BRIEF RESEARCH REPORT article
Front. Aging Neurosci.
Sec. Parkinson’s Disease and Aging-related Movement Disorders
Putative Sympathetic-Predominant Subtype in Body-First Parkinson's Disease is Associated with Accelerated Cognitive Decline
Provisionally accepted
Xining Liu
Zhiheng Xu
Xiuyuan LiChenqin Xu
Shiyu Li
Tianyu Hu
Chen Chen
Xiaoniu Liang*
Yilin Tang*
Jian Wang*- National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China
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Abstract 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: Over follow-up, SPS patients exhibited a significantly faster decline in MMSE scores compared with PPS patients (p = 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.
Keywords: body-first subtype, cognitive decline, disease progression, Parkinson's disease, Sympathetic Nervous System
Received: 17 Nov 2025; Accepted: 28 Jan 2026.
Copyright: © 2026 Liu, Xu, Li, Xu, Li, Hu, Chen, Liang, Tang and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Xiaoniu Liang
Yilin Tang
Jian Wang
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