Research Paper Advance Articles
Carriers of Parkinson’s disease-linked SNCA Rep1 variant have greater non-motor decline: a 4 year follow up study
- 1 Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
- 2 Department of Neurology, National Neuroscience Institute, Tan Tock Seng Hospital, Singapore
- 3 Center for Quantitative Medicine, Duke-NUS Medical School, National University of Singapore, Singapore
- 4 Department of Clinical Translational Research, Singapore General Hospital, Singapore
- 5 Department of Neurology, National Neuroscience Institute, Singapore General Hospital, Singapore
- 6 Neuroscience and Behavioural Disorders, Duke-NUS Medical School, Singapore
Received: April 17, 2024 Accepted: January 17, 2025 Published: February 3, 2025
https://doi.org/10.18632/aging.206196How to Cite
Copyright: © 2025 Santhanakrishnan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Alpha-synuclein gene promoter (SNCA Rep1) polymorphism has been linked to Parkinson's Disease (PD) susceptibility and motor symptom severity, but less is known about its longitudinal relationship with non-motor symptom severity. To address this gap, this is the first longitudinal study over 4 years investigating the relationship between Rep1 allele length and non-motor function amongst 208 early PD patients grouped into long (n = 111) vs. short (n = 97) Rep1 allele carriers. Long Rep1 carriers demonstrated faster decline in global cognition (p = 0.023) and increasing apathy (p = 0.027), with greater decline in attention and memory domains (p = 0.001), highlighting the utility of Rep1 polymorphism in stratifying patients at risk of non-motor symptom decline.