A ketogenic supplement improves white matter energy supply and processing speed in mild cognitive impairment

INTRODUCTIONWhite matter (WM) energy supply is crucial for axonal function and myelin maintenance. Providing ketones, the brains alternative fuel to glucose, is a therapeutic strategy to bypass the brains glucose-specific energy deficit in mild cognitive impairment (MCI). How an additional supply of ketones affects glucose or ketone uptake in specific WM fascicles in MCI has not previously been described. METHODSThis 6-month interventional study included MCI participants randomized to a placebo (n = 16) or ketogenic medium chain triglyceride (kMCT; n = 17) drink. A neurocognitive battery and brain imaging were performed pre- and post-intervention. WM fascicle uptake of ketone and glucose and structural properties were assessed using positron emission tomography and diffusion imaging, respectively. RESULTSKetone uptake was increased by 2.5 to 3.2-fold in nine fascicles of interest (P < 0.001) only in the kMCT group, an effect seen both in deep WM and in fascicle cortical endpoints. Improvement in processing speed was associated with WM ketone uptake globally and in individual fascicles, most importantly the fornix (r = +0.61; P = 0.014). DISCUSSIONA 6-month ketogenic supplementation in MCI improved WM energy supply globally. The significant positive association with processing speed suggests that ketones may have a role in myelin integrity in MCI.