Low Folate Predicts Accelerated Cognitive Decline: 8-year Follow-up of 3140 Older Adults in Ireland

Objective: To examine associations of plasma folate concentrations and risk of global and domain-specific cognitive decline in older people.

Methods: Data of 3140 participants from The Irish Longitudinal Study on Ageing (TILDA), a nationally-representative cohort of adults aged ≥50 years were used over 8-year follow-up. Biannual cognitive assessments included the Mini-Mental State Examination (MMSE), verbal fluency and immediate and delayed word recall tests (Waves 1-5) and the Montreal Cognitive Assessment, (MoCA) (Waves 1 and 3). Plasma folate concentrations were measured in stored blood collected at baseline. Mixed effects Poisson and linear regression determined associations between baseline folate concentrations and cognition.

Results: In multivariable-adjusted models of those aged ≥50 years at baseline, low folate at baseline (<11.2 nmol/L) was associated with higher proportions of MMSE errors (incidence rate ratio [IRR] = 1.10; 95% confidence interval [CI] (1.00, 1.21), lowest vs. highest quintile) over 8 years. Plasma folate <21.8 nmol/L predicted declines in episodic memory for immediate (beta [β] = -0.26; 95% CI (-0.48, -0.03), β = -0.29; 95% CI (-0.50, 0.08) and β = -0.29; (-0.50, -0.08), for lowest three vs. highest quintile) and delayed recall (β = -0.20; 95% CI (-0.38, -0.01), β = -0.18; 95% CI (-0.37, -0.01) and β = -0.19; (-0.36, -0.01) lowest three vs. highest quintile). There were no significant associations in a subsample aged ≥65 years.

Conclusion: In those aged ≥50 years, lower concentrations of folate may have differential relationships with cognitive domains. Folate <11.2 nmol/L predicted a decline in global cognitive function, while <21.8 nmol/L predicted poorer episodic memory. Low folate was associated with accelerated decline in cognitive function and is an important marker for cognitive decline among older people.