Vitamin D Supplementation Improves Cognitive Function Through Reducing Oxidative Stress Regulated by Telomere Length in Older Adults with Mild Cognitive Impairment: A 12-Month Randomized Controlled Trial

Article type: Research Article

Authors: Yang, Tong^{a; b} | Wang, Hualou^{a; b} | Xiong, Ying^c | Chen, Chong^{d; e; f; g} | Duan, Keran^h | Jia, Jingya^{a; b} | Ma, Fei^{a; b; *}

Affiliations: [a] Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China | [b] Tianjin Key Laboratory of Environment, Nutrition and Public Health, Center for International Collaborative Research on environment, Nutrition and Public Health, Tianjin, China | [c] Department of Community Service, Wangdingdi Hospital of Tianjin Nankai District, Tianjin, China | [d] Department of Clinical Laboratory, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China | [e] Key Laboratory of Cancer Prevention and Therapy, Tianjin, China | [f] Tianjin’s Clinical Research Center for Cancer, Tianjin, China | [g] National Human Genetic Resources Sharing Service Platform, Tianjin, China | [h] Biobank, Tianjin First Center Hospital, Tianjin, China

Correspondence: [*] Correspondence to: Fei Ma, MD, Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, No. 22 Qi Xiang Tai Road, He Ping District, Tianjin, China. Tel.: +86 22 83336618; Fax: +86 22 83336608; E-mail: [email protected].

Abstract: Background:Cognitive decline in older adults is a serious public health problem today. Association between vitamin D supplementation and cognition remains controversial. Objective:To determine whether a 12-month vitamin D supplementation improves cognitive function in elderly subjects with mild cognitive impairment (MCI), and whether it is mediated through the mechanism in which telomere length (TL) regulate oxidative stress. Methods:This was a double-blind, randomized, placebo-controlled trial in Tianjin, China. Participants were all native Chinese speakers aged 65 years and older with MCI. 183 subjects were randomized to an intervention group (vitamin D 800 IU/day, n = 93) or a placebo group (the matching starch granules, n = 90), and followed up for 12 months. Tests of cognitive function and mechanism-related biomarkers were evaluated at baseline, 6 months, and 12 months. Results:Repeated-measures ANOVA showed substantial improvements in the full scale intelligence quotient (FSIQ), information, digit span, vocabulary, block design, and picture arrangement scores in the vitamin D group over the placebo group (p < 0.001). Leukocyte TL was significantly higher, while serum 8-OXO-dG, OGG1mRNA, and P16INK4amRNA revealed greater decreases in the vitamin D group over the placebo group (p < 0.001). According to mixed-model repeated-measures ANOVA analysis, vitamin D group showed a significant enhancement in the FSIQ score for 12 months compared with the control (estimate value = 5.132, p < 0.001). Conclusion:Vitamin D supplementation for 12 months appears to improve cognitive function through reducing oxidative stress regulated by increased TL in order adults with MCI. Vitamin D may be a promising public health strategy to prevent cognitive decline.

Keywords: Cognitive performance, oxidative stress, telomere, vitamin D

DOI: 10.3233/JAD-200926

Journal: Journal of Alzheimer's Disease, vol. 78, no. 4, pp. 1509-1518, 2020