Elderly women with cerebrovascular disease had a significantly increased risk for dementia if they took calcium supplements, a retrospective analysis of 2 studies showed.
The odds ratio (OR) for any type of dementia more than doubled, and the risk for stroke-related dementia increased more than 4-fold in calcium users versus nonusers. Stratified analyses showed that calcium supplementation was associated with more than a 6-fold increase in the odds of dementia in women with a history of stroke, and nearly a 3-fold higher risk for dementia in study participants with white-matter lesions (Kern J, et al. Neurology. 2016;87:1674-1680).
“We found a relationship between calcium supplementation and increased risk for dementia in elderly women in this 5-year follow-up study,” Jürgen Kern, MD, PhD, Department of Neuropsychiatric Epidemiology, University of Gothenburg, Mölndal, Sweden, and colleagues concluded. “This association was mainly confined to individuals with cerebrovascular disease...at baseline.”
“Because our sample size was relatively small and the study was observational, these findings need to be confirmed,” Dr Kern and colleagues added.
Dementia and osteoporosis are common causes of disability in older adults. Because calcium deficiency contributes to osteoporosis, many older individuals are advised to increase their dietary intake of calcium and to take calcium supplements. However, a recent study raised questions about the safety of calcium supplementation (Reid IR, et al. J Intern Med. 2015;278:354-368).
Studies have yielded conflicting data regarding the association between calcium supplementation and the risk for vascular events, although a permanent increase in calcium levels increases vascular risk.
“Vascular risk factors are related to vascular dementia and Alzheimer disease,” Dr Kern and colleagues noted. “Thus, if calcium supplement intake increases the risk for vascular events, it might increase the risk for dementia. Calcium supplementation might have direct toxic effects on vulnerable neurons, because the increased calcium levels may amplify ischemic cell death and worsen the outcome after cerebrovascular events,” they explained.
Given the accumulation of direct and indirect evidence regarding calcium supplementation, Dr Kern and colleagues hypothesized that calcium supplementation increases the risk for dementia, particularly in patients already compromised by ischemic cerebrovascular disease, including stroke and ischemic white-matter lesions.
Association Between Dementia Risk and Calcium Supplements
To test their hypothesis, Dr Kern and colleagues analyzed data from 2 sources, including the Prospective Population Study of Women and the H70 Birth Cohort Study in Gothenburg, Sweden. They reviewed records from 700 women aged 70 to 92 years who were alive and free of dementia during the baseline period of 2000-2001 and at follow-up during 2005-2006.
All of the women underwent comprehensive neuropsychiatric and somatic examinations, and 447 of the study participants had brain computed tomography scans at baseline. Investigators documented the use and dosage of calcium supplementation via patient records, and dementia diagnoses were based on the Diagnostic and Statistical Manual of Mental Disorders (Third Edition, Revised).
Overall, 98 patients had a history of taking calcium supplements. Women who took calcium supplements had an OR of 2.10 for dementia (P = .046) versus women who did not take calcium supplements (N = 602). This risk increased more than 4-fold for stroke-related dementia, including ischemic and mixed (OR, 4.40; P = .006).
Calcium supplementation in women with a history of stroke was associated with an OR of 6.77 for dementia (P = .020). In addition, women with ischemic white-matter lesions had an OR of 2.99 for dementia (P = .011). Calcium supplementation in women without either type of condition was not associated with an increased risk for dementia.
Discussing mechanistic explanations for these findings, the authors highlighted that calcium supplements have been hypothesized to affect blood vessel walls, possibly potentiating changes in the vessels of individuals with vascular disease, leading to ischemia and hypoperfusion.
Noting evidence that dietary calcium may protect against vascular disease, Dr Kern and colleagues explained that “the difference between dietary calcium and calcium intake by supplements could be explained by variations in corresponding changes in serum calcium concentration.” They underlined that calcium supplements lead to larger increases in serum calcium levels than dietary calcium.