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Objective: Given the clinical heterogeneity of Parkinson’s disease (PD), identification of early -stage subgroups with shared non-motor symptom (NMS) profiles may clarify its pathophysiology. This study used latent-profile analyses (LPA) to define subgroups based on sleep disturbances, cognitive performance and neuropsychiatric symptoms, and examined dopaminergic function and brain volume differences between them.

Methods: We analyzed data from 51 cognitively normal non-PD older adults and 105 early-stage PD participants from the iPARK trial, including 19 who underwent [11C]-raclopride PET/MR. Participants completed the Hospital Anxiety and Depression Scale, the short version of the Karolinska Sleep Questionnaire and a battery of neuropsychological tests. LPA were used in PD to identify subgroups based on NMS profiles, which were then characterized and examined in relation to dopaminergic integrity and brain morphology.

Results: LPA identified a two-cluster solution as the best fit. Group 1 (N = 49) showed poorer working memory, executive function and processing speed along with greater daytime sleepiness, depression and anxiety. Group 2 (N = 56) exhibited less affected cognitive function and minimal NMS. Groups were similar in demographics, disease duration, motor symptom severity and medication, but differed on UPDRS-1 NMS. Group 1 demonstrated significantly reduced [11C]-raclopride binding potential compared to Group 2 in the left putamen at both ROI- and voxel-wise analysis.

Conclusion: These findings indicate clinically distinct subgroups in early-stage PD. Greater NMS burden is linked to impaired dopaminergic integrity, suggesting a potential neurobiological signature. Early identification of such subgroups may improve understanding of disease heterogeneity and support personalized management and interventions. Clinical trial registration: https://clinicaltrials.gov/study/NCT03680170?id=NCT03680170&rank=1, identifier (NCT03680170).