ABSTRACT: Early-life parental death (PD) may increase suicide and other mortality risk in adulthood. The potential implications of subsequent remarriage of the widowed parent (RWP) for suicide have not been well examined. Data came from the Utah Population Database for birth cohorts between 1886 and 1960, yielding a sample of N = 663,729 individuals, including 4533 suicides. Cox models showed PD was associated with increased adult suicide risk before age 50, and with increased risk of cardiovascular disease deaths (CVD) for adults of all ages. For females, RWP attenuated the suicide relationship before age 50 (though not statistically significant), but significantly exacerbated it after age 50. RWP had no significant impact for males. Further, for females, PD's positive association with suicide was stronger than with CVD before age 50. These findings reinforce the importance of biological and social mechanisms in linking early-life stressors to adult mental and physical health. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Full-text · Article · Feb 2015 · Social Science & Medicine
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    • "Our findings contradict earlier findings that suggested an association between life events and dementia (Persson and Skoog, 1996; Charles et al., 2006; Norton et al., 2009; 2011; Johansson et al., 2010; Tsolaki et al., 2010), yet they are in line with the results from two other studies (Motomura et al., 1998; Fountoulakis et al., 2011). A major strength of this study compared with the existing studies is the extensive life events inventory covering areas of work and private life, social relationships, health of both the index person and his or her relatives and friends, and deaths among friends and relatives. "
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    ABSTRACT: Background: The impact of stressful life events as a risk factor of dementia diseases is inconclusive. We sought to determine whether stressful negative life events are associated with incidental dementia in a population-based study with long-term follow-up. We also tested the hypothesis that the occurrence of positive life events could mitigate or overcome the possible adverse effects of negative life events on dementia conversion. Methods: The study involved 2,462 dementia-free participants aged 55 years and older. Information on life events was ascertained at baseline from a comprehensive Life Event Inventory, which included 56 questions about specific life events. For each life event, the emotional impact (both positive and negative) and emotional adjustment were asked for. Results: During follow-up, 423 participants developed dementia; of these, 240 developed Alzheimer's disease (AD). Cox regression analysis showed no association between the total number of negative life events and the incidence of dementia when adjusted solely for age and gender (hazard ratio = 0.97, 95% CI = 0.92-1.02), or with multiple adjustments for a range of covariates (hazard ratio = 0.96, 95% CI = 0.91-1.01). Similarly, neither emotional impact nor emotional adjustment to these life events was associated with incident dementia. A separate analysis of AD did not alter the results. Conclusions: The result of this population-based study finds no association between negative or positive life events and dementia. Accordingly, our results reject the hypothesis that stressful life events trigger the onset of dementia diseases.
    Full-text · Article · Nov 2013 · International Psychogeriatrics
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    • "Family-based studies provide a promising approach to identify rare variants cause LOAD or result in a substantial risk. Population-based studies have contributed greatly to our understanding of AD; types of study design include linkage analysis [4,15,16], twin studies [17,18], initial AD population risk studies [19], and environmental factors [20,21]. Family-based studies have suggested a significant genetic role in LOAD by finding that first degree relatives of patients with AD have a two- to four-fold increased risk of dementia from ages 65-80 [22], A weakness of such studies though is that probands were referred for diagnostic evaluation and participation in research studies and such cases invariably report a strong family history of dementia. "
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    ABSTRACT: Alzheimer's disease (AD) is an international health concern that has a devastating effect on patients and families. While several genetic risk factors for AD have been identified much of the genetic variance in AD remains unexplained. There are limited published assessments of the familiality of Alzheimer's disease. Here we present the largest genealogy-based analysis of AD to date. We assessed the familiality of AD in The Utah Population Database (UPDB), a population-based resource linking electronic health data repositories for the state with the computerized genealogy of the Utah settlers and their descendants. We searched UPDB for significant familial clustering of AD to evaluate the genetic contribution to disease. We compared the Genealogical Index of Familiality (GIF) between AD individuals and randomly selected controls and estimated the Relative Risk (RR) for a range of family relationships. Finally, we identified pedigrees with a significant excess of AD deaths. The GIF analysis showed that pairs of individuals dying from AD were significantly more related than expected. This excess of relatedness was observed for both close and distant relationships. RRs for death from AD among relatives of individuals dying from AD were significantly increased for both close and more distant relatives. Multiple pedigrees had a significant excess of AD deaths. These data strongly support a genetic contribution to the observed clustering of individuals dying from AD. This report is the first large population-based assessment of the familiality of AD mortality and provides the only reported estimates of relative risk of AD mortality in extended relatives to date. The high-risk pedigrees identified show a true excess of AD mortality (not just multiple cases) and are greater in depth and width than published AD pedigrees. The presence of these high-risk pedigrees strongly supports the possibility of rare predisposition variants not yet identified.
    Preview · Article · Oct 2013 · PLoS ONE
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