Written by Tabish Mehraj, PhD. In this study, during the 9-year follow-up, 506 participants developed dementia. A higher LCD score was associated with lower dementia risk (HR per SD increment: 0.90; 95% CI: 0.82-0.99). Plant-based and healthy LCDs showed stronger inverse associations (0.85, 95% CI, 0.78, 0.94 and 0.82, 95% CI, 0.74, 0.90), while higher animal-based (1.10; 95% CI, 1.00, 1.20) and unhealthy LFDs (1.13; 95% CI, 1.04, 1.24) were linked to higher dementia risk. 

Dementia is a global health concern, and modifiable lifestyle factors may help preserve cognitive health. Low-carbohydrate (LCD) and low-fat diets (LFDs) are primarily promoted for managing weight and cardiometabolic health; their long-term association with dementia risk remains unclear. This prospective cohort study assessed whether LCDs and LFDs were associated with dementia and whether this association differed by genetic susceptibility to Alzheimer’s disease (AD).

Research scientists examined data from 5,301 dementia-free adults, aged 55 years or older, who participated in the Health and Retirement Study. Dietary intake was assessed using a validated food-frequency questionnaire in 2013–2014, and participants were followed for 9 years. Researchers developed overall LCD and LFD scores, as well as plant-based, animal-based, healthy, and unhealthy versions, to account for the sources and quality of macronutrients. Incident dementia was identified using the Langa-Weir algorithm. Genetic susceptibility was evaluated using APOE ε4 carrier status, defined as carrying at least one copy of the ε4 variant of the APOE (apolipoprotein E) gene, and an Alzheimer’s disease polygenic risk score (AD-PRS).

Results/ Key Findings

• During the follow-up study, 506 participants developed dementia; adherence to higher overall LCD was associated with a modestly lower dementia risk (HR 0.90, 95% CI 0.82–0.99 per SD increase).
• Associations were stronger for healthier LCDs; plant-based and healthy LCDs were associated with 15% and 18% lower dementia risk, respectively (HR 0.85 and 0.82).
• Overall, LFD was not significantly associated with dementia risk (HR 1.05), while animal-based and unhealthy LFDs were associated with higher risk (HR 1.10 and 1.13).
• Plant-based and healthy LCDs were also associated with better global and domain-specific cognitive performance.
• Associations were generally consistent across APOE ε4 and AD-PRS levels and remained robust after adjustment for diet quality and competing risk of death.

A major strength of this study was the potential design and a large, nationally representative sample, which allowed researchers to examine dementia incidence over a longer follow-up period. A detailed dietary scoring system was also a strength. Rather than considering carbohydrate or fat intake alone, the researchers distinguished between plant- and animal-based sources and healthy versus unhealthy macronutrient sources. The study and evaluation of genetic information also enabled the investigators to assess whether dietary associations differed by inherited dementia susceptibility. The sensitivity analyses further strengthened the robustness of the findings.

Several limitations should be considered. Dietary intake was self-reported and assessed at a single time point, which may have introduced measurement error and may not have captured dietary changes over the follow-up period. Although numerous potential confounders were adjusted for, residual confounding cannot be excluded because this was an observational study. The dietary patterns represented usual intake ranges rather than extreme carbohydrate restriction, so the findings may not apply to very-low-carbohydrate diets. Selective attrition and missing data may also have introduced bias and could affect generalizability.

This study suggests that the quality and source of macronutrients may matter more for cognitive health than simply reducing carbohydrate or fat intake. Plant-based and higher-quality LCDs were associated with lower dementia risk, whereas animal-based and unhealthy LFD patterns were associated with higher risk. However, the findings demonstrate associations rather than causation. Further research, particularly randomized trials and studies using repeated dietary assessments and more detailed dementia diagnoses, is needed before specific dietary recommendations for dementia prevention can be established.

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Posted August 27, 2026.

Dr. Tabish Mehraj is a pharmaceutical scientist with expertise in pharmaceutics, drug delivery, and formulation development. She earned her PhD in Pharmaceutical Sciences from the University of Mississippi, where her research focused on the formulation, optimization, and characterization of lipid-based nanocarriers for targeted liver delivery of antimalarial therapeutics. Dr. Mehraj has also served as an ORISE Fellow at the U.S. Food and Drug Administration (FDA), where she evaluated the effects of formulation and process design on the quality and performance of intravaginal drug delivery systems and developed bio-relevant in vitro drug release testing methods. She has teaching experience in pharmaceutical and life sciences courses and has authored peer-reviewed publications, book chapters, and conference presentations. Dr. Mehraj is an active member of the American Association of Pharmaceutical Scientists and has been recognized by honor societies including Rho Chi and Gamma Beta Phi.

Reference:

1. Chen, P. H., Wu, P. Z., Ge, M. T., Wu, P. M., Ye, M. J., Shan, M. S., … & Yuan, S. C. (2026). Low-carbohydrate and low-fat diets, genetic susceptibility, and long-term risk of dementia: A prospective cohort study. The American Journal of Clinical Nutrition, 101463.