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Lower Dementia Incidence Linked With Vitamin D Supplements

— But large observational study has significant limitations

MedpageToday
A close up of bottles of vitamin D supplements on a pharmacy shelf.

Vitamin D supplements were linked with lower dementia incidence and longer dementia-free survival, prospective data showed.

In a sample of 12,000 older adults, exposure to vitamin D supplementation was associated with a 40% lower dementia incidence rate compared with no exposure (adjusted HR 0.60, 95% CI 0.55-0.65), reported Zahinoor Ismail, MD, of the University of Calgary in Canada and the University of Exeter in England, and co-authors.

Results were consistent across three vitamin D formulations, the researchers wrote in . Effects were greater in females, in apolipoprotein E ε4 (APOE4) non-carriers, and in people with normal cognition versus those with mild cognitive impairment.

The study may offer insight about who might benefit from vitamin D supplementation, Ismail suggested. "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," he said in a statement.

But the findings don't mean vitamin D supplements should be used to prevent dementia, observed Claire Sexton, DPhil, senior director of scientific programs and outreach at the Alzheimer's Association in Chicago, who wasn't involved with the study. "It is not recommended to start vitamin D supplementation to reduce dementia risk," she told ľֱ.

"It is important to note that this study is an observational study, not an intervention, so it cannot establish causation," Sexton pointed out.

"Also, a significant limitation to the study is that neither vitamin D levels at baseline and follow-up, nor dose and duration of supplementation, were available or analyzed," she added. "As a result, further research is needed in this area."

Ismail and co-authors studied 12,388 participants in the National Institute on Aging (NACC) database who had normal cognition or mild cognitive impairment at baseline. Participants came from Alzheimer's Disease Research Centers from 2005 to 2021.

Exposure to vitamin D supplementation was based on NACC medication forms that assessed three formulations: calcium-vitamin D, cholecalciferol, and ergocalciferol. Participants with baseline exposure to any vitamin D supplement were considered the vitamin D-exposed group, while those without any exposure at all study visits were considered non-exposed. People with no baseline exposure who subsequently were exposed to vitamin D were excluded.

The final sample included 4,637 people in the exposed group and 7,751 people in the non-exposed group.

Mean baseline age was 71.2 years, and there was no significant difference in APOE4 status between groups. However, there were more women (70.5%) in the exposed group than in the non-exposed group (46.9%), and the exposed group had higher education levels. Both mild cognitive impairment and depression were more frequent in the non-exposed group (P<0.001 for all). Results were adjusted for age, sex, education, race, cognitive diagnosis, depression, and APOE4 status.

Over 10 years, 2,696 participants progressed to dementia. Among them, 74.8% (2,017 people) had no exposure to vitamin D supplements.

Five-year dementia-free survival was 83.6% (95% CI 82.3-84.9) for those exposed to vitamin D and 68.4% (95% CI 67.1-69.7) for the non-exposed group. Each vitamin D formulation on its own was linked to a lower dementia incidence rate compared with no exposure.

The study had several limitations, Ismail and co-authors acknowledged. NACC medication sheets did not record information about exposure history, and there was no accounting for differences in exposure duration. Because dosing and baseline vitamin D levels were not available, it's unknown whether incident dementia rates differed based on doses or vitamin D deficiency, the researchers added. Confounding factors also may have influenced results.

  • Judy George covers neurology and neuroscience news for ľֱ, writing about brain aging, Alzheimer’s, dementia, MS, rare diseases, epilepsy, autism, headache, stroke, Parkinson’s, ALS, concussion, CTE, sleep, pain, and more.

Disclosures

This study was supported by the National Institute for Health and Care Research Exeter Biomedical Research Centre. The NACC database is supported by the NIH.

Ismail reported relationships with Otsuka/Lundbeck, Biogen, and Roche. Co-authors had no disclosures.

Sexton had no disclosures.

Primary Source

Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring

Ghahremani M, et al "Vitamin D supplementation and incident dementia: Effects of sex, APOE, and baseline cognitive status" Alzheimer's Dement 2023; DOI: 10.1002/dad2.12404.