Vitamin D and White Matter Abnormalities in Older Adults: A Cross-Sectional Neuroimaging Study

Eur J Neurol. 2014 Dec;21(12):1436-e95. doi: 10.1111/ene.12511. Epub 2014 Jul 10.


Background and purpose: Morphological brain changes related to hypovitaminosis D have been poorly studied. In particular, the age-related decrease in vitamin D concentrations may explain the onset of white matter abnormalities (WMA) in older adults. Our objectives were (i) to investigate whether there was an association between serum 25-hydroxyvitamin D (25OHD) concentration and the grade of WMA in older adults and (ii) to determine whether the location of WMA was associated with 25OHD concentration.

Methods: One hundred and thirty-three Caucasian older community-dwellers with no clinical hydrocephalus (mean 71.6 ± 5.6 years; 43.6% female) received a blood test and a magnetic resonance imaging scan of the brain. The grades of total, periventricular and deep WMA were scored using semiquantitative visual rating scales from T2-weighted fluid-attenuated inversion recovery images. The association of WMA with as-measured and deseasonalized 25OHD concentrations was evaluated with the following covariates: age, gender, body mass index, use of anti-vascular drugs, number of comorbidities, impaired mobility, education level, Mini-Mental State Examination score, medial temporal lobe atrophy, serum concentrations of calcium, thyroid-stimulating hormone and vitamin B12, and estimated glomerular filtration rate.

Results: Both as-measured and deseasonalized serum 25OHD concentrations were found to be inversely associated with the grade of total WMA (adjusted β = -0.32, P = 0.027), specifically with periventricular WMA (adjusted β = -0.15, P = 0.009) but not with deep WMA (adjusted β = -0.12, P = 0.090). Similarly, participants with 25OHD concentration <75 nM had on average a 33% higher grade of periventricular WMA than those with 25OHD ≥75 nM (P = 0.024). No difference in average grade was found for deep WMA (P = 0.949).

Conclusions: Lower serum 25OHD concentration was associated with higher grade of WMA, particularly periventricular WMA. These findings provide a scientific basis for vitamin D replacement trials.

Keywords: brain; leukoaraiosis; magnetic resonance imaging; older adults; vitamin D; white matter.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cross-Sectional Studies
  • Female
  • Humans
  • Leukoencephalopathies / blood*
  • Leukoencephalopathies / pathology*
  • Magnetic Resonance Imaging
  • Male
  • Neuroimaging
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood


  • Vitamin D
  • 25-hydroxyvitamin D