Calcium Supplements Linked to Dementia in CVD

Pauline Anderson

August 17, 2016

Elderly women who take calcium supplements and had a history of stroke or white matter lesions (WMLs) may face an increased risk for dementia, a new study suggests.

Although it's too soon to make recommendations based on these new findings, clinicians may want to consider this new information in older patients who have had a stroke, said co-lead author Silke Kern, MD, PhD, Neuropsychiatric Epidemiology Unit and Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg, Sweden.

"Clinicians should assess the risks and benefits in each individual patient with cerebrovascular disease," Dr Kern.

The findings are published online August 17 in Neurology.

The study, a sample derived from the Prospective Population Study of Women and H70 Birth Cohort in Gothenburg, Sweden, included 700 women, 98 of whom were treated with calcium supplementation. There were no differences between the women who took these supplements and those who didn't in terms of baseline age, Mini-Mental State Examination (MMSE) score, education, and most health factors.

During a period of 5 years (2000 to 2005), 59 women developed dementia.

Compared with women not taking calcium supplements, those who did had a higher risk of developing dementia (odds ratio [OR], 2.10; 95% confidence interval [CI], 1.01 - 4.37; P = .046).

There was an even higher risk for stroke-related dementia (vascular dementia or mixed Alzheimer's disease/vascular dementia) (OR, 4.4; 95% CI, 1.54 - 12.61; P = .006).

Stroke History

In women with a history of stroke, calcium supplementation was associated with an especially high risk for dementia (OR, 6.77; 95% CI, 1.36 - 33.75; P = .020).

There was no relationship between calcium supplements and development of dementia in participants without a history of stroke.

Among the 447 participants for whom computed tomography was performed, 70.7% had WMLs. In these women, calcium supplementation was also associated with development of dementia, whereas in the group without WMLs, none of those who used calcium supplements developed dementia.

Although the frequency of fractures was higher in the group that received supplements (40.8% vs 20.8%) — and that's presumably why they were taking extra calcium — there were no dementia differences in the groups when the researchers controlled for osteoporosis-associated fractures.

"We could still see the same result on dementia development," commented Dr Kern.

Investigators could not tease out the impact of vitamin D on dementia risk because most calcium supplements in Sweden are combined with vitamin D. Just 14 study participants did not take a combination supplement.

The harmful effects of calcium supplements are not fully understood, Dr Kern said, but there are several possible mechanisms. One is that taking supplements leads to "a steep increase" in levels of serum calcium, which may contribute to cell death.

Neurons located in areas of hypoperfusion seen in WMLs and stroke might be especially vulnerable to the excitatory and excite-toxic effects of the calcium-level peaks caused by the supplements, she said.

"The neurons are already a little bit stressed because, for example, they have been in areas close to a stroke."

Dr Kern noted the differences between calcium in the diet and calcium in supplements. For example, she said, "with dietary intake of calcium, you don't see the steep increase in calcium levels that you see with calcium supplements."

As well, she said, dietary intake involves much lower doses of calcium that are consumed throughout the day, and when eating calcium-containing foods, you're also taking in other nutrients.

The study is the first to show the risk for dementia in older women taking calcium supplements. The large 7-year randomized controlled Women's Health Initiative Calcium/vitamin D supplementation study (WHI CaD) did not find a relationship between supplements and cognitive impairment or dementia.

Because about half of participants in that study took non–study-related (or "personal") calcium, vitamin D, or both, there was a reanalysis of only women taking the study protocol supplements.

"That analysis showed that calcium supplementation increased the risk of myocardial infarction or stroke, but there was no such reanalysis for dementia or cognitive decline," said Dr Kern. "So our study is the first to show a relationship between calcium supplement and increased risk for dementia."

Dr Kern stressed that the new results are observational but that if they can be replicated, there could be important implications for clinical practice.

"Clinicians may consider this new information and assess each woman individually," she said, adding that some women may need to continue taking calcium supplements.

Because calcium deficiency contributes to osteoporosis, it's recommended that the elderly get 1000 to 1200 mg of calcium daily. Such an intake through diet alone can be difficult.

Cognitive Functioning

For a comment, Medscape Medical News approached Neelum T. Aggarwal, MD, associate professor, Departments of Neurological Sciences and Rush Alzheimer's Disease Center, director of research, Rush Heart Center for Women, Rush University Medical Center, Chicago, Illinois, and member of the American Academy of Neurology.

Dr Aggarwal noted that unlike other studies, including the WHI CaD, this one looked at the role that calcium supplementation might play in dementia among women with cerebrovascular disease.

The study is important, said Dr Aggarwal, in that "we know that subclinical cerebrovascular disease is common in elderly persons, and given that sex and gender differences occur in cardiovascular risk and stroke in women, perhaps calcium supplementation may exert more of a role in cognitive functioning in these patients."

But the authors provide "very little detail" on calcium assessment, she said. For example, they made no mention of serum levels of calcium, only about self-reported use of calcium supplements. "Multiple factors can influence exactly how much calcium is in the system and blood values of calcium could have been noted if available."

She questioned how stable the calcium supplementation was, how adherent the patients were, and whether dosages were changed over time. "There needs to be comment on this at least in the discussion, especially if one is making a comment that calcium is related to dementia."

It was unclear from the paper how many of the study participants already had mild cognitive impairment (MCI) at baseline, said Dr Aggarwal. "MCI, especially amnestic MCI, has an increased rate of conversion to dementia, and this could explain the increased risk of dementia conversion vs calcium as the potential causal agent to conversion."

She also pointed out the lack of reference in the paper to what types of cognitive testing outside of the MMSE were used to assess cognitive functioning and aid in dementia diagnosis.

And Dr Aggarwal felt the paper might have included information on the location of the stroke.

"When discussing cognitive functioning, especially in patients with a past history of stroke, it's important to note where the location of the stroke is, and the size, if available. Strategic strokes can cause cognitive dysfunction and cognitive impairment and have a clinical picture of vascular MCI that can lead to a dementia over time. Dementia could be due to vascular MCI converting to a dementia, and not necessarily a potential causal relationship to calcium."

Dr Aggarwal pointed out that the study sample size was small, and she stressed that the results need to be reproduced in larger studies and in minority populations.

She said she doubts that the study will change clinical practice. "Osteoporosis is highly prevalent, and fractures, falls, and the disability that come from falls will outweigh changing frequency of prescribing calcium supplements."

The study was supported by grants from the American Alzheimer's Association; Swedish Research Council; and Swedish Research Council for Health, Working Life and Welfare. Dr Kern and Dr Aggarwal have disclosed no relevant financial relationships.

Neurology. Published online August 17, 2016. Abstract

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