A recent study published in Alzheimer’s and dementia uses transcriptomic data to investigate the protective effects of the Mediterranean-DASH neurodegenerative delay diet (MIND) intervention in reducing dementia risk and slowing cognitive decline.
Study: The MIND diet, transcriptomic changes in the brain and dementia. Image credits: 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 related to dementia prevention. Higher MIND diet scores have been associated with slower cognitive decline and a lower risk of dementia.
The authors of the current study previously analyzed ribonucleic acid (RNA) sequencing (RNA-seq) data from autopsy of cortical tissues from the Rush Memory and Aging Project (MAP) and Religious Orders Study (ROS). This study revealed that the expression of several gene clusters in the dorsolateral prefrontal cortex (DLPFC) was associated with cognitive decline, Alzheimer’s disease pathology, and dementia.
In the current study, RNA-seq and clinical data were obtained from 1,204 participants from the ROS and MAP. Enrollment for ROS and MAP began in 1994 and 1997, respectively.
Study participants were free of dementia at enrollment. Clinical assessments were performed at baseline, followed by annual reviews until death.
Cognition was measured using data from 17 tests in five cognitive domains. Raw test scores were standardized and an overall composite score was generated as the mean of the standardized scores.
A neurologist reviewed the clinical data at death to determine the likely cognitive diagnosis. From 2004 onwards, a food frequency questionnaire (FFQ) was administered in the MAP. The MIND diet score was based on repeated FFQ measurements and was very stable; therefore, the MIND diet score based on the first FFQ represented long-term diet quality.
A total of 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 then 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 pathways and the eventual diagnosis of mild cognitive impairment (MCI) or dementia at death.
Findings of the study
Of the 1,204 participants, 68% were women. The mean age at enrollment and death was 81 and 90 years, respectively. A total of 525 and 285 participants had dementia and MCI at death, respectively.
The diet was evaluated approximately six years before death, at which time the average MIND diet score was 7.5.
The elastic net regression model identified 50 genes with robust associations with the MIND diet score, of which 27 and 23 were negatively and positively weighted in the transcriptomic profile, respectively.
Myeloperoxidase (M.P.O) and the transcriptional and immune response regulator (TCIM) had the strongest positive associations, while MAP3K12-binding inhibitory protein 1 (MBIP), coiled coil and C2 domain with 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 risk of dementia and slower cognitive decline. In comparison, the pyridoxal-dependent decarboxylase domain that 2 (PDXDC2P), IGSF5, MBIP, and removing 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 a lower risk of dementia 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 and similar results were obtained after adjusting for compositions, the potential role of confounding factors in these results could not be eliminated.
Furthermore, the study cohort consisted primarily of non-Hispanic white individuals; therefore, future research on diverse populations is needed to confirm these findings.
Magazine reference:
- Li, J., Capuano, A.W., Agarwal, P., et al. (2024). The MIND diet, transcriptomic changes in the brain and dementia. Alzheimer’s and dementia. doi:10.1002/alz.14062