Loneliness Associated with Increased Risk of Developing Parkinson's disease

A large cohort study published in JAMA Neurology suggests that loneliness is associated with an increased risk of developing Parkinson's disease (PD).

Loneliness, defined as a distressing subjective feeling that arises from the discrepancy between one’s desired and perceived social relationships, is characterized by heightened emotional vulnerability, hypervigilance, and perseverative cognition. In addition to its emotional toll, individuals who feel lonely tend to engage in unhealthy lifestyles and have worse clinical profiles. 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.

A fast-growing condition and the second most common neurodegenerative disease, PD is complex and includes heterogeneous presentations of motor and nonmotor symptoms. This study by Terraciano et al examined the prospective association between loneliness and incident PD over a 15-year follow-up period in a population-based UK Biobank cohort. The study further tested 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, including sociodemographic factors; indicators of behavioral (eg, physical activity), mental (eg, depression), physical (eg, diabetes), and social (eg, social isolation) health; or genetic risk.

In this population-based cohort study, it was found that participants who reported loneliness were at higher risk of developing PD during the 15-year follow-up. Loneliness was associated with a higher risk of subsequent PD after accounting for basic demographic variables and other potential risk, protective, prodromal, or confounding factors, including social isolation, socioeconomic status, genetic risk, smoking, physical activity, diabetes and hypertension, depression, and having seen a psychiatrist for anxiety or depression symptoms. While incidence of PD varies by age, sex, and genetic risk, the association between loneliness and PD was similar in males and females and across age and polygenic risk scores. The association was specific to the subjective experience of loneliness and was not observed for the objective measure of social isolation.

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. Indeed, we are not aware of evidence that links loneliness to proteins like α-synuclein or brain structures that play a major role in PD, such as basal ganglia and substantia nigra.

The most probable interpretation for this association is that loneliness is a risk factor for PD through various pathways. This study tested a broad range of covariates that could be potential mediators. Individuals who experience loneliness tend to engage in detrimental behaviors, such as physical inactivity, but this pathway seems unlikely to play a major role given that the association between loneliness and PD was unchanged with the inclusion of 2 prominent health behaviors. Loneliness seems more likely to be associated with increased risk of PD through metabolic, inflammatory, and neuroendocrine pathways, as the association was attenuated by 13.1% after accounting for chronic conditions, such as diabetes. Not surprisingly, the association of loneliness with PD was attenuated the most (by 24.1%) with the inclusion of mental health variables in the model. Longitudinal evidence suggests that there are bidirectional associations between loneliness and depression which are likely to co-occur and share pathways with increased risk of PD. Still, their findings indicated that loneliness remained associated with PD after accounting for mental health variables.

"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", conclude the authors.

Reference:

Terracciano A, Luchetti M, Karakose S, Stephan Y, Sutin AR. Loneliness and Risk of Parkinson Disease. JAMA Neurol. Published online October 02, 2023. doi:10.1001/jamaneurol.2023.3382