A Ketogenic Drink Improves Cognition in Mild Cognitive Impairment: Results of a 6-month RCT

Overview

Journal Alzheimers Dement

Specialties Neurology
Psychiatry

Date 2020 Oct 26

PMID 33103819

Citations 69

Authors

Melanie Fortier

Christian-Alexandre Castellano

Valerie St-Pierre

Etienne Myette-Cote

Francis Langlois

Maggie Roy

Marie-Christine Morin

Christian Bocti

Tamas Fulop

Jean-Philippe Godin

Carla Delannoy

Bernard Cuenoud

Stephen C Cunnane

Affiliations

Soon will be listed here.

Abstract

Introduction: Counteracting impaired brain glucose metabolism with ketones may improve cognition in mild cognitive impairment (MCI).

Methods: Cognition, plasma ketone response, and metabolic profile were assessed before and 6 months after supplementation with a ketogenic drink containing medium chain triglyceride (ketogenic medium chain triglyceride [kMCT]; 15 g twice/day; n = 39) or placebo (n = 44).

Results: Free and cued recall (Trial 1; P = .047), verbal fluency (categories; P = .024), Boston Naming Test (total correct answers; P = .033), and the Trail-Making Test (total errors; P = .017) improved significantly in the kMCT group compared to placebo (analysis of covariance; pre-intervention score, sex, age, education, and apolipoprotein E4 as covariates). Some cognitive outcomes also correlated positively with plasma ketones. Plasma metabolic profile and ketone response were unchanged.

Conclusions: This kMCT drink improved cognitive outcomes in MCI, at least in part by increasing blood ketone level. These data support further assessment of MCI progression to Alzheimer's disease.

Citing Articles

Dysregulation of energy metabolism in Alzheimer's disease.

Yuan Y, Zhao G, Zhao Y J Neurol. 2024; 272(1):2.

PMID: 39621206 PMC: 11611936. DOI: 10.1007/s00415-024-12800-8.

Organic food consumption is positively associated with cognitive function among middle-aged and older adults: cross-sectional and longitudinal analyses.

Li S, Chen H, Zhao R, Wang T, Ye J Eur J Nutr. 2024; 64(1):40.

PMID: 39621138 DOI: 10.1007/s00394-024-03555-z.

Association of circulating ketone bodies with cognitive performance and dementia in the Multi-Ethnic Study of Atherosclerosis (MESA).

Chevli P, Schaich C, Wood A, Tk L, Mehta A, Jain V Alzheimers Dement (Amst). 2024; 16(4):e70039.

PMID: 39583649 PMC: 11585168. DOI: 10.1002/dad2.70039.

A β-hydroxybutyrate shunt pathway generates anti-obesity ketone metabolites.

Moya-Garzon M, Wang M, Li V, Lyu X, Wei W, Tung A Cell. 2024; 188(1):175-186.e20.

PMID: 39536746 PMC: 11724754. DOI: 10.1016/j.cell.2024.10.032.

Gut Microbiome in Alzheimer's Disease: from Mice to Humans.

Liang C, Pereira R, Zhang Y, Rojas O Curr Neuropharmacol. 2024; 22(14):2314-2329.

PMID: 39403057 PMC: 11451315. DOI: 10.2174/1570159X22666240308090741.

References

Zec R, Burkett N, Markwell S, Larsen D . Normative data stratified for age, education, and gender on the Boston Naming Test. Clin Neuropsychol. 2007; 21(4):617-37. DOI: 10.1080/13854040701339356. View

Washburn R, Smith K, Jette A, Janney C . The Physical Activity Scale for the Elderly (PASE): development and evaluation. J Clin Epidemiol. 1993; 46(2):153-62. DOI: 10.1016/0895-4356(93)90053-4. View

Cunnane S, Trushina E, Morland C, Prigione A, Casadesus G, Andrews Z . Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing. Nat Rev Drug Discov. 2020; 19(9):609-633. PMC: 7948516. DOI: 10.1038/s41573-020-0072-x. View

Fiatarone Singh M, Gates N, Saigal N, Wilson G, Meiklejohn J, Brodaty H . The Study of Mental and Resistance Training (SMART) study—resistance training and/or cognitive training in mild cognitive impairment: a randomized, double-blind, double-sham controlled trial. J Am Med Dir Assoc. 2014; 15(12):873-80. DOI: 10.1016/j.jamda.2014.09.010. View

Kashiwaya Y, Takeshima T, Mori N, Nakashima K, Clarke K, Veech R . D-beta-hydroxybutyrate protects neurons in models of Alzheimer's and Parkinson's disease. Proc Natl Acad Sci U S A. 2000; 97(10):5440-4. PMC: 25847. DOI: 10.1073/pnas.97.10.5440. View

Faul F, Erdfelder E, Lang A, Buchner A . G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007; 39(2):175-91. DOI: 10.3758/bf03193146. View

Fortier M, Castellano C, Croteau E, Langlois F, Bocti C, St-Pierre V . A ketogenic drink improves brain energy and some measures of cognition in mild cognitive impairment. Alzheimers Dement. 2019; 15(5):625-634. DOI: 10.1016/j.jalz.2018.12.017. View

Neth B, Mintz A, Whitlow C, Jung Y, Solingapuram Sai K, Register T . Modified ketogenic diet is associated with improved cerebrospinal fluid biomarker profile, cerebral perfusion, and cerebral ketone body uptake in older adults at risk for Alzheimer's disease: a pilot study. Neurobiol Aging. 2019; 86:54-63. PMC: 7266642. DOI: 10.1016/j.neurobiolaging.2019.09.015. View

Liu-Ambrose T, Nagamatsu L, Graf P, Beattie B, Ashe M, Handy T . Resistance training and executive functions: a 12-month randomized controlled trial. Arch Intern Med. 2010; 170(2):170-8. PMC: 3448565. DOI: 10.1001/archinternmed.2009.494. View

10.

Croteau E, Castellano C, Richard M, Fortier M, Nugent S, Lepage M . Ketogenic Medium Chain Triglycerides Increase Brain Energy Metabolism in Alzheimer's Disease. J Alzheimers Dis. 2018; 64(2):551-561. DOI: 10.3233/JAD-180202. View

11.

Folstein M, Folstein S, McHugh P . "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975; 12(3):189-98. DOI: 10.1016/0022-3956(75)90026-6. View

12.

Zilberter M, Ivanov A, Ziyatdinova S, Mukhtarov M, Malkov A, Alpar A . Dietary energy substrates reverse early neuronal hyperactivity in a mouse model of Alzheimer's disease. J Neurochem. 2012; 125(1):157-71. DOI: 10.1111/jnc.12127. View

13.

Nagamatsu L, Chan A, Davis J, Beattie B, Graf P, Voss M . Physical activity improves verbal and spatial memory in older adults with probable mild cognitive impairment: a 6-month randomized controlled trial. J Aging Res. 2013; 2013:861893. PMC: 3595715. DOI: 10.1155/2013/861893. View

14.

Dion M, Potvin O, Belleville S, Ferland G, Renaud M, Bherer L . Normative data for the Rappel libre/Rappel indicé à 16 items (16-item Free and Cued Recall) in the elderly Quebec-French population. Clin Neuropsychol. 2014; 28 Suppl 1:S1-19. DOI: 10.1080/13854046.2014.915058. View

15.

Henderson S, Vogel J, Barr L, Garvin F, Jones J, Costantini L . Study of the ketogenic agent AC-1202 in mild to moderate Alzheimer's disease: a randomized, double-blind, placebo-controlled, multicenter trial. Nutr Metab (Lond). 2009; 6:31. PMC: 2731764. DOI: 10.1186/1743-7075-6-31. View

16.

Grande G, Vanacore N, Vetrano D, Cova I, Rizzuto D, Mayer F . Free and cued selective reminding test predicts progression to Alzheimer's disease in people with mild cognitive impairment. Neurol Sci. 2018; 39(11):1867-1875. DOI: 10.1007/s10072-018-3507-y. View

17.

Ota M, Matsuo J, Ishida I, Takano H, Yokoi Y, Hori H . Effects of a medium-chain triglyceride-based ketogenic formula on cognitive function in patients with mild-to-moderate Alzheimer's disease. Neurosci Lett. 2018; 690:232-236. DOI: 10.1016/j.neulet.2018.10.048. View

18.

Ebert D, Haller R, Walton M . Energy contribution of octanoate to intact rat brain metabolism measured by 13C nuclear magnetic resonance spectroscopy. J Neurosci. 2003; 23(13):5928-35. PMC: 6741266. View

19.

Baker L, Frank L, Foster-Schubert K, Green P, Wilkinson C, McTiernan A . Effects of aerobic exercise on mild cognitive impairment: a controlled trial. Arch Neurol. 2010; 67(1):71-9. PMC: 3056436. DOI: 10.1001/archneurol.2009.307. View

20.

Petersen R, Smith G, Waring S, Ivnik R, Tangalos E, Kokmen E . Mild cognitive impairment: clinical characterization and outcome. Arch Neurol. 1999; 56(3):303-8. DOI: 10.1001/archneur.56.3.303. View