Baseline vitamin D concentrations are strongly associated with the risk of incident all-cause dementia and Alzheimer’s disease, according to research published September 2 in Neurology.
People who are deficient in serum 25-hydroxyvitamin D (25[OH]D) may have a 51% increased risk of all-cause dementia, and people who are severely deficient in 25(OH)D may have an approximately 122% increased risk of all-cause dementia. The association between vitamin D deficiency and incident Alzheimer’s disease may be similarly strong, said the researchers.
“We have conducted what is to our knowledge the first large, prospective, population-based study to examine vitamin D concentrations in relation to a comprehensive adjudicated assessment of dementia and Alzheimer’s disease,” said Thomas J. Littlejohns, a doctoral student at the University of Exeter Medical School in the United Kingdom, and colleagues. “Our results clarify that the threshold above which older adults are unlikely to benefit from supplementation with regard to dementia risk is likely to lie in the region of 50 nmol/L when 25(OH)D concentrations are measured using [liquid chromatography–mass spectrometry].”
The researchers analyzed data for 1,658 participants in the Cardiovascular Health Study, a prospective, population-based study in the United States. Participants were ambulatory and did not have dementia, cardiovascular disease, or stroke. Their mean age was approximately 74. Blood samples were collected in 1992 and 1993, and serum 25(OH)D concentrations were measured by liquid chromatography–mass spectrometry.
In 1998 and 1999, a committee of neurologists and psychiatrists assessed participants’ dementia and Alzheimer’s disease status using annual cognitive assessments, MRI scans, medical records, questionnaires, and proxy interviews. Diagnoses were based on criteria from the National Institute of Neurological and Communicative Disorders and Stroke and from the Alzheimer’s Disease and Related Disorders Association. Mean follow-up was 5.6 years.
During follow-up, 171 patients developed all-cause dementia and 102 developed Alzheimer’s disease. The risk of developing all-cause dementia and Alzheimer’s disease was significantly higher among participants who were deficient or severely deficient in 25(OH)D. Adjustment for potential confounders (eg, age, season of blood collection, education, sex, BMI, smoking status, and alcohol use) did not alter the pattern of results.
A linear trend across groups in all analyses suggested a monotonic association between 25(OH)D deficiency and dementia risk. Multivariate adjusted smoothing spline plots indicated that the risk of all-cause dementia and Alzheimer’s disease increased sharply at 25(OH)D concentrations lower than 50 nmol/L.
Multivariate adjusted risks for incident all-cause dementia and incident Alzheimer’s disease decreased by 18% and 20%, respectively, for each 1-SD increase in 25(OH)D.
Adjusting the data for diabetes, hypertension, ethnicity, income, and occupation did not change the pattern of results. After excluding participants who developed all-cause dementia and Alzheimer’s disease within one year of baseline, the researchers found that the hazard ratio for incident all-cause dementia was 2.42 in participants who were severely 25(OH)D deficient and 1.54 in those who were 25(OH)D deficient, compared with participants with sufficient 25(OH)D. The hazard ratio for Alzheimer’s disease was 2.36 in participants who were severely 25(OH)D deficient and 1.69 for those who were 25(OH)D deficient. These results suggest that the association is not caused by early converters.
“Our findings support the hypothesis that vitamin D may be neuroprotective and that ‘sufficiency’ in the context of dementia risk may be in the region of 50 nmol/L,” they concluded.
—Erik Greb