Widowhood accelerates cognitive decline in those at risk for Alzheimer’s disease

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The death of a spouse often means the loss of intimacy, companionship and everyday support for older adults. A study finds that widowhood can have another profound effect: It may accelerate cognitive decline. Investigators from Brigham and Women’s Hospital and Massachusetts General Hospital analysed older, cognitively normal Americans enrolled in the Harvard Ageing Brain Study whose marital status and brain β-amyloid levels – a marker of Alzheimer’s disease – were determined at the beginning of the study.

The team found that individuals who were widowed experienced a sharper cognitive decline than their married counterparts, especially among those who had high β-amyloid levels. The study suggests that widowhood may be an important and understudied risk factor for cognitive decline associated with Alzheimer’s disease and highlights the need for increased focus on this high-risk population.

“We know that social relationships can be an important buffer against cognitive decline,” said senior author Dr Nancy Donovan, of the division of geriatric psychiatry at the Brigham and an associate researcher at Mass General. “Being married provides opportunity for more social engagement and emotional support from a spouse, it expands one’s social network and it provides more opportunity for cognitive stimulation. All of these benefits are lost in widowhood. Importantly, loss of a spouse is a highly stressful life event which can have deleterious effects on the brain.”

Women are at increased risk for both widowhood and Alzheimer’s disease, both of which increase in frequency with age. The study, which included 260 cognitively unimpaired adults ages 62 to 89 – 153 women and 107 men – classified its subjects into three groups: married, widowed or unmarried (divorced, single, separated or never married). Of these subjects, 66 women and 79 men were married; 31 women and four men were widowed. The researchers measured the subjects’ β-amyloid levels using PET scans at the beginning of the study.

Donovan and colleagues evaluated a participant’s cognitive performance each year for four years using a series of tests to analyse various dimensions of cognition. They found that cognitive performance declined in the widowed group, differing significantly from the married group. There was no difference between the married group and the unmarried group. In addition, they found that among adults with the highest β-amyloid levels, those who were widowed had the sharpest decline in cognition compared to those who were married, declining at a rate three times faster. This finding was independent of many factors including age, sex, socioeconomic status, and depression.

The authors note this is the first study to show a combined and synergistic effect of widowhood and β-amyloid on cognitive decline and will need to be replicated in other studies.

“Our division has become very interested in understanding the physiological effects of widowhood so that we can develop interventions to try to alter these trajectories,” said Donovan. “Our findings also suggest that researchers engaged in Alzheimer’s disease prevention trials may want to pay particular attention to widowed older adults to tailor interventions for this especially susceptible group of patients.”

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 β-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 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.
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 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).
Conclusions and Relevance: 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.

Kelsey D Biddle, Heidi IL 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

Brigham and Women’s Hospital material

JAMA Network Open abstract

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