Lower Serum Calcium as a Potentially Associated Factor for Conversion of Mild Cognitive Impairment to Early Alzheimer’s Disease in the Japanese Alzheimer’s Disease Neuroimaging Initiative

Article type: Research Article

Authors: Sato, Kenichiro^a | Mano, Tatsuo^a | Ihara, Ryoko^b | Suzuki, Kazushi^b | Tomita, Naoki^d | Arai, Hiroyuki^d | Ishii, Kenji^e | Senda, Michio^f | Ito, Kengo^g | Ikeuchi, Takeshi^h | Kuwano, Ryozo^h | Matsuda, Hiroshiⁱ | Iwatsubo, Takeshi^{b; c} | Toda, Tatsushi^a | Iwata, Atsushi^{a; *} | Alzheimer’s Disease Neuroimaging Initiative, and Japanese Alzheimer’s Disease Neuroimaging Initiative^j

Affiliations: [a] Department of Neurology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan | [b] Unit for Early and Exploratory Clinical Development, The University of Tokyo Hospital, Tokyo, Japan | [c] Department of Neuropathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan | [d] Department of Geriatrics and Gerontology, Division of Brain Science, Institute of Development, Aging and Cancer (IDAC), Tohoku University, Sendai, Japan | [e] Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan | [f] Institute of Biomedical Research and Innovation, Kobe, Japan | [g] National Center for Geriatrics and Gerontology, Obu, Japan | [h] Niigata University, Niigata, Japan | [i] National Center for Neurology and Psychiatry, Kodaira, Japan | [j] The full list of members of the Japanese ADNI is provided in the Supplementary Material

Correspondence: [*] Correspondence to: Dr. Atsushi Iwata, Department of Neurology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. Tel.: +81 3 5800 8672; Fax: +81 3 5800 6548; E-mail: [email protected].

Abstract: Background:Effect of serum calcium level to the incidence of mild cognitive impairment (MCI) conversion to early Alzheimer’s disease (AD) remains uncertain. Objective:To investigate association between baseline serum calcium and the MCI conversion in the Japanese Alzheimer’s Disease Neuroimaging Initiative (J-ADNI) study cohort. Methods:In this sub-analysis of J-ADNI study, we reviewed data from MCI participants at baseline regarding their conversion to early AD during the 3 years of observation period and assessed the associated factors including serum calcium level. In addition, we compared our results from the J-ADNI study with the corresponding results from the North American (NA)-ADNI. Results:Of 234 eligible MCI participants from the J-ADNI cohort, 121 (51.7%) converted to AD during the first 36 months of observation. Using univariate analysis, being female, having shorter years of education, and lower serum calcium level were correlated with increased risk of MCI-to-AD conversion exclusively in J-ADNI cohort. The lower corrected serum calcium level remained as one of conversion-associated factors in the J-ADNI cohort even after adjustment for multiple confounding variables, although this was not observed in the NA-ADNI cohort. Conclusion:Our findings suggest that lower serum calcium may be associated with an increased risk of MCI conversion to AD in Japanese cohorts. The reason for this correlation remains unclear and further external validation using other Asian cohorts is needed. It would be interesting for future AD studies to obtain serum calcium levels and other related factors, such as vitamin D levels, culture-specific dietary or medication information.

Keywords: Alzheimer’s disease, calcium, conversion, Japanese Alzheimer’s Disease Neuroimaging Initiative, mild cognitive impairment

DOI: 10.3233/JAD-181115

Journal: Journal of Alzheimer's Disease, vol. 68, no. 2, pp. 777-788, 2019