Frailty Status Predicts Incident Parkinson Disease in High-Risk Individuals

Prefrailty and frailty are both associated with a higher risk for subsequent Parkinson disease.

Prefrailty and frailty are found to be independent predictors for incident Parkinson disease (PD), according to the findings of a large prospective cohort study published in JAMA Neurology.

PD is believed to be caused by dopaminergic neuronal death accompanied by the accumulation of Lewy bodies. As these features are considered to be irreversible, prevention is of the upmost importance. However, few independent risk factors for PD have been identified.

In an effort to evaluate potential PD predictors, researchers from Huazhong University of Science and Technology in China sourced data from the United Kingdom Biobank, which is a large, prospective cohort study. In this analysis, physical predictors for PD were evaluated among 314,998 individuals. Frailty status was defined using these 5 factors: weight loss, exhaustion, low physical activity, slow gait speed, and low grip strength, in which frail individuals met 3 or more criteria and prefrail individuals 1 or 2 criteria.

The study population comprised 168,235 nonfrail, 135,885 prefrail, and 10,877 frail individuals. The cohorts comprised individuals mean age, 55.9-57.9 years; 50.6%-40.8% were men; mean body mass index (BMI) was 26.4-31.2 kg/m2; they had a median Townsend deprivation index of -2.3 to -1.0; and 0.6%-11.2% had 5 or more long-term comorbidities. In general, frailty was positively related with age, male gender, BMI, deprivation, and long-term comorbidities.

Integrating frailty assessment into the primary prevention of PD may favor the identification of high-risk individuals.

The rates of incident PD between 2006 and 2010 were 41.9 per 100,000 person-years (py) for the nonfrail cohort compared with 55.5 per 100,000 py for prefrail and 99.6 per 100,000 py for frail individuals. Compared with the nonfrail group, both prefrailty (adjusted hazard ratio [aHR], 1.26; 95% CI, 1.15-1.39) and frailty (aHR, 1.87; 95% CI, 1.53-2.28) were significant predictors for incident PD.

Stratified by the individual components of frailty, incident PD was related with exhaustion (aHR, 1.41; 95% CI, 1.22-1.62), slow gait speed (aHR, 1.32; 95% CI, 1.13-1.54), and low grip strength (aHR, 1.27; 95% CI, 1.13-1.43) in the fully adjusted model.

A significant interaction between frailty status and polygenic risk score (PRS) for PD was observed (P =.008). In which, compared with frail individuals, those with high PRS for PD who were prefrail (aHR, 0.64; 95% CI, 0.47-0.87) or nonfrail (aHR, 0.58; 95% CI, 0.42-0.79) were at decreased risk for incident PD. Similar trends were observed among individuals with intermediate and low PRS. The greatest relative decrease in PD risk was observed among individuals with intermediate PRS who were nonfrail (aHR, 0.45; 95% CI, 0.32-0.65).

Stratified by patient subgroups, the association between frailty and PD was more pronounced among individuals with more long-term comorbidities (P =.02).

The findings of this study may have been biased as the researchers were unable to account for exposure to 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine.

This study identified a significant association between PD and frailty with a significant genetics-by-frailty interaction, leading the researchers to conclude, “Integrating frailty assessment into the primary prevention of PD may favor the identification of high-risk individuals.”


Zheng Z, Lv Y, Rong S, Sun T, Chen L. Physical frailty, genetic predisposition, and incident Parkinson disease. JAMA Neurol. Published online March 13, 2023. doi:10.1001/jamaneurol.2023.0183