Is loneliness a risk factor for Parkinson’s disease?

A large population-based prospective cohort study finds that loneliness is associated with increased risk of incident Parkinson’s disease (PD) across demographic groups, independently of depression and other prominent risk factors, including genetic risk.

“Loneliness can harm brain health through emotional [eg, depression], behavioural [eg, physical inactivity], and biomedical [eg, diabetes] stressors and is associated with increased risk of psychiatric and neurodegenerative diseases,” wrote the researchers. “However, to our knowledge, there is no longitudinal evidence on whether individuals who report loneliness are at greater risk of developing PD.” [Social Isolation and Loneliness Among Older People: Advocacy Brief. WHO; 2021; Psychol Med 2023;53:227-235]

The present study included 491,603 individuals (mean age, 56.54 years; female, 54.4 percent) from a population-based UK Biobank cohort and examined the prospective association between loneliness and incident PD over a 15-year follow-up period. The researchers also investigated whether the association between loneliness and PD was moderated by age, sex, or genetic risk and whether the association was accounted for by other risk factors, such as indicators of behavioural, mental, physical, and social health or sociodemographic factors. [JAMA Neurol 2023;doi:10.1001/jamaneurol.2023.3382]

Over the course of the study, 2,822 participants developed PD (incidence rate, 47 per 100,000 person-years), of whom 549 reported loneliness (incidence rate, 49 per 100,000 person-years) and 2,273 did not report loneliness (incidence rate, 46 per 100,000 person-years). Compared with individuals who were not diagnosed with PD by the censoring date, those who received PD diagnosis were older, more likely to be male, former smokers, have a higher BMI, higher PD polygenetic risk score, received a diagnosis of diabetes, hypertension, myocardial infarction (MI) or stroke, and have seen a psychiatrist for anxiety or depression. Participants with PD diagnosis were less likely to have a college degree or to be current smokers.

The study’s primary analysis indicated that individuals who reported being lonely had a higher risk of PD (hazard ratio [HR], 1.37; 95 percent confidence interval [CI], 1.25–1.51) – an association that remained across all covariate models. Comparisons of model 1, which only examined effects of age and sex on the association between loneliness and risk of incident PD, with model 2 (additional covariates: education and deprivation index), model 3 (social isolation), model 4 (PD polygenic risk score), and model 5 (smoking and physical activity) indicated that most covariates did not substantially attenuate the association between loneliness and PD risk. “Notably, in model 3, social isolation was not associated with PD risk [HR, 1.05; 95 percent CI, 0.99–1.11],” remarked the researchers.

The association between loneliness and PD was attenuated by 13.1 percent by health variables (model 6: BMI, diabetes, hypertension, MI, and stroke; HR, 1.32; 95 percent CI, 1.20–1.46), by 24.1 percent by mental health variables (model 7: depression, ever seen a psychiatrist; HR, 1.28; 95 percent CI, 1.16–1.42), and by 33.8 percent in the fully adjusted model (model 8; HR, 1.25; 95 percent CI, 1.12–1.39). Still, in the fully adjusted model, the association between loneliness and PD remained.

“Our study found that individuals who felt lonely had greater risk of PD regardless of genetic and established behavioural, social, and clinical risk factors. This study adds evidence on the detrimental health impact of loneliness and supports recent calls for the protective and healing effects of personally meaningful social connection,” concluded the researchers. [Murthy VH, et al, Our epidemic of loneliness and isolation: The U.S. Surgeon General’s advisory on the healing effects of social connection and community. Office of the US Surgeon General; 2023]