Vitamin D has been receiving a lot of attention recently, and now researchers report that inadequate vitamin D levels may be involved in cognitive dysfunction and dementia.
Two papers show in separate populations that low levels of vitamin D are associated with cognitive impairment and cerebrovascular disease, including stroke. A third study of only men finds no such association. The papers will appear in the January issue of Neurology.
"What should we make of these studies?" Joshua Miller, PhD, from the University of California in Sacramento, asked in an accompanying editorial. "First, it is evident that the prevalence of vitamin D deficiency is very high among older adults."
This in and of itself, he says, could warrant expanded screening for vitamin D deficiency and adding supplements. "Whether vitamin D supplements will maintain cognitive function in older adults remains an open question," he notes.
Dr. Miller does not rule out the possibility of reverse causation. "Cognitively impaired older adults may eat poorly or they may have reduced exposure to sunlight, which could lead to reduced vitamin D status."
Investigators led by Cédric Annweiler, MD, from Angers University Hospital in France, conducted a cross-sectional study exploring these questions. Their paper was released early online September 30. The researchers looked at more than 750 community-dwelling older women. Participants were from the French study known as Epidémiologie de l'Ostéoporose. The women were 75 years or older.
The researchers report that 17% of participants had vitamin D deficiency. This was defined as a serum 25-hydroxyvitamin D level of less than 10 ng/mL. Women with vitamin D deficiency had lower mean Short Portable Mental State Questionnaire scores (P < 0.001). They also had an odds ratio for cognitive impairment of about 2 after controlling for relevant confounders.
The authors conclude that inadequate vitamin D is associated with cognitive impairment in elderly women and that vitamin D supplements may improve or maintain cognitive function.
Two Studies, Similar Conclusion
The second report, by investigators led by Jennifer Buell, PhD, from Tufts University in Boston, Massachusetts, and released November 25, came to a similar conclusion. The researchers also conducted a cross-sectional study — this one of more than 300 men and women.
Participants were 65 years or older and were involved in the Nutrition and Memory in Elders study. They were evaluated for dementia and cerebrovascular disease and underwent magnetic resonance imaging to assess overall and regional brain volumes, white matter hyperintensity, and infarcts.
Investigators show that 14% of the study sample had inadequate vitamin D. Another 44% were classified as vitamin D insufficient (10 to 20 ng/mL).
Patients with low vitamin D levels had higher white matter hyperintensity volume and a higher prevalence of large vessel infarcts. Low vitamin D level was also linked with an odds ratio of about 2 for all-cause dementia, Alzheimer's disease, and stroke after controlling for relevant confounders.
The authors conclude that vitamin D deficiency is associated with an increased risk for dementia and cerebrovascular disease and that vitamin D may have vasculoprotective properties.
However, a third report, also released November 25, came to a different conclusion.
Third Study Questions Evidence
Investigators led by Yelena Slinin, MD, from the VA Medical Center and the University of Minnesota at Minneapolis, found little evidence linking vitamin D and cognitive impairment.
The researchers conducted a longitudinal assessment of more than 1600 community-dwelling men. Participants were 65 years or older and were involved in the Osteoporotic Fractures in Men Study.
Investigators assessed cognitive function using the modified Mini-Mental State Examination and the Trails B test.
At baseline, the odds ratios for cognitive impairment were between 1.6 and 1.8 in the lowest vitamin D quartile compared with the highest. However, these odds ratios did not reach statistical significance and were lower after controlling for race, ethnicity, and education.
Low vitamin D level was defined differently in this study at less than 20 ng/mL. In the other 2 studies, vitamin D deficiency was considered less than 10 ng/mL.
For incident cognitive impairment, the odds ratio for a significant decline in Mini-Mental State Examination score was 1.5 in the lowest quartile of vitamin D concentration compared with the highest quartile. The trend across the quartiles was significant. Yet again, control for confounding by race, ethnicity, and education slightly lowered the trend — enough to lose statistical significance.
The authors suggest that additional studies should be performed that include women and tests of other cognitive domains.
Editorialist Dr. Miller argues that this study is limited by a lack of women included in the work. He says it was also limited because the lowest quartile of vitamin D status consisted of all subjects with levels under 20 ng/mL. "Perhaps a reevaluation of the data comparing deficient subjects (<10 ng/mL) to nondeficient subjects would reveal significant associations," he notes.
Next Steps
"What are needed now are placebo-controlled intervention studies to determine if vitamin D supplements will protect against age-related cognitive decline." In the meantime, Dr. Miller says, neurologists, general practitioners, and geriatricians should be aware of the high prevalence of vitamin D deficiency in their patient populations and the possibility that supplementation could be beneficial.
Adequate vitamin D for patients aged 51 to 70 years are defined as 10 µg/day (400 IU). For people older than 70 years, 15 µg/day (600 IU) is suggested or enough to maintain a vitamin D level of about 30 ng/mL or more. These recommendations, he notes, are primarily for maintaining bone health and are evolving.
Dr. Miller suggests, "The appropriate intake amounts to support brain function in older adults remain to be determined."
Dr. Joshua Miller receives research support from the National Institutes of Health, the US Department of Defense, and the American Cancer Society. Dr. Slinin is a full-time employee of the US Department of Veterans Affairs. The other investigators have disclosed no relevant financial relationships.
From: Allison Gandey, Medscape Medical News
Reviewed / Posted by: Scott W Yates, MD, MBA, MS, FACP
