Higher levels of vitamin D in the form of 25(OH)D3 in autopsied brain tissue correlated with a 25-33% reduced risk of developing dementia or mild cognitive impairment in older adults. These are the findings of a study published in the journal Alzheimer’s & Dementia.

Between 2005 and 2019, researchers in the United States conducted antemortem and postmortem measurements of vitamin D levels in brain tissue samples obtained from 499 decedents who formerly participated as community-dwelling adults in the Rush Memory and Aging Project (MAP). Mean age at death averaged around 92±6 years and 77% of decedents were women.

The researchers ascertained that prolonged freezer storage of the samples reduced vitamin D levels, so samples (N=207) obtained longer than 6 years prior to testing and those missing data regarding apolipoprotein E (APOE) genotype (n=2) were excluded.

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They obtained antemortem measurements of plasma levels of circulating total 25(OH)D3, free 25(OH)D, and vitamin D binding protein (DBP) in 270 of the remaining 290 decedents. Additionally, they measured levels of vitamin D3, 25(OH)D3, and 1,25(OH)D3 in the brain tissue samples across 4 regions: the mid-temporal cortex, the mid-frontal cortex, the cerebellum, and the anterior watershed white matter.

These participants from MAP underwent yearly evaluations, including a battery of 19 cognitive assessments totaled to determine a global cognitive function score. At time of death, a neurologist specializing in dementia reviewed all available clinical data and provided a final diagnosis of dementia, mild cognitive impairment, or no cognitive impairment.

Following autopsy, neuropathologists assessed the brain tissue of each decedent for Lewy bodies, neuronal paired helical filaments, amyloid beta proteins, neuritic and diffuse plaques, and neurofibrillary tangles to provide a quantitative summary of global Alzheimer disease pathology based on these counts.

The researchers found that the main concentration of vitamin D in the brain existed in 25(OH)D3 form compared with the other forms. Higher levels of 25(OH)D3 correlated with a 25-33% lower risk of developing dementia or mild cognitive impairment at the last visit prior to death (all P ≤.031). Concentration levels of 25(OH)D3 were associated particularly with outcome measurements for semantic and working memory.

However, higher brain vitamin D levels did not significantly impact postmortem neuropathological autopsy outcomes.

“[I]t is plausible that brain 25(OH)D3 concentrations may be an indicator of cognitive resilience, such that individuals with higher levels may display fewer signs of cognitive impairment despite a high neuropathological burden,” the researchers noted. “It is also possible that 25(OH)D3 may be involved in cognition through pathologies not studied here,” they added.

Study limitations included the prolonged freezing of brain tissue samples impacting vitamin D concentration over time, lack of racial diversity among participants, and the possibilities of residual confounding and reverse causation.

Disclosures: Several study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Many were affiliated with the NIH, NIA, and USDA. Please see original source for full list of disclosures.


Shea MK, Barger K, Dawson-Hughes B, et al. Brain vitamin D forms, cognitive decline, and neuropathology in community-dwelling older adultsAlzheimers Dement. Published online December 7, 2022. doi:10.1002/alz.12836

This article originally appeared on Neurology Advisor