The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 18 No. 8 • December 2015

Vitamin D and the Risk of Dementia and Alzheimer’s Disease

A 2014 paper (Littlejohns, 2014) reports the interesting finding that severe deficiency of Vitamin D (<25nmol/L) and deficiency of Vitamin D (≥25 to <50 nmol/L) was associated with a substantially increased risk of all-cause dementia and Alzheimer disease.

Vitamin D has been shown to mitigate age-related cognitive decline, possibly by reducing inflammation and decreasing amyloid beta burden (Briones and Darwish, 2012). Another paper reported that vitamin D prevents cognitive decline and enhances synaptic function in the hippocampus in aging mice (Latimer, 2014). A recent paper (Mizwicki, 2014) reported that vitamin D3 promoted the recovery of impaired amyloid beta phagocytosis by Alzheimer’s disease macrophages. This is important because the rate of production of amyloid beta in Alzheimer’s brains has been found not to differ from that of normal brains, but the ability of the Alzheimer’s brain to clear amyloid beta is impaired compared to that of normals.

Interestingly, multiple sclerosis is also a disease where damage to myelinated white matter tracts is responsible for failure of linkages between areas of the brain that send commands to motor areas and the motor areas that are supposed to receive those messages. The damage to the white matter tracts blocks these communication pathways. Moreover, multiple sclerosis is known to be increased at higher latitudes, that is the farther north you live, the higher the risk of getting multiple sclerosis. Vitamin D deficiency is associated with that higher risk and, of course, people at higher latitudes are exposed to less sunlight and consequently get less vitamin D via its manufacture in the skin. It may be a stretch but it is still tempting to extend the vitamin D association to Alzheimer’s disease as well.

Moreover, a paper (Huebbe, 2011) has shown that the apoE4 allele, which increases the risk of Alzheimer’s disease, is associated with higher vitamin D levels in targeted replacement mice (where the human apoE4 is substituted for their apoE) and in humans. This is consistent with the fact that in Europe, the apoE4 allele distribution is positively correlated with geographic latitude, with a greater than 4-fold greater frequency in the north than in the south (e.g., 22.7% in Finland vs. 5.2% in Sardinia. The authors (Huebbe, 2011) interpret this to possibly mean that the apoE4 allele may be beneficial early in life but then have a cost in later life (beyond reproductive age). Another paper (Norberg, 2011) also found that there was a north-south difference in the cognitive impairment resulting from apoE4 in non-demented subjects, with data coming from 16 centers across Europe. The latter study showed apoE4 carrier prevalence was 62.7% for the northern region, 42.1% in the middle region and 31.5% in the southern region. “Similar to AD [Alzheimer’s disease], APOE4 status is also associated with white matter (WM) abnormalities that may contribute to age- and disease-related neurodegeneration.” (Foley, 2014).

Durk hypothesizes that taking high dose vitamin D to get into the higher concentration of vitamin D that is still safe may be a way to reduce the damaging effect of having an apoE4 allele, because the gene’s expression may be plausibly assumed to be increased when vitamin D levels are low. Taking high dose vitamin D may, therefore, decrease the expression of apoE4 and reduce its deleterious effects thereby. This is an exciting possibility and one we hope will be tested soon. In the meantime, taking vitamin D at levels up to 4000 iu per day may be reasonable for most.


  • Littlejohns et al. Vitamin D and the risk of dementia and Alzheimer disease. Neurology. 83:920-8 (2014).
  • Huebbe, Nebel, Siegert, et al. ApoE4 is associated with higher vitamin D levels in targeted replacement mice and humans. FASEB J. 25:3262-70 (2011).
  • Latimer, Brewer, Searcy, et al. Vitamin D prevents cognitive decline and enhances hippocampal synaptic function in aging rats. Proc Natl Acad Sci U S A. 111(41):E4359-66. (Sept. 29, 2014).
  • Briones and Darwish. Vitamin D mitigates age-related cognitive decline through the modulation of pro-inflammatory state and decrease in amyloid burden. J Neuroinflammation. 9:244 (2012).
  • Mizwicki, Menegaz, Zhang, et al. Genomic and nongenomic signaling induced by 1 alpha,25(OH)2-vitamin D3 promotes the recovery of amyloid-beta phagocytosis by Alzheimer’s disease macrophages. J Alzheimers Dis. 29:51-62 (2014).
  • Stebbins and Murphy. Diffusion tensor imaging in Alzheimer’s disease and mild cognitive impairment. Behav Neurol. 21:39-49 (2009).
  • Godin, Tzourio, Maillard, et al. Apolipoprotein E genotype is related to progression of white matter lesion load. Stroke. 40:3186-90 (2009).
  • den Heijer, Sijens, Prins, et al. MR spectroscopy of brain white matter in the prediction of dementia. Neurology. 66:540-544 (2006).
  • Norberg, Graff, Almkvist, et al. Regional differences in effects of apoE4 on cognitive impairment in non-demented subjects. Dement Geriatr Cogn Disord. 32(2):135-42 (2011).
  • Alexopoulos, Glatt, Hoptman, et al. BDNF Val66met polymorphism, white matter abnormalities and remission of geriatric depression. J Affect Disord. 125(1-3):262-8 (2010).
  • Alexopoulos. Depression in the elderly. Lancet. 365:1961-70 (2005).
  • Foley, Salat, Stricker, et al. Interactive effects of apolipoprotein e4 and diabetes risk on later myelinating white matter regions in neurologically healthy older aged adults. Am J Alzheimer’s Dis Other Demen. 29(3):222-35 (2014).

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