Serum Neurofilament Dynamics Predicts Cognitive Progression in de novo Parkinson’s Disease

Article type: Research Article

Authors: Ma, Ling-Zhi^a | Zhang, Can^b | Wang, Han^c | Ma, Ya-Hui^a | Shen, Xue-Ning^d | Wang, Jian^d | Tan, Lan^{a; *} | Dong, Qiang^{d; *} | Yu, Jin-Tai^{d; *}

Affiliations: [a] Department of Neurology, Qingdao Municipal Hospital, Qingdao University, China | [b] Genetics and Aging Research Unit, McCance Center for Brain Health, MassGeneral Institute for Neurodegenerative Diseases (MIND), Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA | [c] Department of Neurology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China | [d] Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China

Correspondence: [*] Correspondence to: Prof. Jin-Tai Yu, MD, PhD, and Prof. Qiang Dong, MD, PhD, Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, 12th Wulumuqi Zhong Road, Shanghai 200040, China. Tel.: +86 21 52888160; Fax: +86 21 62483421; E-mail: [email protected]. (JT Yu), E-mail: [email protected]. (Q Dong) and Prof. Lan Tan, MD, PhD, Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao 266071, China. E-mail: [email protected].

Abstract: Background:Neurofilament light (NfL) can reflect the extent of neuron/axon damage, thus providing an opportunity to examine the severity and progression of the diseases with such damage. Objective:Whether serum NfL can be used as an indicator to monitor the cognitive progress of de novo Parkinson’s disease (PD) remains unclear. Methods:In this research, 144 healthy controls and 301 de novo PD patients from Parkinson’s Progression Markers Initiative (PPMI) were recruited. Linear mixed effects models were used to examine the associations of baseline/longitudinal serum NfL with cognitive decline. Cox regression was used to detect cognitive progression in PD participants. Results:We found PD patients had higher serum NfL than controls at baseline (p = 0.031), and NfL increase was faster in PD group (p < 0.001). Both baseline serum NfL and its rate of change predicted measurable cognitive decline in early PD (MoCA, β= –0.014, p < 0.001; β= –0.002, p < 0.001, respectively). Additionally, we observed that NfL levels were also able to predict progression in different diagnostic groups and Amyloid- PD and Amyloid+PD groups. After an average follow-up of 6.37±1.84 years, the baseline NfL of the third tertile of high concentrations was associated with a future high risk of PD dementia (adjusted HR 6.33, 95% CI 2.62–15.29, p < 0.001). Conclusion:In conclusion, our results indicated that the serum NfL concentration could function as an easily accessible biomarker to monitor the severity and progression of cognitive decline in PD.

Keywords: Parkinson’s disease, neurofilament light, Parkinson’s progression markers initiative, cognition, tau

DOI: 10.3233/JPD-212535

Journal: Journal of Parkinson's Disease, vol. 11, no. 3, pp. 1117-1127, 2021