Vitamin D and Slowing the Rate of Cognitive Decline
Vitamin D receptors are found in the brain (see article from Eyles), and various epidemiological studies have found that vitamin D deficiency is associated with increased risk of dementia (Shen and Ji). A recent publication by Miller and co-workers found a further link between vitamin D levels and risk of dementia. They conducted both a cross-sectional and longitudinal analyses on a multi-ethnic cohort of elderly adults residing in the US. 382 adults aged 75 years at baseline were included in the study. Half the participants were cognitively normal, while 33% had mild cognitive impairment, and 18% had dementia. Overall vitamin D status was poor: 61% had a deficient or insufficient status (<12 ng/ml, 12-20 ng/ml).
At baseline, people with dementia were more likely to be deficient (35%) than people with MCI or who were cognitively normal (24%). In addition, for every log increase in vitamin D status, measures of cognition increased, indicating a linear relationship between vitamin D levels and cognitive function.
The researchers were able to follow most of the participants and repeat the cognitive tests five years later. In general, participants’ performance on the cognitive tests declined over the 5-year follow-up period. However, the rate of decline of the vitamin D-deficient group was three times greater than for the vitamin D-replete group. The rates of decline for vitamin D deficient participants was strongest for executive function and episodic memory, which are the key domains affected by Alzheimer’s Disease.
This study, however, was observational. While vitamin D levels and cognition are correlated, and there also appears to be some mechanistic evidence for a causal relationship (Hooshmand), this study does not prove that vitamin D can prevent cognitive decline. It is possible that people with cognitive impairment spend less time outdoors, and therefore have lower vitamin D levels. For example, Suzuki and Murase found that elderly people with cognitive decline were half as likely to leave the house as the cognitively normal. It is also possible that a factor related to vitamin D status, such as an active lifestyle, is associated with both higher vitamin D levels and lower risk of dementia. Grande and co-workers showed that physically active elders with mild cognitive impairment had a lower risk of subsequent dementia.
What is concerning is the high rates of vitamin D deficiency in the cohort. Osteoporosis appears to be under-treated in patients with dementia, and low vitamin D levels are a contributing factor. Haasum and associates found that despite 25% of people with dementia having had one osteoporotic fracture in the previous 4 years, only 5% were taking drugs or supplements to treat osteoporosis. This compares to only 7% of persons without dementia having had an osteoporotic fracture in the same timeframe and 12% being treated for osteoporosis. Preventing vitamin D deficiency in people aged over 65 years, particularly those with dementia, is important in reducing the rate of falls and osteoporotic fractures. The study from Miller et al. shows that there may be an added benefit in preserving cognition.
Miller JW, Harvey DJ, Beckett LA, et al. Vitamin D Status and Rates of Cognitive Decline in a Multiethnic Cohort of Older Adults. JAMA Neurol. Published online September 14, 2015. doi:10.1001/jamaneurol.2015.2115
Eyles DW, Smith S, Kinobe R, Hewison M, McGrath JJ. Distribution of the vitamin D receptor and 1 alpha-hydroxylase in human brain. J Chem Neuroanat. 2005 Jan;29(1):21-30. http://www.ncbi.nlm.nih.gov/pubmed/15589699
Grande G, Vanacore N, Maggiore L, Cucumo V, Ghiretti R, Galimberti D, Scarpini E, Mariani C, Clerici F. Physical activity reduces the risk of dementia in mild cognitive impairment subjects: a cohort study. J Alzheimers Dis. 2014;39(4):833-9. doi: 10.3233/JAD-131808. http://www.ncbi.nlm.nih.gov/pubmed/24296815
Haasum Y, Fastbom J, Fratiglioni L, Johnell K. Undertreatment of osteoporosis in persons with dementia? A population-based study. Osteoporos Int. 2012 Mar;23(3):1061-8. doi: 10.1007/s00198-011-1636-8. Epub 2011 Apr 16. http://www.ncbi.nlm.nih.gov/pubmed/21499775
Hooshmand B, Lökk J, Solomon A, Mangialasche F, Miralbell J, Spulber G, Annerbo S, Andreasen N, Winblad B, Cedazo-Minguez A, Wahlund LO, Kivipelto M. Vitamin D in relation to cognitive impairment, cerebrospinal fluid biomarkers, and brain volumes. J Gerontol A Biol Sci Med Sci. 2014 Sep;69(9):1132-8. doi: 10.1093/gerona/glu022. Epub 2014 Feb 25. http://www.ncbi.nlm.nih.gov/pubmed/24568931
Shen L, Ji HF. Vitamin D deficiency is associated with increased risk of Alzheimer's disease and dementia: evidence from meta-analysis. Nutr J. 2015 Aug 1;14(1):76. doi: 10.1186/s12937-015-0063-7. http://www.ncbi.nlm.nih.gov/pubmed/26231781
Suzuki T, Murase S. Influence of outdoor activity and indoor activity on cognition decline: use of an infrared sensor to measure activity. Telemed J E Health. 2010 Jul-Aug;16(6):686-90. doi: 10.1089/tmj.2009.0175. http://www.ncbi.nlm.nih.gov/pubmed/20575611