Elevated Plasma Orexin-A Levels in Prodromal Dementia with Lewy Bodies

Article type: Research Article

Authors: Gan, Jinghuan^{a; b} | Liu, Shuai^c | Chen, Zhichao^{a; b} | Yang, Yaqi^d | Ma, Lingyun^{a; b} | Meng, Qingbo^d | Wang, Xiao-Dan^c | Liu, Chunyan^e | Li, Xudong^{a; b} | Zhang, Wei^{a; b} | Ji, Yong^{a; b; c; *}

Affiliations: [a] Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China | [b] National Clinical Research Center for Neurological Diseases, Beijing, China | [c] Department of Neurology, Tianjin Dementia Institute, Tianjin Key Laboratory of Cerebrovascular and Neurodegenerative Diseases, Tianjin Huanhu Hospital, Tianjin, China | [d] Tianjin Medical University, Tianjin, China | [e] Department of Neurology, Aviation General Hospital, Beijing, China

Correspondence: [*] Correspondence to: Yong Ji, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China; National Clinical Research Center for Neurological Diseases, 119 Nansihuan West Road, Fengtai District, Beijing, 100070, People’s Republic of China; Tianjin Key Laboratory of Cerebrovascular and of Neurodegenerative Diseases, Tianjin Dementia Institute, Department of Neurology, Tianjin Huanhu Hospital, 6 Jizhao Road, Jinnan District, Tianjin, 300350, People’s Republic of China. Tel.: +86 13612048681; Fax: +86 022 5906 5229; E-mail: [email protected].

Abstract: Background:Studies on plasma orexin-A levels in prodromal dementia with Lewy bodies (DLB) and the relationship with clinical manifestations are rare. Objective:To assess plasma orexin-A levels and evaluate the correlation with clinical features in patients with mild cognitive impairment with Lewy bodies (MCI-LB) and DLB. Methods:Plasma orexin-A levels were measured in 41 patients with MCI-LB, 53 with DLB, and 48 healthy controls (HCs). Informant-based history, neurological examinations, neuropsychological assessments, laboratory tests, and neuroimaging were collected and the correlation between orexin-A and various indicators evaluated. Results:Plasma orexin-A levels in patients with MCI-LB (1.18±0.33 ng/mL, p = 0.014) or DLB (1.20±0.44 ng/mL, p = 0.011) were significantly higher than in HCs (1.02±0.32 ng/mL) and associated with gender and age. DLB patients with fluctuating cognition (FC) (1.01±0.23 versus 1.31±0.50, p = 0.007) or parkinsonism (PARK) (0.98±0.19 versus 1.25±0.47, p = 0.030) had significantly lower plasma orexin-A levels than subjects without FC or PARK. Plasma orexin-A levels were significantly negatively correlated with irritability and UPDRS-III scores and significantly positively correlated with disinhibition scores. Conclusion:This is the first report in which elevated plasma orexin-A levels were observed in patients with MCI-LB or DLB. In addition, lower orexin-A levels were found in patients with DLB and FC or PARK compared with HCs. The plasma orexin-A levels were associated with the presence of core features and motor and neuropsychiatric symptoms in patients with MCI-LB and DLB.

Keywords: Dementia with lewy bodies, fluctuation, hypocretin, mild cognitive impairment with lewy bodies, orexin, parkinsonism

DOI: 10.3233/JAD-220082

Journal: Journal of Alzheimer's Disease, vol. 88, no. 3, pp. 1037-1048, 2022