Early cerebral amyloid-β accumulation and hypermetabolism are associated with subtle cognitive deficits before accelerated cerebral atrophy.
Level 3 - non-randomized controlled study
Prospective longitudinal cohort study with repeated neuroimaging and cognitive assessments
PubMed 38102439 · doi:10.1007/s11357-023-01031-w
What was done
Participants from the Metropolit 1953 Danish Male Birth Cohort underwent [11C]PiB PET imaging (n = 70) to assess amyloid-beta accumulation and [18F]FDG PET imaging (n = 76) to assess glucose metabolism. Brain atrophy rate was calculated from anatomical MRI scans taken at baseline and 10 years earlier. Longitudinal cognitive decline was assessed using neurophysiological testing conducted at baseline and 5 or 10 years earlier.
What was found
Higher amyloid-beta accumulation in Alzheimer's disease-critical brain regions correlated with greater visual memory decline (p = 0.023). Amyloid-beta accumulation did not correlate with brain atrophy rates. Increased cerebral glucose metabolism in Alzheimer's disease-susceptible regions correlated with worse verbal memory performance (p = 0.040). Effect sizes and confidence intervals were not reported in the abstract.
Why it matters
This study shows that subtle memory changes and regional hypermetabolism emerge alongside early amyloid accumulation before the onset of accelerated brain atrophy, helping clarify the sequence of early pathological events in neurodegeneration.
Limits
The study is limited to a single birth cohort of Danish men, restricting generalizability across sexes and diverse populations. The sample size is modest (n = 70 to 76 across PET modalities), and specific numerical effect estimates or confidence intervals were not provided in the abstract.
Cited by
- supports In the early stages of Alzheimer's disease, affected brain regions show an increase in energy demand and hypermetabolism before progressing to hypometabolism as symptoms emerge.