Loneliness and Risk of Alzheimer Disease

TLDR

Social isolation in older adults is linked to dementia risk, yet the impact of perceived loneliness on Alzheimer disease remains unclear. The study aimed to determine whether loneliness increases the risk of Alzheimer disease. A longitudinal clinicopathologic cohort of 823 dementia‑free older adults was followed for up to four years, with annual loneliness assessments and postmortem brain examinations to evaluate AD pathology and cognitive decline. Lonely participants had more than twice the risk of developing Alzheimer disease, lower baseline cognition, faster decline, but no difference in AD pathology or infarctions, indicating loneliness raises dementia risk independent of underlying pathology.

Abstract

Social isolation in old age has been associated with risk of developing dementia, but the risk associated with perceived isolation, or loneliness, is not well understood.To test the hypothesis that loneliness is associated with increased risk of Alzheimer disease (AD).Longitudinal clinicopathologic cohort study with up to 4 years of annual in-home follow-up.A total of 823 older persons free of dementia at enrollment were recruited from senior citizen facilities in and around Chicago, Ill. Loneliness was assessed with a 5-item scale at baseline (mean +/- SD, 2.3 +/- 0.6) and annually thereafter. At death, a uniform postmortem examination of the brain was conducted to quantify AD pathology in multiple brain regions and the presence of cerebral infarctions.Clinical diagnosis of AD and change in previously established composite measures of global cognition and specific cognitive functions.During follow-up, 76 subjects developed clinical AD. Risk of AD was more than doubled in lonely persons (score 3.2, 90th percentile) compared with persons who were not lonely (score 1.4, 10th percentile), and controlling for indicators of social isolation did not affect the finding. Loneliness was associated with lower level of cognition at baseline and with more rapid cognitive decline during follow-up. There was no significant change in loneliness, and mean degree of loneliness during the study was robustly associated with cognitive decline and development of AD. In 90 participants who died and in whom autopsy of the brain was performed, loneliness was unrelated to summary measures of AD pathology or to cerebral infarction.Loneliness is associated with an increased risk of late-life dementia but not with its leading causes.