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Health issues and nutrition in the elderly

Low folate predicts accelerated cognitive decline: 8-year follow-up of 3140 older adults in Ireland



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


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.


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.


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.

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Fig. 1: Univariate and multivariable longitudinal associations between baseline folate and cognitive assessments (MMSE, MoCA, verbal fluency, immediate recall, and delayed recall).

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The authors would like to acknowledge the contribution of the participants in the study, members of the TILDA research team, study nurses and administrative team. This work was supported by the Irish Department of Agriculture, Food and the Marine through the grant 13F492: The Nutritional Biomarker Database Enhancement Initiative of (“BIO-TILDA” 2013–2015). Original funding for TILDA was provided by The Atlantic Philanthropies, the Irish Government and Irish Life plc.


The sponsors played no role in designing or conducting the study or in the collection, management, analysis or interpretation of the data, nor did they have any input into the preparation, review or approval this paper.

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DMAO’C, CAMcG, RAK: Conception of research and study design. DMAO’C, SS, CDL, CAMcG: Analysis and interpretation of data. DMAO’C, SS, CAMcG: Preparation of paper DMAO’C, SS, CDL, AMO’H, EL, AMM, RC, CAMcG, RAK: Critical revision of paper. DMAO’C, CAMcG, RAK: Final approval for publication.

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Correspondence to Deirdre M. A. O’Connor.

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O’Connor, D.M.A., Scarlett, S., De Looze, C. et al. Low folate predicts accelerated cognitive decline: 8-year follow-up of 3140 older adults in Ireland. Eur J Clin Nutr 76, 950–957 (2022).

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