Abstract
BackgroundWe previously found temporoparietal-predominant atrophy patterns in the behavioral variant of Alzheimer’s disease (bvAD), with relative sparing of frontal regions. Here, we aimed to understand the clinico-anatomical dissociation in bvAD based on alternative neuroimaging markers.MethodsWe retrospectively included 150 participants, including 29 bvAD, 28 “typical” amnestic-predominant AD (tAD), 28 behavioral variant of frontotemporal dementia (bvFTD), and 65 cognitively normal participants. Patients with bvAD were compared with other diagnostic groups on glucose metabolism and metabolic connectivity measured by [18F]FDG-PET, and on subcortical gray matter and white matter hyperintensity (WMH) volumes measured by MRI. A receiver-operating-characteristic-analysis was performed to determine the neuroimaging measures with highest diagnostic accuracy.ResultsbvAD and tAD showed predominant temporoparietal hypometabolism compared to controls, and did not differ in direct contrasts. However, overlaying statistical maps from contrasts between patients and controls revealed broader frontoinsular hypometabolism in bvAD than tAD, partially overlapping with bvFTD. bvAD showed greater anterior default mode network (DMN) involvement than tAD, mimicking bvFTD, and reduced connectivity of the posterior cingulate cortex with prefrontal regions. Analyses of WMH and subcortical volume showed closer resemblance of bvAD to tAD than to bvFTD, and larger amygdalar volumes in bvAD than tAD respectively. The top-3 discriminators for bvAD vs. bvFTD were FDG posterior-DMN-ratios (bvAD<bvFTD), MRI posterior-DMN-ratios (bvAD<bvFTD), MRI salience-network-ratios (bvAD>bvFTD, area under the curve [AUC] range 0.85–0.91, all p < 0.001). The top-3 for bvAD vs. tAD were amygdalar volume (bvAD>tAD), MRI anterior-DMN-ratios (bvAD<tAD), FDG anterior-DMN-ratios (bvAD<tAD, AUC range 0.71–0.84, all p < 0.05).ConclusionsSubtle frontoinsular hypometabolism and anterior DMN involvement may underlie the prominent behavioral phenotype in bvAD.
Highlights
We previously found temporoparietal-predominant atrophy patterns in the behavioral variant of Alzheimer’s disease, with relative sparing of frontal regions
Neuroimaging markers in behavioral variant of Alzheimer’s disease (bvAD) Glucose hypometabolism Compared to cognitively normal controls, marked hypometabolism was found in the posterior cingulate, precuneus, and lateral temporoparietal regions in both bvAD and tAD, while behavioral variant of frontotemporal dementia (bvFTD) displayed hypometabolism mainly in frontal regions and the temporal poles (Fig. 1a, b)
Head-to-head comparison between FDG hypometabolic patterns with Magnetic resonance imaging (MRI) atrophy patterns showed that the observed differences in the MR analysis were confined to a limited amount of regions (Supplement 8), while the differences were more pronounced on FDG-PET (Fig. 1)
Summary
We previously found temporoparietal-predominant atrophy patterns in the behavioral variant of Alzheimer’s disease (bvAD), with relative sparing of frontal regions. Functional measures such as glucose hypometabolic patterns or alterations in metabolic connectivity may be more sensitive than structural MRI [6] and allow the assessment of large-scale networks rather than sole investigation of localized associations [7] Structural measures such as subcortical atrophy or white matter damage affecting frontosubcortical tracts have consistently been associated with neuropsychiatric symptoms [8, 9]. Exploring these neuroimaging features will enhance our neurobiological understanding of the prominently behavioral phenotype in bvAD. We had two objectives: (i) to increase our understanding of the relative lack of frontal atrophy in patients with the behavioral variant of AD through the assessment of multiple neuroimaging markers and (ii) to identify the diagnostic accuracy of several neuroimaging measures in the differential diagnosis of bvAD vs. typical AD and bvFTD
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