A cross-sectional comparison of brain glucose and ketone metabolism in cognitively healthy older adults, mild cognitive impairment and early Alzheimer's disease.
Level 4 - case-series / case-control
Cross-sectional comparative imaging study with three diagnostic groups
PubMed 28709938 · doi:10.1016/j.exger.2017.07.004
What was done
Researchers compared brain energy metabolism and morphology in 24 cognitively healthy controls, 20 individuals with mild cognitive impairment (MCI), and 19 individuals with early Alzheimer's disease (AD) matched for age and metabolic phenotype. Participants underwent dual-tracer PET using [18F]-fluorodeoxyglucose ([18F]-FDG) and [11C]-acetoacetate ([11C]-AcAc) to measure uptake rate constants and cerebral metabolic rates of glucose (KGlu, CMRGlu) and ketones (KAcAc, CMRAcAc). Brain volume and cortical thickness were measured using T1-weighted MRI.
What was found
Compared to controls, participants with AD had ~11% lower CMRGlu across frontal, parietal, and temporal lobes and the cingulate gyrus (p < 0.05), and ~15% lower KGlu in these same regions as well as subcortical areas. In MCI compared to controls, CMRGlu was ~7% lower specifically in the cingulate gyrus. Neither regional nor whole-brain CMRAcAc or KAcAc differed significantly between controls and MCI or AD. Widespread gray matter volume loss and cortical thinning were present in AD, whereas MCI showed volume loss restricted to the temporal cortex and thinning primarily in temporal and cingulate regions.
Why it matters
This study demonstrates that energy hypometabolism in early Alzheimer's disease and MCI is specific to glucose, supporting the biological rationale for ketogenic interventions to supply alternative brain fuel.
Limits
The study is limited by a small sample size (63 participants across three groups) and a cross-sectional design that cannot establish longitudinal metabolic trajectories. The abstract does not evaluate clinical or cognitive outcomes following ketone supplementation.
Cited by
- supports Recent research shows that ketones can cross into the brain and be metabolized more easily than glucose, leading to improvements in cognitive function.