Lower brain 18F-fluorodeoxyglucose uptake but normal 11C-acetoacetate metabolism in mild Alzheimer's disease dementia.
Level 4 - case-series / case-control
Case-control study comparing metabolic PET imaging in mild AD patients and matched controls
PubMed 25147107 · doi:10.3233/JAD-141074
What was done
Researchers compared 10 patients with mild Alzheimer's disease dementia (mean age 76 years) with 29 age- and gender-matched cognitively normal older controls (mean age 75 years). Participants underwent dual-tracer PET/MRI to measure the cerebral metabolic rate and rate constants for glucose (CMRg, Kg using 18F-FDG) and the ketone acetoacetate (CMRa, Ka using 11C-acetoacetate), evaluated via region-of-interest (ROI) and voxel-based analyses.
What was found
ROI analysis revealed a 13% lower global gray matter CMRg in the mild AD group compared to controls (34.2 ± 5.0 vs. 38.3 ± 4.7 μmol/100 g/min; p = 0.015), with the greatest deficits in the parietal cortex, posterior cingulate, and thalamus (all p ≤ 0.022). In contrast, global and regional ketone metabolism (CMRa and Ka) showed no significant differences between groups (all p ≥ 0.188). Voxel-based analysis confirmed seven clusters of lower CMRg in AD (uncorrected p ≤ 0.005) with no corresponding differences in CMRa.
Why it matters
These findings suggest that cerebral energy hypometabolism in mild Alzheimer's disease is specific to impaired glucose utilization while ketone metabolism remains intact, providing a mechanistic rationale for ketogenic interventions.
Limits
The study is limited by a small sample size (n = 10 AD, 29 controls), a cross-sectional design that cannot establish causality or track disease progression, and voxel-level comparisons reported at uncorrected thresholds. The study evaluated acetoacetate but did not directly image the other primary ketone body, β-hydroxybutyrate.
Cited by
- supports Research by Dr. Stephen Cunnane using C-11 acetoacetate PET shows that brain ketone utilization remains preserved in early to mild-mid stage Alzheimer's disease.