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Background and purposeCerebral microbleeds (MB) and superficial siderosis (SS) are frequent neuroimaging findings in patients with logopenic progressive aphasia (LPA), often with frontal lobe predilection. Cerebral amyloid angiopathy (CAA) is hypothesized to be the major pathologic determinant of MB/SS in these patients; however, neuroimaging‐pathologic data are limited.MethodsAll patients who had been prospectively recruited by the Neurodegenerative Research Group at the Mayo Clinic (Rochester, MN) between 2010 and 2015 and met the following inclusion criteria were included: (i) received an antemortem LPA diagnosis, (ii) had a gradient‐recalled echo T2*‐weighted magnetic resonance imaging (MRI) performed, (iii) died and completed a brain autopsy. Demographic, genetic, neuroimaging, and clinical and pathologic characteristics were compared between patients with/without MB/SS. Two‐tailed Fisher exact and Wilcoxon rank sum tests were used for comparison of categorical and continuous variables, respectively.ResultsThirteen patients met inclusion criteria, six (46%) had MB/SS on MRI. Moderate/severe CAA was associated with the presence of MB/SS (p = 0.029). As expected, MB/SS most frequently involved the frontal lobes, followed by the parietal lobes. No clear associations were found between regional MB/SS distribution and regional distribution of CAA or hypometabolism on [18F]‐fluorodeoxyglucose–positron emission tomography. There was some evidence for a regional association between MB/SS and uptake on Pittsburgh compound B, although not in all patients. No formal statistical analyses to assess topographic relationships were performed due to the small sample size.ConclusionsThe presence of MB/SS is a strong indicator of underlying moderate/severe CAA in LPA, although the biological mechanisms underlying the topographic distribution of MB/SS remain unclear.

Background: Posterior cortical atrophy (PCA) and logopenic progressive aphasia (LPA) are two of the most common variants of atypical Alzheimer’s disease (AD). Both PCA and LPA are associated with relative sparing of hippocampus compared to neocortex, although hippocampal atrophy is observed. It is unclear whether regional patterns of hippocampal subfield involvement differ between PCA and LPA, and whether they differ from typical AD. Objective: To assess volume of specific subfields of the hippocampus in PCA, LPA, and typical AD. Methods: Fifty-nine patients with PCA and 77 patients with LPA were recruited and underwent T1-weighted MRI and Pittsburgh Compound B (PiB) PET at Mayo Clinic. Thirty-six probable AD patients and 100 controls were identified from the Alzheimer’s Disease Neuroimaging Initiative. Hippocampal subfield volumes were calculated using Freesurfer, and volumes were compared between PCA, LPA, AD, and controls using Kruskal-Wallis and Dunn tests. Results: The LPA and PCA groups both showed the most striking abnormalities in CA4, presubiculum, molecular layer of the hippocampus, molecular and granule cell layers of the dentate gyrus, and the hippocampal-amygdala transition area, although atrophy was left-sided in LPA. PCA showed smaller volume of right presubiculum compared to LPA, with trends for smaller volumes of right parasubiculum and fimbria. LPA showed a trend for smaller volumes of left CA1 compared to PCA. The AD group showed smaller volumes of the right subiculum, CA1, and presubiculum compared to LPA. Conclusion: Patterns of hippocampal subfield atrophy differ across the different syndromic variants of AD.

ObjectiveTo examine associations between tau and amyloid β (Aβ) molecular positron emission tomography (PET) and both Alzheimer‐related pathology and 4‐repeat tau pathology in autopsy‐confirmed frontotemporal lobar degeneration (FTLD).MethodsTwenty‐four patients had [18F]‐flortaucipir–PET and died with FTLD (progressive supranuclear palsy [PSP], n = 10; corticobasal degeneration [CBD], n = 10; FTLD‐TDP, n = 3; and Pick disease, n = 1). All but 1 had Pittsburgh compound B (PiB)‐PET. Braak staging, Aβ plaque and neurofibrillary tangle counts, and semiquantitative tau lesion scores were performed. Flortaucipir standard uptake value ratios (SUVRs) were calculated in a temporal meta region of interest (meta‐ROI), entorhinal cortex and cortical/subcortical regions selected to match the tau lesion analysis. Global PiB SUVR was calculated. Autoradiography was performed in 1 PSP patient, with digital pathology used to quantify tau burden.ResultsNine cases (37.5%) had Aβ plaques. Global PiB SUVR correlated with Aβ plaque count, with 100% specificity and 50% sensitivity for diffuse plaques. Twenty‐one (87.5%) had Braak stages I to IV. Flortaucipir correlated with neurofibrillary tangle counts in entorhinal cortex, but entorhinal and meta‐ROI SUVRs were not elevated in Braak IV or primary age‐related tauopathy. Flortaucipir uptake patterns differed across FTLD pathologies and could separate PSP and CBD. Flortaucipir correlated with tau lesion score in red nucleus and midbrain tegmentum across patients, but not in cortical or basal ganglia regions. Autoradiography demonstrated minimal uptake of flortaucipir, although flortaucipir correlated with quantitative tau burden across regions.InterpretationMolecular PET shows expected correlations with Alzheimer‐related pathology but lacks sensitivity to detect mild Alzheimer pathology in FTLD. Regional flortaucipir uptake was able to separate CBD and PSP. ANN NEUROL 2020;88:1009–1022

Purpose Individuals with primary progressive apraxia of speech (AOS) have AOS in which disruptions in articulation and prosody predominate the speech pattern. Many develop aphasia and/or dysarthria later in the disease course. The aim of this study was to describe the communication limitations in these patients, as measured by (a) the patient via the Communicative Participation Item Bank (CPIB) and (b) the speech-language pathologist via the American Speech-Language-Hearing Association's (ASHA) Functional Communication Measures (FCMs) and an adapted motor speech disorder (MSD) severity rating. Method Speech and language evaluations were completed for 24 patients with progressive AOS ( n = 7 with isolated AOS; n = 17 with a combination of AOS and aphasia). Descriptive comparisons were utilized to evaluate differences in communication measures among patients with various combinations of MSDs and aphasia. Differences associated with phonetic predominant or prosodic predominant AOS were also examined. Across the entire cohort, correlations were calculated between the participation ratings and other clinical assessment measures. Results The CPIB reflected greater limitations for those with aphasia and AOS compared to isolated AOS, but was not notably different when dysarthria occurred with AOS ( n = 9/24). Across the cohort, there were statistically significant correlations between the CPIB and ASHA FCM–Motor Speech and Language Expression ratings and the MSD severity rating. The CPIB did not correlate with the ASHA FCM–Language Comprehension or other speech-language measures. Conclusions Patients with neurodegenerative AOS experience reduced participation in communication that is further exacerbated by co-occurring language deficits. The study suggests measures of severity cannot be assumed to correlate with measures of participation restrictions and offers a foundation for further research examining the day-to-day sequela of progressive speech and language disorders. Supplemental Material https://doi.org/10.23641/asha.12743252