Plasma Ceramides and Neuropsychiatric Symptoms of Alzheimer’s Disease

Article type: Research Article

Authors: Xing, Yi^{a; 1} | Tang, Yi^{b; 1} | Zhao, Lina^a | Wang, Qi^a | Qin, Wei^a | Zhang, Jin-Lan^{c; *} | Jia, Jianping^{b; *}

Affiliations: [a] Department of Neurology, Xuan Wu Hospital, Capital Medical University, Beijing, China | [b] Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing, China | [c] State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China

Correspondence: [*] Correspondence to: Jianping Jia, 95 Yongan Road, Xicheng District, Beijing 100050, P.R. China. Tel.: +86 010 63014411; E-mail: jiajp@vip.126.com.

Correspondence: [*] Correspondence to: Jin-Lan Zhang, 2 Nanwei Road, Beijing 100050, China. Tel.: +86 10 83154880; E-mail: zhjl@imm.ac.cn.

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

Abstract: Background: Various evidence demonstrates the influences of ceramides on Alzheimer’s disease (AD) pathogenesis. Furthermore, increased ceramides were also suggested to be related to cognitive decline. However, the association between ceramides and neuropsychiatric symptoms of AD remains unclear. Objective: This study sought to investigate the association between plasma ceramide levels and multiple neuropsychiatric symptoms in AD. Methods: A total of 98 patients and 92 cognitively normal controls participated in this study, including 56 with mild AD and 42 with moderate to severe AD. The Neuropsychiatric Inventory (NPI) was used to assess neuropsychiatric symptoms. Considering the influences of dementia severity on ceramide levels and neuropsychiatric symptoms, a subgroup analysis was conducted by dementia severity. Results: Except for C24 : 0, all ceramide species were significantly higher in AD patients than in controls. After controlling for confounding factors, the C16 : 0 and C20 : 0 levels were positively associated with delusions, and the quartiles of C22 : 0 and C24 : 0 were positively associated with depression. In the subgroup analysis, association between ceramide species and delusions were only observed in mild AD, and the association between ceramides and depression were prominent in moderate to severe AD. In mild AD, after controlling for age, gender, anti-dementia medications, diabetes status, and ApoE ɛ4 status, the C16 : 0, C20 : 0, and quartiles of C24 : 1 were associated with delusions. In moderate to severe AD, depression was associated with C22 : 0 and C24 : 0. Conclusion: There were stage-specific associations between ceramides and neuropsychiatric symptoms of AD. The potential mechanisms deserve further investigation.

Keywords: Alzheimer’s disease, ceramides, plasma, psychiatry

DOI: 10.3233/JAD-151158

Journal: Journal of Alzheimer's Disease, vol. 52, no. 3, pp. 1029-1035, 2016