Putative sympathetic-predominant subtype in body-first Parkinson’s disease is associated with accelerated cognitive decline

Background: Parkinson's disease (PD) can be classified into brain-first and body-first subtypes based on the initial site of α-synuclein pathology. Postmortem studies further suggest that body-first PD may be divided into two phenotypes: sympathetic-predominant subtype (SPS) and parasympathetic-predominant subtype (PPS). However, studies on longitudinal clinical characteristics of the two putative body-first subtypes are limited. Objectives: We aim to investigate the clinical features of these subtypes. Methods: In a cohort of 73 body-first PD patients, we identified 14 patients with orthostatic hypotension (OH) without constipation (putative SPS) and 40 with constipation without OH (putative PPS). Linear mixed models were used to assess disease progression. Results: = 0.045). Progression of other motor and non-motor features was comparable between the groups. Conclusion: These findings indicated that sympathetic-predominant body-first PD may be associated with a more rapid trajectory of cognitive decline, although the observed effect was modest and warrants cautious interpretation.