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

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.