Abstract
BACKGROUND: Clinical and genetic studies have implicated lipid dysfunction in Alzheimer Disease (AD) pathogenesis. While the etiologic impact of lipid intake on individuals is receiving attention, the role of food systems in shaping community-level incidence remains uncharacterized. METHODS: Mean country-level lipid intakes were compared to Age-Standardized Alzheimer-and-other-Dementia Incidence Rates (ASAIR) in 183 countries across all inhabited continents. Free-knot penalized spline regression and multivariable-adjusted linear regression, including a lag between intake and incidence, were used to assess the relationships between five lipid intakes and ASAIR. Validation was conducted using longitudinal within-country changes between 1990 and 2019. RESULTS: Here we show that omega-6 Polyunsaturated-Fatty-Acid (omega-6) intake exhibits a positive linear relationship with ASAIR (multivariable-adjusted model: β = 2.44; 95%CI: 1.70, 3.19; p = 1.38 × 10(-9)). ASAIR also increases with saturated-fat, trans-fat, and dietary-cholesterol up to a threshold. The association between omega6-PUFA and ASAIR is confirmed using longitudinal intake changes. The scale of predicted benefits varies by country but, our results predict a 2 standard deviation decrease (-3.8% as a percent of daily energy intake) in omega-6 intake would reduce ASAIR by 8% in the US. This level of consumption has already been achieved in 20 countries. If our other findings are validated in future work, decreasing all four lipids could potentially yield large ASAIR reductions (in the US: a 35% decrease). CONCLUSIONS: Higher levels of omega-6 consumption associate with increased ASAIR. Thus, decreasing omega-6 consumption on the country-level may have substantial benefits in reducing the burden of dementia.