“Our study has huge strengths in expanding the sample size and in adding demographics compared to what previous research has done,” said Tamar Sofer, PhD, and director of the Biostatistics Core Program in Sleep Medicine Epidemiology and a member of the Division of Sleep and Circadian Disorders at the Brigham. “It also illustrates that studies that begin by focusing on minorities can give rise to insights that may be beneficial to other populations. We hope our findings will help people in making specific nutritional choices and in improving their cognitive health.”
Nowadays, researchers can discover biomarkers associated with health changes and diseases by utilizing approaches like metabolomic profiling, which can survey thousands of metabolites within blood samples. An initial study in Boston looking at older adults of Puerto Rican descent found a series of metabolites that were associated with measured cognitive functions. Building off that work, Brigham researchers tested metabolite-cognitive function associations in 2,222 U.S. Hispanic/Latinx adults from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), and in 1,365 Europeans and 478 African Americans from the Atherosclerosis Risk In Communities (ARIC) Study. They then applied Mendelian Randomization (MR) analyses to determine causal associations between the metabolites and cognitive function, as well as between a Mediterranean diet and cognitive function.
The team discovered that six metabolites were consistently associated with a lower global cognitive function across all of the studies. Four of them were sugars or derivatives of sugars. Another metabolite, beta-cryptoxanthin, was associated with a higher global cognitive function in the HCHS/SOL and is also strongly correlated with fruit consumption.
“It is possible that these metabolites are biomarkers of a more direct relationship between diet and cognitive function,” said lead author Einat Granot‐Hershkovitz, PhD, who worked on this study as a postdoctoral fellow in Sofer’s lab at the Brigham.
Diet itself can be an important source of many metabolites, including some with positive or negative associations with cognitive function. In this study, the Mediterranean diet score was associated with higher levels of beta-cryptoxanthin, which was positively associate with cognitive function. The Mediterranean diet was also negatively associated with the levels of other metabolites, which were associated with lower cognitive function. Previous research has also shown that adherence to the Mediterranean diet is associated with cognitive benefits.
While the study did have limitations like its cross-sectional, observational design which limited conclusions about the potential influence of modifying metabolite levels on cognitive function (causal inference), the researchers attempted to use MR analyses to account for unmeasured confounding and establish some level of causal inference. Their results showed weak causal effects between specific metabolites and global cognitive function. The researchers recommend that future studies assess metabolite associations with cognitive function and work to evaluate whether observed associations indeed indicate that changes in diet – manifesting in changing metabolite levels – can improve cognitive health.
“While the causal effect seen in our study may be weak, repeated research has shown that the Mediterranean diet is associated with better health outcomes, including cognitive health,” said Sofer. “Our study further supports the importance of a healthy diet towards safeguarding cognitive function, consistent across races and ethnicities.”
Disclosures: Co-author Bruce Kristal is the inventor of general metabolomics-related IP that has been licensed to Metabolon via Weill Medical College of Cornell University and for which he receives royalty payments via Weill Medical College of Cornell University. He also consults for and has a small equity interest in the company. Metabolon offers biochemical profiling services and is developing molecular diagnostic assays detecting and monitoring disease. Metabolon has no rights or proprietary access to the research results presented and/or new IP generated under these grants/studies.
Funding: The Hispanic Community Health Study/Study of Latinos is a collaborative study supported by contracts from the National Heart, Lung, and Blood Institute (HHSN268201300001I / N01-HC-65233, HHSN268201300004I / N01-HC-65234, HHSN268201300002I / N01-HC-65235, HHSN268201300003I / N01- HC-65236, HHSN268201300005I / N01-HC-65237). The following Institutes/Centers/Offices have contributed to the HCHS/SOL through a transfer of funds to the NHLBI: National Institute on Minority Health and Health Disparities, National Institute on Deafness and Other Communication Disorders, National Institute of Dental and Craniofacial Research, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, NIH Institution-Office of Dietary Supplements. Additionally, this work was supported by the National Institute on Aging (R21AG070644, R01AG048642, RF1AG054548, RF1AG061022, and R21AG056952, P30AG062429 and P30AG059299). Support for metabolomics data was provided by the JLH Foundation (Houston, Texas). The Atherosclerosis Risk in Communities study has been funded in whole or in part with Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services under contract numbers (HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700004I, and HHSN268201700005I).
Paper Cited: Granot-Hershkovitz et al. “Plasma metabolites associated with cognitive function across race/ethnicities affirming the importance of healthy nutrition.” Alzheimer’s & Dementia DOI: 10.1002/alz.12786