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

被引:23
作者
Kuriyama, Nagato [1 ,2 ]
Ozaki, Etsuko [1 ]
Mizuno, Toshiki [2 ]
Ihara, Masafumi [3 ]
Mizuno, Shigeto [7 ]
Koyama, Teruhide [1 ]
Matsui, Daisuke [1 ]
Watanabe, Isao [1 ]
Akazawa, Kentaro [4 ]
Takeda, Kazuo [5 ]
Takada, Akihiro [5 ]
Inaba, Masaaki [9 ]
Yamada, Shinsuke [9 ]
Motoyama, Koka [9 ]
Takeshita, Wakiko [1 ]
Iwai, Komei [1 ]
Hashiguchi, Kanae [1 ]
Kobayashi, Daiki [8 ]
Kondo, Masaki [2 ,3 ]
Tamura, Aiko [2 ]
Yamada, Kei [4 ]
Nakagawa, Masanori [6 ]
Watanabe, Yoshiyuki [1 ]
机构
[1] Kyoto Prefectural Univ Med, Dept Epidemiol Community Hlth & Med, 465 Kajii Cho, Kyoto 6028566, Japan
[2] Kyoto Prefectural Univ Med, Dept Neurol, 465 Kajii Cho, Kyoto 6028566, Japan
[3] Natl Cerebral & Cardiovasc Ctr, Dept Stroke & Cerebrovasc Dis, Div Neurol, Osaka, Japan
[4] Kyoto Prefectural Univ Med, Dept Radiol, Kyoto, Japan
[5] Kyoto Ind Hlth Assoc, Kyoto, Japan
[6] Kyoto Prefectural Univ Med, North Med Ctr, Kyoto, Japan
[7] Kindai Univ, Nara Hosp, Dept Endoscopy, Osaka, Japan
[8] St Lukes Int Hosp, Dept Med, Div Gen Internal Med, Tokyo, Japan
[9] Osaka City Univ, Grad Sch Med, Dept Metab Endocrinol & Mol Med, Osaka, Japan
关键词
alpha-Klotho; deep white matter lesion; dementia; magnetic resonance imaging; CHRONIC KIDNEY-DISEASE; ALZHEIMERS-DISEASE; COGNITIVE IMPAIRMENT; ENHANCES COGNITION; HORMONE KLOTHO; BETA-KLOTHO; VITAMIN-D; DEMENTIA; PROGRESSION; MICE;
D O I
10.3233/JAD-170466
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Background: The anti-aging protein, alpha-Klotho, may be involved in cognitive decline and has potential as a surrogate marker that reflects dementia. However, the role of alpha-Klotho in the brain has not been sufficiently investigated. Objective: Here, we investigated the association between alpha-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 forDWMLs, and the Fazekas scale (Grade) was assessed following brain magnetic resonance imaging. Aquestionnaire concerning lifestyle and neuropsychological tests was administered, and their associations with the blood alpha-Klotho level were retrospectively investigated. Results: The alpha-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 alpha-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 alpha-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 alpha-Klotho level was correlated with grading of cerebral DWMLs and was accompanied by cognitive decline as an independent risk factor. The alpha-Klotho level may serve as a useful clinical index of vascular cognitive impairment.
引用
收藏
页码:145 / 155
页数:11
相关论文
共 45 条
[1]   Characteristics of urinary and serum soluble Klotho protein in patients with different degrees of chronic kidney disease [J].
Akimoto, Tetsu ;
Yoshizawa, Hiromichi ;
Watanabe, Yuko ;
Numata, Akihiko ;
Yamazaki, Tomoyuki ;
Takeshima, Eri ;
Iwazu, Kana ;
Komada, Takanori ;
Otani, Naoko ;
Morishita, Yoshiyuki ;
Ito, Chiharu ;
Shiizaki, Kazuhiro ;
Ando, Yasuhiro ;
Muto, Shigeaki ;
Kuro-o, Makoto ;
Kusano, Eiji .
BMC NEPHROLOGY, 2012, 13
[2]   Diagnostic utility of letter fluency, category fluency, and fluency difference scores in Alzheimer's disease [J].
Cerhan, JH ;
Ivnik, RJ ;
Smith, GE ;
Tangalos, EC ;
Petersen, RC ;
Boeve, BF .
CLINICAL NEUROPSYCHOLOGIST, 2002, 16 (01) :35-42
[3]   Decline in renal functioning is associated with longitudinal decline in global cognitive functioning, abstract reasoning and verbal memory [J].
Davey, Adam ;
Elias, Merrill F. ;
Robbins, Michael A. ;
Seliger, Stephen L. ;
Dore, Gregory A. .
NEPHROLOGY DIALYSIS TRANSPLANTATION, 2013, 28 (07) :1810-1819
[4]   White Matter Lesions: Prevalence and Clinical Phenotype in Asymptomatic Individuals Aged ≥50 Years [J].
David, Jean-Philippe ;
Ferrat, Emilie ;
Parisot, Juliette ;
Naga, Henri ;
Lakroun, Samia ;
Menasria, Feriel ;
Saddedine, Sofiane ;
Natella, Pierre-Andre ;
Paillaud, Elena ;
Fromentin, Isabelle ;
Bastuji-Garin, Sylvie .
DEMENTIA AND GERIATRIC COGNITIVE DISORDERS, 2016, 42 (3-4) :159-168
[5]  
de Groot JC, 2000, ANN NEUROL, V47, P145
[6]   Life Extension Factor Klotho Prevents Mortality and Enhances Cognition in hAPP Transgenic Mice [J].
Dubal, Dena B. ;
Zhu, Lei ;
Sanchez, Pascal E. ;
Worden, Kurtresha ;
Broestl, Lauren ;
Johnson, Erik ;
Ho, Kaitlyn ;
Yu, Gui-Qiu ;
Kim, Daniel ;
Betourne, Alexander ;
Kuro-o, Makoto ;
Masliah, Eliezer ;
Abraham, Carmela R. ;
Mucke, Lennart .
JOURNAL OF NEUROSCIENCE, 2015, 35 (06) :2358-2371
[7]   Life Extension Factor Klotho Enhances Cognition [J].
Dubal, Dena B. ;
Yokoyama, Jennifer S. ;
Zhu, Lei ;
Broestl, Lauren ;
Worden, Kurtresha ;
Wang, Dan ;
Sturm, Virginia E. ;
Kim, Daniel ;
Klein, Eric ;
Yu, Gui-Qiu ;
Ho, Kaitlyn ;
Eilertson, Kirsten E. ;
Yu, Lei ;
Kuro-o, Makoto ;
De Jager, Philip L. ;
Coppola, Giovanni ;
Small, Gary W. ;
Bennett, David A. ;
Kramer, Joel H. ;
Abraham, Carmela R. ;
Miller, Bruce L. ;
Mucke, Lennart .
CELL REPORTS, 2014, 7 (04) :1065-1076
[8]   Progression of cerebral white matter lesions - Clinical and radiological considerations [J].
Enzinger, Christian ;
Fazekas, Franz ;
Ropele, Stefan ;
Schmidt, Reinhold .
JOURNAL OF THE NEUROLOGICAL SCIENCES, 2007, 257 (1-2) :5-10
[9]   MR SIGNAL ABNORMALITIES AT 1.5-T IN ALZHEIMER DEMENTIA AND NORMAL AGING [J].
FAZEKAS, F ;
CHAWLUK, JB ;
ALAVI, A ;
HURTIG, HI ;
ZIMMERMAN, RA .
AMERICAN JOURNAL OF ROENTGENOLOGY, 1987, 149 (02) :351-356
[10]   Comparison of the pathology of cerebral white matter with post-mortem magnetic resonance imaging (MRI) in the elderly brain [J].
Fernando, MS ;
O'Brien, JT ;
Perry, RH ;
English, P ;
Forster, G ;
McMeekin, W ;
Slade, JY ;
Golkhar, A ;
Matthews, FE ;
Barber, R ;
Kalaria, RN ;
Ince, PG .
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, 2004, 30 (04) :385-395