FDG PET and MRI in logopenic primary progressive aphasia versus dementia of the Alzheimer's type

Abstract

Objectives: The logopenic variant of primary progressive aphasia is an atypical clinical variant of Alzheimer's disease which is typically characterized by left temporoparietal atrophy on magnetic resonance imaging and hypometabolism on F-18 fluorodeoxyglucose positron emission tomography. We aimed to characterize and compare patterns of atrophy and hypometabolism in logopenic primary progressive aphasia, and determine which brain regions and imaging modality best differentiates logopenic primary progressive aphasia from typical dementia of the Alzheimer's type.

Methods: A total of 27 logopenic primary progressive aphasia subjects underwent fluorodeoxyglucose positron emission tomography and volumetric magnetic resonance imaging. These subjects were matched to 27 controls and 27 subjects with dementia of the Alzheimer's type. Patterns of atrophy and hypometabolism were assessed at the voxel and region-level using Statistical Parametric Mapping. Penalized logistic regression analysis was used to determine what combinations of regions best discriminate between groups.

Results: Atrophy and hypometabolism was observed in lateral temporoparietal and medial parietal lobes, left greater than right, and left frontal lobe in the logopenic group. The logopenic group showed greater left inferior, middle and superior lateral temporal atrophy (inferior p = 0.02; middle p = 0.007, superior p = 0.002) and hypometabolism (inferior p = 0.006, middle p = 0.002, superior p = 0.001), and less right medial temporal atrophy (p = 0.02) and hypometabolism (p<0.001), and right posterior cingulate hypometabolism (p<0.001) than dementia of the Alzheimer's type. An age-adjusted penalized logistic model incorporating atrophy and hypometabolism achieved excellent discrimination (area under the receiver operator characteristic curve = 0.89) between logopenic and dementia of the Alzheimer's type subjects, with optimal discrimination achieved using right medial temporal and posterior cingulate hypometabolism, left inferior, middle and superior temporal hypometabolism, and left superior temporal volume.

Conclusions: Patterns of atrophy and hypometabolism both differ between logopenic primary progressive aphasia and dementia of the Alzheimer's type and both modalities provide excellent discrimination between groups.

Figure 1. Region-level imaging comparison of lvPPA and DAT.

Age-adjusted odds ratios and 95% CIs on the logarithm scale for a 1-SD change in the imaging variable. The vertical dashed line represents an odds ratio of 1.0. Estimates to the left of the vertical line indicate pathology tended to be greater in lvPPA. Estimates to the right of the vertical line indicate pathology tended to be less in lvPPA. 95% CIs that do not cross the dashed line represent significant differences between groups.

Figure 2. Voxel-level imaging findings in lvPPA and DAT when compared to controls.

Three dimensional renderings show regions of reduced FDG metabolism and gray matter (GM) volume in lvPPA compared to controls and in DAT compared to controls. All images were generated using an FDR corrected statistical threshold of p<0.0005 and an extent threshold of 100 voxels. A decrease in brightness of the render reflects increased distance from the surface of the tissue.

Figure 3. Voxel-level imaging comparison of lvPPA and DAT.

Three dimensional renderings show regions of reduced FDG metabolism and gray matter (GM) volume in lvPPA compared to DAT, and in DAT compared to lvPPA. All images were generated using an uncorrected statistical threshold of p<0.001 and an extent threshold of 100 voxels. A decrease in brightness of the render reflects increased distance from the surface of the tissue.

Figure 4. Estimated coefficients from multivariable penalized logistic regression analyses.

Estimated AUROC and a 95% bootstrap confidence interval are shown in the top left of each panel.