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Vitamin D and brain health: an observational and Mendelian randomization study.
Am J Clin Nutr. 2022 08 04; 116(2):531-540.AJ

Abstract

BACKGROUND

Higher vitamin D status has been suggested to have beneficial effects on the brain.

OBJECTIVES

To investigate the association between 25-hydroxyvitamin D [25(OH)D], neuroimaging features, and the risk of dementia and stroke.

METHODS

We used prospective data from the UK Biobank (37-73 y at baseline) to examine the association between 25(OH)D concentrations with neuroimaging outcomes (N = 33,523) and the risk of dementia and stroke (N = 427,690; 3414 and 5339 incident cases, respectively). Observational analyses were adjusted for age, sex, ethnicity, month, center, and socioeconomic, lifestyle, sun behavior, and illness-related factors. Nonlinear Mendelian randomization (MR) analyses were used to test for underlying causality for neuroimaging outcomes (N = 23,901) and dementia and stroke (N = 294,514; 2399 and 3760 cases, respectively).

RESULTS

Associations between 25(OH)D and total, gray matter, white matter, and hippocampal volumes were nonlinear, with lower volumes both for low and high concentrations (adjusted P-nonlinear ≤ 0.04). 25(OH)D had an inverse association with white matter hyperintensity volume [per 10 nmol/L 25(OH)D; adjusted β: -6.1; 95% CI: -11.5, -7.0]. Vitamin D deficiency was associated with an increased risk of dementia and stroke, with the strongest associations for those with 25(OH)D <25 nmol/L (compared with 50-75.9 nmol/L; adjusted HR: 1.79; 95% CI: 1.57, 2.04 and HR: 1.40; 95% CI: 1.26, 1.56, respectively). Nonlinear MR analyses confirmed the threshold effect of 25(OH)D 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. 25(OH)D was not associated with neuroimaging outcomes or the risk of stroke in MR analyses. 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.

CONCLUSIONS

Low vitamin D status was associated with neuroimaging outcomes and the risks of dementia and stroke even after extensive covariate adjustment. MR analyses support a causal effect of vitamin D deficiency on dementia but not on stroke risk.

Links

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Authors+Show Affiliations

Navale SS
Australian Centre for Precision Health, Unit of Clinical and Health Sciences, University of South Australia, Adelaide, Australia.
Mulugeta A
Australian Centre for Precision Health, Unit of Clinical and Health Sciences, University of South Australia, Adelaide, Australia. South Australian Health and Medical Research Institute, Adelaide, Australia. Department of Pharmacology and Clinical Pharmacy, College of Health Science, Addis Ababa University, Addis, Ababa, Ethiopia.
Zhou A
Australian Centre for Precision Health, Unit of Clinical and Health Sciences, University of South Australia, Adelaide, Australia. South Australian Health and Medical Research Institute, Adelaide, Australia.
Llewellyn DJ
College of Medicine and Health, University of Exeter, Devon, United Kingdom. Alan Turing Institute, London, United Kingdom.
Hyppönen E
Australian Centre for Precision Health, Unit of Clinical and Health Sciences, University of South Australia, Adelaide, Australia. South Australian Health and Medical Research Institute, Adelaide, Australia.

MeSH

BrainDementiaHumansMendelian Randomization AnalysisProspective StudiesRisk FactorsStrokeVitamin DVitamin D DeficiencyVitamins

Pub Type(s)

Journal Article
Observational Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

35451454

Citation

Navale, Shreeya S., et al. "Vitamin D and Brain Health: an Observational and Mendelian Randomization Study." The American Journal of Clinical Nutrition, vol. 116, no. 2, 2022, pp. 531-540.
Navale SS, Mulugeta A, Zhou A, et al. Vitamin D and brain health: an observational and Mendelian randomization study. Am J Clin Nutr. 2022;116(2):531-540.
Navale, S. S., Mulugeta, A., Zhou, A., Llewellyn, D. J., & Hyppönen, E. (2022). Vitamin D and brain health: an observational and Mendelian randomization study. The American Journal of Clinical Nutrition, 116(2), 531-540. https://doi.org/10.1093/ajcn/nqac107
Navale SS, et al. Vitamin D and Brain Health: an Observational and Mendelian Randomization Study. Am J Clin Nutr. 2022 08 4;116(2):531-540. PubMed PMID: 35451454.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Vitamin D and brain health: an observational and Mendelian randomization study. AU - Navale,Shreeya S, AU - Mulugeta,Anwar, AU - Zhou,Ang, AU - Llewellyn,David J, AU - Hyppönen,Elina, PY - 2021/09/27/received PY - 2022/04/05/revised PY - 2022/04/19/accepted PY - 2022/4/23/pubmed PY - 2022/8/6/medline PY - 2022/4/22/entrez KW - 25-hydroxyvitamin D KW - Mendelian randomization KW - UK Biobank KW - brain volume KW - dementia KW - magnetic resonance imaging KW - prospective cohort study KW - stroke KW - vitamin D SP - 531 EP - 540 JF - The American journal of clinical nutrition JO - Am J Clin Nutr VL - 116 IS - 2 N2 - BACKGROUND: Higher vitamin D status has been suggested to have beneficial effects on the brain. OBJECTIVES: To investigate the association between 25-hydroxyvitamin D [25(OH)D], neuroimaging features, and the risk of dementia and stroke. METHODS: We used prospective data from the UK Biobank (37-73 y at baseline) to examine the association between 25(OH)D concentrations with neuroimaging outcomes (N = 33,523) and the risk of dementia and stroke (N = 427,690; 3414 and 5339 incident cases, respectively). Observational analyses were adjusted for age, sex, ethnicity, month, center, and socioeconomic, lifestyle, sun behavior, and illness-related factors. Nonlinear Mendelian randomization (MR) analyses were used to test for underlying causality for neuroimaging outcomes (N = 23,901) and dementia and stroke (N = 294,514; 2399 and 3760 cases, respectively). RESULTS: Associations between 25(OH)D and total, gray matter, white matter, and hippocampal volumes were nonlinear, with lower volumes both for low and high concentrations (adjusted P-nonlinear ≤ 0.04). 25(OH)D had an inverse association with white matter hyperintensity volume [per 10 nmol/L 25(OH)D; adjusted β: -6.1; 95% CI: -11.5, -7.0]. Vitamin D deficiency was associated with an increased risk of dementia and stroke, with the strongest associations for those with 25(OH)D <25 nmol/L (compared with 50-75.9 nmol/L; adjusted HR: 1.79; 95% CI: 1.57, 2.04 and HR: 1.40; 95% CI: 1.26, 1.56, respectively). Nonlinear MR analyses confirmed the threshold effect of 25(OH)D 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. 25(OH)D was not associated with neuroimaging outcomes or the risk of stroke in MR analyses. 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. CONCLUSIONS: Low vitamin D status was associated with neuroimaging outcomes and the risks of dementia and stroke even after extensive covariate adjustment. MR analyses support a causal effect of vitamin D deficiency on dementia but not on stroke risk. SN - 1938-3207 UR - https://www.unboundmedicine.com/medline/citation/35451454/Vitamin_D_and_brain_health:_an_observational_and_Mendelian_randomization_study_ DB - PRIME DP - Unbound Medicine ER -