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

Abstract

Objectives: This study examined the association between loneliness and risk of incident all-cause dementia and whether the association extends to specific causes of dementia. Design: Longitudinal. Setting: Community. Participants: Participants were from the UK Biobank (N = 492,322). Intervention: None. Measurements: 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. Results: 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. Conclusion: Loneliness is associated with increased risk of multiple types of dementia.

Loneliness and Risk of Parkinson Disease

“…For example, a meta-analysis found that loneliness was associated with a 23% increased risk of dementia. Expanding on the meta-analysis, a UK Biobank study that used the same loneliness measure as the present study found that feeling lonely was associated with an increased risk of Alzheimer disease and vascular and frontotemporal dementia. The current and previous findings suggest that loneliness may be associated with increased risk of neurodegenerative diseases and that the detrimental effects of loneliness are not limited to a single etiologic or neuropathologic pathway.…”

“…Responses were coded as 0 for no and 1 for yes. Pre-vious research 7 has found that this item has a similar association with dementia risk as continuous multi-item scales.…”

“…All analyses included age and sex as covariates. The additional covariates were relevant to loneliness and PD, could be considered confounding factors or mediators, and have been used in relevant previous studies . Education was coded as a college or university degree or equivalent.…”

“…In part through emotional (eg, depression), behavioral (eg, physical inactivity), and biomedical (eg, diabetes) stressors, loneliness can harm brain health and is associated with increased risk of psychiatric and neurodegenerative diseases . Indeed, loneliness has been associated with neurological conditions, such as Alzheimer disease and related dementias . However, to our knowledge, there is no longitudinal evidence on whether individuals who report loneliness are at greater risk of developing Parkinson disease (PD).…”

Affective Neuroscience of Loneliness: Potential Mechanisms underlying the Association between Perceived Social Isolation, Health, and Well-Being

“…Loneliness impacts an estimated 25%–50% of the US population at a given time [ 3 , 5 ], and older adults may be particularly at risk—1 out of 3 individuals over age 45 report feeling lonely, rising to 1 out of 2 individuals over 45 with low income [ 6 ]. Critically, loneliness is recognized as a social determinant of health [ 7 – 10 ], associated with greater risk for cardiovascular disease [ 11 – 13 ], dementia and cognitive decline [ 14 – 23 ], the development and exacerbation of mood disorders including depression [ 2 , 24 – 29 ], and increases in mortality comparable with smoking [ 26 , 30 – 33 ]. Eliminating loneliness could prevent an estimated 11%–18% of cases in depression in individuals over 50 [ 2 ].…”