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

Abstract

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. To determine whether widowhood status and level of brain β-amyloid (ie, the Alzheimer disease pathologic protein) are additively or interactively associated with cognitive decline among cognitively unimpaired older adults. 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 β-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. Cognitive performance was measured using the Preclinical Alzheimer Cognitive Composite. 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 β-amyloid levels (β = -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 β-amyloid levels exhibited steeper cognitive decline (β = -0.22; 95% CI, -0.42 to -0.03; P = .02), indicating both independent and interactive associations of β-amyloid levels and widowhood with cognition. In a secondary model using dichotomous β-amyloid-marital status groupings, the rate of cognitive decline among widowed participants with high β-amyloid was nearly 3 times faster than among married participants with high β-amyloid (widowed, high β-amyloid: β, -0.33; 95% CI, -0.46 to -0.19; P < .001; married, high β-amyloid: β, -0.12; 95% CI, -0.18 to -0.01; P < .001). In a sample of cognitively unimpaired older adults, being widowed was associated with accelerated β-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.