Higher circulating vitamin D levels in early midlife were associated with lower tau deposition on brain imaging about 16 years later among dementia-free adults, while no association was observed with amyloid burden, researchers reported in Neurology Open Access.
In a prospective cohort study of 435 participants in the Framingham Heart Study Generation 3 cohort, researchers measured serum 25-hydroxyvitamin D between 2002 and 2005, when participants were a mean age of 39 years. They later assessed positron emission tomography imaging during follow-up, including 369 tau scans and 424 amyloid scans.
Baseline serum 25-hydroxyvitamin D averaged 38 ng/mL; 34% of participants had levels below 30 ng/mL, and 5% were taking vitamin D supplements at baseline.
Higher vitamin D levels, analyzed as a continuous measure, were associated with lower global tau burden and lower tau burden in brain regions vulnerable to early Alzheimer disease, including the entorhinal cortex, parahippocampal gyrus, fusiform gyrus, amygdala, and the inferior and middle temporal cortices, wrote lead researcher Martin David Mulligan, MB, of the University of Galway, Ireland, and colleagues. No association was observed between vitamin D levels and amyloid burden in any model.
Researchers also analyzed vitamin D using a clinical cutoff of 30 ng/mL. In the fully adjusted models, vitamin D levels above vs below that threshold were not associated with global tau, regional tau, or amyloid burden.
In sensitivity analyses excluding participants taking vitamin D supplements at baseline, the overall findings were materially unchanged. Additional adjustment for amyloid burden did not materially change the association between continuous vitamin D levels and lower tau burden. Researchers found no statistically significant interactions by sex or apolipoprotein E epsilon 4 carrier status.
The study population was relatively young and free of dementia, which allowed researchers to examine whether vitamin D status in early midlife was linked to later preclinical markers of dementia. The findings suggest vitamin D may be a potentially modifiable factor associated with preclinical tau burden, but they do not establish causation and require confirmation in other cohorts and clinical trials.
Limitations included the predominantly White cohort, lack of repeated vitamin D measurements over time, and the long interval between blood sampling and brain imaging, which may have led to exposure misclassification. The study also included relatively few participants with low vitamin D levels, limiting the researchers’ ability to evaluate lower thresholds.
The researchers concluded that, in dementia-free asymptomatic adults, higher serum 25-hydroxyvitamin D in early midlife was associated with lower tau deposition on brain imaging a mean of 16 years later.
The researchers reported no relevant disclosures.
Source: Neurology
