Impact of biological sex and motor reserve on recovery following motor telerehabilitation in Parkinson’s disease

Background and aims Biological sex differences in Parkinson’s Disease (PD) remain an underexplored topic, with early studies identifying distinct clinical phenotypes. Typically, treatment outcomes are assessed through the motor reserve paradigm rather than sex-related mechanisms. This study examined both factors in response to a structured telerehabilitation program. Methods Data of the present study were collected within the MNESYS project (A multiscale integrated approach to the study of the nervous system in health and disease . PROJECT ID: PE00000006. CUP: B43D22000650006 . Avviso: Decreto Direttoriale n. 341 del 15 marzo 2022 Proposte di intervento per la creazione di “Partenariati estesi alle università, ai centri di ricerca, alle aziende per il finanziamento di progetti di ricerca di base” nell’ambito del Piano Nazionale di Ripresa e Resilienza). Forty individuals with early PD (21 males) underwent a four-month intensive rehabilitation program, with baseline diffusionweighted MR imaging and motor assessments pre- and postintervention. Patients were classified as responders or non-responders based on the Minimal Clinically Important Difference of the 6-Minute Walk Test. A motor reserve index was calculated using a residuals-based approach incorporating nigrostriatal degeneration, Hoehn & Yahr score, age, and education. Results No sex differences were found in baseline demographics or clinical profiles. However, chi-squared analysis indicated that males responded more favorably to treatment (81 % vs. 42 % in females), with a 54 % higher probability of gait function improvement. Conclusions Motor reserve significantly influenced treatment response, even in individuals with low motor reserve, regardless of sex. These findings highlight the importance of considering sex-related mechanisms in rehabilitation outcomes for PD patients.