Loneliness and risk of all-cause, Alzheimer's, vascular, and frontotemporal dementia: a prospective study of 492,322 individuals over 15 years.

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This study examined the association between loneliness and risk of incident all-cause dementia and whether the association extends to specific causes of dementia. Longitudinal. Community. Participants were from the UK Biobank (N = 492,322). None. Loneliness was measured with a standard item. The diagnosis of dementia was derived from health and death records, which included all-cause dementia and the specific diagnoses of Alzheimer's disease (AD), vascular dementia (VD), and frontotemporal dementia (FTD), over 15 years of follow-up. Feeling lonely was associated with a nearly 60% increased risk of all-cause dementia (HR = 1.59, 95% CI = 1.51-1.65; n = 7,475 incident all-cause). In cause-specific analyses, loneliness was a stronger predictor of VD (HR = 1.82, 95% CI = 1.62-2.03; n = 1,691 incident VD) than AD (HR = 1.40, 95% CI = 1.28-1.53; n = 3135 incident AD) and was, surprisingly, a strong predictor of FTD (HR = 1.64, 95% CI = 1.22-2.20; n = 252 incident FTD). The associations were robust to sensitivity analyses and were attenuated but remained significant accounting for clinical (e.g. diabetes) and behavioral (e.g. physical activity) risk factors, depression, social isolation, and genetic risk. The association between loneliness and all-cause and AD risk was moderated by APOE ϵ4 risk status such that the increased risk was apparent in both groups but stronger among non-carriers than carriers of the risk allele. Loneliness is associated with increased risk of multiple types of dementia.