Vitamin D supplementation and incident dementia: Effects of sex, APOE, and baseline cognitive status

Abstract

Introduction Despite the association of vitamin D deficiency with incident dementia, the role of supplementation is unclear. We prospectively explored associations between vitamin D supplementation and incident dementia in 12,388 dementia‐free persons from the National Alzheimer's Coordinating Center. Methods Baseline exposure to vitamin D was considered D+; no exposure prior to dementia onset was considered D−. Kaplan–Meier curves compared dementia‐free survival between groups. Cox models assessed dementia incidence rates across groups, adjusted for age, sex, education, race, cognitive diagnosis, depression, and apolipoprotein E ( APOE ) ε4. Sensitivity analyses examined incidence rates for each vitamin D formulation. Potential interactions between exposure and model covariates were explored. Results Across all formulations, vitamin D exposure was associated with significantly longer dementia‐free survival and lower dementia incidence rate than no exposure (hazard ratio = 0.60, 95% confidence interval: 0.55–0.65). The effect of vitamin D on incidence rate differed significantly across the strata of sex, cognitive status, and APOE ε4 status. Discussion Vitamin D may be a potential agent for dementia prevention. Highlights In a prospective cohort study, we assessed effects of Vitamin D on dementia incidence in 12,388 participants from the National Alzheimer's Coordinating Center dataset. Vitamin D exposure was associated with 40% lower dementia incidence versus no exposure. Vitamin D effects were significantly greater in females versus males and in normal cognition versus mild cognitive impairment. Vitamin D effects were significantly greater in apolipoprotein E ε4 non‐carriers versus carriers. Vitamin D has potential for dementia prevention, especially in the high‐risk strata.

Biomarkers of neurodegeneration in post-traumatic stress disorder: an integrative review

“…Second, PTSD has been associated with low serum vitamin D, as well as with functional polymorphisms of the Gc protein that binds vitamin D and influences its levels. Vitamin D deficiency is associated with a modest but significant increase in the risk of dementia [78], as well as reductions in gray and white matter volumes [79], and there has been recent interest in vitamin D supplementation as a preventive measure against neurocognitive disorders [80]. Though both these findings require replication, they represent plausible pathways that could mediate the association between PTSD and neurodegeneration.…”

The effects of the interplay between vitamins, antibiotics, and gut microbiota on the pathogenesis and progression of dementia: A systematic review and meta‐analysis

“…49 Vitamin D deficiency may increase oxidative stress and inflammation, which are linked to dementia. 53 Fat-soluble vitamin D is needed for phosphorus, calcium, bone health, and immunological function. Recent research show vitamin D may be involved in dementia pathogenesis.…”

Focusing on Earlier Management of Alzheimer Disease

“…26 Regarding dietary interventions, the LipiDiDiet trial 27 showed that the multi-nutrient combination Fortasyn Connect slowed cognitive decline in patients with prodromal AD, while a prospective cohort study in dementia-free people from the National Alzheimer Coordinating Center in Canada showed vitamin D to be a potential agent for dementia prevention, especially in APOE-ε4 non-carriers. 28 In terms of modifiable vascular risk factors, prospective analyses from 4932 Framingham Heart Study participants showed that a 15 mg/dL increase in high-density lipoprotein cholesterol was linked with a lower risk of AD dementia in early (35-50 y) (15.4%, P = 0.041) and middle (51-60 y) (17.9%, P = 0.014) adulthood; similarly, a 15 mg/dL increase in glucose measured in middle adulthood was linked with a higher risk for AD dementia (14.5%, P = 0.00029). Thus, by monitoring and managing blood glucose and cholesterol levels in early adulthood, the risk for AD dementia may be decreased.…”

“…Regarding dietary interventions, the LipiDiDiet trial 27 showed that the multi-nutrient combination Fortasyn Connect slowed cognitive decline in patients with prodromal AD, while a prospective cohort study in dementia-free people from the National Alzheimer Coordinating Center in Canada showed vitamin D to be a potential agent for dementia prevention, especially in APOE-ε4 non-carriers 28 …”