A ketogenic intervention improves dorsal attention network functional and structural connectivity in mild cognitive impairment

Ketones, the brain's alternative fuel to glucose, bypass the brain glucose deficit and improve cognition in mild cognitive impairment (MCI). Our goal was to assess the impact of a 6-month ketogenic inter-vention on the functional connectivity within eight major brain resting-state networks, and its possible relationship to improved cognitive outcomes in the BENEFIC trial. MCI participants were randomized to a placebo ( n = 15) or ketogenic medium chain triglyceride (kMCT; n = 17) intervention. kMCT was associ-ated with increased functional connectivity within the dorsal attention network (DAN), which correlated to improvement in cognitive tests targeting attention. Ketone uptake ( 11 C-acetoacetate PET) specifically in DAN cortical regions was highly increased in the kMCT group and was directly associated with the improved DAN functional connectivity. Analysis of the structural connectome revealed increased fiber density within the DAN following kMCT. Our findings suggest that ketones in MCI may prove beneficial for cognition at least in part because they improve brain network energy status, functional connectivity and axonal integrity. (c) 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

Automated summary

This study aimed to assess the impact of a 6-month ketogenic intervention on the functional connectivity within brain resting-state networks and its relationship to improved cognitive outcomes. The findings suggest that ketones can improve functional connectivity in the dorsal attention network and cognitive abilities in individuals with mild cognitive impairment.