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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.

We examined the associations between baseline neuropsychiatric symptoms (NPS) and longitudinal changes in functional performance among 5,394 non-demented individuals aged ≥50 years (2,729 males; median age 74.2 years; 4,716 cognitively unimpaired, 678 mild cognitive impairment). After adjusting for age, sex, education, and medical comorbidities, NPS assessed by the Neuropsychiatric Inventory Questionnaire, clinical depression (Beck Depression Inventory score ≥13) and anxiety (Beck Anxiety Inventory score ≥10) were significantly associated with an increase in the Functional Activities Questionnaire score, indicating functional decline over time. This association may vary depending on the degree of cognitive impairment at baseline.

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.

AbstractThe mechanisms through which tau and amyloid-beta (Aβ) accumulate in the brain of Alzheimer’s disease patients may differ but both are related to neuronal networks. We examined such mechanisms on neuroimaging in 58 participants with atypical Alzheimer’s disease (posterior cortical atrophy or logopenic progressive aphasia). Participants underwent Aβ-PET, longitudinal tau-PET, structural MRI and resting-state functional MRI, which was analyzed with graph theory. Regions with high levels of Aβ were more likely to be functional hubs, with a high number of functional connections important for resilience to cascading network failures. Regions with high levels of tau were more likely to have low clustering coefficients and degrees, suggesting a lack of trophic support or vulnerability to local network failures. Regions strongly functionally connected to the disease epicenters were more likely to have higher levels of tau and, less strongly, of Aβ. The regional rate of tau accumulation was associated with tau levels in functionally connected regions, in support of tau accumulation in a functional network. This study elucidates the relations of tau and Aβ to functional connectivity metrics in atypical Alzheimer’s disease, strengthening the hypothesis that the spread of the 2 proteins is driven by different biological mechanisms related to functional networks.

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