Amyloid imaging in atypical dementia using 11C-PIB PET

Abstract

11C-PIB is a thioflavin PET tracer which binds to fibrillar beta-amyloid with nanomolar affinity. The presence of amyloidplaques and neurofibrillary tangles is the pathological hallmark of Alzheimer disease. Amyloid pathology is, however, also associated with other dementias in varying proportions. 18F-FDG measures regional cerebral glucose metabolism rCMRGlc. To assess the prevalence of increased amyloid load in atypical dementia (frontotemporal dementia and logopenic aphasia) compared to sporadic AD and amnestic MCI. 10 frontotemporal dementia (FTD) subjects and two logopenic aphasic subjects were compared with 36 AD, 22 MCI, and 42 control subjects (50-82yrs). Each subject underwent detailed clinical evaluation, neuropsychological assessment, T1 and T2 MRI and a 90minute 11C-PIB PET scan. Amyloid load was quantitated as 60-90'target:cerebellar uptake ratios (RATIO). Object maps were created by segmenting individual MRIs and spatially transforming the grey matter images into standard stereotaxic MNI space and then superimposing a probabilistic atlas. Cortical 11C-PIB uptake was assessed by ROI (region of interest) analysis. None of the FTD subjects showed a raised amyloid load, while the two logopenic aphasic subjects both showed increased 11C-PIB binding. Individually 33 out of 36 AD subjects showed significant 50-100% increases in cingulate, frontal, temporal, parietal and occipital cortical 11C-PIB uptake. 13 out of 22 MCI subjects showed significant (50-100%) AD levels of increase in cortical 11C-PIB uptake, while 9 had normal scans. Three of the 42 age-matched control subjects showed borderline increases in 11C-PIB uptake in cingulate cortex. Eight of the nine FTD subjects showed frontal reductions in glucose metabolism while one subject had a normal glucose metabolism. Absence of amyloidin FTD suggests that 11C-PIB may be helpful for differentiating this from AD. Logopenic aphasia is associated with amyloid deposition. This confirms that amyloid imaging is not a specific diagnostic tool for AD but may be useful in excluding the presence of Alzheimer pathology.