Vitamin D Levels and Cognitive Function: Does It Make a Difference?

By Judith Turner, DVM, PharmD, and Martin Lipsky, MD

Dr. Turner is Community Pharmacy Resident, Roseman University College of Pharmacy, South Jordan, UT. Dr. Lipsky is Chancellor, South Jordan Campus, Roseman University of Health Sciences, South Jordan, UT.

Drs. Turner and Lipsky report no financial relationships relevant to this field of study.

SYNOPSIS: Similar to previous studies, vitamin D deficiency and insufficiency rates were not significantly different between those with normal cognitive status, mild cognitive impairment, or dementia. However, cognitive decline occurred at a significantly greater rate in individuals with low 25-hydroxyvitamin D levels in the areas of episodic memory and executive function.

SOURCE: Miller JW, et al. Vitamin D status and rates of cognitive decline in a multiethnic cohort of older adults. JAMA Neurol 2015;72:1295-1303.

The effect of vitamin D deficiency has been questioned in relation to a growing number of disease states, including levels of cognitive dysfunction ranging from mild cognitive impairment to diagnosed Alzheimer’s disease. The authors of this prospective longitudinal cohort study examined the relationship between 25-hydroxyvitamin D [25(OH)D] status and cognitive function from February 2002 to August 2010 in an ethnically diverse population of older (mean age of 75.5 years) adults in Northern California. Study subjects included those > 60 years of age who lived in a community setting and had risk factors for cognitive decline. Individuals with a primary psychiatric diagnosis, unstable major medical illness, or history of substance abuse in the previous 5 years were excluded from the study population.

Neuropsychological function was evaluated at baseline and annually for a mean of 5 years, using previously validated Spanish and English Neuropsychological Assessment Scales. Assessed domains included executive function, visual perception, episodic memory, and semantic memory. Vascular risk factors, including hypertension, diabetes mellitus, and hypercholesterolemia, were recorded. The researchers assessed serum 25(OH)D concentrations at baseline and during some annual follow-up visits.

A total of 382 participants were enrolled, of which 29.6% were African American and 25.1% were Hispanic. The prevalence of vitamin D deficiency (defined using Institute of Medicine guidelines) was more than twice as high in Hispanic (28.1%) as in white (13.3%) study participants. African Americans experienced almost triple the prevalence (42.5%) in the white population. Similar to some previous studies, vitamin D deficiency and insufficiency rates were not significantly different among those with normal cognitive status, mild cognitive impairment, or dementia. Vitamin D-deficient individuals had a lower performance baseline than those with adequate levels in the domains of visuospatial ability, executive function, and semantic memory; however, the associations were weak. Baseline cognitive differences between those with insufficient vs adequate vitamin D levels were not significant. After an average of 5 years of follow-up, changes in semantic and visual spatial memory were not statistically significant.

COMMENTARY

Ethnic diversity is a key feature of this study, which distinguishes it from many of its predecessors. This may be significant, since vitamin D deficiency is so much more prevalent in non-white patients. Geographic diversity may have increased the external validity. Also, unlike many other studies of its type, this one did not use a form of the Mini-Mental State Exam (MMSE), although there is a Spanish language version available. The neuropsychological test used has validity, but the choice of test makes comparison against previous studies challenging. An ever-increasing number of published studies have examined the correlation between vitamin D deficiency and cognitive impairment.^1-8 Two of the largest and longest investigations on the subject to date found a significant association between the lowest levels of vitamin D (< 25 nM/L), clinically relevant changes in MMSE scores, and new cognitive diagnosis.^2,3

By contrast, two other studies did not find an association between either lower baseline cognition or rate of cognitive decline.^4,5 The former study examined an exclusively male population, which may have had an effect on the outcome. The study by Schneider et al was distinctive in that vitamin D levels were examined in a late-middle age rather than an elderly population.

A further question in any study examining relationships between vitamin D and cognitive decline is the extent to which other variables are taken into account. Miller et al considered and controlled for season, age, race and ethnicity, education, body mass index, vascular risk score (utilized as percent presence of diabetes, hypertension, and hypocholesterolemia), and apolipoprotein E4 genotypes.¹ Factors not controlled in that study were accounted for in other studies and included depression, smoking, alcohol use, activity level, renal function, and activities of daily living impairment. The authors also mentioned sun exposure and dairy intake as other possible factors to consider. Results from this relatively small study, as well as some others with more robust data, add support to the theory that there is a relationship between vitamin D deficiency and rate of cognitive decline. What remains unclear is whether causation, or perhaps reverse causation, is at play. It’s also possible that hypovitaminosis D is a more general marker of poor health rather than a specific harbinger for cognitive decline. The more tantalizing question of whether vitamin D supplementation for deficient individuals could alter outcomes remains for a future interventional study to answer. However, while the jury is still out on the value of supplementing vitamin D to improve cognition, it remains prudent to treat those with insufficient levels.

REFERENCES

1. Miller JW, et al. Vitamin D status and rates of cognitive decline in a multiethnic cohort of older adults. JAMA Neurol 2015;72:1295-1303.
2. Slinin Y, et al. Association between serum 25(OH) vitamin D and the risk of cognitive decline in older women. J Gerontol A Biol Sci Med Sci 2012;67:1092-1098.
3. Afzal S, et al. Reduced 25-hydroxyvitamin D and risk of Alzheimer’s disease and vascular dementia. Alzheimers Dement 2014;10:296-302.
4. Slinin Y, et al. 25-Hydroxyvitamin D levels and cognitive performance and decline in elderly men. Neurology 2010;74:33-41.
5. Schneider AL, et al. Vitamin D and cognitive function and dementia risk in a biracial cohort: The ARIC Brain MRI Study. Eur J Neurol 2014;21:1211-1218, e69-70.
6. Wilson VK, et al. Relationship between 25-hydroxyvitamin D and cognitive function in older adults: The Health, Aging and Body Composition Study. J Am Geriatr Soc 2014;62:636-641.
7. Llewellyn DJ, et al. Vitamin D and risk of cognitive decline in elderly persons. Arch Intern Med 2010;170:1135-1141.
8. Granic A, et al. Serum 25-hydroxyvitamin D and cognitive decline in the very old: The Newcastle 85+ Study. Eur J Neurol 2015;22:106-115, e6-7.
9. Littlejohns TJ, et al. Vitamin D and the risk of dementia and Alzheimer disease. Neurology 2014;83:920-928.