25-Hydroxyvitamin D, APOE ɛ4 genotype and cognitive function: findings from the 1958 British birth cohort

Abstract

Both high and low vitamin D statuses have been associated with lower memory function. Apolipoprotein E (APOE) ɛ4 alleles have been associated with reduced memory function, and separately with higher vitamin D concentrations. This report aims to examine if the presence of APOE ɛ4 alleles contributes to the relationship between vitamin D and memory function. A total of 4848 (46% female) participants from the 1958 British birth cohort had information on APOE genotypes and completed memory tests at 50 years, where 4644 also had 25-hydroxyvitamin D (25(OH)D) concentrations measured at 45 years. Both low and high 25(OH)D concentrations were associated with lower memory function after adjustment for number of APOE ɛ4 alleles (P curvature=0.02). There was evidence of interaction between APOE ɛ4 and 25(OH)D, suggesting the association between 25(OH)D concentrations and memory function is different for those with two APOE ɛ4 alleles compared with those with zero or one APOE ɛ4 alleles (recessive model P interaction=0.01). Among participants with two APOE ɛ4 alleles, higher 25(OH)D concentrations were associated with higher memory function, whereas in others, memory scores were slightly lower for individuals with higher versus lower concentrations. Further studies are required to replicate these findings.

Clinical Application of Apoe in Alzheimer’s Prevention: A Precision Medicine Approach

“…This non-linear association was further described in a recent study investigating the impact of vitamin D concentrations and APOE ε4 carrier status on cognitive function. In this study, researchers demonstrated that ε4 homozygotes with high vitamin D concentrations had higher cognitive functioning and those with low vitamin D concentrations had lower cognitive functioning (60). However, ε4 heterozygotes and non-carriers with high vitamin D concentrations had lower cognitive functioning.…”

Study protocol: A randomised, double blinded, placebo-controlled clinical trial testing the effects of a vitamin D-enriched mushroom supplement on cognitive performance and mood in healthy elderly adults

“…It has been reported that memory status and serum vitamin D concentrations may be modifiable by APOE genotype [50]. Carriers of two APOE-ε4 alleles appear to possess higher memory function with higher vitamin D status than those with zero or one APOE-ε4 allele [50]. These data are from a single study and more evidence is required to determine any true relationship between cognition, vitamin D status and APOE genotype.…”

“…The rare ε2 allele (~7%) is thought to be protective against AD [49]. It has been reported that memory status and serum vitamin D concentrations may be modifiable by APOE genotype [50]. Carriers of two APOE-ε4 alleles appear to possess higher memory function with higher vitamin D status than those with zero or one APOE-ε4 allele [50].…”

Epigenetic considerations of the APOE gene

“…For example, exercise (71), education (72), and vitamin D status (73) have all been shown to impact the effects of APOE genotype on cognitive functions. Also, lifestyle factors such as alcohol consumption and physical activity were found to significantly interact with APOE genotype in determining plasma lipid concentrations in a gender-specific manner (74).…”