Vitamin D and Risk of Cognitive Decline in Elderly Persons

Abstract

Background To our knowledge, no prospective study has examined the association between vitamin D and cognitive decline or dementia. Methods We determined whether low levels of serum 25-hydroxyvitamin D (25[OH]D) were associated with an increased risk of substantial cognitive decline in the InCHIANTI population–based study conducted in Italy between 1998 and 2006 with follow-up assessments every 3 years. A total of 858 adults 65 years or older completed interviews, cognitive assessments, and medical examinations and provided blood samples. Cognitive decline was assessed using the Mini-Mental State Examination (MMSE), and substantial decline was defined as 3 or more points. The Trail-Making Tests A and B were also used, and substantial decline was defined as the worst 10% of the distribution of decline or as discontinued testing. Results The multivariate adjusted relative risk (95% confidence interval [CI]) of substantial cognitive decline on the MMSE in participants who were severely serum 25 (OH)D deficient (levels <25 nmol/L) in comparison with those with sufficient levels of 25(OH)D (≥75 nmol/L) was 1.60 (95% CI, 1.19-2.00). Multivariate adjusted random-effects models demonstrated that the scores of participants who were severely 25(OH)D deficient declined by an additional 0.3 MMSE points per year more than those with sufficient levels of 25(OH)D. The relative risk for substantial decline on Trail-Making Test B was 1.31 (95% CI, 1.03-1.51) among those who were severely 25(OH)D deficient compared with those with sufficient levels of 25(OH)D. No significant association was observed for Trail-Making Test A. Conclusion Low levels of vitamin D were associated with substantial cognitive decline in the elderly population studied over a 6-year period, which raises important new possibilities for treatment and prevention.

Hypovitaminosis D and Executive Dysfunction in Older Adults with Memory Complaint: A Memory Clinic-Based Study

“…Consistently, hypovitaminosis D has been associated with the presence of brain morphological abnormalities including brain atrophy [5] and vascular lesions [6]; epidemiological literature of the past decade has revealed that hypovitaminosis D is associated with a 2.4 times higher risk of cognitive impairment as a whole [7,8,9], and specifically with Alzheimer's disease (AD) [10,11]. Recent studies indicate that the association between hypovitaminosis D and AD can be explained in part by the onset of executive dysfunction [12,13,14,15,16]. Executive functions refer to a heterogeneous set of high-level processes that control and regulate other abilities and behaviors [17,18].…”

Serum Vitamin D Deficiency as a Predictor of Incident Non-Alzheimer Dementias: A 7-Year Longitudinal Study

“…Low serum 25-hydroxyvitamin D (25OHD) concentrations are highly prevalent among older adults with prevalence reaching 90% [1], and have been associated with deterioration of global cognitive performance [2,3,4,5,6,7]. For instance, a significant association between severe 25OHD deficiency <10 ng/ml and advanced-stage dementia was found among 288 elderly inpatients aged 86 years on average, regardless of the type of dementia [6].…”

“…It thus remains unclear whether dementia precipitates vitamin D deficiency – due to low dietary vitamin D intakes or a lack of sunlight exposure for example – or whether vitamin D deficiency plays a role in the onset of dementia. The latter assumption seems likely given that vitamin D deficiency was recently associated with faster cognitive decline compared to normal vitamin D status [4]. Anyway, the type of dementia specifically associated with vitamin D deficiency (i.e., Alzheimer’s disease, AD, or non-Alzheimer dementias, NAD) is not conclusively clarified.…”

Neuroprotective Effects of Vitamin D in Multiple Sclerosis

“…Pryzbelski and Binkley [57] reported similar findings using the MMSE to assess cognition in older adults. Moreover, Llewellyn et al [58] found that low levels of vitamin D were associated with substantial cognitive decline, as measured by scores on the MMSE and the Trail-Making Test, in 858 elderly participants who were studied prospectively over a 6-year period. Although the mechanisms that mediate these cognitive effects are not well understood, several possibilities have been suggested: increasing brain cholinergic levels via effects on choline acetyltransferase, increasing neurotrophin activity via effects on nerve growth factor synthesis, decreasing free radicals by downregulating nitric oxide and upregulating γ glutamyl transpeptidase, and prevention of excitotoxic damage by promoting calcium homeostasis [57].…”