Highlight
The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) trial is the first dietary intervention study providing a comprehensive genetic dataset linked to cognitive outcomes. It validated high-quality genotyping and imputation methods with strong APOE concordance and replicated key genetic associations influencing nutritional biomarkers. This novel resource enables precision nutrition research targeting personalized cognitive health strategies.
Study Background and Disease Burden
Alzheimer’s disease (AD) and related dementias present an escalating global health challenge, with no curative treatment and high socio-economic burden. Preventive strategies focusing on modifiable lifestyle factors such as diet are, therefore, a critical public health priority. The MIND diet, a hybrid of Mediterranean and DASH diets emphasizing brain-healthy foods, has demonstrated potential to slow cognitive decline and reduce AD risk. However, interindividual variability in response to dietary interventions necessitates understanding genetic contributions that modulate this variability.
Study Design
The MIND trial was a rigorously designed 3-year, multicenter, randomized controlled trial involving 604 individuals at elevated risk for Alzheimer’s dementia based on age and cognitive status. Participants were randomized to the MIND diet intervention, aimed at encouraging adherence to dietary recommendations known to support neurocognitive health, or to control dietary conditions. Cognitive decline was the primary endpoint, assessed through validated neuropsychological batteries. As part of the trial, DNA samples were collected from whole blood or serum to develop a genetic resource facilitating investigation into gene-diet interactions influencing cognitive outcomes.
Methods for Genotyping and Genetic Data Quality Control
Genetic profiling employed the Illumina Infinium Global Diversity Array, enabling broad coverage across diverse ancestral backgrounds. Standard quality control procedures were applied, including filtering for sample integrity, call rate, and variant quality, to ensure robust data reliability. Genetic imputation utilized the 1000 Genomes Phase 3 v5 reference panel, maximizing genome-wide variant coverage. The final dataset comprised 494 participants of inferred European ancestry and 58 of inferred African ancestry.
Key Findings
Analysis revealed significant batch, specimen type, and study site effects on genotyping quality, underscoring the importance of rigorous QC measures. The imputed APOE genotype—a well-established genetic risk factor for AD—showed high concordance (98.2%) against gold-standard sequencing data, confirming data accuracy and validity for downstream analyses.
Furthermore, researchers replicated several known genome-wide significant single nucleotide polymorphisms (SNPs) previously associated with biomarkers relevant to dietary components and metabolic pathways, such as adiponectin (rs16861209, p = 1.5 × 10-5), alpha-linolenic acid (rs174547, p = 1.3 × 10-7), and alpha-tocopherol (rs964184, p = 0.003). These replications support the genotyping and imputation quality and highlight potential metabolic pathways influencing the diet’s cognitive effects.
Importantly, the resultant dataset establishes a genetic backbone to explore how genetic variability influences the cognitive response to the MIND diet. This enables integrative analyses combining genomics with other omics platforms (e.g., metabolomics, epigenomics), offering mechanistic insight into diet-induced neuroprotection and pathways involved in cognitive decline.
Expert Commentary
The MIND trial’s genetic resource represents a pioneering advancement in neuro-nutritional research by linking high-fidelity genetic data directly to an evidence-based dietary intervention with cognitive endpoints. This approach aligns closely with emerging precision nutrition paradigms, which seek to tailor dietary recommendations based on individual genetic profiles and molecular phenotypes.
However, there are limitations to note. The majority European ancestry of participants may limit generalizability across diverse populations, highlighting the need for additional multiethnic studies. The observed batch and specimen type effects also call for careful analytic adjustment to avoid confounding. Further longitudinal follow-up and replication of gene-diet interactions and their biological implications are needed to solidify clinical translation.
Conclusion
The MIND trial’s genetic dataset is a unique and valuable resource that lays the foundation for precision nutrition approaches targeting cognitive aging and Alzheimer’s disease risk. By enabling detailed exploration of genetic factors underlying variability in dietary intervention benefit, this resource can accelerate identification of individuals most likely to benefit from the MIND diet. Such personalized strategies hold promise to optimize cognitive health outcomes and mitigate dementia burden globally.
Future studies integrating multi-omics data will deepen mechanistic understanding, informing targeted therapies and public health strategies to harness nutrition as a modifiable factor in neurodegenerative disease prevention.
References
1. Liu Y, Fowler H, Wang DD, Barnes LL, Cornelis MC. Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) Trial: Genetic Resource for Precision Nutrition. Nutrients. 2025 Aug 4;17(15):2548. doi: 10.3390/nu17152548. PMID: 40806132; PMCID: PMC12348084.
2. Morris MC, Tangney CC, Wang Y, Sacks FM, Bennett DA, Aggarwal NT. MIND diet associated with reduced incidence of Alzheimer’s disease. Alzheimer’s & Dementia. 2015 Sep;11(9):1007-1014.
3. Crane PK, Walker R, Hubbard RA, et al. Glucose levels and risk of dementia. N Engl J Med. 2013 Mar 28;368(13):1178-1186.
