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Robert S. Wilson, PhD; Kristin R. Krueger, PhD; Steven E. Arnold, MD; Julie A. Schneider, MD; Jeremiah F. Kelly, MD; Lisa L. Barnes, PhD; Yuxiao Tang, PhD; David A. Bennett, MD

Arch Gen Psychiatry. 2007;64(2):234-240.

Context  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.

Objective  To test the hypothesis that loneliness is associated with increased risk of Alzheimer disease (AD).

Design  Longitudinal clinicopathologic cohort study with up to 4 years of annual in-home follow-up.

Participants  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.

Main Outcome Measures  Clinical diagnosis of AD and change in previously established composite measures of global cognition and specific cognitive functions.

Results  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.

Conclusion  Loneliness is associated with an increased risk of late-life dementia but not with its leading causes.

Author Affiliations: Rush Alzheimer's Disease Center (Drs Wilson, Krueger, Schneider, Kelly, Barnes, and Bennett), Rush Institute for Healthy Aging (Dr Tang), and Departments of Neurological Sciences (Drs Wilson, Schneider, Barnes, and Bennett), Behavioral Sciences (Drs Wilson, Krueger, and Barnes), Pathology (Dr Schneider), and Internal Medicine (Drs Kelly and Tang), Rush University Medical Center, Chicago, Ill; and Center for Neurobiology and Behavior, and Department of Psychiatry, University of Pennsylvania, Philadelphia (Dr Arnold).

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