Associations of Widowhood and β-Amyloid With Cognitive Decline in Cognitively Unimpaired Older Adults

Kelsey D. Biddle, Heidi I. L. Jacobs, Federico d'Oleire Uquillas, Benjamin S. Zide, Dylan R. Kirn, Michael R. Properzi, Dorene M. Rentz, Keith A. Johnson, Reisa A. Sperling, Nancy J. Donovan*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Importance To reduce the rising incidence of clinical impairment due to Alzheimer disease, it is essential to define older adults at highest risk. Widowhood may be an unrecognized factor contributing to accelerated clinical progression along the Alzheimer disease pathway among cognitively unimpaired older adults. Objective To determine whether widowhood status and level of brain beta-amyloid (ie, the Alzheimer disease pathologic protein) are additively or interactively associated with cognitive decline among cognitively unimpaired older adults. Design, Setting, and Participants In this cohort study, 257 married, widowed, and unmarried (ie, never married, divorced, or separated) participants from the Harvard Aging Brain Study longitudinal cohort underwent baseline evaluation of neocortical beta-amyloid levels using Pittsburgh compound B positron emission tomography and 4 annual cognitive assessments. Data were collected from September 2010 to February 2017 and analyzed from July 2018 to July 2019. Main Outcomes and Measures Cognitive performance was measured using the Preclinical Alzheimer Cognitive Composite. Results Of the 257 participants, 153 (59.5%) were women, and the mean (SD) age was 73.5 (6.1) years; 145 participants (56.4%) were married (66 [45.5%] women), 77 (30.0%) were unmarried (56 [72.7%] women), and 35 (13.6%) were widowed (31 [88.6%] women). Compared with married participants, widowed participants demonstrated worsening cognitive performance after adjusting for age, sex, socioeconomic status, depression, and beta-amyloid levels (beta = -0.11; 95% CI, -0.19 to -0.04; P = .002) with no difference observed between married and unmarried participants. Furthermore, widowed participants with higher baseline beta-amyloid levels exhibited steeper cognitive decline (beta = -0.22; 95% CI, -0.42 to -0.03; P = .02), indicating both independent and interactive associations of beta-amyloid levels and widowhood with cognition. In a secondary model using dichotomous beta-amyloid-marital status groupings, the rate of cognitive decline among widowed participants with high beta-amyloid was nearly 3 times faster than among married participants with high beta-amyloid (widowed, high beta-amyloid: beta, -0.33; 95% CI, -0.46 to -0.19; P <.001; married, high beta-amyloid: beta, -0.12; 95% CI, -0.18 to -0.01; P <.001). Conclusions and Relevance In a sample of cognitively unimpaired older adults, being widowed was associated with accelerated beta-amyloid-related cognitive decline during 3 years. Cognitively unimpaired, widowed older adults were particularly susceptible to Alzheimer disease clinical progression, emphasizing the need for increased research attention and evidenced-based interventions for this high-risk group.

This cohort study evaluates whether widowhood status and amyloid-beta level are additively or interactively associated with cognitive decline among cognitively unimpaired older adults.

Question Is widowhood a specific risk factor associated with more rapid cognitive decline among cognitively unimpaired older adults with higher levels of brain beta-amyloid, the Alzheimer disease biomarker? Findings In this cohort study of 257 community-dwelling cognitively unimpaired older adults, widowhood and beta-amyloid were additively and interactively associated with cognitive decline. These results were independent of demographic factors, cardiovascular disease risk, depression, health-related behaviors, and social support factors. Meaning These findings suggest that widowhood may be an understudied risk factor for cognitive decline associated with Alzheimer disease and highlight the need for increased research and clinical attention to this high-risk group.

Original languageEnglish
Article numbere200121
Number of pages13
JournalJama network open
Issue number2
Publication statusPublished - 26 Feb 2020


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