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Incidence and Associated Factors for Phenoconversion of Parkinson’s Disease in the Chinese Community Older Adults with LRRK2 G2385R and R1628P Variants

J. Liu, T. Mi, Z. Gu, Y. Li, M. Cao, Z. Ren, H. Zhang, M. Chen, J. Chen, L. Ma, X. Xu, C. Han, L. Zhang, J. An, P. Chan (Beijing, China)

Meeting: 2025 International Congress

Keywords: Leucine-rich repeat kinase 2(LRRK2), Parkinson’s

Category: Parkinson's Disease: Epidemiology, Phenomenology, Clinical Assessment, Rating Scales

Objective: To investigate the 10-year accumulated incidence and associated factors for phenoconversion of Parkinson’s disease (PD) in community older adults carrying LRRK2 G2385R or/and R1628P variants.

Background: Previous studies have suggested that LRRK2 G2385R or R1628P variants can increase the risk for PD, yet large-scale prospective data regarding to incidence and associated factors for phenoconversion from community-population remain limited.

Method: With the Beijing Longitudinal Study on Aging II (BLSAII) [ref1], participants screening positive for G2385R and R1628P variants but without PD were followed up for ten years. Evaluations including clinical examinations and questionnaires on lifestyle factors (e.g., tea/coffee intake) and non-motor symptoms (e.g., olfactory loss, constipation, REM sleep behavior disorder) were assessed in 2010, 2014, and 2019. respectively. PD diagnoses were confirmed by movement disorder specialists according MDS diagnostic criteria.

Results: Of 9,935 enrolled participants who had genetic testing and were consented, total 6.89% carried G2385R or R1628P. Over a decade follow-up, 3.49% (11/315) of carriers have converted to PD. The converters were found to have significantly higher frequencies of non-motor symptoms including hyposmia (OR=4.20, 95%CI: 1.08~16.35) and constipation (OR=10.61, 95%CI: 2.16~52.40), and reported lower tea/coffee consumption (OR=0.12, 95%CI: 0.02~0.97) as compared to none-converters.

Conclusion: Despite recognized links between LRRK2 and PD, the G2385R and R1628P variants showed only modest effect on PD phenoconversion. non-motor symptoms were associated with increased risk, while tea/coffee intake appeared to be protective. These findings suggest that lifestyle may modify the clinical expression of LRRK2-related PD in aging populations.

References: 1. Zheng Zheng, Shaochen Guan, Hui Ding, Zhihui Wang, Jin Zhang, Jing Zhao, Jinghong Ma, Piu Chan; Prevalence and Incidence of Frailty in Community-Dwelling Older People: Beijing Longitudinal Study of Aging II Journal of the American Geriatrics Society 2016 06;64(6):1281-6 doi:10.1111/jgs.1413

To cite this abstract in AMA style:

J. Liu, T. Mi, Z. Gu, Y. Li, M. Cao, Z. Ren, H. Zhang, M. Chen, J. Chen, L. Ma, X. Xu, C. Han, L. Zhang, J. An, P. Chan. Incidence and Associated Factors for Phenoconversion of Parkinson’s Disease in the Chinese Community Older Adults with LRRK2 G2385R and R1628P Variants [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/incidence-and-associated-factors-for-phenoconversion-of-parkinsons-disease-in-the-chinese-community-older-adults-with-lrrk2-g2385r-and-r1628p-variants/. Accessed October 5, 2025.
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MDS Abstracts - https://www.mdsabstracts.org/abstract/incidence-and-associated-factors-for-phenoconversion-of-parkinsons-disease-in-the-chinese-community-older-adults-with-lrrk2-g2385r-and-r1628p-variants/

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