Research highlights

Abstract

 Cognitive decline in Parkinson’s disease (PD) is heterogeneous, and predictors of dementia conversion remain inconsistent. We applied Subtype and Stage Inference (SuStaIn) to baseline neuropsychological data from 474 drug-naïve patients with early-stage PD. SuStaIn identified three cognitive subtypes: verbal memory-dominant, visuospatial/visual memory-dominant, and frontal/executive-dominant patterns.

 During follow-up, the visuospatial-dominant subtype showed the highest risk of dementia conversion after 3.5 years. These findings suggest that early visuospatial dysfunction may serve as a clinically useful marker for identifying patients with PD at increased risk of future dementia.

Introduction

 Cognitive impairment is common in PD, but its clinical course varies widely across patients. Previous studies have reported inconsistent cognitive predictors of dementia conversion, partly because cognitive decline has often been evaluated using selected tests or cross-sectional approaches. A data-driven model that captures the temporal evolution of domain-specific cognitive impairment may help identify patients at high risk of dementia earlier.

Methods

We retrospectively analyzed 474 drug-naïve patients with early-stage PD who underwent comprehensive neuropsychological testing at diagnosis. Age- and education-adjusted z-scores from 13 cognitive subtests were entered into the SuStaIn model to identify cognitive subtypes and progression sequences. Dementia conversion during follow-up was evaluated, and subtype-specific risk was compared using time-dependent Cox regression analyses.

Results

SuStaIn identified three cognitive impairment subtypes: Subtype 1, characterized by early verbal memory impairment; Subtype 2, characterized by early visuospatial and visual memory dysfunction; and Subtype 3, characterized by early frontal/executive dysfunction. An additional 158 patients showed no baseline cognitive impairment. During follow-up, dementia conversion was most frequent in Subtype 2. After 3.5 years, Subtype 2 showed a significantly higher risk of dementia conversion than Subtype 1 and Subtype 3.

Conclusion

Data-driven cognitive subtyping revealed distinct trajectories of cognitive decline in early-stage PD. Early visuospatial dysfunction may indicate an increased risk of future dementia conversion and could help guide personalized monitoring strategies in clinical practice.