Physical Frailty, Genetic Predisposition, and Incident Parkinson Disease

Abstract

ImportanceCross-sectional evidence implicates high prevalent frailty in patients with Parkinson disease (PD), whereas the longitudinal association remains unknown.ObjectivesTo examine the longitudinal association of the frailty phenotype with the development of PD and to explore the modification role of genetic risk of PD in such an association.Design, Setting, and ParticipantsThis prospective cohort study launched in 2006 to 2010 with a follow-up of 12 years. Data were analyzed from March 2022 to December 2022. The UK Biobank recruited over 500 000 middle-aged and older adults from 22 assessment centers across the United Kingdom. Participants who were younger than 40 years (n = 101), diagnosed with dementia or PD at baseline, and developed dementia, PD, or died within 2 years from baseline were excluded (n = 4050). Participants who had no genetic data or mismatch between genetic sex and reported gender (n = 15 350), were not of self-reported British White descent (n = 27 850), and had no data for frailty assessment (n = 100 450) or any covariates were also excluded (n = 39 706). The final analysis included 314 998 participants.ExposuresThe physical frailty was assessed by the Fried criteria’s frailty phenotype through 5 domains, ie, weight loss, exhaustion, low physical activity, slow walking speed, and low grip strength. The polygenic risk score (PRS) for PD comprised 44 single-nucleotide variants.Main Outcomes and MeasuresNew-onset PD was identified through the hospital admission electronic health records and death register.ResultsAmong 314 998 participants (mean age, 56.1 years; 49.1% male), 1916 new-onset PD cases were documented. Compared with nonfrailty, the hazard ratio (HR) of incident PD in prefrailty and frailty was 1.26 (95% CI, 1.15-1.39) and 1.87 (95% CI, 1.53-2.28), respectively, and the absolute rate difference per 100 000 person-years was 1.6 (95% CI, 1.0-2.3) for prefrailty and 5.1 (95% CI, 2.9-7.3) for frailty. Exhaustion (HR, 1.41; 95% CI, 1.22-1.62), slow gait speed (HR, 1.32; 95% CI, 1.13-1.54), low grip strength (HR, 1.27; 95% CI, 1.13-1.43), and low physical activity (HR, 1.12; 95% CI, 1.00-1.25) were associated with incident PD. A significant interaction between frailty and PRS on PD was found and the highest hazard was observed in participants with frailty and high genetic risk.Conclusions and RelevancePhysical prefrailty and frailty were associated with incident PD independent of sociodemographic factors, lifestyles, multiple morbidities, and genetic background. These findings may have implications for the assessment and management of frailty for PD prevention.

Association of handgrip strength and walking pace with incident Parkinson's disease

“…The results of this study 12 may mainly apply to those with young‐onset PD, as the mean age at diagnosis is relatively young. Consistently, another study reported that slow gait speed and low grip strength, which were dichotomized by the cut‐off points of frailty, correlated with PD 13 . Our current study extended further to the general adult population and found a dose–response linear relationship of handgrip strength and walking pace with the risk of incident PD in adult women and men.…”

“…Consistently, another study reported that slow gait speed and low grip strength, which were dichotomized by the cut-off points of frailty, correlated with PD. 13 Our current study extended further to the general adult population and found a doseresponse linear relationship of handgrip strength and walking pace with the risk of incident PD in adult women and men. More importantly, our study showed that handgrip strength and walking pace had an additive effect on incident PD.…”

“…However, evidences regarding the relationship of grip strength and walking pace with the risk of new‐onset PD were scarce. To date, one cohort has reported an association between low muscle strength around age 18 and the incidence of PD later in life, 12 while another study has found that components of frailty, including slow gait speed and low grip strength, were associated with PD 13 . Of note, the findings of the former study 12 may be mainly applicable to participants with young‐onset PD and cannot be extrapolated to the general population due to the relatively young mean age at diagnosis, while the latter study 13 only assessed the effects of dichotomous grip strength and walking pace, without considering the continuous association of grip strength and walking pace with PD incidence, which may provide more granular information.…”

Osteoporosis in Parkinson’s disease and the role of lean body mass: a cross-sectional study in a Brazilian tertiary center

“…According to Tables 1 and 3 , patients with PD and osteoporosis exhibit lower BMI, reduced handgrip strength, decreased appendicular muscle mass (resulting in smaller calf circumference), and slower gait speed. These factors together point to indicators of frailty which is very prevalent in PD patients ( 24 ).…”

Loneliness and Risk of Parkinson Disease

“…All analyses included age and sex as covariates. The additional covariates were relevant to loneliness and PD, could be considered confounding factors or mediators, and have been used in relevant previous studies . Education was coded as a college or university degree or equivalent.…”