Oral Presentation 1st Asia Pacific Herbert Fleisch Workshop 2025

Does long-term calcium supplementation increase the risk of dementia? A post-hoc analysis from a 5-year randomised clinical trial of calcium supplements to prevent fractures in older women. (#2)

Negar Ghasemifard 1 , Joshua R Lewis 1 2 , Simone Radavelli Bagatini 1 , Simon M Laws 1 , Blossom Stephan 3 , Jonathan Hodgson 1 , Kun (Kathy) Zhu 2 4 , Richard L Prince 2 , Marc Sim 1
  1. School of Medical & Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia
  2. Medical School, The University Western Australia, Perth, Western Australia, Australia
  3. Dementia Centre of Excellence, Curtin enAble Institute, Curtin University, Perth, Western Australia, Australia
  4. Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia

Background & aim: Calcium supplementation is commonly adopted to prevent and treat osteoporosis. Previous concerns around calcium supplements exacerbating vascular calcification and cardiovascular disease (CVD) have led to speculation around the potential negative impacts for dementia; given the strong nexus between vascular and cognitive health. Data supporting such concerns are limited to two observational studies1,2. This post-hoc analysis of a 5-year randomised controlled trial of calcium supplements evaluated its effect on the long-term risk for dementia in older women.

Methods: 1460 community-dwelling Australian women (mean age 75 years), without cognitive impairment, received either 1200 mg of calcium carbonate per day (n=730) or an identical placebo (n=730) for 5 years. Dementia events (n=296, 18.4%), comprising dementia-related hospitalisation (n=243, 16.6%) or death (n=114, 7.8%), were obtained from linked health records from baseline over the next 14.5 years. Effects of calcium supplementation on dementia outcomes were examined using Kaplan-Meier survival curves and unadjusted Cox regression analysis under both intention-to-treat (ITT) and per-protocol criteria (PP, ≥80% tablet compliance, n=830).

Results: No significant differences in the cumulative survival rates between the calcium and placebo groups for any dementia outcomes in both ITT and PP analysis were recorded (log-rank test p>0.2 for all). In unadjusted ITT analysis, compared to placebo, women randomised to calcium supplements did not have increased risk of dementia-related events (HR 0.90 95%CI 0.71-1.15), hospitalisation (HR 0.89 95%CI 0.69-1.15) or death (HR 0.78, 95%CI 0.54-1.20). Similar results were observed in the PP analyses and in multivariable-adjusted sensitivity analysis, including prevalent CVD, lifestyle and genetic risk factors.

Conclusion: Five-years of calcium supplements did not increase the long-term risk for dementia in older women. Our findings support the safety of calcium supplements in relation to cognitive health in a population most likely to use and benefit from it due to their high risk for osteoporosis.

  1. Payne et al. 2014, British Journal of Nutrition
  2. Kern et al. 2016, Neurology