Early detection of Alzheimer's disease using PiB and FDG PET

Abstract

Use of biomarkers in the detection of early and preclinical Alzheimer's disease (AD) has become of central importance following publication of the NIA-Alzheimer's Association revised criteria for the diagnosis of AD, mild cognitive impairment (MCI) and preclinical AD. The use of in vivo amyloid imaging agents, such a Pittsburgh Compound-B and markers of neurodegeneration, such as fluoro-2-deoxy-D-glucose (FDG) is able to detect early AD pathological processes and subsequent neurodegeneration. Imaging with PiB and FDG thus has many potential clinical benefits: early or perhaps preclinical detection of disease and accurately distinguishing AD from dementias of other etiologies in patients presenting with mild or atypical symptoms or confounding comorbidities in which the diagnostic distinction is difficult to make clinically. From a research perspective, this allows us to study relationships between amyloid pathology and changes in cognition, brain structure, and function across the continuum from normal aging to MCI to AD. The present review focuses on use of PiB and FDG-PET and their relationship to one another.

Keywords: Alzheimer's disease; Amyloid; FDG; Glucose metabolism; Neuroimaging; Pittsburgh compound B.

Figure 1

From Jack et al. (2012): Changes in AD biomarker data on the vertical axis vs. AD clinical stage, with preclinical staging highlighted in yellow Each biomarker is scaled from maximally normal (bottom) to maximally abnormal (top) with PET amyloid imaging (red line), biomarkers of neurodegeneration are FDG-PET or atrophy on MRI (blue line), and cognitive (purple line).

Figure 2

Representative PiB and FDG scans from control and AD participants. Arrows indicate areas of typical hypometabolism (FDG) or typical amyloid deposition (Head et al.).

Figure 3

From Aizenstein et al. (2008): Mean distribution volume ratio images for PiB-negative clinically unimpaired participants (left), PiB-positive clinically unimpaired participants (center), and patients with Alzheimer disease (AD) (right).

Figure 4

From Cohen et al. (While we hypothesize that enrichment will enhance the function of the DMN et al.): Voxel-based correlations in AD and MCI. T values associated with negative correlations (blue) and positive correlations (red). Data are thresholded with FDR control at q = 0.1.

Figure 5

From Johnson et al. (2014): FDG group voxel wise differences, regions where the PiB-positive (red) and PiB-intermediate (green) groups, with yellow showing overlap, exhibited FDG hypermetabolism compared to the PiB-negative group.