title: Loneliness and risk of Alzheimer disease.
abstract: BACKGROUND
  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).
  
  
  METHODS
  Longitudinal clinicopathologic cohort study with up to 4 years of annual in-home follow-up.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  Loneliness is associated with an increased risk of late-life dementia but not with its leading causes.
authors.affiliation: Rush Alzheimer's Disease Center, Rush Institute for Healthy Aging, Rush University Medical Center, Chicago, IL 60612, USA. rwilson@rush.edu
authors.forename: Robert S
authors.initials: RS
authors.lastname: Wilson
authors.forename: Kristin R
authors.initials: KR
authors.lastname: Krueger
authors.forename: Steven E
authors.initials: SE
authors.lastname: Arnold
authors.forename: Julie A
authors.initials: JA
authors.lastname: Schneider
authors.forename: Jeremiah F
authors.initials: JF
authors.lastname: Kelly
authors.forename: Lisa L
authors.initials: LL
authors.lastname: Barnes
authors.forename: Yuxiao
authors.initials: Y
authors.lastname: Tang
authors.forename: David A
authors.initials: DA
authors.lastname: Bennett
mesh_terms: D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000453:epidemiology* / Q000523:psychology; D001921:Brain / Q000473:pathology; D002544:Cerebral Infarction / Q000453:epidemiology / Q000473:pathology; D003072:Cognition Disorders / Q000175:diagnosis / Q000453:epidemiology / Q000523:psychology; D015331:Cohort Studies; D015897:Comorbidity; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008132:Loneliness / Q000523:psychology*; D008137:Longitudinal Studies; D008297:Male; D009483:Neuropsychological Tests; D010555:Personality Inventory; D012307:Risk Factors; D012934:Social Isolation / Q000523:psychology