Deficient Vitamin D Levels Associated with Increased Risk of Dementia

by | Aug 4, 2022 | 2022, Brain Health, Vitamin D - Mental Health

Written by Taylor Woosley, Staff Writer. Nonlinear MR analyses show the threshold effect of 25(OH)D levels on dementia, with the risk predicted to be 54% (95% CI: 1.21, 1.96) higher for participants at 25 nmol/L compared with 50 nmol/L. 

Cerebrovascular disease refers to diseases that occur in the brain and are found mostly in the elderly population1. Two major types of cerebrovascular accidents, hemorrhagic and ischemic stroke, involve obstruction of blood flow to an area of the brain and blood vessel damage, resulting in central nervous system damage2. Furthermore, as life expectancy continues to increase, elderly populations are at a greater risk of developing dementia3. Alzheimer’s disease (AD) is the most common type of dementia and refers to cerebrovascular dysfunction with extensive neuronal loss over time4.

Vitamin D (25(OH)D), a steroid hormone, has been researched for its potential brain modulation abilities, while also exerting antiviral and anti-inflammatory properties5. Furthermore, vitamin D is involved in several processes of the adaptive and innate immune systems6. It is recognized as a neurosteroid that modulates brain development, maintains adult brain function, and delays brain aging7. Vitamin D deficiency is a global problem and affects over 50% of the US population and is associated with metabolic disorder and cognitive impairment8.

To better explore the potential role of vitamin D in neuroimaging and risks of dementia and stroke, Navale et. al conducted an observational study using data from the UK Biobank, a large-scale prospective study. Participants (n=33,523 aged 37-73) with recorded 25(OH)D concentrations and a range of brain neuroimaging were used in one analysis sample. A second analysis was focused on examining participants (n=427,690) potential association between 25(OH)D concentrations and risks of stroke and dementia using the MR approach to test for causal effects of increasing 25(OH)D levels in instance of severe vitamin D deficiency.

During the baseline visit, participant’s lifestyle, socioeconomic status, and health was obtained through self-reported questionnaires, interviews, physical measurements and blood samples. Serum 25(OH)D concentration was collected at baseline using direct competitive chemiluminescent immunoassay and MRI scans were preformed using a Siemens Skyra 3T scanner. Covariates such as participants’ age at baseline, sex, ethnic group, along with sociodemographic factors were included in analysis. Linear regression was used to assess the association between 25(OH)D and brain neuroimaging outcomes. Cox proportional hazards model was used to investigate the association between 25(OH)D and risk of dementia and stroke. Linear and nonlinear MR analyses were used to observe the casual effects of 25(OH)D on brain volumes and the risk of dementia and stroke. Potential impact fraction was calculated to estimate dementia incidence that may be preventable by correction of low vitamin D status using data obtained from the nonlinear MR analyses.

Significant results of the study are as follows:

  • The association between 25(OH)D and total brain, gray matter, white matter, and hippocampal volume was nonlinear (P-linear < 0.04 for all).
  • There was slight heterogeneity in the significance of the association between 25(OH)D and total brain, gray matter, and white matter volume between males and females (P-interaction < 0.01 for all), with associations appearing stronger for males.
  • Based on the nonlinear MR, individuals with serum 25(OH)D at 25 nmol/L had 54% (95% CI: 1.21, 1.96) higher odds of dementia compared with those with 50 nmol/L.
  • Potential impact fraction suggests 17% (95% CI: 7.22, 30.58) of dementia could be prevented by increasing 25(OH)D to 50 nmol/L.

Results obtained using prospective data from the UK Biobank show that low vitamin D status was associated with increased risks of dementia and stroke, along with neuroimaging outcomes. A nonlinear casual association between 25(OH)D and dementia risk was observed in the MR analyses. Study limitations include the potential for influences by residual confounding, the possibility of healthy volunteer bias, and lack of population diversity which may not be generalizable to other populations.

Source: Navale, Shreeya S., Anwar Mulugeta, Ang Zhou, David J. Llewellyn, and Elina Hyppönen. “Vitamin D and brain health: an observational and Mendelian randomization study.” The American Journal of Clinical Nutrition (2022).

© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. 

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Posted August 4, 2022.

Taylor Woosley studied biology at Purdue University before becoming a 2016 graduate of Columbia College Chicago with a major in Writing. She currently resides in Glen Ellyn, IL.

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