Amyloid status as a moderator of the association between physical activity and progression of Parkinson's disease

초록

Objectives: We investigated a modulation effect of amyloid copathology on the influence of regular physical activity on the progression of Parkinson disease (PD). Methods: The study included 245 PD patients from the Parkinson's Progression Markers Initiative (PPMI) who completed the Physical Activity Scale for the Elderly (PASE) at least three times over more than four years. Regular physical activity was quantified using both average and adjusted PASE scores, with the adjusted scores accounting for age at onset and baseline motor severity. The influence of regular physical activity levels and amyloid copathology on motor severity and biomarker levels were investigated using linear mixed effect (LME) models. Results: In the LME model for overall motor severity, amyloid positivity showed a significant modulation on the effect of physical activity. (interaction term between physical activity levels, disease duration, and amyloid positivity; average PASE, estimate 5.949 × 10−5, p = 0.037; adjusted PASE, estimate 5.065 × 10−3, p = 0.011) In amyloid-negative group, average PASE was associated with a slower increase of serum neurofilament light chain (estimate −2.030 × 10−4, p = 0.014)Physical activity levels were also associated with an attenuated increase of total tau in cerebrospinal fluid (average PASE, estimate −8.140 × 10−6, p = 0.001; adjusted PASE, estimate −3.875 × 10−4, p = 0.033). However, influence of physical activity was not observed in patients with amyloid burden. Conclusion: Our findings indicate that amyloid copathology may attenuate the protective effects of regular physical activity on the progression of motor severity and neurodegeneration in PD patients. © 2026 Elsevier Ltd

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