Association between α-Klotho and Deep White Matter Lesions in the Brain: A Pilot Case Control Study Using Brain MRI

Article type: Research Article

Authors: Kuriyama, Nagato^{a; b; *} | Ozaki, Etsuko^a | Mizuno, Toshiki^b | Ihara, Masafumi^c | Mizuno, Shigeto^g | Koyama, Teruhide^a | Matsui, Daisuke^a | Watanabe, Isao^a | Akazawa, Kentaro^d | Takeda, Kazuo^e | Takada, Akihiro^e | Inaba, Masaakiⁱ | Yamada, Shinsukeⁱ | Motoyama, Kokaⁱ | Takeshita, Wakiko^a | Iwai, Komei^a | Hashiguchi, Kanae^a | Kobayashi, Daiki^h | Kondo, Masaki^b | Tamura, Aiko^b | Yamada, Kei^d | Nakagawa, Masanori^f | Watanabe, Yoshiyuki^a

Affiliations: [a] Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan | [b] Department of Neurology, Kyoto Prefectural University of Medicine, Kyoto, Japan | [c] Division of Neurology, Department of Stroke and Cerebrovascular Diseases, National Cerebral and Cardiovascular Center, Osaka, Japan | [d] Department of Radiology, Kyoto Prefectural University of Medicine, Kyoto, Japan | [e] Kyoto Industrial Health Association, Kyoto, Japan | [f] North Medical Center, Kyoto Prefectural University of Medicine, Kyoto, Japan | [g] Department of Endoscopy, Kindai University Nara Hospital, Japan | [h] Department of Medicine, Division of General Internal Medicine, St. Luke’s International Hospital, Tokyo, Japan | [i] Department of Metabolism, Endocrinology, and Molecular Medicine, Graduate School of Medicine, Osaka City University, Osaka, Japan

Correspondence: [*] Correspondence to: Nagato Kuriyama, MD, PhD, Departments of Epidemiology for Community Health and Medicine, and Neurology, Kyoto Prefectural University of Medicine, 465Kajii-cho, Kawaramachi-hirokoji, Kamigyo-ku, Kyoto-city, 602-8566, Japan. Tel.: +81 75 251 5789; Fax: +81 75 251 5799; Email: [email protected].

Abstract: Background:The anti-aging protein, α-Klotho, may be involved in cognitive decline and has potential as a surrogate marker that reflects dementia. However, the role of α-Klotho in the brain has not been sufficiently investigated. Objective:Here, we investigated the association between α-Klotho and cognitive decline that is associated with cerebral deep white matter lesions (DWMLs). Methods:Two hundred-eighty participants (187 males and 93 females, mean age: 70.8 years old) were evaluated for DWMLs, and the Fazekas scale (Grade) was assessed following brain magnetic resonance imaging. A questionnaire concerning lifestyle and neuropsychological tests was administered, and their associations with the blood α-Klotho level were retrospectively investigated. Results:The α-Klotho level was 685.1 pg/mL in Grade 0 (68 subjects), 634.1 in G1 (134), 596.0 in G2 (62), and 571.6 in G3 (16), showing that the level significantly decreased with advanced grades. Significant correlations were noted between the α-Klotho level and higher brain function tests including the Mini-Mental State Examination and word fluency tests (p < 0.05). When a 90th percentile value of the level in the G0 group (400 pg/mL) or lower was defined as a low α-Klotho level, the odds ratio of the high-grade G3 group was 2.9 (95% confidence interval: 1.4–7.8) (after correction for age, sex, hypertension, and chronic kidney disease), which was significant. Conclusion:A reduced blood α-Klotho level was correlated with grading of cerebral DWMLs and was accompanied by cognitive decline as an independent risk factor. The α-Klotho level may serve as a useful clinical index of vascular cognitive impairment.

Keywords: α-Klotho, deep white matter lesion, dementia, magnetic resonance imaging

DOI: 10.3233/JAD-170466

Journal: Journal of Alzheimer's Disease, vol. 61, no. 1, pp. 145-155, 2018