Associations of vitamin B12 status with cognitive domain performance in cognitively healthy older adults

Abstract

AbstractBackgroundIncreasing longevity worldwide has resulted in an unprecedented high burden of dementia. Several lines of research have implicated factors affecting B‐vitamin status among risk factors for cognitive decline and dementia. We aimed to determine the prevalence of vitamin B12 deficiency among cognitively healthy volunteers from the Cognitive Health in Ageing Register: Investigational, Observational, and Trial Studies in Dementia Research: Prospective Readiness cOhort (CHARIOT:PRO) SubStudy (CPRO‐SS) and also, to explore associations with cognitive performance at screening.MethodThis analysis includes data from cognitively healthy volunteers (n=1946) aged 60‐85 years who underwent, as part of screening, Repeatable Battery for Neuropsychological Status (RBANS), vitamin B12 and folate measures. Levels of B12 biomarkers, homocysteine and methylmalonic acid, were assayed for those with low vitamin B12 (<133 pmol/L); high levels indicating severe B12 deficiency. Gender‐specific linear regression models were computed for associations of B vitamin biomarkers and BMI with RBANS domain indices and individual tests, controlling for confounders. Regression by B12 status group (normal, deficient, severely deficient) for RBANS associations were analysed for all participants.ResultVitamin B12 deficiency (<148 pmol/L) was detected in 17.2% of the cohort; folate <10nmol/L in 1%. Low vitamin B12 was associated with subtle deficits in immediate and delayed memory test scores (p<0.03) in men. Elevated folate was associated with poorer Attention index in men (β ‐0.12; p=0.019), and individual subtests in men and women (p<0.03). High BMI was associated with poorer Attention and Visuospatial indices and subtests in men and women (P<0.05), but no interaction with B12 was detected (p>0.05). Regression by B12 status group revealed deficits in Attention (β ‐6.46; p=0.004) for B12 Deficient, and Immediate Memory (β ‐2.99; p=0.019) for Severely Deficient (with elevated homocysteine and/or methylmalonic acid and/or low folate), relative to the Normal group.ConclusionThis study highlights subtle domain‐specific cognitive deficits that varied between men and women, with evidence of graded cognitive deterioration with increasing severity of vitamin B12 deficiency. High BMI had negative effects on attention and visuospatial skills in this cohort. These results will be discussed in the context of clinical trials for prevention of AD and therapeutic strategies for subgroups.