Association of Higher Cortical Amyloid Burden With Loneliness in Cognitively Normal Older Adults

Abstract

IMPORTANCE Emotional and behavioral symptoms in cognitively normal older people may be direct manifestations of Alzheimer disease (AD) pathophysiology at the preclinical stage, prior to the onset of mild cognitive impairment. Loneliness is a perceived state of social and emotional isolation that has been associated with cognitive and functional decline and an increased risk of incident AD dementia. We hypothesized that loneliness might occur in association with elevated cortical amyloid burden, an in vivo research biomarker of AD. OBJECTIVE To determine whether cortical amyloid burden is associated with greater loneliness in cognitively normal older adults. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional analyses using data from the Harvard Aging Brain Study of 79 cognitively normal, community-dwelling participants. A continuous, aggregate measure of cortical amyloid burden, determined by Pittsburgh Compound B–positron emission tomography (PiB-PET), was examined in association with loneliness in linear regression models adjusting for age, sex, apolipoprotein E ε4 (APOEε4), socioeconomic status, depression, anxiety, and social network (without and with the interaction of amyloid and APOEε4). We also quantified the association of high amyloid burden (amyloid-positive group) to loneliness (lonely group) using logistic regression, controlling for the same covariates, with the amyloid-positive group and the lonely group, each composing 32%of the sample (n = 25). MAIN OUTCOMES AND MEASURES Loneliness, as determined by the 3-item UCLA Loneliness Scale (possible range, 3–12, with higher score indicating greater loneliness). RESULTS The 79 participants included 43 women and 36 men with a mean (SD) age of 76.4 (6.2) years. Mean (SD) cortical amyloid burden via PiB-PET was 1.230 (0.209), and the mean (SD) UCLA-3 loneliness score was 5.3 (1.8). Twenty-two (28%) had positive APOEε4 carrier status, and 25 (32%) were in the amyloid-positive group with cortical PiB distribution volume ratio greater than 1.2. Controlling for age, sex, APOEε4, socioeconomic status, depression, anxiety, and social network, we found that higher amyloid burden was significantly associated with greater loneliness: compared with individuals in the amyloid-negative group, those in the amyloid-positive group were 7.5-fold (95%CI, 1.7-fold to 34.0-fold) more likely to be classified as lonely than nonlonely (β = 3.3, partial r = 0.4, P = .002). Furthermore, the association of high amyloid burden and loneliness was stronger in APOEε4 carriers than in noncarriers. CONCLUSIONS AND RELEVANCE We report a novel association of loneliness with cortical amyloid burden in cognitively normal older adults, suggesting that loneliness is a neuropsychiatric symptom relevant to preclinical AD. This work will inform new research into the neural underpinnings and disease mechanisms involved in loneliness and may enhance early detection and intervention research in AD.

Are loneliness and social isolation associated with cognitive decline?

“…For instance, individuals reporting feelings of loneliness or social isolation might engage to a greater extent in unhealthy behaviors (eg, physical inactivity or poor dietary choices), which in turn are associated with increased odds of developing cardiovascular diseases and cognitive impairment . Alternatively, loneliness and social isolation might appear as a response of the cognitive impairment or as a result of an underlying neuropathology leading to dementia . Consistently with this hypothesis, various longitudinal studies showed that global cognitive function and discrete cognitive domains predicted changes in perceived social isolation over time .…”

The Pathophysiology of Perceived Social Isolation: Effects on Health and Mortality

“…This has driven inquiries to a relatively novel concept, PSI, which has also been referred to in many studies as ‘loneliness’ [3-4] and a perceived lack of social support [5]. It merges the subjective feeling of loneliness and the objective deficiencies associated with social interactions and networks [3].…”

A Practical Approach to Assessing and Mitigating Loneliness and Isolation in Older Adults

“…For example, it may be difficult to motivate some patients to better control their diabetes or hypertension by explaining their relationship to heart disease. Yet older adults are often especially concerned about losing independence and cognition, and they may be highly motivated to address contributing factors such as loneliness and isolation . In addition, the link between social isolation/loneliness and cardiovascular health may be an additional way to provide upstream guidance to patients by focusing on their social connections.…”

“…Although the IOM report focused on measures of social connection and isolation, loneliness was considered a subcomponent of these measures, and several different measures of loneliness have been used to establish its relevance to health and risk for mortality. Loneliness may be easily identified using the UCLA three‐item loneliness scale (Supplementary Table S1) . Efforts are underway to incorporate this loneliness screen into EHRs.…”