Association of Structural Measurements of Brain Reserve With Motor Progression in Patients With Parkinson Disease

Neurology. 2022 Sep 5;99(10):e977-e988. doi: 10.1212/WNL.0000000000200814.


Background and objectives: To investigate the relationship between baseline structural measurements of brain reserve and clinical progression in Parkinson disease (PD). To further provide a possible underlying mechanism for structural measurements of brain reserve in PD, we combined functional and transcriptional data and investigated their relationship with progression-associated patterns derived from structural measurements and longitudinal clinical scores.

Methods: This longitudinal study collected data from June 2010 to March 2019 from 2 datasets. The Parkinson's Progression Markers Initiative (PPMI) included controls and patients with newly diagnosed PD from 24 participating sites worldwide. Results were confirmed using data from the Huashan dataset (Shanghai, China), which included controls and patients with PD. Clinical symptoms were assessed with Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) scores and Schwab & England activities of daily living (ADL). Both datasets were followed up to 5 years. Linear mixed-effects (LME) models were performed to examine whether changes in clinical scores over time differed as a function of brain structural measurements at baseline.

Results: A total of 389 patients with PD (n = 346, age 61.3 ± 10.03, 35% female, PPMI dataset; n = 43, age 59.4 ± 7.3, 38.7% female, Huashan dataset) with T1-MRI and follow-up clinical assessments were included in this study. Results of LME models revealed significant interactions between baseline structural measurements of subcortical regions and time on longitudinal deterioration of clinical scores (MDS-UPDRS Part II, absolute β > 0.27; total MDS-UPDRS scores, absolute β > 1.05; postural instability-gait difficulty (PIGD) score, absolute β > 0.03; Schwab & England ADL, absolute β > 0.59; all p < 0.05, false discovery rate corrected). The interaction of baseline structural measurements of subcortical regions and time on longitudinal deterioration of the PIGD score was replicated using data from Huashan Hospital. Furthermore, the β-coefficients of these interactions recapitulated the spatial distribution of dopaminergic, metabolic, and structural changes between patients with PD and normal controls and the spatial distribution of expression of the α-synuclein gene (SNCA).

Discussion: Patients with PD with greater brain resources (that is, higher deformation-based morphometry values) had greater compensatory capacity, which was associated with slower rates of clinical progression. This knowledge could be used to stratify and monitor patients for clinical trials.

MeSH terms

  • Activities of Daily Living
  • Aged
  • China
  • Cognitive Reserve*
  • Disease Progression
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Parkinson Disease* / diagnosis
  • alpha-Synuclein


  • alpha-Synuclein