Modified Mediterranean ketogenic diet resolves default mode network connectivity differences between adults with normal and impaired cognition

Background In the absence of disease modifying/preventative therapy for Alzheimer’s disease (AD), there has been increased focus on alternate therapeutic approaches, including the ketogenic diet, which supplies auxiliary metabolic fuel to brain and has potential neuroprotective effects. Our goal was to examine the modified Mediterranean‐ketogenic diet (MMKD) and an American Heart Association Diet (AHAD) in older adults at risk for AD with respect to cognitive performance and associated brain functional connectivity within the default mode network (DMN), which has been implicated in cognitive processes directed toward the self, such as introspection and autobiographic memory. Method Eighteen participants with normal cognition and subjective memory complaints (SMC) (n = 10, mean age = 65 ± 7) or Mild Cognitive Impairment (MCI) (n = 8, mean age = 64 ± 4) completed six weeks on both diets in a randomized crossover design. Before and after each diet, participants underwent 3T brain MRI and cognitive testing. MRI included T1‐weighted imaging for gray/white matter segmentation, and blood oxygen level dependent (BOLD) imaging for resting‐state functional connectivity. Cognitive function was evaluated using two memory tests, the Free and Cued Selective Reminding Test (FCSRT) and story recall, which were composited into a single memory score. BOLD data were pre‐processed and de‐noised using standard techniques, and normalized to the Mayo Clinic Adult Lifespan Template (MCALT). Connectivity analyses were performed using CONN functional connectivity toolbox. Briefly, functional connectivity of the DMN was analyzed utilizing the PCC for a seed to voxel connectivity analysis. Result At baseline, there were statistically significant differences in DMN connectivity between MCI and cognitively normal participants with SMC (Figure‐1), with connectivity increases between DMN and superior frontal gyrus, and decreases between DMN and superior parietal gyrus, which were significantly correlated with baseline memory scores (Figure‐2). After both diets, there were no detectable differences in DMN connectivity between the two groups. However, MMKD had a more pronounced effect on reducing DMN hyper‐connectivity among MCI participants than AHAD (Figure‐3). Conclusion Our results suggest that a ketogenic intervention may augment aberrant DMN network connectivity patterns in adults at risk for AD and lessen cognitive decline.