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Brain Vitamin D Tied to Cognitive Function

— No links seen with Alzheimer's or dementia pathology, however

Ƶ MedicalToday
A computer rendering of the molecular model of calcifediol over a human brain.

Vitamin D levels in post-mortem brain tissue were linked with cognitive function, an autopsy study showed.

Higher concentrations of 25(OH)D3 -- the main form of vitamin D assessed in the study -- in four areas of the brain were tied to 25% to 33% lower odds of dementia or mild cognitive impairment, according to Sarah Booth, PhD, of Tufts University in Boston, and colleagues.

However, brain concentrations of vitamin D were not associated with any neuropathology or biomarker outcome, Booth and co-authors reported in .

Relationships between vitamin D and cognition have been investigated previously with mixed results, noted Claire Sexton, DPhil, senior director of scientific programs and outreach at the Alzheimer's Association in Chicago, in an email to Ƶ. "Some studies found a connection; some did not."

While "an interesting possible connection," Sexton observed, "this study, because it is an observational study and not an intervention, cannot establish that the vitamin D levels cause the lower risk, only that there is a connection to lower risk. More research is needed to answer those questions."

"Finding an association between vitamin levels and reduced risk is not the same as endorsing supplementation," Sexton pointed out. "Previous clinical trials of vitamin D supplementation to reduce dementia risk found mixed and varying results and had side effects. It is not recommended to start vitamin D supplementation to reduce dementia risk."

The study aimed to analyze brain concentrations of vitamin D and determine whether associations with cognitive measures and neuropathology outcomes existed.

"Many studies have implicated dietary or nutritional factors in cognitive performance or function in older adults, including many studies of vitamin D, but all of them are based on either dietary intakes or blood measures of vitamin D," said coauthor M. Kyla Shea, PhD, also of Tufts, in a statement. "We wanted to know if vitamin D is even present in the brain, and if it is, how those concentrations are linked to cognitive decline."

The researchers evaluated 25(OH)D3 and other vitamin D forms in four brain regions -- mid-frontal and mid-temporal cortex, cerebellum, and anterior watershed -- in post-mortem tissue of 290 deceased participants in the . Decedents whose brains were stored for more than 6 years were excluded.

Global Alzheimer's pathology included counts of neuritic plaques, diffuse plaques, and neurofibrillary tangles. Macroscopic and microscopic cerebral infarctions were identified as were Lewy bodies.

Participants had a mean age of 92 at death. Most were female (77%) and had at least 12 years of education (72%).

Cognitive evaluations were performed annually. At their last clinic visit, 40% of participants had diagnosed dementia, 24% had mild cognitive impairment, and 36% had no cognitive impairment.

Odds of having dementia or mild cognitive impairment at the last visit were 25%-33% lower per doubling of 25(OH)D3 in the four brain regions (OR 0.669-0.754, P≤0.031 for all). Brain vitamin D concentrations were correlated across the regions (intra-class correlation coefficient 0.87) but were not associated with any neuropathology outcome evaluated.

Plasma total 25(OH)D3 and free 25(OH)D were moderately correlated with brain 25(OH)D3 (r 0.32-0.39, P≤0.0001), but free 25(OH)D was not significantly associated with cognitive function.

Other forms of vitamin D were below the lower limit of detection in over half of the brains analyzed, limiting the ability to evaluate associations of 1,25(OH)2D3 -- the biologically active form of vitamin D -- with cognition or pathology, the researchers acknowledged. Most decedents were white and results may not apply to others, they added. Residual confounding also may have occurred.

"We now know that vitamin D is present in reasonable amounts in human brains, and it seems to be correlated with less decline in cognitive function," Shea said. "But we need to do more research to identify the neuropathology that vitamin D is linked to in the brain before we start designing future interventions."

  • Judy George covers neurology and neuroscience news for Ƶ, writing about brain aging, Alzheimer’s, dementia, MS, rare diseases, epilepsy, autism, headache, stroke, Parkinson’s, ALS, concussion, CTE, sleep, pain, and more.

Disclosures

The research was supported by National Institute on Aging and the USDA Agricultural Research Service.

Booth reported relationships with NIH and USDA. Co-authors had relationships with NIH, USDA, and industry.

Primary Source

Alzheimer's & Dementia

Shea MK, et al "Brain vitamin D forms, cognitive decline, and neuropathology in community-dwelling older adults" Alzheimer's Dement 2022; DOI: 10.1002/alz.12836.