Loneliness and Risk of Alzheimer Disease

Abstract

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.

Can Clinical Data Predict Progression to Dementia in Amnestic Mild Cognitive Impairment?

“…Other new risk factors include diet and recent weight loss and this was also not assessed properly. 95,96 There is also recent evidence that loneliness and chronic distress increase the risk of AD, [97][98][99] but these psychological factors were not assessed in this study. Finally, we did not assess formally for the use of particular medications with anticholinergic side effects, which have been found in 9% of MCI subjects.…”

The Involvement of Cdk5 Activator p35 in Social Isolation-Triggered Onset of Early Alzheimer’s Disease-Related Cognitive Deficit in the Transgenic Mice

“…A study analyzing the association between social isolation and AD showed that the risk of developing AD was more than doubled in isolated person. Social isolation was associated with lower level of cognition at baseline and with more rapid decline during follow-up (Wilson et al, 2007). However, social isolation was not related to any change of the brain hallmarks associated with AD suggesting that social isolation may contribute to risk of AD and does so through some mechanisms other than AD pathology.…”

Loneliness and Social Isolation: Risk Factors Long Overdue for Surveillance

“…• Diminished physical activity 13 • Diminished motor function 14,15 • Symptoms of depression 16 • Disrupted sleep and daytime dysfunction 17 • Impaired mental and cognitive function 18 • Increased systolic blood pressure 19 • Increased sympathetic tone and vascular resistance 20,21 • Increased hypothalamic pituitary adrenocortical activity 22,23 • Altered gene expression related to anti-inflammatory responses 24 • Altered immunity 25,26 Of greater concern, however, is an accumulating volume of research that highlights loneliness as a risk factor for both functional decline as well as increased mortality. 4,8,[27][28][29] In short, there is evidence that the subjective experience of loneliness can significantly contribute to premature death independently of other physical, behavioral, or psychological factors.…”