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Semantic therapy in post-stroke aphasia typically focusses on strengthening links between conceptual representations and their lexical-articulatory forms to aid word retrieval. However, research has shown that semantic deficits in this group can affect both verbal and non-verbal tasks, particularly in patients with deregulated retrieval as opposed to degraded knowledge. This study, therefore, aimed to facilitate semantic cognition in a sample of such patients with post-stroke semantic aphasia (SA) by training the identification of both strong and weak semantic associations and providing explicit pictorial feedback that demonstrated both common and more unusual ways of linking concepts together. We assessed the effects of this training on (i) trained and untrained items; and (ii) trained and untrained tasks in eleven individuals with SA. In the training task, the SA group showed improvement with practice, particularly for trained items. A similar untrained task using pictorial stimuli (Camel and Cactus Test) also improved. Together, these results suggest that semantic training can be beneficial in patients with SA and may show some degree of generalization to untrained situations. Future research should seek to understand which patients are most likely to benefit from this type of training. [ABSTRACT FROM AUTHOR]

The ability to efficiently select specific aspects of our semantic representations that are relevant for current goals or the context is supported by semantic control processes (controlled semantic cognition framework). This semantic control component is impaired in patients with semantic aphasia, who have multimodal semantic impairment following left hemisphere stroke and are highly sensitive to the control demands of semantic tasks. However, relatively little is known about how this control deficit interacts with aspects of semantic representation. Here we tested whether the relevance of semantic features can influence the demands of control resources in the selection of information within the semantic store in patients with semantic aphasia. Participants performed a feature selection task, where they were asked to indicate which of three features was semantically related to a given concept. We found that patients with semantic aphasia had a greater impairment on low relevance features, suggesting that the selection of target features with low relevance requires greater semantic control than target features with high relevance. Our results confirm the necessity of control processes for the selection of aspects of conceptual knowledge that are only weakly activated within semantic storage when these are task-relevant. The study therefore highlights that semantic cognition emerges from the interaction of control and representational systems. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) neuropathologic changes are β‐amyloid (Aβ) deposition, pathologic tau, and neurodegeneration. Dual‐phase amyloid‐PET might be able to evaluate Aβ deposition and neurodegeneration with a single tracer injection. Early‐frames of amyloid‐PET scans provide a proxy for cerebral perfusion, which has shown good correlations with neural dysfunction measured through metabolic consumption, while the late‐frames depict amyloid distribution. Our study aims to assess the comparability between early frames of amyloid‐PET scans and [18F]fluorodeoxyglucose (FDG) PET in their topography and their ability to discriminate patients in the AD continuum. Method: 166 subjects evaluated at the Geneva Memory Center (Cognitively Unimpaired, CU = 61; Mild Cognitive Impairment, MCI = 73; Dementia = 21) underwent early‐phase amyloid‐PET – using either [18F]florbetapir (eFBP) (n = 95) or [18F]flutemetamol (eFMM) (n = 72) – and FDG PET. Standardized uptake value ratios (SUVR) were extracted within key regions sensitive for AD (metaROI) to evaluate the correlation of eFBP/eFMM and their respective FDG PET scans. To compare the discriminative power of eFBP, eFMM, and FDG SUVR between Aβ‐negative CU and Aβ‐positive impaired patients, receiver operating characteristic analyses and voxel‐wise t‐tests were performed. SPM single‐subject procedure was applied to investigate hypometabolic and hypoperfusion maps and their spatial overlap by means of DICE. Result: Strong positive correlations were found between eFBP/eFMM and FDG SUVR independently of Aβ status and Aβ radiotracers (r>0.85, p<0.001). Both eFBP and eFMM, and FDG SUVR significantly discriminated AD cognitively impaired patients from CU in the metaROI (AUCFBP = 0.768; AUCFMM = 0.778), with FDG performing slightly better than others (AUCFDG = 0.797). For all tracers, voxel‐wise analyses confirmed reduced signals in regions typically belonging to AD hypometabolic pattern in AD patients when compared to controls. SPM single‐subject analysis revealed different hypometabolism and hypoperfusion patterns with a high spatial concordance, differing between stages (DICE average: AD dementia = 0.91; Aβ‐positive MCI = 0.61). Conclusion: Distribution of perfusion was comparable to that of metabolism at group level and at single‐subject level. Our findings indicate that eFBP and eFMM imaging provide information closely related to brain regional glucose metabolism supporting their use for individual classification in clinical practice. [ABSTRACT FROM AUTHOR]

Background: The Apolipoprotein E ε4 (ApoE4) is the strongest genetic risk factor for Alzheimer's disease (AD). Previous studies have found a link between ApoE4 genotype and tau (T) deposition in the medial temporal lobe (MTL). However, further studies disentangling the influence of genotype on tau deposition and amyloid (A) are still needed. The aim of this study was to assess tau and amyloid deposition depending on subject genotype in a memory clinic cohort. Method: 89 subjects from the Geneva Memory Center underwent amyloid and tau PET imaging, and ApoE genotyping (ApoE2 carriers, ApoE3 homozygotes, ApoE4 carriers). The remaining subjects were classified as ApoE3. Amyloid uptake has been calculated as centiloid values and tau uptake as standardized uptake value ratio (SUVR), normalized to cerebellar uptake. Positivity for each biomarker was based on thresholds published by previous studies. Correlation between amyloid centiloid and tau SUVR in general and by genotype was calculated. ANOVA with Tuckey correction for multiple comparisons was used to assess differences between tau or amyloid PET uptake across different genotypes. Result: 85% of the A+T+ subjects were carriers of the ApoE4 gene. The association between neocortical amyloid and MTL tau stratified by genotype showed that these measures are correlated in ApoE4 carriers (r = 0.52, p = 0.001). The correlation was not significant in non‐carriers. MTL tau SUVR was higher in ApoE4 carriers and significantly different when compared to non‐carriers. Furthermore, tau SUVR from lateral and superior temporal lobes were also significantly different in ApoE4 carriers vs. non‐carriers even when not considering the centiloid value, showing an amyloid‐independent association between tau SUVR and genotype is not limited to the MTL. Centiloid values showed similar differences when comparing ApoE4 carriers with non‐carriers. Conclusion: ApoE4 gene carriers present a significant increase of both tau and amyloid load with respect to non‐carriers. Furthermore, increased tau deposition independent from amyloid load is not limited to the MTL, with the entire temporal lobe showing higher tau pathology in ApoE4 carriers. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) neuropathologic changes are β-amyloid (Aβ) deposition, pathologic tau, and neurodegeneration. Dual-phase amyloid-PET might be able to evaluate Aβ deposition and neurodegeneration with a single tracer injection. Early-phase amyloid-PET scans provide a proxy for cerebral perfusion, which has shown good correlations with neural dysfunction measured through metabolic consumption, while the late frames depict amyloid distribution. Our study aims to assess the comparability between early-phase amyloid-PET scans and 18 F-fluorodeoxyglucose ( 18 F-FDG)-PET brain topography at the individual level, and their ability to discriminate patients. Methods: 166 subjects evaluated at the Geneva Memory Center, ranging from cognitively unimpaired to Mild Cognitive Impairment (MCI) and dementia, underwent early-phase amyloid-PET - using either 18 F-florbetapir (eFBP) ( n = 94) or 18 F-flutemetamol (eFMM) ( n = 72) - and 18 F-FDG-PET. Aβ status was assessed. Standardized uptake value ratios (SUVR) were extracted to evaluate the correlation of eFBP/eFMM and their respective 18 F-FDG-PET scans. The single-subject procedure was applied to investigate hypometabolism and hypoperfusion maps and their spatial overlap by Dice coefficient. Receiver operating characteristic analyses were performed to compare the discriminative power of eFBP/eFMM, and 18 F-FDG-PET SUVR in AD-related metaROI between Aβ-negative healthy controls and cases in the AD continuum. Results: Positive correlations were found between eFBP/eFMM and 18 F-FDG-PET SUVR independently of Aβ status and Aβ radiotracer (R>0.72, p<0.001). eFBP/eFMM single-subject analysis revealed clusters of significant hypoperfusion with good correspondence to hypometabolism topographies, independently of the underlying neurodegenerative patterns. Both eFBP/eFMM and 18 F-FDG-PET SUVR significantly discriminated AD patients from controls in the AD-related metaROIs (AUCFB P = 0.888; AUCFMM=0.801), with 18 F-FDG-PET performing slightly better, however not significantly (all p-value higher than 0.05), than others (AUCFDG=0.915 and 0.832 for subjects evaluated with 18 F-FBP and 18 F-FMM, respectively). Conclusion: The distribution of perfusion was comparable to that of metabolism at the single-subject level by parametric analysis, particularly in the presence of a high neurodegeneration burden. Our findings indicate that eFBP/eFMM imaging can replace 18 F-FDG-PET imaging, as they reveal typical neurodegenerative patterns, or allow to exclude the presence of neurodegeneration. The finding shows cost-saving capacities of amyloid-PET and supports the routine use of the modality for individual classification in clinical practice., (Copyright © 2022 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)