Parkinson's Risk Factor Spotted in 12-Year Study

Adults ages 40 to 69 with physical frailty or prefrailty were more likely to have subsequent Parkinson's disease, prospective data from the U.K. Biobank cohort showed.

Over 12 years, frailty was tied to an 87% increased risk of Parkinson's compared with nonfrailty (HR 1.87, 95% CI 1.53-2.28), reported Liangkai Chen, PhD, of Huazhong University of Science and Technology in Wuhan, China, and colleagues in JAMA Neurology. Prefrailty was linked with a 26% increased risk (HR 1.26, 95% CI 1.15-1.39).

Parkinson's genetic risk scores modified the association between frailty and new-onset Parkinson's disease.

"These findings indicate that physical frailty is a potential risk factor for Parkinson's disease and the assessment and management of frailty might have clinical significance in the at-risk population," Chen and colleagues wrote.

Cross-sectional data have shown links between Parkinson's and frailty, but "little longitudinal evidence has been reported on physical frailty and incident Parkinson's disease," the researchers noted. Few risk factors for Parkinson's have been recognized so far, they added.

Frailty has been implicated in other neurodegenerative disorders. In a post-mortem study, frailty appeared to modify the association between Alzheimer's pathology and Alzheimer's dementia in older adults.

Chen and colleagues used criteria for five domains of the Fried frailty phenotype -- weight loss, exhaustion, low physical activity, slow gait speed, and low grip strength -- to assess frailty in their study. All except grip strength were self-reported. Participants who met three or more criteria were defined as having frailty, and those who met one or two criteria were classified as having prefrailty.

The cohort was recruited from 2006 to 2010. Participants younger than 40, who were diagnosed with dementia or Parkinson's at baseline, or who developed dementia or Parkinson's or died 2 years from baseline, were excluded from the study.

New-onset Parkinson's was identified by hospital admission records and death registers. All participants had a polygenic risk score composed of 44 single-nucleotide variants associated with Parkinson's incidence in white populations. Findings were adjusted for age, sex, smoking status, alcohol consumption, BMI, long-term morbidities, and other variables.

Among 314,998 people in the U.K. Biobank cohort, 3.5% met the criteria for frailty, 43.1% for prefrailty, and 53.4% for nonfrailty. Mean age was 56 and 49.1% were men. During a mean follow-up of 12.3 years, 1,916 new-onset Parkinson's cases were documented.

Compared with nonfrailty, the absolute rate difference for incident Parkinson's disease per 100,000 person-years was 5.1 (95% CI 2.9-7.3) for frailty and 1.6 (95% CI 1.0-2.3) for prefrailty. Four domains were associated with incident Parkinson's: exhaustion (HR 1.41), slow walking speed (HR 1.32), low grip strength (HR 1.27), and low physical activity (HR 1.12).

The highest hazard for incident Parkinson's emerged in people with frailty and highest genetic risk (HR 3.22, 95% CI 2.35-4.41, compared with nonfrailty and lowest genetic risk).

"Our findings support that frailty might be a valuable tool in Parkinson's disease screening," Chen's group wrote. "In addition, when patients present with prefrailty or frailty, strategies to change patients' lifestyles should be tailored to prevent or delay the development of Parkinson's disease."

The study had several limitations, Chen and colleagues acknowledged. Because the genetic instrument used in the study was constructed with a white population, only participants of white British descent were included in the analysis.

Some Parkinson's risk factors like neurotoxin exposure could not be accounted for, they added. With the exception of grip strength, frailty components and some covariates were self-reported, and reporting bias may exist.

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