Title: P2–328: Imaging of cerebral amyloid angiopathy with Pittsburgh Compound B
Abstract: Cerebrovascular deposition of β–amyloid (cerebral amyloid angiopathy, CAA) is the major cause of hemorrhagic stroke and a likely contributor to vascular cognitive impairment. Research in CAA has been hampered by the inability to detect vascular β–amyloid in living subjects. To evaluate PET imaging with the β–amyloid–binding compound Pittsburgh Compound B (PIB) as a potential noninvasive method for detection of CAA. We performed PIB–PET imaging on 5 subjects (mean age 71.4±8.8) diagnosed with probable CAA according to the Boston criteria based on brain biopsy (n=3) or multiple strictly lobar bleeds (n=2). All 5 CAA subjects were nondemented (Mini–Mental State Exam ≥27 or Blessed Information–Memory–Concentration Scale ≤3). PIB–PET images were acquired over 60 minutes following injection of 10–15 mCi PIB. Results were compared with 16 older (mean age 74.7±7.3) cognitively normal controls (NC) and 9 subjects with probable Alzheimer's disease (AD). Specific PIB binding was calculated using the Logan graphical analysis method, yielding a distribution volume ratio (DVR) with cerebellar grey matter as reference. DVRs were calculated in an aggregated cortical (bilateral superior frontal, anterior cingulate, parietal, and precuneus cortex) region–of–interest (ROI) and a bilateral occipital ROI. PIB retention was significantly elevated in CAA relative to NC (DVR mean± SD 1.25±0.07 versus 1.03±0.10, p<0.0005 for aggregated cortical ROI; 1.25±0.09 versus 1.10±0.12, p<0.02 for occipital ROI). PIB retention in the CAA subjects was significantly lower than AD in the aggregated cortical ROI (DVR for AD subjects 1.40±0.15, p<0.03) but not in the occipital ROI (1.34±0.17 in AD, p>0.2). Inspection of the pattern of PIB retention among CAA subjects suggested relatively strong specific binding in occipital cortex, consistent with the known predilection of CAA pathology for this region. Increased PIB retention in nondemented CAA subjects relative to similar aged controls suggests that PIB–PET imaging can detect cerebrovascular β–amyloid. The data also raise the possibility that PIB–PET may identify a pattern of occipital predominance characteristic of CAA.