Objective: To identify longitudinal trajectories of cognitive decline in Parkinson’s disease (PD) and to characterize neuroimaging and neurodegenerative blood biomarker correlates.

Background: Cognitive impairment affects up to 80% of patients with PD. The trajectories of decline are heterogeneous, which may reflect not only the extent and distribution of Lewy body pathology, but also co-morbid Alzheimer’s disease. Latent class approaches can identify meaningful trajectory subgroups and their biological correlates.

Method: The Ontario Neurodegenerative Disease Research Initiative PD cohort (n=140) was analysed across three timepoints. Raw neuropsychological tests scores were standardized to W-scores using healthy controls (Brain-Eye Amyloid Study;n=45). Latent class mixed models (LCMM) were fit; fixed effects included all cognitive domains regressed on time, a random intercept, and baseline MoCA as a classifier covariate. Between-class differences in baseline neurodegenerative blood biomarkers (Aβ40, Aβ42, GFAP, NfL, pTau181) were tested with linear models adjusted for age and sex. Longitudinal cortical (34 Desikan-Killiany regions) and subcortical (14 regions) volumes were compared via Bonferroni corrected linear mixed-effects models with class-by-time interactions, adjusted for age, sex, APOE-e4 dosage, intracranial volume, and site.

Results: A three-class solution had the lowest BIC and adequate entropy (0.80), featuring cognitively stable (n=87), slow-declining (n=43), and rapidly-declining (n=10) groups. Both declining groups showed accelerated bilateral lateral, inferior lateral, and third ventricular expansion (p<0.001). The slow-declining group demonstrated left amygdala, right thalamus, left parahippocampal, right isthmus cingulate atrophy (p<0.001). The rapidly-declining group did not show cortical changes. The rapidly-declined group had elevated baseline GFAP and NfL relative to stable (p=0.004;p<0.001) and slow-declining groups (p=0.015;p=0.005). No differences emerged for Aβ40, Aβ42, pTau181.

Conclusion: LCMM identified three cognitive trajectories in PD. Both declining groups demonstrated ventricular expansion. The slow-declining group exhibited some subcortical and cortical atrophy. The rapidly-declining group showed elevated baseline NfL and GFAP. Structural MRI and neurodegenerative blood biomarkers may help to identify patients with PD who are at risk for cognitive decline.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/latent-classes-of-cognitive-decline-in-parkinsons-disease-neuroimaging-and-neurodegenerative-blood-biomarker-correlates/