Abstract
BACKGROUND: Chronic neuroinflammation contributes to Alzheimer's disease (AD) pathogenesis, and diet is a modifiable factor influencing inflammation. The impact of an anti-inflammatory diet on AD-specific mortality remains unclear. OBJECTIVES: To examine the association between adherence to an anti-inflammatory diet (measured as the percentage of dietary energy from anti-inflammatory foods) and AD-specific mortality, as well as all-cause mortality, in a large national cohort, and to determine whether associations differ by sex or race/ethnicity. METHODS: We analyzed 18,795 U.S. adults (≥18 years) from the 2007-2014 National Health and Nutrition Examination Survey. Anti-inflammatory diet adherence was defined as the percentage of total energy intake from anti-inflammatory foods, categorized as 0 %, <5 %, 5-9.99 %, or ≥10 %. Outcomes were AD-specific mortality and all-cause mortality ascertained via the National Death Index. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) for mortality across intake categories, adjusting for demographic, lifestyle, and health factors. Analyses were stratified by sex, race/ethnicity, and age (≥45 years for AD mortality). RESULTS: Participants with 0 % anti-inflammatory intake had a higher all-cause mortality risk (HR 3.82, 95 % CI 1.18-12.33) compared to those with ≥10 % intake. In the overall analysis, 0 % anti-inflammatory intake showed a trend of reduced AD-specific mortality although its did not reach statistical significance after full adjustment (HR 3.04, 95 % CI 0.74-12.46 vs. ≥10 % intake; p>0.05). Notably, the inverse association between anti-inflammatory diet and AD mortality emerged in subgroup analyses. Male participants and non-Hispanic White participants with 0 % intake had the highest AD mortality hazards (HR 12.83 and 3.77, respectively, vs. ≥10 % intake), indicating significant risk reductions with anti-inflammatory diet in these groups. In contrast, no significant associations were observed in female or non-White subgroups. Even a modest intake of anti-inflammatory foods (≥10 % of calories) was associated with lower AD mortality risk in the above subgroups and with lower all-cause mortality overall. CONCLUSION: Greater consumption of anti-inflammatory foods was associated with lower all-cause and a trend toward lower AD-specific mortality. The observed protective effects were confined to certain subpopulations (notably men and non-Hispanic Whites). Even a small portion of the diet (10 % of calories) being anti-inflammatory was linked to reduced mortality risk in these groups, suggesting that achievable dietary changes could have an impact. These findings support modifying dietary content is a practical, low-cost intervention that could mitigate neuroinflammation to reduce AD mortality risk.