Mediterranean Diet May Mitigate Genetic Risk for Alzheimer Disease
For those carrying the APOE4 gene, following a Mediterranean diet may lower the risk of developing Alzheimer disease and dementia, suggest study results published in Nature Medicine.
“Elucidating the pathogenic mechanisms underlying Alzheimer disease-related dementias (ADRD) and identifying modifiable factors capable of targeting these mechanisms are critical for prevention,” wrote Yuxi Liu, PhD, and co-authors.
The authors analyzed data from 4,215 women in the Nurses’ Health Study and replicated key findings in 1,490 men from the Health Professionals Follow-Up Study. To assess diet, the authors used semiquantitative food frequency questionnaires in both cohorts, with dietary quality evaluated using the MedDiet Index. Blood samples were also taken to examine metabolites. A subset of 1,037 women completed regular cognitive testing via telephone.
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The authors found that individuals who adhered most closely to the MedDiet had a significantly lower risk of dementia and better cognitive function. These benefits were most pronounced amongst those with 2 copies of the APOE4 gene, compared to noncarriers and those with only 1 copy of the gene. In particular, nuts, fruits, and monosaturated fats were strongly associated with overall metabolomic patterns.
The study also revealed that 39.5% of the association between MedDiet adherence and dementia risk was mediated by a set of metabolites among APOE4 carriers (P=0.05), while no mediation effect was observed in noncarriers. “These findings collectively indicated that the MedDiet’s potential to modulate cognitive health-related metabolites varied by APOE4 genotype, suggesting that this dietary pattern could be an effective strategy to delay dementia onset in APOE4 homozygotes, despite their higher risk profile,” the authors suggested.
Additionally, authors noted that the study builds the case for a broader understanding of how APOE4 contributes to the emergence of Alzheimer disease-related dementia. In addition to the gene’s role in distorting lipid metabolism, it also affects other pathways, including betaine and the urea cycle metabolism.
“In conclusion, our study highlights the substantial influence of genetic variants, particularly APOE4 homozygosity, on plasma metabolites and their associations with ADRD risk,” wrote Liu and co-authors. “These genetic effects are widespread across the plasma metabolome and our findings identify the MedDiet as a promising approach to mitigate genetically dependent ADRD risk by targeting a broad spectrum of metabolic pathways.”
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