Association between hypertension, diabetes, depression, and serum calcium with the risk of all-cause and vascular dementia: findings from the UK biobank

Purpose The associations between serum calcium levels and the risk of all-cause dementia and vascular dementia (VaD) are not well understood. Additionally, the potential roles of hypertension, diabetes, and depression in this association need to be explored. This study aimed to investigate the links between serum calcium and all-cause dementia and VaD and to assess the role of hypertension, diabetes, and depression in that association. Methods For this cohort study, data were extracted from the UK Biobank, a population-based longitudinal survey with baseline assessments from 2006 to 2010 in England, Wales, and Scotland. A total of 363 182 participants without dementia at baseline were included. Cases of all-cause dementia and VaD were identified through database linkage until December 31, 2022. The hazards of all-cause dementia and VaD were estimated using Cox proportional hazards regression models. Mediation analyses were performed to evaluate the mediation effect of hypertension, diabetes, and depression. Results During a median follow-up of 13.8 years, 5 836 cases of all-cause dementia and 1 301 cases of VaD were identified. Participants with higher levels of serum calcium (in the third and fourth quartile, > 2.37 to <= 2.43 mmol/L and > 2.43 mmol/L) had a lower risk of all-cause dementia compared to those in the first quartile (<= 2.32 mmol/L) (Hazard Ratio [HR] [95% Confidence Interval (CI)] in Q3: 0.87 (0.81-0.93), HR [95% CI] in Q4: 0.90 [0.84-0.97]). For VaD, HRs (95% CIs) in the second, third, and fourth quartiles were 0.80 (0.69-0.93), 0.76 (0.65-0.89), and 0.80 (0.69-0.93), respectively. Hypertension, diabetes, and depression significantly explained 18.67%, 2.57%, and 18.91% of the mediation effects on serum calcium-related dementia, respectively. Diabetes and depression contributed 1.85% and 15.34% of mediation effects on the association between serum calcium and the risk of VaD. Conclusion This study found that individuals with higher serum calcium levels (> 2.37 mmol/L) had a reduced risk of developing dementia. Hypertension, diabetes, and depression significantly mediated the association. These findings highlight the significance of considering serum calcium levels as a potential indicator for the development of dementia. Further, optimizing the treatment of associated diseases and managing risk factors, particularly for individuals with lower serum calcium levels, is important.