Is keto neuroprotective in individuals with impaired cognition?

Two studies presented at AAIC 2021 showed a potential neuroprotective effect of a ketogenic supplement or diet: In one study, consumption of a keto drink was associated with improvements in dorsal attention network (DAN) functional connectivity in mild cognitive impairment (MCI). Another study showed the keto diet’s potential to improve aberrant default mode network (DMN) connectivity patterns in adults at risk for Alzheimer’s disease (AD).

BENEFIC trial: Keto drink

This trial randomized 32 participants 1:1 to consume either a ketogenic medium chain triglyceride (kMCT) or a placebo drink for 6 months. Neurocognitive imaging studies were conducted prior to and after intervention. [AAIC 2021, abstract 57660]

Changes in DAN functional connectivity was significantly greater in the kMCT vs the placebo arm (p=0.024). This difference remained after adjusting for confounding factors*, with a large effect size (p=0.043).

The changes in specific tests** targeting attention, as well as in attention and processing speed composite Z-score, were significantly associated with increased DAN functional connectivity. (p=0.021).

Change in ketone uptake, specifically in the DAN cortical regions, was significantly greater in the kMCT vs the placebo arm (p=0.001). This was also directly associated with the improved DAN functional connectivity, with a large effect size (Spearman r=0.69; p=0.002).

“Functional connectivity in the DAN deteriorates early in MCI … [Our findings show that] a 6-month ketogenic intervention improves DAN functional connectivity in MCI, an improvement that is directly linked to increased [ketone] supply to the DAN,” said the researchers. “The beneficial effect of ketones – the brain’s alternative fuel to glucose – on cognition in MCI may be linked to improved DAN connectivity.”

The current findings boost the initial findings of BENEFIC reflecting improved measures of cognition in several domains after consuming the ketogenic drink for 6 months. [Alzheimers Dement 2019;15:625-634]

Modified Mediterranean-keto

Eighteen participants with normal cognition and subjective memory complaints (SMC; n=10) or MCI (n=8) followed and completed two diets – a modified Mediterranean-ketogenic diet (MMKD) and an American Heart Association Diet (AHAD) diet – for 6 weeks. Participants underwent 3T brain MRI and cognitive testing before and after each diet. [AAIC 2021, abstract 56711]

At baseline, significant differences in DMN connectivity were seen between participants with MCI and SMC, with connectivity improvements between DMN and the superior frontal gyrus (p=0.0064) and the superior parietal gyrus (p=0.033). These were significantly associated with baseline memory scores.

After following both diet regimens, no detectable differences were seen in DMN connectivity between individuals with SMC (p=0.327 [MMKD] vs p=0.277 [AHAD]) and MCI (p=0.326 vs p=0.175).

However, when comparing the two diets in individuals with MCI, a more pronounced effect was seen with MMKD vs AHAD (p=0.002 vs p=0.244) in terms of reduced DMN hyperconnectivity.

“In the absence of disease modifying/preventative therapy for 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,” said the researchers.

The improvements in the aberrant DMN connectivity with MMKD among adults with impaired cognition may eventually reduce cognitive decline, they said.