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Low Vitamin B12 and High Folate Status - Cause for Concern? Findings from The Irish Longitudinal Study on Ageing (TILDA)

Background: Recent data suggest that an imbalance of low vitamin B₁₂ (B₁₂) and high folate status may be associated with cognitive impairment in older adults. However, few studies have examined this interaction in representative cohorts. We therefore, examined the relationship between interactions of vitamins B₁₂ and folate with global cognition in older Irish adults

Methods: Data from Wave 1 of TILDA, a nationally representative cohort of community-dwelling adults aged ≥50 (n = 8,175) were used. Blood samples were analysed for plasma B₁₂ and folate and were classified into four profiles on the basis of B₁₂ (<or ≥258 pmol/L) and folate concentrations (≤ or >45.3 nmol/L). Global cognition was examined using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Those without both MMSE and MoCA measurements and B₁₂ and folate were excluded (final sample n = 3,872). Multiple regression analyses examined relationships of each B₁₂:folate profile with MMSE and MoCA, controlling for known covariates.

Results: The mean (SD) age was 61.8 years (8.8), 51.0% were female. The estimated prevalence of Profile 1 ‘normal B₁₂/normal folate’ (B₁₂≥258pmol/L, folate≤45.3 nmol/L) was 62.0% [60.2,64.0]; Profile 2 ‘normal B₁₂/high folate’ (B₁₂≥258 pmol/L, folate > 45.3 nmol/L) was 7.6% [6.6,8.8]; Profile 3 ‘low B₁₂/high folate’ (B₁₂ < 258 pmol/L, folate > 45.3 nmol/L) was 1.5% [1.1,2.0] and Profile 4 ‘low B₁₂/normal folate’ (B₁₂ < 258 pmol/L, folate≤45.3 nmol/L) was 28.9% [27.3,31.0]. Relative to Profile 1, Profile 3 was not associated with a significant increase in error rates for either MMSE (0.88 [0.64,1.21] IRR [95% CI]; P = 0.429) or MoCA (0.90 [0.79,1.02]; P = 0.089).

Conclusion: Low B₁₂ and high folate status was not associated with cognitive impairment in older adults. These findings may have important implications for policy recommendations in Ireland, where a voluntary folic acid fortification programme is in place.