No association between high plasma ionized calcium and minor neuropsychological symptoms in two general population...

Hypercalcemia has been associated with various non-specific minor neuropsychological symptoms but mainly in patient cohorts. Whether hypercalcemia is the cause or an innocent bystander in relation to these symptoms remains unclear.

We included 5,917 individuals from the Copenhagen City Heart Study (CCHS) and 106,025 individuals from the Copenhagen General Population Study (CGPS) with baseline plasma ionized calcium available and tested the hypothesis that high plasma ionized calcium is associated with self-reported minor neuropsychological symptoms in a cross-sectional design. We used parathyroidectomy and kidney stones during follow-up as positive control outcomes. Minor neuropsychological symptoms were self-reported based on baseline questionnaires on well-being, energy, mood, and sleep, while information on parathyroidectomy and kidney stones was from Danish health registries. We used logistic regression for cross-sectional analyses and Cox regression for prospective analyses.

No association was found between high plasma ionized calcium and self-reported minor neuropsychological symptoms at baseline in either study. In contrast, in individuals with plasma ionized calcium >1.40 mmol/L the multivariable adjusted hazard ratios for parathyroidectomy during follow-up were 214 (95 % CI: 52-873) in the CCHS and 206 (54-277) in the CGPS; corresponding hazard ratios for kidney stones were 1.71 (0.54-5.44) and 2.97 (1.96-4.49).

Hypercalcemia was not associated with minor neuropsychological symptoms, while it was associated with higher risk of parathyroidectomy and kidney stones in the general population. Thus, in patients with hypercalcemia, minor neuropsychological symptoms are likely linked to other causes.