Associations Between Plasma Orexin-A Level and Constipation in Cognitive Impairment

Article type: Research Article

Authors: Yang, Mengli^{a; 1} | Gan, Jinghuan^{b; 1} | Liu, Shuai^c | Yang, Yaqi^c | Han, Jiuyan^d | Meng, Qingbo^e | Yang, Fan^e | Ji, Yong^{c; *}

Affiliations: [a] Department of Neurology, Henan Provincial People’s Hospital, Henan Provincial Key Medicine Laboratory of Nursing, Zhengzhou University People’s Hospital, Zhengzhou, China | [b] Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing, China | [c] Department of Neurology, Tianjin Dementia Institute, Tianjin Key Laboratory of Cerebrovascular and Neurodegenerative Diseases, Tianjin Huanhu Hospital, Tianjin, China | [d] Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China National Clinical Research Center for Neurological Diseases, Beijing, China | [e] Tianjin Medical University, Tianjin, China

Correspondence: [*] Correspondence to: Yong Ji, 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: jiyongusa@126.com.

Note: [1] These authors contributed equally to this work.

Abstract: Background:Constipation is a common symptom in dementia, and the cause is controversial. Rare clinical studies focused on plasma orexin-A levels and constipation in dementia. Objective:To evaluate the associations between orexin-A and constipation in patients with cognitive impairment. Methods:A total of 21 patients with mild cognitive impairment (MCI), 142 with Alzheimer’s disease (AD), and 57 with Lewy body dementia (LBD) were conducted. Besides informant-based history, neurological examinations or neuropsychological assessments, plasma levels of orexin-A, and constipation were assessed. The associations between orexin-A and constipation were evaluated by logistic regression models. Results:There were 47/220 (21.36%) cognitive impairment patients having constipation, and the proportion of constipation in LBD (61.40%) was significantly higher than AD (5.63%) and MCI (19.05%). No significant age or sex differences in the prevalence of constipation were found in the MCI, AD, and LBD groups. We found the cognitive impairment patients with constipation had lower levels of plasma orexin-A [1.00 (0.86, 1.28) versus 1.29 (1.01, 1.50) ng/ml, p < 0.001] than those without. And the plasma levels of orexin-A were significantly associated with the occurrence of constipation after adjusting for all variables in all patients with cognitive impairment (OR = 0.151, 95% CI: 0.042–0.537, p = 0.003). And the same finding was more prominent in the LBD group (p = 0.048). Conclusions:The decrease of plasma level of orexin-A is closely associated with the occurrence of constipation. Orexin-A has an intestinal protective effect and is involved in the gastrointestinal symptoms of patients with cognitive impairment.

Keywords: Alzheimer’s disease, brain-gut axis, constipation, intestinal epithelial barrier, Lewy body dementia, orexin-A

DOI: 10.3233/JAD-230625

Journal: Journal of Alzheimer's Disease, vol. 97, no. 1, pp. 409-419, 2024