Citations

Background: The agrammatic variant of primary progressive aphasia (PAA), primary progressive apraxia of speech (PPAOS), or a combination of both (AOS-PAA) are neurodegenerative disorders characterized by speech-language impairments and together compose the AOS-PAA spectrum disorders. These patients typically have an underlying 4-repeat tauopathy, although they sometimes show evidence of amyloid-β and tau deposition on PET, suggesting Alzheimer’s disease (AD). Given the growing number of pharmacologic treatment options for AD, it is important to better understand the incidence of AD pathology in these patients. Objective: This study aimed to evaluate the frequency of amyloid-β and tau positivity in AOS-PAA spectrum disorders. Sixty-five patients with AOS-PAA underwent a clinical speech-language battery and PiB PET and flortaucipir PET imaging. Methods: Global PiB PET standardized uptake value ratios (SUVRs) and flortaucipir PET SUVRs from the temporal meta region of interest were compared between patient groups. For 19 patients who had died and undergone autopsy, their PET and pathology findings were also compared. Results: The results showed that although roughly half of the patients are positive for at least one biomarker, their clinical symptoms and biomarker status were not related, suggesting that AD is not the primary cause of their neurodegeneration. All but one patient in the autopsy subset had a Braak stage of IV or less, despite four being positive on tau PET imaging. Conclusions: Inclusion criteria for clinical trials should specify clinical presentation or adjust the evaluation of such treatments to be specific to disease diagnosis beyond the presence of certain imaging biomarkers.

AbstractBackgroundPrevious studies have shown that magnetic susceptibility is increased in several subcortical regions in progressive supranuclear palsy (PSP). However, it is still unclear how subcortical and cortical susceptibilities vary across different PSP variants, Parkinson's disease (PD), and corticobasal syndrome (CBS).ObjectiveThis study aims to clarify the susceptibility profiles in the subcortical and cortical regions in different PSP variants, PD, and CBS.MethodsSixty‐four patients, 20 PSP‐Richardson syndrome (PSP‐RS), 9 PSP‐parkinsonism (PSP‐P), 7 PSP‐progressive gait freezing, 4 PSP‐postural instability, 11 PD, and 13 CBS, and 20 cognitively normal control subjects underwent a 3‐Tesla magnetic resonance imaging scan to reconstruct quantitative susceptibility maps. Region‐of‐interest analysis was performed to obtain susceptibility in several subcortical and cortical regions. Bayesian linear mixed effect models were used to estimate susceptibility within group and differences between groups.ResultsIn the subcortical regions, patients with PSP‐RS and PSP‐P showed greater susceptibility than control subjects in the pallidum, substantia nigra, red nucleus, and cerebellar dentate (P < 0.05). Patients with PSP‐RS also showed greater susceptibility than patients with PSP‐progressive gait freezing, PD, and CBS in the red nucleus and cerebellar dentate, and patients with PSP‐P showed greater susceptibility than PD in the red nucleus. Patients with PSP‐postural instability and CBS showed greater susceptibility than control subjects in the pallidum and substantia nigra. No significant differences were observed in any cortical region.ConclusionsThe PSP variants and CBS had different patterns of magnetic susceptibility in the subcortical regions. The findings will contribute to our understanding about iron profiles and pathophysiology of PSP and may provide a potential biomarker to differentiate PSP variants, PD, and CBS. © 2023 International Parkinson and Movement Disorder Society.

Background: Posterior cortical atrophy (PCA) and logopenic progressive aphasia (LPA) are associated with characteristic patterns of structural network degeneration. Little is known about longitudinal patterns of white matter tract degeneration in these phenotypes. Objective: To assess longitudinal patterns of white matter degeneration and identify phenotype specific cross-sectional and longitudinal diffusion tensor imaging (DTI) biomarkers in PCA and LPA. Methods: Twenty-five PCA, 22 LPA and 25 cognitively unimpaired (CU) individuals were recruited and underwent structural MRI that included a DTI sequence with a follow-up one year later. Cross-sectional and longitudinal mixed effects models were fit to assess the effects of diagnosis on baseline and annualized change in regional DTI metrics. Discriminatory power was investigated using the area under the receiver operating characteristic curves (AUROC). Results: PCA and LPA showed overlapping white matter degeneration profiles predominantly in the left occipital and temporal lobes, the posterior thalamic radiation and sagittal stratum at baseline, as well as the parietal lobe longitudinally. PCA showed degeneration in the occipital and parietal white matter, cross-sectionally and longitudinally, compared to CU, while LPA showed greater degeneration in the temporal and inferior parietal white matter and the inferior fronto-occipital fasciculus cross-sectionally, and in parietal white matter longitudinally compared to CU. Cross-sectionally, integrity of the inferior occipital white matter was best able to differentiate PCA from LPA, with an AUROC of 0.82. Conclusion: These findings contribute to our understanding of white matter degeneration and support usage of DTI as a useful additional diagnostic biomarker for PCA and LPA.

AbstractObjectivePrimary progressive apraxia of speech (PPAOS) is associated with imaging abnormalities in the lateral premotor cortex (LPC) and supplementary motor area (SMA). It is not known whether greater involvement of these regions in either hemisphere is associated with demographics, presenting, and/or longitudinal features.MethodsIn 51 prospectively recruited PPAOS patients who completed [18F]‐fluorodeoxyglucose (FDG) positron emission tomography (PET), we classified patients as left‐dominant, right‐dominant, or symmetric, based on visual assessment of the LPC and SMA on FDG‐PET. SPM and statistical analyses of regional metabolic values were performed. Diagnosis of PPAOS was made if apraxia of speech was present and aphasia absent. Thirteen patients completed ioflupane‐123I (dopamine transporter [DAT]) scans. We compared cross‐sectional and longitudinal clinicopathological, genetic, and neuroimaging characteristics across the three groups, with area under the receiver‐operating curve (AUROC) determined as a measure of effect size.ResultsIn all, 49% of the PPAOS patients were classified as left‐dominant, 31% as right‐dominant, and 20% as symmetric, which was supported by results from the SPM and regional analyses. There were no differences in baseline characteristics. Longitudinally, right‐dominant PPAOS showed faster rates of progression of ideomotor apraxia (AUROC 0.79), behavioral disturbances (AUROC 0.84), including disinhibition symptoms (AUROC 0.82) and negative behaviors (AUROC 0.82), and parkinsonism (AUROC 0.75) compared to left‐dominant PPAOS. Symmetric PPAOS showed faster rates of dysarthria progression compared to left‐dominant (AUROC 0.89) and right‐dominant PPAOS (AUROC 0.79). Five patients showed abnormal DAT uptake. Braak neurofibrillary tangle stage differed across groups (p = 0.01).ConclusionsPatients with PPAOS and a right‐dominant pattern of hypometabolism on FDG‐PET have the fastest rates of decline of behavioral and motor features.