Cognitive function in different motor subtypes of Parkinson's disease: A systematic review protocol.

Background and Aims: As the fastest-growing neurological disorder globally, a better understanding of Parkinson's disease (PD) is needed to improve patient outcomes and reduce the increasing economic and healthcare burden associated with the disease. Whilst classified as a movement disorder, this disease is highly heterogeneous, encompassing a broad range of both motor and non-motor symptoms (NMS). Cognitive impairment, presenting as either mild cognitive impairment or PD-dementia, is one of the most prevalent and disabling NMS. To better understand heterogeneity in PD, researchers have sought to identify subtypes of individuals who share similar symptom profiles. To date, this research has predominantly focused on motor subtyping, with many studies comparing these motor subtypes on non-motor outcomes, such as cognitive impairment. However, despite evidence of a motor-cognitive relationship in healthy aging, findings regarding the presence of a motor-cognitive relationship in PD are inconsistent. In our proposed systematic review, we will investigate motor subtyping studies that have evaluated the relationship between motor and cognitive function in PD. We aim to examine what is currently known about the relationship between motor and cognitive impairment in PD and evaluate the state of the field with respect to the subtyping methods and quality of cognitive assessment tools used. Methods: Systematic literature searches will be conducted in PubMed, PsycINFO, CINAHL, Scopus, and Web of Science. Results: Results will be synthesized using meta-analysis and, where meta-analysis is not feasible, narrative synthesis. Conclusion: Despite the preponderance of motor subtyping research in PD, our study will be the first to systematically review evidence regarding the association between motor subtypes and cognitive impairment. Understanding the nature of the motor-cognitive relationship in PD may lead to important insights regarding shared underlying disease pathology, which would have significant implications for early diagnosis, prognosis, and treatment of cognitive impairment in PD.

Influence of cognitive reserve on cognitive and motor function in α-synucleinopathies: A systematic review and multilevel meta-analysis.

Cognitive reserve has shown promise as a justification for neuropathologically unexplainable clinical outcomes in Alzheimer's disease. Recent evidence suggests this effect may be replicated in conditions like Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. However, the relationships between cognitive reserve and different cognitive abilities, as well as motor outcomes, are still poorly understood in these conditions. Additionally, it is unclear whether the reported effects are confounded by medication. This review analysed studies investigating the relationship between cognitive reserve and clinical outcomes in these α-synucleinopathy cohorts, identified from MEDLINE, Scopus, psycINFO, CINAHL, and Web of Science. 85 records, containing 176 cognition and 31 motor function effect sizes, were pooled using multilevel meta-analysis. There was a significant, positive association between higher cognitive reserve and both better cognition and motor function. Cognition effect sizes differed by disease subtype, cognitive reserve measure, and outcome type; however, no moderators significantly impacted motor function. Review findings highlight the clinical implications of cognitive reserve and importance of engaging in reserve-building behaviours.

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.