Plasma Concentrations of Calcium and Risk of Alzheimer Disease--Observational and Genetic Studies.

The article investigates the association between plasma calcium ion concentrations and the risk of Alzheimer disease (AD) through observational and genetic studies in a large Danish cohort of 97,968 individuals from the Copenhagen General Population Study (CGPS). Observational analyses found that higher plasma calcium ion levels were associated with an increased risk of AD, with a hazard ratio of 1.24 comparing the highest to lowest quartile; however, no association was observed with vascular-related dementia (VaRD). A genome-wide association study (GWAS) identified three genetic loci linked to plasma calcium ion levels, but Mendelian randomization (MR) analyses using these and other genetic instruments showed no evidence of a causal relationship between genetically determined plasma calcium (ion or total) concentrations and AD risk. These findings suggest that the observed association may be due to reverse causation or residual confounding rather than a direct causal effect of plasma calcium on AD development.