How the MIND diet may protect against dementia

By Tarun Sai LomteReviewed by Benedette Cuffari, M.Sc.Aug 20 2024

A recent study published in Alzheimer’s & Dementia utilizes transcriptomic data to examine the protective effects of the Mediterranean-DASH intervention for neurodegenerative delay (MIND) diet in reducing the risk of dementia and slowing cognitive decline.

Study: The MIND diet, brain transcriptomic alterations, and dementia. Image Credit: New Africa / Shuterstock.com

About the study

Preliminary evidence from randomized clinical trials suggests that the Dietary Approaches to Stop Hypertension (DASH) and Mediterranean diets may be protective against cognitive decline. The MIND diet was originally designed to emphasize nutrients and foods linked to dementia prevention. Higher MIND diet scores have been associated with slower cognitive decline and lower dementia risk.

The authors of the current study previously analyzed ribonucleic acid (RNA)-sequencing (RNA-seq) data from autopsied cortical tissues from the Rush Memory and Aging Project (MAP) and Religious Orders Study (ROS). This study revealed dorsolateral prefrontal cortex (DLPFC) expression of various gene clusters was associated with cognitive decline, Alzheimer’s disease pathology, and dementia.

In the present study, RNA-seq and clinical data were obtained from 1,204 participants from the ROS and MAP. Enrollment in ROS and MAP commenced in 1994 and 1997, respectively.

Study participants were free of dementia at enrollment. Clinical assessments were performed at baseline, followed by annual evaluations until death.

Cognition was measured using data from 17 tests in five cognitive domains. Raw test scores were standardized and a global composite score was generated as the average of standardized scores.

A neurologist reviewed clinical data at death to determine the likely cognitive diagnosis. A food frequency questionnaire (FFQ) was administered from 2004 onwards in the MAP. The MIND diet score was based on repeated FFQ measures was highly stable; therefore, the MIND diet score based on the first FFQ represented long-term dietary quality.

Overall, 17,255 quality-controlled, annotated genes were included in the analyses. An elastic net regression model was used to regress the MIND diet score on 17,255 genes in 482 individuals with FFQ and RNA-seq data. The model selected genes whose weighted transcriptomic profile was strongly correlated with the MIND diet score.

Linear regression analysis was used to examine associations between the MIND diet score and its components with individual genes. The elastic net model was subsequently applied to an independent set of 772 people with only RNA-seq data. The researchers also examined associations between the transcriptomic profile score with cognitive trajectories and final diagnosis of mild cognitive impairment (MCI) or dementia at death.

Study findings

Of the 1,204 participants, 68% were female. The average ages at enrollment and death were 81 and 90 years, respectively. A total of 525 and 285 participants had dementia and MCI at death, respectively.

Diet was evaluated about six years before death, at which point the average MIND diet score was 7.5.

The elastic net regression model identified 50 genes with robust associations with the MIND diet score, 27 and 23 of which were negatively and positively weighted in the transcriptomic profile, respectively.

Myeloperoxidase (MPO) and the transcriptional and immune response regulator (TCIM) had the strongest positive associations, whereas MAP3K12 binding inhibitory protein 1 (MBIP), coiled-coil and C2 domain containing 2B (CC2D2B), and immunoglobulin superfamily member 5 (IGSF5) had the strongest negative associations with the MIND diet. When this model was applied to 722 people with only RNA-seq data, a higher transcriptomic profile score was associated with a reduced risk of dementia and slower cognitive decline.

TCIM, MPO, zinc finger protein 827 (ZNF827), and C14orf132 expression was associated with higher MIND diet scores, reduced dementia risk, and slower cognitive decline. Comparatively, pyridoxal dependent decarboxylase domain containing 2 (PDXDC2P), IGSF5, MBIP, and decapping exoribonuclease (DXO) expression levels were associated with lower MIND diet scores and poor cognitive outcomes.

Conclusions

The current study identified a transcriptomic profile of 50 genes that correlated with the MIND diet, which was significantly associated with lower dementia risk and slower cognitive decline. Some limitations of the current study include the use of bulk RNA-seq data from DLPFC, which includes multiple cell types.

Although cell-type proportions were estimated, with similar results obtained after adjusting for compositions, the potential role of confounding factors in these results could not be eliminated.

Furthermore, the study cohort was primarily comprised of non-Hispanic White individuals; therefore, future research on diverse populations is needed to corroborate these findings.