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. 2025 Jul 31;5(1):326.
doi: 10.1038/s43856-025-01059-3.

Country-level incidence of Alzheimer disease and related dementias is associated with increased omega-6-PUFA consumption

Timothy H Ciesielski  1 , Giuseppe Tosto  2 , Razaq O Durodoye  3 , Farid Rajabli  4 , Rufus O Akinyemi  5 , Goldie S Byrd  6 , William S Bush  3   7 , Brian W Kunkle  4 , Christiane Reitz  2 , Jeffery M Vance  4 , Margaret A Pericak-Vance  5 , Jonathan L Haines  3   7 , Scott M Williams  3   7
Affiliations

Country-level incidence of Alzheimer disease and related dementias is associated with increased omega-6-PUFA consumption

Timothy H Ciesielski et al. Commun Med (Lond). .

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.

Plain language summary

Scientific evidence from several fields indicates that lipids (fats) play a role in Alzheimer Disease development. However, studies conducted on the individual-level are not well suited to inform population-level interventions. In other words, we need population-based approaches to study how fat intakes vary between people in different countries and food systems. Here we used statistical models to adjust for potential biases, and we observed that the incidence of Alzheimer Disease and other dementias increased with mean country-level intake of omega-6 polyunsaturated fatty acids (omega-6). It also increased with saturated-fat, trans-fat, and cholesterol intake up to a threshold. The country-level omega-6 finding was validated in a second set of analyses that evaluated changes in fat intake over time. If future research confirms these observations, they indicate that incidence of dementia could be reduced by lowering the mean intake of omega-6 globally.

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Conflict of interest statement

Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. The shared biochemical pathway for omega-6 and omega-3 processing.
This lipid processing pathway is central to research in omega-3 and omega-6. The same set of enzymes process both of these lipid classes, and thus an excess of omega-6 can alter and impair omega-3 processing. In short, an imbalance in substrates can produce a corresponding imbalance in products. The omega-6 products are largely proinflammatory mediators, while the omega-3 products are primarily inflammation resolving factors. This biochemistry predicts that excess omega-6 will drive excess inflammation. This figure is adapted from ref. (reuse under the Creative Commons Attribution license; http://creativecommons.org/licenses/by/4.0/).
Fig. 2
Fig. 2. Free-knot penalized splines showing the relationship between country-level lipid intakes and ASAIR.
Incidence is on the y-axis and the y axis range is the same for all 5 plots, for ease of comparison. Each plot depicts the penalized regression spline for a distinct class of country-level lipid data: a omega-6, b omega-3, c saturated fat, d trans-fat, and e dietary cholesterol intake. The dashed lines depict 95% CIs and the hash marks along the x-axis depict data density (n = 183 countries). Estimates are imprecise in regions of low data density. Nonlinear relationships were detected by the generalized cross-validation (GCV) process for saturated fat, trans-fat, and dietary cholesterol (c–e). Apparent thresholds are indicated with a vertical red line.
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