Positive Association Between Cognitive Function and Cerebrospinal Fluid Orexin A Levels in Alzheimer’s Disease

Article type: Research Article

Authors: Shimizu, Soichiro^{a; *} | Takenoshita, Naoto^a | Inagawa, Yuta^a | Tsugawa, Akito^a | Hirose, Daisuke^a | Kaneko, Yoshitsugu^a | Ogawa, Yusuke^a | Serisawa, Shuntaro^a | Sakurai, Shu^a | Hirao, Kentaro^a | Kanetaka, Hidekazu^a | Kanbayashi, Takashi^b | Imanishi, Aya^c | Sakurai, Hirofumi^a | Hanyu, Haruo^a

Affiliations: [a] Department of Geriatric Medicine, Tokyo Medical University, Shinjuku-ku, Tokyo, Japan | [b] International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki, Japan | [c] Department of Neuropsychiatry, Akita University School of Medicine, Akita, Japan

Correspondence: [*] Correspondence to: Soichiro Shimizu, MD, Department of Geriatric Medicine, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan. Tel.: +81 3 3342 6111; E-mail: soichiroshimizu@gmail.com.

Abstract: Background:Recently, many studies have investigated the association between orexin A and Alzheimer’s disease (AD). However, it remains to be determined whether the observed changes in orexin A levels are associated with pathological changes underlying AD, or cognitive function. In particular, a direct association between cerebrospinal fluid (CSF) orexin A levels and cognitive function has not been reported to date. Objective:The aim of this study was to identify whether there is a direct association between the orexinergic system and cognitive function in AD. Methods:For this study, we included 22 patients with AD and 25 control subjects who underwent general physical, neurological, and psychiatric examinations, neuroimaging, and CSF collection by lumbar puncture were enrolled. Correlations between CSF orexin A levels and CSF AD biomarker levels (i.e., levels of phosphorylated tau [p-tau], Aβ42, and Aβ42/Aβ40) were assessed to confirm the results of previous studies. Moreover, the correlation between CSF orexin A levels and Mini-Mental State Examination (MMSE) and Japanese version of the Montreal Cognitive Assessment (MoCA-J) scores were analyzed. Results:There was a significant positive correlation between CSF orexin-A levels and cognitive function (MMSE scores: r = 0.591, p = 0.04, MoCA score: r = 0.571, p = 0.006) in AD patients. Conclusion:This is the first study to our knowledge demonstrating an association between cognitive function and CSF orexin A levels in AD. Our results suggest the possibility that orexinergic system overexpression is not always a negative factor for cognitive function In AD.

Keywords: Alzheimer’s disease, cerebrospinal fluid Alzheimer’s disease biomarker, cognitive function, hypocretin 1, orexin A

DOI: 10.3233/JAD-190958

Journal: Journal of Alzheimer's Disease, vol. 73, no. 1, pp. 117-123, 2020