Influence of cognitive reserve on cognitive and motor function in α-synucleinopathies: A systematic review protocol

Cognitive reserve has been used to justify neuropathologically unexplainable mismatches in Alzheimer's disease outcomes. Recent evidence has suggested this effect may be replicable across other conditions. However, it is still unclear whether cognitive reserve applies to α-synucleinopathies or to motor outcomes, or if medication confounds effects. This review protocol follows PRISMA-P guidelines and aims to investigate whether cognitive reserve can predict both cognitive and motor outcomes for α-synucleinopathy patients. MEDLINE (via PubMed), Scopus, psycINFO (via Ovid), CINAHL (via EBSCO), and Web of Science have been searched. Cross-sectional, cohort, case-control, and longitudinal studies investigating the association between cognitive reserve and cognitive and/or motor outcomes for Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy will be included. Reviewers will independently perform screening, while also extracting data, assessing the risk of bias (using a version of the Quality in Prognostic Studies tool), and rating evidence quality (using GRADE). If possible, random-effects meta-analyses will be conducted for each unique outcome variable and α-synucleinopathy; otherwise, a narrative synthesis will be performed. Depending on the number of studies, exploratory analyses may involve meta-regression to assess potential confounding effects. Understanding the broader protective effect of cognitive reserve has significant implications for preventive interventions in the wider population.