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Primary progressive aphasia (PPA) is an overarching term for a heterogeneous group of neurodegenerative diseases which affect language processing. Impaired picture naming has been linked to atrophy of the anterior temporal lobe in the semantic variant of PPA. Although atrophy of the anterior temporal lobe proposedly impairs picture naming by undermining access to semantic knowledge, picture naming also entails object recognition and lexical retrieval. Using multivariate analysis, we investigated whether cortical atrophy relates to different types of naming errors generated during picture naming in 43 PPA patients (13 semantic, 9 logopenic, 11 nonfluent, and 10 mixed variant). Omissions were associated with atrophy of the anterior temporal lobes. Semantic errors, for example, mistaking a rhinoceros for a hippopotamus, were associated with atrophy of the left mid and posterior fusiform cortex and the posterior middle and inferior temporal gyrus. Semantic errors and atrophy in these regions occurred in each PPA subtype, without major between-subtype differences. We propose that pathological changes to neural mechanisms associated with semantic errors occur across the PPA spectrum. ispartof: NEUROBIOLOGY OF AGING vol:88 pages:71-82 ispartof: location:United States status: published

Purpose To assess the binding of the PET tracer [18F]THK5351 in patients with different primary progressive aphasia (PPA) variants and its correlation with clinical deficits. The majority of patients with nonfluent variant (NFV) and logopenic variant (LV) PPA have underlying tauopathy of the frontotemporal lobar or Alzheimer disease type, respectively, while patients with the semantic variant (SV) have predominantly transactive response DNA binding protein 43-kDa pathology. Methods The study included 20 PPA patients consecutively recruited through a memory clinic (12 NFV, 5 SV, 3 LV), and 20 healthy controls. All participants received an extensive neurolinguistic assessment, magnetic resonance imaging and amyloid biomarker tests. [18F]THK5351 binding patterns were assessed on standardized uptake value ratio (SUVR) images with the cerebellar grey matter as the reference using statistical parametric mapping. Whole-brain voxel-wise regression analysis was performed to evaluate the association between [18F]THK5351 SUVR images and neurolinguistic scores. Analyses were performed with and without partial volume correction. Results Patients with NFV showed increased binding in the supplementary motor area, left premotor cortex, thalamus, basal ganglia and midbrain compared with controls and patients with SV. Patients with SV had increased binding in the temporal lobes bilaterally and in the right ventromedial frontal cortex compared with controls and patients with NFV. The whole-brain voxel-wise regression analysis revealed a correlation between agrammatism and motor speech impairment, and [18F]THK5351 binding in the left supplementary motor area and left postcentral gyrus. Analysis of [18F]THK5351 scans without partial volume correction revealed similar results. Conclusion [18F]THK5351 imaging shows a topography closely matching the anatomical distribution of predicted underlying pathology characteristic of NFV and SV PPA. [18F]THK5351 binding correlates with the severity of clinical impairment. ispartof: European journal of nuclear medicine and molecular imaging vol:45 issue:13 pages:2342-2357 ispartof: location:Germany status: published

Primary progressive aphasia (PPA) is a heterogeneous syndrome with various neuropathological causes for which no medical treatment with proven efficacy exists. Basal forebrain (BF) volume loss has been reported in PPA but its relation to cholinergic depletion is still unclear. The primary objective of this study was to investigate whether cholinergic alterations occur in PPA variants and how this relates to BF volume loss. An academic memory clinic based consecutive series of 11 PPA patients (five with the semantic variant (SV), four with the logopenic variant (LV) and two with the nonfluent variant (NFV)) participated in this cross-sectional in vivo PET imaging study together with 10 healthy control subjects. Acetylcholinesterase (AChE) activity was quantitatively measured in the neo- and allocortex using N-[11C]-Methylpiperidin-4-yl propionate (PMP)-PET with arterial sampling and metabolite correction. Whole brain and BF volumes were quantified using voxel-based morphometry on high-resolution magnetic resonance imaging (MRI) scans. In the PPA group, only LV cases showed decreases in AChE activity levels compared to controls. Surprisingly, a substantial number of SV cases showed significant AChE activity increases compared to controls. BF volume did not correlate with AChE activity levels in PPA. To conclude, in our sample of PPA patients, LV but not SV was associated with cholinergic depletion. BF atrophy in PPA does not imply cholinergic depletion., Graphical abstract Image 1, Highlights • Using PET we examined cholinesterase activity in PPA. • Cholinergic depletion occurred in the logopenic variant. • Basal forebrain atrophy mainly occurred in the semantic variant. • Cholinergic depletion did not correlate with basal forebrain atrophy. • Unexpectedly, semantic variant was associated with cholinergic activity increases.

Objective: In some patients with apraxia of speech (AOS), we observed impaired perceptual timing abilities, which lead us to propose a shared mechanism of impaired perceptual timing underlying impaired rhythm discrimination (perceptual processing) and AOS (motor speech output). Given that considerable white matter damage is often observed in these patients, we here investigate whether white matter changes are related to impaired rhythm processing as one possible mechanism underlying AOS. Methods: We applied deformation-based morphometry (DBM) and diffusion tensor imaging (DTI) in 12 patients with the nonfluent variant (NFV) of Primary Progressive Aphasia (PPA) with AOS, as well as 11 patients with the semantic variant and 24 controls. Results: Seventy-five percent of the patients with NFV displayed impaired rhythm processing and the severity of their impairment correlated with their degree of AOS. Moreover, left frontal white matter volume loss adjacent to the supplementary motor area (SMA) correlated with impaired rhythm processing. In addition, we obtained tract-based metrics of the left Aslant tract, which is typically damaged in NFV. The structural integrity of the left Aslant tract also correlated with rhythmic discrimination abilities in NFV. Conclusions: Our data suggest that a shared white matter substrate adjacent to the SMA contributes to impaired rhythm perception and motor speech impairments. This indicates that impaired perceptual timing may be one of the neurocomputational mechanisms underlying AOS. Our observation that regional variations in left frontal lobe atrophy are linked to the phenotypical heterogeneity in NFV may lead the way for earlier diagnosis.

Theory of mind (ToM) refers to the ability to attribute mental states to others. Behavioral variant frontotemporal dementia (bvFTD) is a neurodegenerative disorder characterized by profound deficits in social cognition, including ToM. We investigate whether bvFTD affects intention attribution tendency while viewing abstract animations and whether this might represent a primary deficit. A sample of 15 bvFTD patients and 19 matched controls were assessed on cognition and performed an implicit ToM task. They were instructed to describe what they observed in movement patterns displayed by geometrical shapes (triangles). These movement patterns either represented animacy, goal-directed actions or manipulation of mental state (ToM). The responses were scored for both accuracy and intentionality attribution. Using Voxel-Based Morphometry, we investigated the structural neuroanatomy associated with intention attribution tendency. The behavioral results revealed deficits in the bvFTD group on intentionality attribution that were specific for the ToM condition after controlling for global cognitive functioning (MMSE-score), visual attention (TMT B-score), fluid intelligence (RCPMT-score) and confrontation naming (BNT-score). In the bvFTD sample, the intention attribution tendency on the ToM-condition was associated with grey matter volume of a cluster in the cerebellum, spanning the right Crus I, Crus II, VIIIb, IX, left VIIb, IX and vermal IX and X. The results reveal a specific, primary, implicit domain-general ToM deficit in bvFTD that cannot be explained by cognitive dysfunction. Furthermore, the findings point to a contribution of the cerebellum in the social-cognitive phenotype of bvFTD., Highlights • We show a reduction in intention attribution tendency to abstract shapes in bvFTD. • Cognitive or subordinate processes did not explain the reduction. • The reduction was associated with structural integrity of a cerebellar cluster.

Purpose To assess the binding of the PET tracer [18F]THK5351 in patients with different primary progressive aphasia (PPA) variants and its correlation with clinical deficits. The majority of patients with nonfluent variant (NFV) and logopenic variant (LV) PPA have underlying tauopathy of the frontotemporal lobar or Alzheimer disease type, respectively, while patients with the semantic variant (SV) have predominantly transactive response DNA binding protein 43-kDa pathology. Methods The study included 20 PPA patients consecutively recruited through a memory clinic (12 NFV, 5 SV, 3 LV), and 20 healthy controls. All participants received an extensive neurolinguistic assessment, magnetic resonance imaging and amyloid biomarker tests. [18F]THK5351 binding patterns were assessed on standardized uptake value ratio (SUVR) images with the cerebellar grey matter as the reference using statistical parametric mapping. Whole-brain voxel-wise regression analysis was performed to evaluate the association between [18F]THK5351 SUVR images and neurolinguistic scores. Analyses were performed with and without partial volume correction. Results Patients with NFV showed increased binding in the supplementary motor area, left premotor cortex, thalamus, basal ganglia and midbrain compared with controls and patients with SV. Patients with SV had increased binding in the temporal lobes bilaterally and in the right ventromedial frontal cortex compared with controls and patients with NFV. The whole-brain voxel-wise regression analysis revealed a correlation between agrammatism and motor speech impairment, and [18F]THK5351 binding in the left supplementary motor area and left postcentral gyrus. Analysis of [18F]THK5351 scans without partial volume correction revealed similar results. Conclusion [18F]THK5351 imaging shows a topography closely matching the anatomical distribution of predicted underlying pathology characteristic of NFV and SV PPA. [18F]THK5351 binding correlates with the severity of clinical impairment. Electronic supplementary material The online version of this article (10.1007/s00259-018-4075-3) contains supplementary material, which is available to authorized users.

Background Epilepsy surgery often causes changes in cognition and cerebral glucose metabolism. Our aim was to explore relationships between pre- and postoperative cerebral metabolism as measured with 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and neuropsychological test scores in patients with left mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS), who were rendered seizure-free after epilepsy surgery. Results Thirteen patients were included. All had neuropsychological testing and an interictal FDG-PET scan of the brain pre- and postoperative. Correlations between changes in neuropsychological test scores and metabolism were examined using statistical parametric mapping (SPM). There were no significant changes in the neuropsychological test scores pre- and postoperatively at the group level. Decreased metabolism was observed in the left mesial temporal regions and occipital lobe. Increased metabolism was observed in the bi-frontal and right parietal lobes, temporal lobes, occipital lobes, thalamus, cerebellum, and vermis. In these regions, we did not find a correlation between changes in metabolism and neuropsychological test scores. A significant negative correlation, however, was found between metabolic changes in the precuneus and Boston Naming Test (BNT) scores. Conclusions There are significant metabolic decreases in the left mesial temporal regions and increases in the bi-frontal lobes; right parietal, temporal, and occipital lobes; right thalamus; cerebellum; and vermis in patients with left MTLE-HS who were rendered seizure-free after epilepsy surgery. We could not confirm that these changes translate into significant cognitive changes. A significant negative correlation was found between changes in confrontation naming and changes in metabolism in the precuneus. We speculate that the precuneus may play a compensatory role in patients with postoperative naming difficulties after left TLE surgery. Understanding of these neural mechanisms may aid in designing cognitive rehabilitation strategies. Electronic supplementary material The online version of this article (10.1186/s13550-018-0385-5) contains supplementary material, which is available to authorized users.

Background A subset of patients with the nonfluent variant of primary progressive aphasia (PPA) exhibit concomitant single-word comprehension problems, constituting a ‘mixed variant’ phenotype. This phenotype is rare and currently not fully characterized. The aim of this study was twofold: to assess the prevalence and nature of single-word comprehension problems in the nonfluent variant and to study multimodal imaging characteristics of atrophy, tau, and amyloid burden associated with this mixed phenotype. Methods A consecutive memory-clinic recruited series of 20 PPA patients (12 nonfluent, five semantic, and three logopenic variants) were studied on neurolinguistic and neuropsychological domains relative to 64 cognitively intact healthy older control subjects. The neuroimaging battery included high-resolution volumetric magnetic resonance imaging processed with voxel-based morphometry, and positron emission tomography with the tau-tracer [18F]-THK5351 and amyloid-tracer [11C]-Pittsburgh Compound B. Results Seven out of 12 subjects who had been classified a priori with nonfluent variant PPA showed deficits on conventional single-word comprehension tasks along with speech apraxia and agrammatism, corresponding to a mixed variant phenotype. These mixed variant cases included three females and four males, with a mean age at onset of 65 years (range 44–77 years). Object knowledge and object recognition were additionally affected, although less severely compared with the semantic variant. The mixed variant was characterized by a distributed atrophy pattern in frontal and temporoparietal regions. A more focal pattern of elevated [18F]-THK5351 binding was present in the supplementary motor area, the left premotor cortex, midbrain, and basal ganglia. This pattern was closely similar to that seen in pure nonfluent variant PPA. At the individual patient level, elevated [18F]-THK5351 binding in the supplementary motor area and premotor cortex was present in six out of seven mixed variant cases and in five and four of these cases, respectively, in the thalamus and midbrain. Amyloid biomarker positivity was present in two out of seven mixed variant cases, compared with none of the five pure nonfluent cases. Conclusions A substantial proportion of PPA patients with speech apraxia and agrammatism also have single-word comprehension deficits. At the neurobiological level, the mixed variant shows a high degree of similarity with the pure nonfluent variant of PPA. Trial registration EudraCT, 2014–002976-10. Registered on 13-01-2015. Electronic supplementary material The online version of this article (10.1186/s13195-018-0393-8) contains supplementary material, which is available to authorized users.

We investigated the critical contribution of right ventral occipitotemporal cortex to knowledge of visual and functional-associative attributes of biological and non-biological entities and how this relates to category-specificity during confrontation naming. In a consecutive series of 7 patients with lesions confined to right ventral occipitotemporal cortex, we conducted an extensive assessment of oral generation of visual-sensory and functional-associative features in response to the names of biological and nonbiological entities. Subjects also performed a confrontation naming task for these categories. Our main novel finding related to a unique case with a small lesion confined to right medial fusiform gyrus who showed disproportionate naming impairment for nonbiological versus biological entities, specifically for tools. Generation of visual and functional-associative features was preserved for biological and non-biological entities. In two other cases, who had a relatively small posterior lesion restricted to primary visual and posterior fusiform cortex, retrieval of visual attributes was disproportionately impaired compared to functional-associative attributes, in particular for biological entities. However, these cases did not show a category-specific naming deficit. Two final cases with the largest lesions showed a classical dissociation between biological versus nonbiological entities during naming, with normal feature generation performance. This is the first lesion-based evidence of a critical contribution of the right medial fusiform cortex to tool naming. Second, dissociations along the dimension of attribute type during feature generation do not co-occur with category-specificity during naming in the current patient sample. publisher: Elsevier articletitle: Noun and knowledge retrieval for biological and non-biological entities following right occipitotemporal lesions journaltitle: Neuropsychologia articlelink: http://dx.doi.org/10.1016/j.neuropsychologia.2014.07.021 content_type: article copyright: Copyright © 2014 Elsevier Ltd. All rights reserved. ispartof: Neuropsychologia vol:62 issue:1 pages:163-74 ispartof: location:England status: published