Drubach, Daniel A.

AbstractThe relationship between clinicopathologic diagnosis and 123I‐FP‐CIT SPECT in 18 patients with dementia (12 with Lewy body disease) from one center in the United States was assessed. The sensitivity and specificity of abnormal 123I‐FP‐CIT SPECT with reduced striatal uptake on visual inspection for predicting Lewy body disease were 91.7% and 83.3%, respectively. The mean calculated putamen to occipital ratio (mPOR) based on regions of interest was significantly reduced in Lewy body disease compared to non‐Lewy body disease cases (P = 0.002). In this study, abnormal 123I‐FP‐CIT SPECT was strongly associated with underlying Lewy body disease pathology, supporting the utility of 123I‐FP‐CIT SPECT in the clinical diagnosis of dementia with Lewy bodies.

ObjectiveTo use a cluster analysis of [18F]AV‐1451 tau‐PET data to determine how subjects with Alzheimer's disease (AD) vary in the relative involvement of the entorhinal cortex and neocortex, and determine whether relative involvement of these two regions can help explain variability in age and clinical phenotype in AD.MethodsWe calculated [18F]AV‐1451 uptake in entorhinal cortex and neocortex in 62 amyloid‐positive AD patients (39 typical and 23 atypical presentation). tau‐PET (positron emission tomography) values were normalized to the cerebellum to create standard uptake value ratios (SUVRs). tau‐PET SUVRs were log‐transformed and clustered blinded to clinical information into three groups using K‐median cluster analysis. Demographics, clinical phenotype, cognitive performance, and apolipoprotein e4 frequency were compared across clusters.ResultsThe cluster analysis identified a cluster with low entorhinal and cortical uptake (ELo/CLo), one with low entorhinal but high cortical uptake (ELo/CHi), and one with high cortical and entorhinal uptake (EHi/CHi). Clinical phenotype differed across clusters, with typical AD most commonly observed in the ELo/CLo and EHi/CHi clusters, and atypical AD most commonly observed in the ELo/CHi cluster. The ELo/CLo cluster had an older age at PET and onset than the other clusters. Apolipoprotein e4 frequency was lower in the ELo/CHi cluster. The EHi/CHi cluster had the worst memory impairment, whereas the ELo/CHi cluster had the worst impairment in nonmemory domains.InterpretationThis study demonstrates considerable variability in [18F]AV‐1451 tau‐PET uptake in AD, but shows that a straightforward clustering based on entorhinal and cortical uptake maps well onto age and clinical presentation in AD. Ann Neurol 2018 Ann Neurol 2018;83:248–257

Background: Different clinical syndromes can arise from Alzheimer’s disease (AD) neuropathology, including dementia of the Alzheimer’s type (DAT), logopenic primary progressive aphasia (lvPPA), and posterior cortical atrophy (PCA). Objective: To assess similarities and differences in patterns of white matter tract degeneration across these syndromic variants of AD. Methods: Sixty-four subjects (22 DAT, 24 lvPPA, and 18 PCA) that had diffusion tensor imaging and showed amyloid-β deposition on PET were assessed in this case-control study. A whole-brain voxel-based analysis was performed to assess differences in fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity across groups. Results: All three groups showed overlapping diffusion abnormalities in a network of tracts, including fornix, corpus callosum, posterior thalamic radiations, superior longitudinal fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, and uncinate fasciculus. Subtle regional differences were also observed across groups, with DAT particularly associated with degeneration of fornix and cingulum, lvPPA with left inferior fronto-occipital fasciculus and uncinate fasciculus, and PCA with posterior thalamic radiations, superior longitudinal fasciculus, posterior cingulate, and splenium of the corpus callosum. Conclusion: These findings show that while each AD phenotype is associated with degeneration of a specific structural network of white matter tracts, striking spatial overlap exists among the three network patterns that may be related to AD pathology.