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Improved brain energetics and cognition after a 6‐month ketogenic intervention in mild cognitive impairment: Final results of the Benefic Trial
Author(s) -
Cunnane Stephen,
Fortier Melanie,
Castellano ChristianAlexandre,
Pierre Valerie St.,
Morin MarieChristine,
Langlois Francis,
Cuenoud Bernard,
Delannoy Carla,
Bocti Christian,
Fulop Tamas
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.037961
Subject(s) - cognition , placebo , psychology , audiology , stroop effect , cognitive training , effects of sleep deprivation on cognitive performance , randomized controlled trial , verbal fluency test , medicine , physical therapy , neuropsychology , psychiatry , alternative medicine , pathology
Background Ketones can partially substitute for glucose as a brain fuel and may be beneficial for cognition in older people. The objective of the randomized, placebo‐controlled Benefic Trial (NCT02551419) was to assess whether counteracting the brain energy (glucose) deficit with a ketogenic medium chain triglyceride (kMCT) supplement could improve cognitive performance in mild cognitive impairment (MCI). Methods A cognitive battery was used to screen for MCI and cognitive outcomes after the intervention. Cognitive outcomes pre‐ and post‐intervention were obtained for the active arm (15 g kMCT twice/day in a lactose‐free skim milk emulsion; n=39 completers) and placebo arm (non‐ketogenic vegetable oil of equivalent energy value and formulation as for the kMCT; n=44 completers). Brain ketone and glucose PET were done before and at the end of the 6‐month intervention on a sub‐group of both arms (n=19/group). Results Several cognitive domains improved post‐intervention in the kMCT group (p≤0.01; ANCOVA; age and education as covariates). Specifically, Trial 1 of the Free and Cued Recall Test showed a +1 word improvement on kMCT (+0.5 Δ Z‐score), correct answers on the Verbal Fluency Test increased by 2 words on kMCT (+0.3 Δ Z‐score) but decreased by 1 word on placebo (‐0.1 Δ Z‐score), correct answers on the Boston Naming Test increased by 1.1 on kMCT only, time taken on the Stroop Colour Naming Test decreased by 1 sec on the kMCT ( p =0.09), and errors on the Trail Making Test decreased by 0.9 on kMCT but increased by 0.8 on placebo ( p =0.02). Brain ketone uptake increased in the kMCT arm only and directly as the increase in plasma ketones (r = 0.87, p<0.01). Average drop‐out rate on both arms was 31% and, in completers, protocol adherence was 89% over six months. Conclusions In MCI, a kMCT supplement had a clinically meaningful effect on some cognitive outcomes directly related to risk of progression toward Alzheimer’s disease, and significantly improved brain energy supply. It is feasible for an MCI population to consume a kMCT supplement daily for six months. Acknowledgements: Financial support was provided by the Alzheimer Association USA, FRQS, Université de Sherbrooke and Nestlé Health Science.