Effects of Beta-Hydroxybutyrate on Cognition in Memory-Impaired Adults

Neurobiol Aging. 2004 Mar;25(3):311-4. doi: 10.1016/S0197-4580(03)00087-3.

Abstract

Glucose is the brain's principal energy substrate. In Alzheimer's disease (AD), there appears to be a pathological decrease in the brain's ability to use glucose. Neurobiological evidence suggests that ketone bodies are an effective alternative energy substrate for the brain. Elevation of plasma ketone body levels through an oral dose of medium chain triglycerides (MCTs) may improve cognitive functioning in older adults with memory disorders. On separate days, 20 subjects with AD or mild cognitive impairment consumed a drink containing emulsified MCTs or placebo. Significant increases in levels of the ketone body beta-hydroxybutyrate (beta-OHB) were observed 90 min after treatment (P=0.007) when cognitive tests were administered. beta-OHB elevations were moderated by apolipoprotein E (APOE) genotype (P=0.036). For 4+ subjects, beta-OHB levels continued to rise between the 90 and 120 min blood draws in the treatment condition, while the beta-OHB levels of 4- subjects held constant (P<0.009). On cognitive testing, MCT treatment facilitated performance on the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) for 4- subjects, but not for 4+ subjects (P=0.04). Higher ketone values were associated with greater improvement in paragraph recall with MCT treatment relative to placebo across all subjects (P=0.02). Additional research is warranted to determine the therapeutic benefits of MCTs for patients with AD and how APOE-4 status may mediate beta-OHB efficacy.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 3-Hydroxybutyric Acid / blood
  • 3-Hydroxybutyric Acid / metabolism*
  • Aged
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / physiopathology
  • Apolipoprotein E4
  • Apolipoproteins E / genetics
  • Apolipoproteins E / metabolism
  • Brain / drug effects
  • Brain / metabolism
  • Brain Chemistry / drug effects*
  • Brain Chemistry / physiology
  • Cognition / drug effects
  • Cognition Disorders / drug therapy*
  • Cognition Disorders / metabolism
  • Cognition Disorders / psychology
  • Double-Blind Method
  • Energy Metabolism / drug effects
  • Energy Metabolism / physiology
  • Genotype
  • Glucose / metabolism
  • Humans
  • Ketone Bodies / blood
  • Ketone Bodies / metabolism
  • Memory Disorders / drug therapy*
  • Memory Disorders / metabolism
  • Memory Disorders / psychology
  • Neuropsychological Tests
  • Treatment Outcome
  • Triglycerides / metabolism
  • Triglycerides / pharmacology
  • Triglycerides / therapeutic use*

Substances

  • Apolipoprotein E4
  • Apolipoproteins E
  • Ketone Bodies
  • Triglycerides
  • Glucose
  • 3-Hydroxybutyric Acid