Vitamin D supplementation has the potential to be a viable dementia prevention strategy, especially when initiated early, new research suggests.

In a large prospective cohort study, people who took vitamin D were 40% less likely to develop dementia than peers who did not take vitamin D. The effects of vitamin D were most pronounced in women, those with normal cognitive function, and apolipoprotein E (APOE) ε4 noncarriers.

“We know that vitamin D has some effects in the brain that could have implications for reducing dementia; however, so far, research has yielded conflicting results,” lead researcher Zahinoor Ismail, MD, with the Hotchkiss Brain Institute, University of Calgary, said in a news release.

“Our findings give key insights into groups who might be specifically targeted for vitamin D supplementation. Overall, we found evidence to suggest that earlier supplementation might be particularly beneficial before the onset of cognitive decline,” said Ismail.

The study was published online March 1 in Alzheimer’s and Dementia: Diagnosis, Assessment and Disease Monitoring.

Promising, but Preliminary

The findings are based on 12,388 adult participants (mean age, 71 years) in the US National Alzheimer’s Coordinating Center database who had normal cognition or mild cognitive impairment (MCI) at the outset. A total of 4637 (37%) took vitamin D supplements, and 7751 did not.

Those who took vitamin D supplements were more likely to be women and to have higher education levels. Depression and MCI were more common in those not taking vitamin D.

Over 10 years, 2696 participants developed dementia, including 2017 (75%) who had no exposure to vitamin D supplements. The 5-year dementia-free survival rate was 84% in vitamin D group, vs 68% in the group that did not take vitamin D.

After adjusting for age, sex, education, race, cognition, depression, and APOE4 status, vitamin D exposure (vs no exposure) was significantly associated with a lower incidence of dementia (adjusted hazard ratio, 0.60; 95% CI, 0.55 – 0.65; P < .001).

This was true across all three formulations ― calcium-vitamin D, cholecalciferol, and ergocalciferol.

While exposure to vitamin D was associated with lower dementia incidence across all strata of sex, cognitive diagnosis, and APOE ε4 status, the rates were lower in women vs men, in those with normal cognition vs those with MCI, and in APOE ε4 noncarriers vs carriers, the investigators note.

They caution that the study has several limitations. They were no data on dose or duration of vitamin D exposure or baseline serum vitamin D levels. “Clarifying exposure duration, dose-response relationships, and the role of vitamin D deficiency will be necessary to inform intervention studies,” the researchers note.

“Preventing dementia or even delaying its onset is vitally important given the growing numbers of people affected,” study co-author Byron Creese, PhD, with University of Exeter, said in the news release. “The link with vitamin D in this study suggests that taking vitamin D supplements may be beneficial in preventing or delaying dementia, but we now need clinical trials to confirm whether this is really the case.”

Creese noted that the ongoing VitaMIND study at the University of Exeter is exploring this issue further by randomly assigning participants to either take vitamin D or placebo. The researchers are examining changes in memory and thinking tests over time.

Key Questions Remain

Reached for comment, Ihab Hajjar, MD, professor of neurology and internal medicine, UT Southwestern Medical Center in Dallas, said the “big confounder” in this and similar studies is not having baseline data on vitamin D levels.

“We know that people with low vitamin D are at higher risk of developing cognitive problems. That’s been reproducible in multiple epidemiological studies. But if we take people with normal vitamin D levels and supplement with vitamin D, do we lower their risk of future cognitive impairment? I think that’s where the controversy lies,” Hajjar, who wasn’t involved in the study, told Medscape Medical News.

“It’s also important to know that additional vitamin D in people who have normal vitamin D may cause increased calcium and may have some side effects,” Hajjar said.

However, he noted there is no question that low vitamin D levels should be corrected. “That’s something we all practice, because vitamin D deficiency has been linked not only with cognitive impairment but also mobility issues, muscle weakness, and falls.”

“The question that remains to be answered is whether there is any cognitive benefit to adding vitamin D if the level is normal. Right now, there is no strong evidence that it actually makes a difference,” Hajjar said.

The study was supported by the National Institute for Health and Care Research Exeter Biomedical Research Center. Ismail has relationships with Otsuka/Lundbeck, Biogen, and Roche. Hajjar has disclosed no relevant financial relationships.

Alz Dement Diagn Assess Dis Monit. Published online March 1, 2023. Full text

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