Midlife Vitamin D Levels Tied to Alzheimer’s-Related Brain Changes

Higher serum levels of 25-hydroxyvitamin D in midlife were tied to lower levels of subsequent tau pathology, an Alzheimer’s disease biomarker, in a prospective cohort study.

Over 16 years, higher vitamin D levels in midlife were associated with lower global tau PET (β = -0.022, 95% CI -0.040 to -0.004, P=0.010) and composite tau PET deposition (β = -0.023, 95% CI -0.043 to -0.003, P=0.016), reported Martin Mulligan, MBBCh, of the University of Galway in Ireland, and co-authors.

There was no association between vitamin D levels and subsequent amyloid PET burden, Mulligan and colleagues wrote in Neurology Open Access.

“This study suggests that higher vitamin D levels in midlife may offer protection against pathological tau deposition in the brain, while low vitamin D may represent a potentially modifiable risk factor for healthy middle-aged individuals seeking to reduce dementia risk,” said co-author Emer McGrath, MBBCh, MSc, PhD, also of the University of Galway.

“However, this requires further testing in clinical trials,” McGrath told MedPage Today.

“To our knowledge, there have been no previous studies evaluating an association between serum vitamin D and neuroimaging markers of preclinical dementia,” she continued. “Notably, our study included individuals in early midlife, when there is greater opportunity for risk modification.”

Low circulating vitamin D levels measured in late life have been tied to an increased risk of cognitive impairment. Meta-analyses have shown correlations between vitamin D deficiency in older adults and both dementia and Alzheimer’s disease.

Autopsy studies also have linked vitamin D levels in brain tissue with cognitive function in elderly adults. Other observational data suggested that people who took vitamin D supplements may be less likely to develop dementia.

Mulligan and colleagues studied Framingham Heart Study Generation 3 participants who were dementia-free at the time of brain imaging, had serum vitamin D measured from 2002 to 2005, and had amyloid or tau PET scans between 2016 and 2019. Outcomes included global tau PET deposition, composite tau in regions most susceptible to early involvement in Alzheimer’s dementia, and amyloid PET deposition.

Overall, 793 participants had serum vitamin D measured; 424 had amyloid PET, 369 had tau PET, and 360 had both amyloid and tau PET imaging. Findings were adjusted for age, sex, depression symptoms, and other variables.

The analysis included 435 participants. Mean age was 39.2 years and 53.8% were women. The average time between blood sampling and PET was 16.2 years.

A high level of vitamin D was defined as greater than 30 ng/mL; a low level was less than that. The mean serum vitamin D level was 38 ng/mL. A third (34%) of participants had baseline levels below 30 ng/mL, and 5.1% (22 participants) were taking vitamin D supplements.

The researchers acknowledged several limitations to the study, including that the cohort was mostly Caucasian. Serum vitamin D was measured once and may have changed over time. Only 22 participants used vitamin D supplements at baseline, likely due to the group’s relatively young age, hindering the ability to assess effects of exogenous vitamin D.

The results require validation in other studies, McGrath noted. “While our results support a hypothesis that modifying vitamin D levels in early to midlife could reduce the future risk of clinical dementia, this will require formal evaluation in clinical trials,” she pointed out.

The study does not prove causality, she emphasized. If patients think they need vitamin D treatment, they should discuss it with their physician, she said.