Abstract
Relationship between serum calcium and Alzheimer’s disease (AD) remains unclear. The aim of this study is to test whether serum calcium is associated with other AD-associated biomarkers and could predict clinical progression in nondemented elders. This was a longitudinal population-based study. The sample was derived from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort, which included 1224 nondemented elders: 413 cognitively normal (CN) and 811 mild cognition impairment (MCI). Associations were investigated between serum calcium and longitudinal changes in Aβ/tau pathologic features, brain structure, cognitive function, and disease progression. Serum calcium concentrations increased with disease severity. Serum calcium predicted longitudinal cognitive decline and conversion from nondemented status to AD dementia (adjusted HR = 1.41, 95% CI 1.13–1.76). Furthermore, serum calcium levels were negatively correlated with CSF-Aβ42 (β = − 0.558, P = 0.008), FDG-PET (β = − 0.292, P < 0.001), whole brain volume (β = − 0.148, P = 0.001), and middle temporal volume (β = − 0.216, P = 0.042). Similar results were obtained in CN and MCI groups. Higher serum calcium status (even if not hypercalcemia) may increase the risk of AD in elders. Serum calcium is a useful biomarker in predicting clinical progression in nondemented elders. More researches are needed in the future to explore the underlying mechanism.
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Funding
Data collection and sharing for this project was funded by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. This study was supported by grants from the National Natural Science Foundation of China (91849126, 81571245, and 81771148), the National Key R&D Program of China (2018YFC1314700), Shanghai Municipal Science and Technology Major Project (No.2018SHZDZX01) and ZHANGJIANG LAB, Tianqiao and Chrissy Chen Institute, and the State Key Laboratory of Neurobiology and Frontiers Center for Brain Science of Ministry of Education, Fudan University.
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Ling-Zhi Ma, Zi-Xuan Wang, Qiang Dong, Lan Tan, and Jin-Tai Yu planed the work and drafted the manuscript; Ling-Zhi Ma, Zi-Xuan Wang, Zuo-Teng Wang, and Xiao-He Hou helped in the manuscript preparation; Ling-Zhi Ma, Zi-Xuan Wang, Xue-Ning Shen, and Ya-Nan Ou designed and has drawn the figures and pathway; Lan Tan and Jin-Tai Yu guided throughout the manuscript.
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Ma, LZ., Wang, ZX., Wang, ZT. et al. Serum Calcium Predicts Cognitive Decline and Clinical Progression of Alzheimer’s Disease. Neurotox Res 39, 609–617 (2021). https://doi.org/10.1007/s12640-020-00312-y
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DOI: https://doi.org/10.1007/s12640-020-00312-y