Vit D and dementia study: experts question cause and effect

New research​ investigating the link between vitamin D (VD) supplementation and dementia in over 12,388 participants of the US National Alzheimer's Coordinating Center, reports that taking VD is associated with living dementia-free for longer.

The researchers from the University of Calgary's Hotchkiss Brain Institute in Canada and the University of Exeter, UK, conclude that VD exposure is associated with 40% lower dementia incidence versus no exposure, adding: “Findings implicate vitamin D as a potential agent for dementia prevention and provide additional support for its use in at-risk individuals for AD dementia.”

The study

The study reports that during the course of 10 years, 2,696 participants developed dementia; of these, 2,017 (75%) had no exposure to vitamin D during all visits prior to dementia diagnosis, whereas 679 (25%) had baseline exposure.

After adjusting for baseline age, sex, education, race, cognitive diagnosis, depression, and APOE​ ε4 status, exposure to vitamin D was associated with 40% lower incidence of dementia (HR = 0.60, 95% CI: 0.55–0.65, p​ < 0.001) compared to no exposure.

The authors note a study limitation includes the lack of information on participant-level sun exposure - a key confounder to results. However Professor Zahinoor Ismail who led the research, said: “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.”

Co-author of the study, Dr Byron Creese at the University of Exeter, adds: “Preventing dementia or even delaying its onset is vitally important given the growing numbers of people affected.”

Cause and effect

Experts in the field state the study’s key strengths lie in the large number of people included in the analysis, and the fact that this was done prior to the onset of disease.

However, they note a lack of confirmation of cause and effect.

Prof Martin Hewison, interim director of the Institute of Metabolism and Systems Research, notes that although exposure to vitamin D was associated with higher dementia-free survival and lower dementia incidence rates over 10 years  “this does not necessarily mean that vitamin D deficiency is a cause of dementia,” especially considering  that “the onset of dementia may prevent people from outdoor activities that normally stimulate their vitamin D production - the action of UVB light on skin is a major driver of vitamin D levels even in northern countries such as the UK.”

Dr Tom Russ, director of the Alzheimer Scotland Dementia Research Centre, notes limitations in the methodology of the study.  

“Like all observational studies, this research is limited in its conclusions,” he says. “It used a large, high quality database to conduct the research, but the vitamin D supplementation was based on self-report and participants may or may not have been taking these consistently.”

And Prof Gill Livingston, Professor of Psychiatry at UCL, expresses concerns over timelines, saying:  “Dementia takes a long time to develop. [In this study] The rates of diagnosis begin to separate immediately and this suggests that many people were already developing dementia.”

Further investigation

The study’s authors note that further research is needed, stating: “Neither dosing nor baseline vitamin D levels were available and thus, it is unknown if rates of incident dementia differed based on dosing or vitamin D deficiency.

“Future clinical trials should consider dosing of vitamin D supplementation, while paying close attention to baseline serum vitamin D levels.”

In agreement, Susan Fairweather-Tait Professor of Mineral Metabolism at University of East Anglia, states: “The findings described in this paper are intriguing and warrant further investigation. Examining an association between two variables requires robust and accurate measures of both, and using the intake of supplements as a proxy for vitamin D exposure means the study has a high risk of bias.

“I fully support the authors’ suggestion on future directions, namely that measurements of serum 25(OH)D are required.”

Journal: The Alzheimer’s Association – Diagnosis, Disease and Monitoring

Vitamin D supplementation and incident dementia: Effects of sex, APOE​, and baseline cognitive status

https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/dad2.12404​

Authors: Maryam Ghahremani​, Eric E. Smith​, Hung-Yu Chen​, Byron Creese​, Zahra Goodarzi​ and Zahinoor Ismail​