Recent research has revealed that individuals carrying the APOE4 risk gene for Alzheimer's disease may reduce their chances of developing dementia by adhering to the Mediterranean diet. This observational study, conducted by healthcare professionals at Mass General Brigham in Boston, highlights the significant impact of dietary choices on cognitive health, particularly for those with a genetic predisposition to dementia.
Dr. Dong Wang, MD, ScD, and his team published their findings in Nature Medicine, indicating that following the Mediterranean diet more effectively influenced dementia-related metabolites in individuals who are APOE4 homozygotes compared to those with a lower genetic risk. Co-author Dr. Yuxi Liu, PhD, emphasized that a greater adherence to the Mediterranean diet was associated with a significantly lower risk of dementia and a slower cognitive decline across the study population.
Among participants carrying two copies of the APOE4 allele, each one-unit increase in adherence to the Mediterranean diet was linked to an approximately 35% lower risk of dementia. These findings suggest that the Mediterranean diet may provide a protective effect against the heightened genetic risk associated with APOE4.
The APOE gene is recognized as the most substantial genetic risk factor for sporadic Alzheimer's disease. The APOE4 allele has been correlated with an increased risk and an earlier onset of Alzheimer's, while the APOE2 allele appears to offer some degree of protection. Studies show that carrying one APOE4 allele can increase the risk of Alzheimer's disease by three to four times, while having two alleles can elevate the risk by eight to twelve times. Remarkably, up to 25% of the population carries one copy of the APOE4 allele, and between 2% to 5% of individuals have two copies.
Research suggests that the APOE4 allele may influence Alzheimer's risk by hindering amyloid clearance and promoting amyloid aggregation. It is also closely linked to disruptions in lipid metabolism and impaired brain glucose metabolism.
In 2015, the randomized PREDIMED trial established a connection between the Mediterranean diet—a dietary pattern rich in antioxidants and anti-inflammatory properties—and cognitive benefits. The current research aimed to determine whether these benefits varied according to genetic backgrounds while also examining the role of blood metabolites, which reflect the body's processing of food.
The study analyzed data from 4,215 women in the Nurses' Health Study, who were followed from 1989 to 2023 for incidents of dementia. Additionally, researchers examined similar data from 1,490 men in the Health Professionals Follow-Up Study, monitored from 1993 to 2023. Dietary patterns were identified using food frequency questionnaires, and blood samples were assessed for various metabolites.
A subset of 1,037 women underwent regular cognitive testing via telephone. Researchers identified 57 metabolites linked to dementia risk, with variations based on the APOE4 genotype and other genetic variants. In APOE4 homozygotes, specific metabolites like cholesteryl esters and sphingomyelins were closely associated with increased dementia risk, while glycerides showed an inverse relationship.
A Mendelian randomization analysis revealed 19 potential causal relationships between metabolites and cognitive outcomes. The research indicated that individual components of the Mediterranean diet, such as nuts, fruits, and monounsaturated fats, were strongly associated with overall metabolomic patterns, suggesting a broader influence on key metabolic pathways.
The findings indicate that dietary strategies, particularly the Mediterranean diet, could be effective in reducing the risk of cognitive decline and delaying the onset of dementia. This recommendation is particularly pertinent for individuals at a higher genetic risk, such as those with two copies of the APOE4 genetic variant.
However, the study's authors noted that their research was conducted on a population primarily composed of well-educated individuals of European ancestry. They also highlighted that metabolomics are not typically included in clinical risk prediction models for Alzheimer's disease. Given that the study was observational, there is a possibility that the results may have been influenced by unknown confounding factors.
Looking ahead, the researchers expressed a desire to explore whether targeting specific metabolites through dietary changes or other interventions could lead to a more personalized approach in reducing dementia risk. Dr. Liu emphasized the potential for dietary modifications to play a crucial role in cognitive health, particularly for those genetically predisposed to Alzheimer's disease.
