Objective: To identify neuropsychological markers at the PD-MCI stage associated with the progression severity to PDD using a multivariate, data-driven approach with longitudinal validation.

Background: Parkinson’s disease–mild cognitive impairment (PD-MCI) is a prodromal stage of dementia (PDD), yet progression rates vary widely. Identifying early neuropsychological markers is essential for clinical intervention. While the Seoul Neuropsychological Screening Battery–Second Edition (SNSB-II) is standard in Korea, the specific measures most sensitive to PDD progression remain unclear.

Method: We retrospectively analyzed 52 patients who progressed from PD-MCI to PDD at two medical centers between 2019 and 2025. All patients completed longitudinal SNSB-II, Korean Instrumental Activities of Daily Living (K-IADL), and Clinical Dementia Rating (CDR) assessment, and those with atypical parkinsonism, major cognitive-affecting comorbidities, or incomplete normative data were excluded. Partial least squares regression with variable importance in projection indices was used to identify and rank cognitive markers of progression, and linear mixed-effects models examined their longitudinal associations with clinical decline indexed by CDR- Sum of Boxes (SB).

Results: PLS regression identified a single latent component as the optimal predictor of PDD severity (follow-up CDR-SB). Poorer baseline cognitive performance significantly predicted more severe subsequent dementia, with key markers (VIP > 1) including verbal memory, executive function, and processing speed. Longitudinal analysis revealed that faster clinical progression was associated with steeper declines in processing speed and visuospatial function. Significant Time × progression interactions (all FDR < .05) were observed for K-CWST Color Reading (β = -0.52), RCFT Copy (β = −0.40), Digit Symbol Coding (β = −0.38), SVLT-E Delayed Recall (β = -0.35), SVLT-E Recognition (β = -0.30), and RCFT Immediate Recall (β = -0.27).

Conclusion: Baseline multivariate cognitive patterns in PD-MCI significantly predict subsequent PDD severity. While verbal memory and executive function are key initial markers, rapid clinical progression is specifically characterized by accelerated declines in processing speed and visuospatial function. These findings highlight the clinical utility of data-driven neuropsychological profiling for identifying high-risk patients.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/multivariate-cognitive-markers-of-dementia-progression-in-parkinsons-disease/