パーキンソン病の症状を抑える「脳の底力」～運動習慣と適切な薬物療法が「脳の底力(運動予備能)」を高める～

2026-01-05

2026-01-05 京都大学

パーキンソン病では脳内ドパミン神経の減少が起こるが、同程度の神経変性でも運動症状の重さには個人差がある。この差を生む要因として、脳がネットワーク機能で障害を補う力「運動予備能(Motor Reserve)」が注目されている。京都大学の月田和人特定講師らの研究グループは、国際多施設共同観察研究の大規模データを解析し、運動予備能の維持・向上には適切なドパミン補充療法と日常的な運動習慣が極めて重要であることを明らかにした。特に発症早期に高い運動予備能を保つことで、長期的に重度の運動障害へ進行するリスクが大幅に低下することが示された。本成果は、症状進行を抑える治療戦略の科学的根拠を提供し、患者の生活の質向上につながる重要な知見である。

運動習慣を保ち、適切なドパミン補充療法を行うことで、運動予備能を高めることは、パーキンソン病の症状進行抑制に寄与する。

<関連情報>

パーキンソン病における運動予備能の経時的変化およびその関連因子と予後に関する研究 Temporal Dynamics and Cross-Sectional and Longitudinal Factors Associated With Motor Reserve and Outcome in Patients With Parkinson Disease

Kazuto Tsukita, Akihiro Kikuya, Kenji Yoshimura, Etsuro Nakanishi, Riki Matsumoto, and Ryosuke Takahashi
Neurology Published:December 26, 2025
DOI:https://doi.org/10.1212/WNL.0000000000214475

Abstract

Background and Objectives

“Motor reserve” refers to the brain’s dynamic resilience against dopaminergic degeneration in Parkinson disease (PD). However, its clinical significance remains unclear because of critical limitations, including the lack of data on its longitudinal trajectories. Using Parkinson’s Progression Markers Initiative data with serial dopamine transporter (DAT) imaging from the drug-naive stage, we investigated its trajectories, determinants, and prognostic implications.

Methods

This retrospective observational cohort study assessed motor reserve using 2 complementary approaches. The residual-based approach calculated deviations in Movement Disorders Society–sponsored Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part 3 scores from expected values derived from a linear regression model incorporating putamen DAT specific binding ratio (putamen SBR), age, sex, and disease duration. The interaction-based approach extended this model by introducing interaction terms between putamen SBR and each factor, analyzing the corresponding β coefficients. We examined motor reserve’s cross-sectional associations with clinical parameters, its mediation effects, and its longitudinal trajectories—up to 4 years—based on DAT imaging data availability, while identifying factors influencing its changes. Finally, we assessed its impact on long-term prognosis using Cox proportional hazards and linear mixed-effects models (LMEMs).

Results

We included 566 drug-naive patients with PD (median age 62.3 [interquartile range 56.3–69.6] years; 33.7% female). At baseline, regular physical activity was significantly associated with motor reserve in both approaches, with mediation analysis indicating that motor reserve largely mediated the effect of physical activity on motor symptom improvement. Longitudinally, adequate medication and sustained regular physical activity levels were strongly associated with a slower early-years decline in motor reserve. It is important to note that early-years average motor reserve, not the baseline value, was a strong predictor of long-term motor outcomes (Cox: Hoehn/Yahr stage 3, hazard ratio = 0.50, 95% CI 0.37–0.66; LMEMs: MDS-UPDRS Part 3 score, fixed-effects standardized interaction coefficient = -0.57, 95% CI -0.79 to -0.35). These findings were further validated through propensity score matching.

Discussion

Maintaining motor reserve in the early years after diagnosis strongly predicts favorable long-term motor outcomes, with adequate treatment and regular physical activity—both modifiable factors—supporting this maintenance. Because our study includes early-stage, drug-naive PD, further research in later stages is warranted.