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Loneliness was linked with incident Parkinson's disease independently of genes, depression, and other major risk factors, a prospective study of nearly half a million people showed.

After accounting for a host of variables -- demographic factors, socioeconomic status, social isolation, genetic risk, smoking, physical activity, body mass index, diabetes, hypertension, stroke, myocardial infarction, depression, and seeing a psychiatrist -- the risk of a subsequent Parkinson's diagnosis was higher in people who said they often felt lonely (HR 1.25, 95% CI 1.12-1.39), reported Antonio Terracciano, PhD, of Florida State University in Tallahassee, and co-authors in .

"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," Terracciano and colleagues wrote.

Loneliness has been linked with cardiovascular disease, stroke, and . Earlier research showed that loneliness raised the 10-year risk of developing dementia. In older adults without dementia, loneliness was associated with poorer executive function, lower total cerebral volume, and greater white matter injury.

Earlier this year, U.S. Surgeon General Vivek Murthy, MD, MBA, about the epidemic of loneliness and isolation, calling for a national strategy to advance social connection.

In their study, Terracciano and colleagues followed 491,603 participants in the cohort from 2006 to 2021. At baseline, participants had a mean age of 56.5. About half (54%) were female, and mean follow-up was 12.3 years.

Loneliness was self-reported and measured by the answer to the question, "Do you often feel lonely?" Social isolation was assessed objectively as the sum of household size, frequency of friend or family visits, and frequency of leisure or social activities. Incident Parkinson's disease was determined through U.K. National Health Service health records.

A total of 2,822 people developed Parkinson's disease during the 15-year follow-up period. In a model adjusted only for sex and age, the risk of Parkinson's in people who reported feeling lonely was 1.37 (95% CI 1.25-1.51). While the subjective feeling of loneliness was associated with Parkinson's risk, the objective measure of social isolation was not (HR 1.05, 95% CI 0.99-1.11).

The relationship between loneliness and incident Parkinson's disease was similar in men and women, and across age and genetic risk scores. Sensitivity analysis excluding participants under age 50 confirmed the relationship. Loneliness was not associated with incident Parkinson's during the first 5 years after baseline, but it was in the subsequent 10 years.

The findings add to the evidence that loneliness is a substantial psychosocial determinant of health, Terracciano and co-authors observed.

The link between loneliness and Parkinson's is likely "through metabolic, inflammatory, and neuroendocrine pathways, as the association was attenuated by 13.1% after accounting for chronic conditions, such as diabetes," they noted. "Not surprisingly, the association of loneliness with Parkinson's disease was attenuated the most (by 24.1%) with the inclusion of mental health variables in the model."

Longitudinal evidence has suggested bidirectional relationships between loneliness and depression, the researchers pointed out. "Still, our findings indicated that loneliness remained associated with Parkinson's disease after accounting for mental health variables," they wrote.

The study was observational and could not determine causality, or whether reverse causality played a role, Terracciano and colleagues acknowledged. Loneliness was assessed by a single yes or no item.

While the study population was relatively young, excluding younger participants had no effect on the estimated effect size, the researchers noted. The U.K. Biobank sample may not be representative of other people, including those in low- and middle-income countries, they added.

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