Q. Shi, QY. Hu, CZ. Xu, J. Zhou and F. Yin (2026). Association between ketogenic diet and cognitive function in older adults: The mediating role of neutrophil to high-density lipoprotein cholesterol ratio. Medicine, 105(5), e47441. https://doi.org/10.1097/MD.0000000000047441

PubMed 41630286

[Abstract]
The ketogenic diet (KD), characterized by high fat and low carbohydrate intake, has shown potential neuroprotective effects, but its association with cognitive function in older adults and the underlying mechanisms remain unclear. This study aimed to investigate the relationship between KD and cognitive function and explore the mediating role of the neutrophil to high-density lipoprotein cholesterol ratio (NHR), a marker of inflammation and lipid metabolism. We conducted a cross-sectional analysis using data from the National Health and Nutrition Examination Survey 2011 to 2014, involving 2166 participants aged ≥ 60 years. Dietary ketogenic ratio (DKR) was calculated to assess KD adherence, and cognitive function was evaluated using the word learning and recall modules of the Consortium to Establish a Registry for Alzheimer Disease, animal fluency test, digital symbol substitution test and summary Z scores. NHR was computed as the ratio of neutrophil count to HDL-C level. Linear regression, restricted cubic splines model, threshold effect analysis, subgroup analysis and mediation analysis were employed to examine associations and mediating effects. Sensitivity analysis was used to check the robustness of the results. Higher DKR was significantly associated with improved cognitive function, Conversely, elevated NHR was negatively correlated with cognitive function, particularly when exceeding a certain threshold. Mediation figure revealed that NHR mediated 4.83% and 4.75% of the association between DKR and digital symbol substitution test scores and Summary Z scores, respectively, and cognitive function. Subgroup analyses indicated that the associations of DKR and summary Z scores were robust across all subgroups. Sensitivity analysis confirmed the robustness of the results. Our findings suggest that KD is significantly associated with cognitive function in older adults, partially through reducing NHR. These results provide insights into the potential mechanisms linking dietary patterns, inflammation, lipid metabolism, and cognitive health. Further prospective and experimental studies are needed to validate these findings.