Vitamin D deficiency may accelerate cognitive decline in female apolipoprotein E ε4 non-carriers

Abstract

Background & aims: The impact of vitamin D deficiency (VDD) on cognition remains controversial. Evidences suggest that variability based on apolipoprotein E (APOE) ε4 status and gender, given APOE ε4's influence on vitamin D metabolism and women's heightened vitamin D sensitivity. We investigated the interplay between APOE ε4, gender, and VDD in cognitive decline among older adults.

Methods: In a population-based cohort of 1547 cognitively normal Koreans aged ≥60 years, Mini Mental State Examination (MMSE) changes were tracked biennially (2010-2020). VDD was defined as serum 25-hydroxyvitamin D < 10 ng/mL. Linear mixed models analyzed VDD effects, with subgroup analyses for APOE ε4 status and gender.

Results: VDD was present in 21.3 % at baseline and was linked to faster MMSE decline (estimate = -0.054, 95 % CI [-0.091, -0.017], p = 0.004), particularly in APOE ε4 non-carriers (estimate = -0.070, 95 % CI [-0.112, -0.029], p = 0.001). A gender-based analysis revealed that this effect was significant only in female non-carriers (estimate = -0.097, 95 % CI [-0.156, -0.038], p = 0.001). Conversely, male non-carriers demonstrated an absence of a statistically significant association (estimate = -0.017, 95 % CI [-0.076, 0.041], p = 0.562).

Conclusions: VDD accelerates cognitive decline in cognitively normal APOE ε4 non-carriers, particularly women, underscoring the importance of tailored prevention strategies.

Keywords: Apolipoprotein E4; Cognition; Cohort studies; Gender; Old; Vitamin D deficiency.