Abstract
BACKGROUND: Age-related musculoskeletal diseases (ARMDs), including sarcopenia, osteoporosis, and osteoarthritis, may contribute to declines in intrinsic capacity and co-occur with neurodegenerative disorders such as Parkinson’s disease (PD). We examined the association between ARMDs and PD risk.
METHODS: In 362,656 UK Biobank participants (mean age 56.48 years; median follow-up 13.65 years), ARMDs were assessed individually and cumulatively. Cox models estimated PD risk, adjusting for demographic, lifestyle, and genetic factors. Subgroup and sensitivity analyses were conducted to ensure robustness. A nested case-control analysis further explored the relationship between the duration of ARMDs exposure and the odds of PD diagnosis. Multivariable regression models assessed the associations between ARMDs and brain structure, including cortical, gray matter, and white matter integrity.
RESULTS: During follow-up, 2,057 participants developed PD. Sarcopenia (hazard ratio [HR]: 1.74, 95% confidence interval [CI]: 1.45-2.08, P < 0.001) and osteoporosis (HR: 1.76, 95% CI: 1.34-2.32, P < 0.001) were independently associated with higher PD risk. PD risk increased with the number of ARMDs (HR 1.30, 95% CI 1.19-1.41; Ptrend<0.001) and the odds of PD diagnosis was highest within 5 years of the ARMDs diagnosis (odds ratio [OR] 2.19, 95% CI: 1.59-2.96, P < 0.001). Neuroimaging analysis indicated that ARMDs were associated with widespread and significant brain structural alterations, including in regions related to motor control.
CONCLUSIONS: ARMDs are linked to elevated PD risk and brain structural changes. Interventions targeting musculoskeletal health may help preserve intrinsic capacity and delay or prevent PD onset in aging populations.