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Prediction of cognitive outcome and progression to dementia using ω6-PUFA/ω3-PUFA ratio.

Alzheimer's & dementia : the journal of the Alzheimer's Association

Authors: Víctor Andrade, Luca Kleineidam, Holger Wagner-Thelen, Tommaso Ballarini, Rafael Campos-Martin, Pamela Martino-Adami, Kumar Parijat Tripathi, Sophie Guyonnet, Bruno Vellas, Martin Scherer, Wolfgang Maier, Michael Pentzek, Matthias Schmid, Steffi Riedel-Heller, Siegfried Weyerer, Horst Bickel, Birgitt Wiese, Sarah Egert, Michael Wagner, Alfredo Ramírez

INTRODUCTION: The polyunsaturated fatty acids (PUFAs) omega-6 (ω6) and omega-3 (ω3) are linked to cognitive performance and Alzheimer's-type dementia (DAT), but ω3-PUFA supplementation offers limited benefits. We propose that the ω6-PUFA/ω3-PUFA ratio better explains cognitive decline and DAT risk.

METHODS: PUFA profiles were examined in the AgeCoDe cohort (n = 3327) and MAPT trial (n  = 1679). Cox and linear mixed models evaluated associations of individual PUFAs and the ω6-PUFA/ω3-PUFA ratio with DAT progression and cognitive decline. Mendelian randomization (MR) assessed genetic causal effects. The effect of ω3-PUFA on ω6-PUFA levels was analyzed.

RESULTS: Higher ω6-PUFA/ω3-PUFA ratio increased DAT risk beyond ω3-PUFA levels alone. A baseline high (detrimental) ratio predicted faster cognitive decline, whereas longitudinal improvements slowed decline. MR supported a genetic non-causal link. Higher ω3-PUFA levels correlated with lower ω6-PUFA species.

DISCUSSION: The ω6-PUFA/ω3-PUFA ratio better predicts cognitive decline and DAT progression than individual PUFAs, suggesting that dietary adjustments may help prevent dementia.

© 2026 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

PMID: 42271192

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