Objective: This study aimed to use multimodal MRI to explore the relative importance of cognitive reserve (CR) proxies, compared to CR- and Parkinson’s disease (PD)-related brain measures, for cognition, motor function and mood differences in PD.

Background: CR is suggested to be the neural manifestation of neuroprotective lifetime experiences.[1] The relationship between neurodegeneration and PD task performance may be attenuated by CR,[2] although the interplay between brain characteristics and CR is unclear in PD. Studies evaluating the unique predictive value of CR in determining PD outcomes, beyond brain measures, are lacking.

Method: We recruited 45 people with PD who underwent two CR assessments (Cognitive Reserve Index questionnaire and verbal intelligence), a comprehensive neuropsychological test battery (working memory, visual processing speed, decision time, and reasoning ability), objective motor function assessments (bradykinesia, tremor, balance, response time, and gait), and mood evaluations (depression, anxiety, and stress). Each participant completed an MRI that included structural, diffusion, and functional sequences. Composite scores for CR- and PD-related brain measures, and behavioural assessments, were generated via principal component analyses (Tables 1 and 2). After regressing out age, sex, levodopa equivalent daily dose, and disease duration, multiple linear regression and ANOVAs were used to examine CR and brain measures as predictors of functional outcome differences.

Results: Models including CR-related brain measures found that only CR explained a significant portion of variance in both overall cognition and motor function (Table 3). CR was also the only significant predictor of overall cognition and motor function in models that used PD-related brain measures. However, neither CR nor brain measures were significant predictors of mood, and the overall models were non-significant for motor function. ANOVAs of specific outcome models demonstrated that only the removal of CR, but not brain measures, resulted in a significant loss of explained variance for certain tests (Table 4).

Conclusion: These findings suggest that CR is associated with cognition and motor function beyond brain measures in PD. This highlights CR’s potential prognostic utility in explaining PD outcome heterogeneity.

Table 2

Table 1

Table 3

Table 4

References: [1] Stern Y. (2009). Cognitive reserve. Neuropsychologia, 47(10), 2015–2028. https://doi.org/10.1016/j.neuropsychologia.2009.03.004
[2] Lucero, C., Campbell, M. C., Flores, H., Maiti, B., Perlmutter, J. S., & Foster, E. R. (2015). Cognitive reserve and β-amyloid pathology in Parkinson disease. Parkinsonism & related disorders, 21(8), 899–904. https://doi.org/10.1016/j.parkreldis.2015.05.020

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-associations-between-cognitive-reserve-proxies-multimodal-mri-brain-measures-and-cognition-motor-function-and-mood-in-parkinsons-disease/