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

https://doi.org/10.1097/JGP.0b013e3182011b38Get rights and content

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.

Section snippets

OBJECTIVE

Parental death during childhood is often a significant stressor affecting long-term emotional, cognitive, social, spiritual, and physical well-being. Bereaved children and adolescents are at increased risk for psychiatric disorders1 including major depression and posttraumatic stress disorder2 and alcohol or substance abuse3 after parental death. Childhood stressors such as early parental death and divorce have been shown to extend into adulthood with increased risk for poorer cardiovascular

Subjects

In 1995, we asked all permanent elderly (age 65 or older) residents of Cache County to participate in the first wave of the CCMS. A total of 5,092 participants (90%) consented. In primary analyses of AD, we excluded 294 cases of non-AD dementia, 189 subjects where cognitive status could not be determined, and 501 subjects with missing data. In a final sample of 4,108 participants, 570 were with a diagnosis of AD and 3,538 without dementia. Among the 294 subjects who were diagnosed with non-AD

RESULTS

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), or 11–17 years (n = 108), whereas early paternal death included participants who experienced paternal death at age 0–4 years (n = 69), 5–10 years (n = 122), or 11–17 years (n = 174; Table 1). Subject's education, mother's and father's age at his or her birth, and AD diagnosis in late life were associated with early maternal death and early paternal death, with

DISCUSSION

In this population-based study of AD, we capitalized on a rich genealogical and vital statistics database to reexamine associations between parental death during childhood and risk of AD during late life. The use of the vital statistics data base removed recall bias as a potential confound. Mother's death during offspring adolescence was uniquely associated with more than double the risk of AD, with attenuated effects if the widowed father remarried, with equivalent correlations for sons and

CONCLUSION

The present study provides further evidence that the traumatic event of parental death during childhood is associated with higher rates of AD in late life. Of particular note is the finding that the strength of association between mother's or father's death and AD depends on timing within childhood during the parent's death and that effects are stronger when the widowed parent does not remarry. This finding extends our prior work by demonstrating that this association is specific to AD and

References (40)

  • BK Lee et al.

    Associations of salivary cortisol with cognitive function in the Baltimore memory study

    Arch GenPsychiatry

    (2007)
  • AM MacLullich et al.

    Plasma cortisol levels, brain volumes and cognition in healthy elderly men

    Psychoneuroendocrinology

    (2005)
  • BS McEwen

    Physiology and neurobiology of stress and adaptation: central role of the brain

    Physiol Reviews

    (2007)
  • AR Borenstein et al.

    Early-life risk factors for Alzheimer disease

    Alzheimer Dis Assoc Disord

    (2006)
  • B Coffino

    The role of childhood parent figure loss in the etiology of adult depression: findings from a prospective longitudinal study

    Attach Hum Dev

    (2009)
  • BL Neugarten et al.

    Changing meanings of age

    Psychol Today

    (1987)
  • VM Moceri et al.

    Using census data and birth certificates to reconstruct the early life socioeconomic environment and the relation to the development of Alzheimer's disease

    Epidemiology

    (2001)
  • RC Green et al.

    Depression as a risk factor for Alzheimer disease: the Mirage study

    Arch Neurol

    (2003)
  • G Persson et al.

    A prospective population study of psychosocial risk factors for late onset dementia

    Int J Geriat Psychiatr

    (1996)
  • MC Norton et al.

    Early parental death and late-life dementia risk: findings from the Cache County Study

    Age Ageing

    (2009)
  • Cited by (66)

    • Adverse Childhood Experiences and Dementia: Interactions With Social Capital in the Japan Gerontological Evaluation Study Cohort

      2021, American Journal of Preventive Medicine
      Citation Excerpt :

      Adverse childhood experiences (ACEs) have been linked to a wide range of health problems, including dementia.1–11

    • Early-life stress induces the development of Alzheimer's disease pathology via angiopathy

      2021, Experimental Neurology
      Citation Excerpt :

      It is considered that the acquired predisposition to AD increases with age and that trauma during adulthood increases the likelihood of developing AD. Moreover, recent epidemiological research has suggested that stressful environmental factors during the developmental period, including mistreatment, neglect, and the loss of a parent, can also increase the likelihood of developing AD (Norton et al., 2011; Radford et al., 2017; Seifan et al., 2015). However, these findings are generally based on retrospective cohort studies, and it is unclear whether early-life stress affects the onset and progression of AD.

    View all citing articles on Scopus

    This work was supported by National Institute of Health grants: AG-031272, AG-011380, and AG-021136. Partial support for all data sets within the Utah Population Database (UPDB) was provided by the University of Utah Huntsman Cancer Institute and the Huntsman Cancer Institute Cancer Center Support grant, P30 CA42014 from National Cancer Institute. The authors thank the following individuals whose activities have helped to ensure the success of the project: Cara Brewer, B.A., Tony Calvert, B.S.C., Carol Leslie, M.S., Georgiann Sanborn, M.S., Michelle Mc. Cart., Heidi Wengreen, Ph.D., R.D., James Wyatt, and Peter P. Zandi, Ph.D., M.P.H., Roxane Pfister, M.S., and Nancy Sassano, Ph.D.

    Neuropsychological testing and clinical assessment procedures were developed by Dr. Welsh-Bohmer and Dr. Breitner. Dr. Tschanz provided training and oversight of all field staff and reviewed all individual neuropsychological test results to render professional diagnoses. The board-certified or board-eligible geriatric psychiatrists or neurologists who examined the study members included Drs. Steinberg, Breitner, Steffens, Lyketsos, Gagliardi, Raj, Christopher, and Green. Dr. Williams also examined several subjects and provided expert neurologic consultation. Autopsy examinations were conducted by Dr. Townsend. Ms. Leslie coordinated the autopsy enrollment program. Diagnosticians at the expert consensus conferences included Drs Breitner, Burke, Lyketsos, Plassman, Steffens, Steinberg, Toohill, Tschanz, and Welsh-Bohmer.

    Drs. Norton, Breitner, Corcoran, Smith, Tschanz, Østbye, and Ms. Schwartz have no disclosures. Dr. Skoog got research funding from the Swedish Research Council, Swedish Council for Working Life and Social Research, The Alzheimer's Association. Dr. Steffens got travel support from Bristol-Myers Squibb to present at a scientific meeting and grant support from the National Institute of Mental Health.

    View full text