CNS Drugs

, Volume 25, Issue 8, pp 629–639 | Cite as

Vitamin D, Cognitive Dysfunction and Dementia in Older Adults

  • Andy P. Dickens
  • Iain A. Lang
  • Kenneth M. Langa
  • Katarina Kos
  • David J. LlewellynEmail author
Leading Article


The physiologically active form of vitamin D, 1,25-dihydroxyvitamin D3, is a fat-soluble steroid hormone with a well established role in skeletal health. A growing body of evidence suggests low vitamin D levels also play a role in the pathogenesis of a wide range of non-skeletal, age-associated diseases including cancer, heart disease, type 2 diabetes mellitus and stroke. Low levels of serum 25-hydroxyvitamin D [25(OH)D], a stable marker of vitamin D status, are also associated with increased odds of prevalent cognitive dysfunction, Alzheimer’s disease and all-cause dementia in a number of studies, raising the possibility that vitamin D plays a role in the aetiology of cognitive dysfunction and dementia. To date, the majority of human studies reporting associations between vitamin D and cognition or dementia have been cross-sectional or case-control designs that do not permit us to exclude the possibility that such associations are a result of disease progression rather than being causal. Animal and in vitro experiments have identified a number of neuroprotective mechanisms that might link vitamin D status to cognitive dysfunction and dementia, including vasoprotection and amyloid phagocytosis and clearance, but the clinical relevance of these mechanisms in humans is not currently clear. Two recent, large, prospective studies go some way to establish the temporal relationship with cognitive decline. The relative risk of cognitive decline was 60% higher (relative risk = 1.6, 95% CI 1.2, 2.0) in elderly Italian adults with severely deficient 25(OH)D levels (<25 nmol/L) when compared with those with sufficient levels (≥75 nmol/L). Similarly, the odds of cognitive decline were 41% higher (odds ratio= 1.4, 95% CI 0.9, 2.2) when elderly US men in the lowest quartile (≤49.7 nmol/L) were compared with those in the highest quartile (≥74.4 nmol/L). To our knowledge, no prospective studies have examined the association between 25(OH)D levels and incident dementia or neuroimaging abnormalities. The possible therapeutic benefits of vitamin D have attracted considerable interest as over 1 billion people worldwide are thought to have insufficient 25(OH)D levels and these levels can be increased using inexpensive and well tolerated dietary supplements. However, no large randomized controlled trials have yet examined the effect of vitamin D supplements on cognitive decline or incident dementia. Further studies are urgently needed to establish which mechanisms have clinical relevance in human populations and whether vitamin D supplements are effective at minimizing cognitive decline or preventing dementia.


Dementia Cognitive Decline Cognitive Dysfunction Sunlight Exposure White Matter Hyperintensity Volume 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Drs Dickens, Llewellyn and Lang are supported by the UK National Institute for Health Research (NIHR)-funded Peninsula Collaboration for Leadership in Applied Health Research and Care. The views expressed in this publication are those of the authors and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health. Dr Llewellyn is also supported by grants from the James Tudor Foundation, the Sir Halley Stewart Trust, the Norman Family Charitable Trust, the Peninsula Medical School Foundation and the Age Related Diseases and Health Trust. Prof. Langa was supported by the National Institute on Aging grant R01 AG030155. The sponsors were not involved in the data collection, analysis, interpretation, writing or review of this manuscript.

The authors have no conflicts of interest that are directly relevant to the content of this article.


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Copyright information

© Adis Data Information BV 2011

Authors and Affiliations

  • Andy P. Dickens
    • 1
  • Iain A. Lang
    • 1
    • 2
  • Kenneth M. Langa
    • 3
    • 4
    • 5
  • Katarina Kos
    • 6
  • David J. Llewellyn
    • 6
    Email author
  1. 1.Peninsula Collaboration for Leadership in Applied Health Research and Care, Peninsula College of Medicine and DentistryUniversity of ExeterExeterUK
  2. 2.Public Health DirectorateNational Health Service (NHS) DevonExeterUK
  3. 3.Department of Internal MedicineUniversity of MichiganAnn ArborUSA
  4. 4.Institute for Social ResearchUniversity of MichiganAnn ArborUSA
  5. 5.Department of Veterans AffairsVA Center for Practice Management and Outcomes Research, VA Ann Arbor Healthcare SystemAnn ArborUSA
  6. 6.Institute of Biomedical and Clinical Science, Peninsula College of Medicine and DentistryUniversity of Exeter, Royal Devon and Exeter HospitalExeterUK

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