Early Caudate Involvement Marks a Lewy Body Spectrum Phenotype in Parkinsonism: A 5-Year Longitudinal Study

Abstract

Background: Parkinsonian syndromes are increasingly recognized as part of a heterogeneous spectrum of Lewy body diseases, ranging from Parkinson's disease (PD) to dementia with Lewy bodies (DLB). Identifying early markers of clinical heterogeneity remains challenging. Objective: To investigate whether striatal dopaminergic denervation patterns on DAT-SPECT are associated with distinct clinical phenotypes and long-term cognitive trajectories in early parkinsonism. Methods: Twenty-eight patients with early parkinsonism fulfilling clinical diagnostic criteria for PD underwent DAT-SPECT and were classified according to the topography of dopaminergic denervation into isolated putaminal involvement (P group) or combined putaminal and caudate involvement (PC group). Motor, neuropsychiatric, and cognitive assessments, including the MoCA, were performed at baseline and after five years. Results: At baseline, patients with caudate involvement (n=16) showed greater motor impairment and a higher prevalence of psychiatric symptoms than the P group. Early cognitive impairment was observed in 32% of the PC group versus 0% of the P group. Over five years, the PC group showed greater cognitive deterioration, with 83% scoring below the cognitive impairment threshold compared with 9% in the P group. Visual hallucinations developed in a subset of PC patients during follow-up. Conclusions: Early caudate dopaminergic denervation identifies a parkinsonian phenotype associated with greater motor severity, neuropsychiatric manifestations, and accelerated cognitive decline. Its longitudinal evolution may reflect a trajectory toward the cognitive and neuropsychiatric end of the Lewy body disease spectrum, including a DLB-like phenotype. DAT-SPECT may provide prognostic information beyond its diagnostic utility.