Brain vitamin D forms, cognitive decline and neuropathology in community-dwelling older adults

Authors: SHEA, KYLA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; BARGER, KATHRYN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; DAWSON-HUGHES, BESS - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; LEURGANS, SUE - Rush University; FU, XUEYAN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; JAMES, BRYAN - Rush University; HOLLAND, THOMAS - Rush University; AGARWAL, PUJA - Rush University; WANG, JIFAN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; MATUSZEK, GREGORY - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; HEGER, NICHOLAS - Tufts Medical Center; SCHNEIDER, JULIE - Rush University; BOOTH, SARAH - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Alzheimer's & Dementia
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/13/2022
Publication Date: 12/7/2022
Citation: Shea, K., Barger, K., Dawson-Hughes, B., Leurgans, S.E., Fu, X., James, B.D., Holland, T.M., Agarwal, P., Wang, J., Matuszek, G.H., Heger, N., Schneider, J.A., Booth, S.L. 2022. Brain vitamin D forms, cognitive decline and neuropathology in community-dwelling older adults. Alzheimer's & Dementia. https://doi.org/10.1002/alz.12836.
DOI: https://doi.org/10.1002/alz.12836

Interpretive Summary: Accumulating evidence implicates dietary and nutritional factors in reducing cognitive decline and dementia risk, including vitamin D. The purpose of this study was to analyze postmortem brain concentrations of vitamin D and related metabolites in 290 decedents of the well-characterized, community-based Rush Memory and Aging Project, and determine the association of these different forms with ante-mortem measures of cognitive function. To further obtain mechanistic insight, we also evaluated the association of brain vitamin D3 concentrations with Alzheimer's disease and other dementia-related neuropathologies. The vitamin D metabolite, 25-hydroxyvitamin D (25(OH) D), was the main form of vitamin D in all brain regions evaluated. The odds of having dementia or mild cognitive impairment at the last visit prior to death were 25% - 33% lower per doubling of 25(OH)D in the brain. However, brain 25(OH)D concentrations were not associated with any post-mortem neuropathology outcome studied. Additional research is needed to clarify the biological mechanism linking lower brain 25(OH)D to cognitive impairment.

Technical Abstract: INTRODUCTION: Vitamin D purportedly protects against cognitive decline and dementia based on observational data using circulating 25-hydroxyvitamin D3 (25(OH)D3). Little is known about vitamin D in the human brain and the association with dementia or neuropathology METHODS: Decedents of the Rush Memory and Aging Project (n=290) had vitamin D concentrations measured in four brain regions. Associations with cognitive and neuropathological outcomes were estimated using linear and logistic regression. RESULTS: The main form of vitamin D in all brain regions was 25-hydroxyvitamin D3 (25(OH)D3). Higher brain 25(OH)D3 concentrations were associated with a 25% to 33% lower odds of dementia or mild cognitive impairment at the last visit before death (all p = 0.031). However, brain 25(OH)D3 concentrations were not associated with any post-mortem neuropathology outcome studied. DISCUSSION: Higher brain 25(OH)D3 concentrations were associated with better cognitive function prior to death. Additional research is needed to clarify the specific mechanisms underlying this potential protective relationship.