# Multimodal data-driven eye-movement subtypes and their cerebral glucose metabolic patterns in Parkinson’s disease

## TL;DR

This study identifies two distinct eye-movement subtypes in Parkinson’s disease and links them to differences in brain glucose metabolism.

## Contribution

The novel contribution is the integration of multi-task eye-movement data with FDG-PET to derive subtypes and metabolic profiles in Parkinson’s disease.

## Key findings

- Two PD subtypes were identified: oculomotor-efficient (PD-E) and oculomotor-inefficient (PD-I).
- PD-E showed higher FDG uptake in frontotemporal cortices compared to PD-I.
- Metabolic differences aligned with cognitive performance patterns between subtypes.

## Abstract

Previously reported Parkinson’s disease (PD) subtyping schemes often show limited stability and cross-cohort generalizability.

To derive data-driven oculomotor subtypes in PD using multi-task eye-movement assessment and to characterize their cerebral glucose metabolic patterns.

We administered a non-invasive multi-task eye-movement battery to 122 patients with PD and 69 healthy controls. Multidimensional oculomotor features were analyzed using unsupervised k-means clustering to identify PD subtypes. In a PD subset undergoing 18F-fluorodeoxyglucose positron emission tomography (FDG-PET; n = 30), regional cerebral glucose metabolism was quantified to compare metabolic profiles between subtypes.

Clustering identified two PD subtypes: an oculomotor-efficient subtype (PD-E) and an oculomotor-inefficient subtype (PD-I). The subtypes differed across multiple oculomotor parameters, with antisaccade (AS) metrics showing the most prominent divergence. Compared with PD-I, PD-E showed higher FDG uptake in frontotemporal cortices. Metabolic differences were directionally concordant with groupwise patterns in cognitive measures.

Integrating eye-movement digital phenotypes with FDG-PET metabolism may provide complementary information for cognitive-domain profiling and assessment in PD. Longitudinal studies and independent cohort validation are needed to confirm stability and clinical translatability.