Abstract
Background: Widowhood and divorce are extremely stressful life events and have been associated with high risk of dementia and cognitive impairment. However, the neurobiological mechanisms underlying how this risk is conferred requires further investigation. Alzheimer's disease (AD) pathology, such as β-amyloid (Aβ), may explain influences of chronic stress, such as those seen in disruptive marital transitions, on declines in cognition. Therefore, we examined whether Aβ mediates associations between marital dissolution (through widowhood or divorce) and executive functioning (EF) and episodic memory (EM) performance in cognitively normal (CN) individuals. Methods: Data from 543 CN participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were analysed. Outcomes included marital status, Aβ PET tracer uptake, and composite EF and EM scores. Primary analyses assessed relationships between marital dissolution and Aβ pathology, and marital dissolution and cognitive performance, and explored whether Aβ mediated associations between the latter. Results: Marriage dissolution was associated with increased Aβ burden (β= 0.56; 95% CI: 0.11 to 1.02; P= 0.015) and worse EM performance (β= -0.09; 95% CI: -0.15 to -0.03; P= 0.003). Level of Aβ neuropathology was also identified as a significant mediator for the relationship between marriage dissolution and EM (ACME= -0.007; P= 0.029). Conclusions: Aβ pathology was identified as a potential neurobiological mediator for the impacts of chronic stress due to marital dissolution on poorer memory performance. This suggests that stressful life events, such as the dissolution of one's marriage might exert a direct effect on AD proteinopathy, which may subsequently influence poor cognition.
Competing Interest Statement
Dr. Sheena Waters has received funding from UKRI Innovate UK. Professor Charles R Marshall has received research grant funding from NIHR, Innovate UK, Michael J Fox Foundation, Alzheimer's Research UK, and Tom and Sheila Springer Charity. Dr. Avinash Chandra, Miss Rifah Anjum, Dr. Petroula Proitsi, and Dr. Laura J Smith report no biomedical financial interests or potential conflicts of interest related to this work.
Funding Statement
This study did not receive any funding
Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
Yes
The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
The public dataset ADNI was used after registration for access was obtained by Dr Avinash Chandra. All ethical permissions and oversight was conducted within the ADNI study. ADNI acquired all IRB approvals and met all ethical standards during data collection. Ethics committees and institutional review boards that approved the ADNI study included Albany Medical Center Committee on Research Involving Human Subjects Institutional Review Board, Boston University Medical Campus and Boston Medical Center Institutional Review Board, Butler Hospital Institutional Review Board, Cleveland Clinic Institutional Review Board, Columbia University Medical Center Institutional Review Board, Duke University Health System Institutional Review Board, Emory Institutional Review Board, Georgetown University Institutional Review Board, Health Sciences Institutional Review Board, Houston Methodist Institutional Review Board, Howard University Office of Regulatory Research Compliance, Icahn School of Medicine at Mount Sinai Program for the Protection of Human Subjects, Indiana University Institutional Review Board, Institutional Review Board of Baylor College of Medicine, Jewish General Hospital Research Ethics Board, Johns Hopkins Medicine Institutional Review Board, Lifespan - Rhode Island Hospital Institutional Review Board, Mayo Clinic Institutional Review Board, Mount Sinai Medical Center Institutional Review Board, Nathan Kline Institute for Psychiatric Research & Rockland Psychiatric Center Institutional Review Board, New York University Langone Medical Center School of Medicine Institutional Review Board, Northwestern University Institutional Review Board, Oregon Health and Science University Institutional Review Board, Partners Human Research Committee Research Ethics, Board Sunnybrook Health Sciences Centre, Roper St. Francis Healthcare Institutional Review Board, Rush University Medical Center Institutional Review Board, St. Joseph's Phoenix Institutional Review Board, Stanford Institutional Review Board, The Ohio State University Institutional Review Board, University Hospitals Cleveland Medical Center Institutional Review Board, University of Alabama Office of the IRB, University of British Columbia Research Ethics Board, University of California Davis Institutional Review Board Administration, University of California Los Angeles Office of the Human Research Protection Program, University of California San Diego Human Research Protections Program, University of California San Francisco Human Research Protection Program, University of Iowa Institutional Review Board, University of Kansas Medical Center Human Subjects Committee, University of Kentucky Medical Institutional Review Board, University of Michigan Medical School Institutional Review Board, University of Pennsylvania Institutional Review Board, University of Pittsburgh Institutional Review Board, University of Rochester Research Subjects Review Board, University of South Florida Institutional Review Board, University of Southern, California Institutional Review Board, UT Southwestern Institution Review Board, VA Long Beach Healthcare System Institutional Review Board, Vanderbilt University Medical Center Institutional Review Board, Wake Forest School of Medicine Institutional Review Board, Washington University School of Medicine Institutional Review Board, Western Institutional Review Board, Western University Health Sciences Research Ethics Board, and Yale University Institutional Review Board.
I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.
Yes
I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).
Yes
I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.
Yes
Data Availability
The ADNI dataset can be accessed by approved users on https://adni.loni.usc.edu
