Citation and Abstract


Ossenkoppele R, Zwan M, Adriaanse S, Boellaard R, Windhorst A, Barkhof F, Lammertsma A, Scheltens P, van der Flier W, van Berckel B. Increased Parietal Amyloid Burden and Metabolic Dysfunction in Alzheimer’s Disease with Early Onset. Human Amyloid Imaging Abstract. 2012 Jan 1;

 
  ABSTRACT
Background: Alzheimer’s disease (AD) with an early onset often presents with a distinct cognitive profile compared to late-onset AD, potentially reflecting a different distribution of underlying neuropathology. The purpose of this study was to examine the relationships between age-at-onset with both in vivo fibrillary amyloid deposition and glucose metabolism.
Methods: Dynamic [11C]Pittsburgh compound-B (PIB) (90 minutes) and static [18F]fluorodeoxyglucose (FDG) scans were obtained in 100 AD patients. Parametric non-displaceable binding potential (BPND) images of [11C]PIB and standardized uptake value ratio (SUVr) images of [18F]FDG were generated using cerebellar grey matter as reference tissue. Nine [11C]PIB-negative patients were excluded. The remaining AD patients were categorized into younger (n=45, mean age at diagnosis: 56±4) and older (n=46, mean age at diagnosis: 69±5) groups, based on the median age (62 years) at time of diagnosis.
Results: Although groups did not differ on Mini-Mental State Examination, younger patients showed more severe impairment on visuo-spatial function, attention and executive function composite scores (p<0.05) as compared to older patients. In contrast, we found a trend towards poorer memory performance for the older AD group (p=0.11). Younger and older patients did not differ in global cortical [11C]PIB BPND (p=0.29) or in global cortical [18F]FDG SUVr (p=0.30). Regional distributions of both [11C]PIB BPND (p for interaction ><0.01) and [18F]FDG SUVr (p for interaction ><0.05), however, differed between groups. This was largely due to increased [11C]PIB binding and decreased [18F]FDG uptake in the parietal cortex of younger patients. >
Conclusion: These findings suggest that clinical differences between younger and older AD patients are related not only to topographical differentiation in downstream processes, but may originate from distinctive distributions of early upstream events. As such, increased amyloid burden, together with metabolic dysfunction, in the parietal lobe of younger AD patients may explain the distinct cognitive profile in these patients.