Effects of β-hydroxybutyrate on cognition in memory-impaired adults

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 β-hydroxybutyrate (β-OHB) were observed 90min after treatment (P=0.007) when cognitive tests were administered. β-OHB elevations were moderated by apolipoprotein E (APOE) genotype (P=0.036). For ε4+ subjects, β-OHB levels continued to rise between the 90 and 120min blood draws in the treatment condition, while the β-OHB levels of ε4− 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 ε4− subjects, but not for ε4+ 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-ε4 status may mediate β-OHB efficacy.

Keywords: β-Hydroxybutyrate, Ketone bodies, Alzheimer’s disease, Mild cognitive impairment, APOE, Cognition, Neuropsychology