2-(4--(methylamino)phenyl)-6-hydroxybenzothiazole and Aphasia--Primary-Progressive

Semantic variant primary progressive aphasia (svPPA) is a subtype of primary progressive aphasia characterized by two-way anomia and disturbance in word comprehension, with focal atrophy in the left temporal lobe. [. Two patients, 64- and 79-year-old men, without notable medical or family history, exhibited disturbances in word comprehension and mild anomia with fluent speech and spared repetition. In both cases, surface dyslexia was observed but prosopagnosia was absent. Although mild depression was detected in 1 of the 2 patients, no behavioral disorders were present in either case. In both cases, MRI revealed atrophy in the anterior and inferior portions of the left temporal lobe. Technetium-99-ethyl cysteinate dimer ([. [

Topics: Aged; Aminopyridines; Aniline Compounds; Aphasia, Primary Progressive; Atrophy; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Organotechnetium Compounds; Positron-Emission Tomography; Quinolines; Semantics; Temporal Lobe; Thiazoles; Tomography, Emission-Computed, Single-Photon

To assess whether Alzheimer disease (AD) clinical presentation and. We studied 119 Aβ-positive symptomatic patients aged 48-95 years, including 29 patients with logopenic variant primary progressive aphasia (lvPPA) and 21 with posterior cortical atrophy (PCA). Pittsburgh compound B (PiB)-Aβ and flortaucipir (tau)-PET standardized uptake value ratio (SUVR) images were created. General linear models assessed relationships between demographic/clinical variables (phenotype, age),. PiB-PET binding showed a widespread cortical distribution with subtle differences across phenotypes and was unrelated to demographic/clinical variables or. Clinical phenotypes are associated with differential patterns of tau but not amyloid pathology. Older age and

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Amyloid beta-Peptides; Aniline Compounds; Aphasia, Primary Progressive; Apolipoprotein E4; Carbolines; Cerebral Cortex; Female; Frontal Lobe; Genotype; Humans; Magnetic Resonance Imaging; Male; Mental Status and Dementia Tests; Middle Aged; Occipital Lobe; Parietal Lobe; Phenotype; Positron-Emission Tomography; Radiopharmaceuticals; Retrospective Studies; tau Proteins; Temporal Lobe; Thiazoles; Visual Pathways

We report a patient presenting with clinical features of logopenic variant primary progressive aphasia (lvPPA) who was later diagnosed with probable dementia with Lewy bodies. LvPPA is a neurodegenerative disease that is characterized by anomia, word-finding difficulty, impaired comprehension, and phonological errors. The most common underlying pathology for lvPPA is Alzheimer's disease. However, our patient with clinical features of logopenic progressive aphasia was later diagnosed with probable dementia with Lewy bodies. This case demonstrates that lvPPA can also be an initial manifestation of a phenotype of dementia with Lewy bodies.

Topics: Aged; Aniline Compounds; Aphasia, Primary Progressive; Humans; Lewy Body Disease; Magnetic Resonance Imaging; Male; Neuropsychological Tests; Positron-Emission Tomography; Thiazoles

The utility of tau PET imaging in non-Alzheimer's disease (AD) tauopathies like behavioural frontotemporal dementia (bvFTD), which is mainly underlain by TDP-43 or tau pathology, remains debated. We aim to test the hypothesis that [

Topics: Aged; Alzheimer Disease; Aniline Compounds; Aphasia, Primary Progressive; Carbolines; Female; Frontotemporal Dementia; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Positron-Emission Tomography; tau Proteins; Tauopathies; Thiazoles

To compare [. Thirty-one participants with svPPA underwent MRI and Pittsburgh compound B-PET scanning, and 17 of these also underwent [. Although [

Topics: Aged; Alzheimer Disease; Amyloid beta-Peptides; Aniline Compounds; Aphasia, Primary Progressive; Brain; Carbolines; Contrast Media; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Positron-Emission Tomography; Semantics; Thiazoles

Little is known about the role of age on neurodegeneration and protein deposition in atypical variants of Alzheimer's disease (AD).. Regional tau and β-amyloid positron emission tomography standard uptake value ratios and gray matter volumes were calculated in a cohort of 42 participants with atypical AD. The relationship between regional metrics and age was modeled using a Bayesian hierarchical linear model.. Age was strongly associated with tau uptake across all cortical regions, particularly parietal, with greater uptake in younger participants. Younger age was associated with smaller parietal and lateral temporal volumes. Regional β-amyloid differed little by age. Age showed a stronger association with tau than volume and β-amyloid in all cortical regions. Age was not associated with cognitive performance.. Age is an important determinant of severity of cortical tau uptake in atypical AD, with young participants more likely to show widespread and severe cortical tau uptake.

Topics: Age Factors; Aged; Alzheimer Disease; Amyloid; Aniline Compounds; Aphasia, Primary Progressive; Atrophy; Brain; Cohort Studies; Female; Gray Matter; Humans; Male; Positron-Emission Tomography; tau Proteins; Thiazoles

The ability to predict the pathology underlying different neurodegenerative syndromes is of critical importance owing to the advent of molecule-specific therapies.. To determine the rates of positron emission tomography (PET) amyloid positivity in the main clinical variants of primary progressive aphasia (PPA).. This prospective clinical-pathologic case series was conducted at a tertiary research clinic specialized in cognitive disorders. Patients were evaluated as part of a prospective, longitudinal research study between January 2002 and December 2015. Inclusion criteria included clinical diagnosis of PPA; availability of complete speech, language, and cognitive testing; magnetic resonance imaging performed within 6 months of the cognitive evaluation; and PET carbon 11-labeled Pittsburgh Compound-B or florbetapir F 18 brain scan results. Of 109 patients referred for evaluation of language symptoms who underwent amyloid brain imaging, 3 were excluded because of incomplete language evaluations, 5 for absence of significant aphasia, and 12 for presenting with significant initial symptoms outside of the language domain, leaving a cohort of 89 patients with PPA.. Clinical, cognitive, neuroimaging, and pathology results.. Twenty-eight cases were classified as imaging-supported semantic variant PPA (11 women [39.3%]; mean [SD] age, 64 [7] years), 31 nonfluent/agrammatic variant PPA (22 women [71.0%]; mean [SD] age, 68 [7] years), 26 logopenic variant PPA (17 women [65.4%]; mean [SD] age, 63 [8] years), and 4 mixed PPA cases. Twenty-four of 28 patients with semantic variant PPA (86%) and 28 of 31 patients with nonfluent/agrammatic variant PPA (90%) had negative amyloid PET scan results, while 25 of 26 patients with logopenic variant PPA (96%) and 3 of 4 mixed PPA cases (75%) had positive scan results. The amyloid positive semantic variant PPA and nonfluent/agrammatic variant PPA cases with available autopsy data (2 of 4 and 2 of 3, respectively) all had a primary frontotemporal lobar degeneration and secondary Alzheimer disease pathologic diagnoses, whereas autopsy of 2 patients with amyloid PET-positive logopenic variant PPA confirmed Alzheimer disease. One mixed PPA patient with a negative amyloid PET scan had Pick disease at autopsy.. Primary progressive aphasia variant diagnosis according to the current classification scheme is associated with Alzheimer disease biomarker status, with the logopenic variant being associated with carbon 11-labeled Pittsburgh Compound-B positivity in more than 95% of cases. Furthermore, in the presence of a clinical syndrome highly predictive of frontotemporal lobar degeneration pathology, biomarker positivity for Alzheimer disease may be associated more with mixed pathology rather than primary Alzheimer disease.

Topics: Aged; Amyloid; Aniline Compounds; Aphasia, Primary Progressive; Brain; Ethylene Glycols; Female; Humans; Imaging, Three-Dimensional; Longitudinal Studies; Magnetic Resonance Imaging; Male; Middle Aged; Neuropsychological Tests; Positron-Emission Tomography; Retrospective Studies; Severity of Illness Index; Thiazoles

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.. 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 [. 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 [. 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.. EudraCT, 2014-002976-10 . Registered on 13-01-2015.

Topics: Aged; Aged, 80 and over; Aminopyridines; Amyloid beta-Peptides; Aniline Compounds; Aphasia, Primary Progressive; Brain; Cognition Disorders; Comprehension; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neuropsychological Tests; Positron-Emission Tomography; Quinolines; Thiazoles; Tomography Scanners, X-Ray Computed; Vocabulary

Neuropathological and in vivo studies have revealed a tight relationship between tau pathology and cognitive impairment across the Alzheimer's disease spectrum. However, tau pathology is also intimately associated with neurodegeneration and amyloid pathology. The aim of the present study was therefore to assess whether grey matter atrophy and amyloid pathology contribute to the relationship between tau pathology, as measured with 18F-AV-1451-PET imaging, and cognitive deficits in Alzheimer's disease. We included 40 amyloid-positive patients meeting criteria for mild cognitive impairment due to Alzheimer's disease (n = 5) or probable Alzheimer's disease dementia (n = 35). Twelve patients additionally fulfilled the diagnostic criteria for posterior cortical atrophy and eight for logopenic variant primary progressive aphasia. All participants underwent 3 T magnetic resonance imaging, amyloid (11C-PiB) positron emission tomography and tau (18F-AV-1451) positron emission tomography, and episodic and semantic memory, language, executive and visuospatial functions assessment. Raw cognitive scores were converted to age-adjusted Z-scores (W-scores) and averaged to compute composite scores for each cognitive domain. Independent regressions were performed between 18F-AV-1451 binding and each cognitive domain, and we used the Biological Parametric Mapping toolbox to further control for local grey matter volumes, 11C-PiB uptake, or both. Partial correlations and causal mediation analyses (mediation R package) were then performed in brain regions showing an association between cognition and both 18F-AV-1451 uptake and grey matter volume. Our results showed that decreased cognitive performance in each domain was related to increased 18F-AV-1451 binding in specific brain regions conforming to established brain-behaviour relationships (i.e. episodic memory: medial temporal lobe and angular gyrus; semantic memory: left anterior temporal regions; language: left posterior superior temporal lobe and supramarginal gyrus; executive functions: bilateral frontoparietal regions; visuospatial functions: right more than left occipitotemporal regions). This pattern of regional associations remained essentially unchanged-although less spatially extended-when grey matter volume or 11C-PiB uptake maps were added as covariates. Mediation analyses revealed both direct and grey matter-mediated effects of 18F-AV-1451 uptake on cognitive performance. Together, these results show that tau pat

Topics: Aged; Alzheimer Disease; Amyloid; Aniline Compounds; Aphasia, Primary Progressive; Benzothiazoles; Brain; Carbolines; Carbon Radioisotopes; Case-Control Studies; Cognitive Dysfunction; Female; Fluorine Radioisotopes; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neuropsychological Tests; Positron-Emission Tomography; Regression Analysis; tau Proteins; Thiazoles

Different clinical syndromes can arise from Alzheimer's disease (AD) neuropathology, including dementia of the Alzheimer's type (DAT), logopenic primary progressive aphasia (lvPPA), and posterior cortical atrophy (PCA).. To assess similarities and differences in patterns of white matter tract degeneration across these syndromic variants of AD.. Sixty-four subjects (22 DAT, 24 lvPPA, and 18 PCA) that had diffusion tensor imaging and showed amyloid-β deposition on PET were assessed in this case-control study. A whole-brain voxel-based analysis was performed to assess differences in fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity across groups.. All three groups showed overlapping diffusion abnormalities in a network of tracts, including fornix, corpus callosum, posterior thalamic radiations, superior longitudinal fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, and uncinate fasciculus. Subtle regional differences were also observed across groups, with DAT particularly associated with degeneration of fornix and cingulum, lvPPA with left inferior fronto-occipital fasciculus and uncinate fasciculus, and PCA with posterior thalamic radiations, superior longitudinal fasciculus, posterior cingulate, and splenium of the corpus callosum.. These findings show that while each AD phenotype is associated with degeneration of a specific structural network of white matter tracts, striking spatial overlap exists among the three network patterns that may be related to AD pathology.

Topics: Aged; Alzheimer Disease; Aniline Compounds; Anisotropy; Aphasia, Primary Progressive; Case-Control Studies; Diffusion Tensor Imaging; Female; Humans; Image Processing, Computer-Assisted; Male; Middle Aged; Nerve Fibers, Myelinated; Neurodegenerative Diseases; Neuropsychological Tests; Positron-Emission Tomography; Psychiatric Status Rating Scales; Retrospective Studies; Thiazoles; White Matter

Diagnostic distinction of primary progressive aphasias (PPA) remains challenging, in particular for the logopenic (lvPPA) and nonfluent/agrammatic (naPPA) variants. Recent findings highlight that episodic memory deficits appear to discriminate these PPA variants from each other, as only lvPPA perform poorly on these tasks while having underlying amyloid pathology similar to that seen in amnestic dementias like Alzheimer's disease (AD). Most memory tests are, however, language based and thus potentially confounded by the prevalent language deficits in PPA. The current study investigated this issue across PPA variants by contrasting verbal and non-verbal episodic memory measures while controlling for their performance on a language subtest of a general cognitive screen. A total of 203 participants were included (25 lvPPA; 29 naPPA; 59 AD; 90 controls) and underwent extensive verbal and non-verbal episodic memory testing, with a subset of patients (n = 45) with confirmed amyloid profiles as assessed by Pittsburgh Compound B and PET. The most powerful discriminator between naPPA and lvPPA patients was a non-verbal recall measure (Rey Complex Figure delayed recall), with 81% of PPA patients classified correctly at presentation. Importantly, AD and lvPPA patients performed comparably on this measure, further highlighting the importance of underlying amyloid pathology in episodic memory profiles. The findings demonstrate that non-verbal recall emerges as the best discriminator of lvPPA and naPPA when controlling for language deficits in high load amyloid PPA cases.

Topics: Aged; Alzheimer Disease; Amyloid; Aniline Compounds; Aphasia, Primary Progressive; Brain; Diagnosis, Differential; Female; Humans; Logistic Models; Male; Memory, Episodic; Neuropsychological Tests; Positron-Emission Tomography; Radiopharmaceuticals; Speech Perception; Thiazoles

To decipher the cognitive and linguistic feature of logopenic variant primary progressive aphasia (lv-PPA) and nonfluent variant primary progressive aphasia (nfv-PPA) and to explore the extent to which cognitive and language impairment contribute to the dysfunction of activity of daily living(ADL).. Seven lv-PPA and five nfv-PPA were enrolled in memory clinic of Xuanwu Hospital, Capital Medical University from January 2015 to January 2016 accordig to the international consensus criteria for PPA and its three subtypes. 20 age-matched normal controls (NC) were included. Both the patients and the NC completed a battery of neuropsychological test, lingusitic test and brain magnetic resonance imaging. All the patients conducted (11)C Pittsburgh compound B (PiB) PET imaging.. Lv-PPA patients were characterized by deficits in lexical retrieval and long sentenses repetition, while nfv-PPA were with motor speech apraxia and phonetic distortion. Compared with nfv-PPA, lv-PPA patient displayed more severe cognitive deficit with younger onset of age (56±5 vs 61±5, P<0.05) , rapid decline of MMSE score within 1.5 years and pariental cortex dysfunctions such as ideomotor praxis, Gerstmann syndrome and contructional apraxia. Correlation analysis indicated that there was more significant association between pariental cortex dysfunction and ADL/mini-mental state examination(MMSE) than that of language deficit(r=-0.868, r=-0.922; r=0.312, r=-0.257). All seven lv-PPA were PiB-PET positive and five nfv-PPA were negative.. This study enriched the chinical and linguistic characterization of lv-PPA and nfv-PPA, which has implication for diagnosis, disease management and treatment for clinicians.

Topics: Aniline Compounds; Aphasia, Primary Progressive; Cognition; Cognition Disorders; Humans; Language; Magnetic Resonance Imaging; Memory; Neuropsychological Tests; Thiazoles

Today, ligands that bind to fibrillar β-amyloid are detectable by Positron Emission Tomography (PET) allowing for in vivo visualization for Abeta burden. However, amyloid plaques detection per se does not establish Alzheimer's Disease diagnosis. In this sense, the utility of amyloid imaging to improve clinical diagnosis was settled only for specific clinical scenarios and few studies have assessed amyloid molecular neuroimaging in a broader clinical setting. The aim of this study is to determine the frequency of PiB amyloid findings in different diagnostic syndromes grouped into high and low probability pre- test categories, taking into account pre-test clinical assumption of the presence of AD related pathology.. 144 patients were assigned into categories of high or low pretest probability according to clinical suspicion of AD pathology. The high probability group included: amnestic Mild Cognitive Impairment (MCI), amnestic and other domains MCI, Dementia of Alzheimer's Type (DAT), Posterior Cortical Atrophy (PCA), logopenic Primary Progressive Aphasia (PPA), Cerebral Amyloid Angiopathy and mixed dementia. The low assumption group included: normal controls, non-amnestic MCI, non-logopenic PPA and Frontotemporal Dementia (FTD).. Only normal controls and DAT patients (typical and atypical presentation) were the most consistent across clinical and molecular diagnostics. MCI, non-logopenic PPA and FTD were the syndromic diagnoses that most discrepancies were found.. This study demonstrates that detecting in vivo amyloid plaques by molecular imaging is considerably frequent in most of the dementia syndromes and shows that there are frequent discordance between molecular diagnosis and clinical assumption.

Topics: Aged; Alzheimer Disease; Amnesia; Amyloid beta-Peptides; Aniline Compounds; Aphasia, Primary Progressive; Atrophy; Benzothiazoles; Cerebral Amyloid Angiopathy; Cerebral Cortex; Cognitive Dysfunction; Dementia; Female; Frontotemporal Lobar Degeneration; Humans; Male; Middle Aged; Positron-Emission Tomography; Retrospective Studies; Thiazoles

Microbleeds have been associated with Alzheimer's disease (AD), although it is unclear whether they occur in atypical presentations of AD, such as the logopenic variant of primary progressive aphasia (lvPPA). We aimed to assess the presence and clinical correlates of microbleeds in lvPPA.. Thirteen lvPPA subjects underwent 3T T2*-weighted and fluid-attenuated inversion recovery magnetic resonance imaging and Pittsburgh compound B (PiB) positron emission tomography imaging. Microbleeds were identified on manual review and assigned a regional location. Total and regional white matter hyperintensity (WMH) burden was measured.. Microbleeds were observed in four lvPPA subjects (31%), most commonly in the frontal lobe. Subjects with microbleeds were older, more likely female, and had a greater burden of WMH than those without microbleeds. The regional distribution of microbleeds did not match the regional distribution of WMH. All cases were PiB positive.. Microbleeds occur in approximately one third of subjects with lvPPA, with older women at the highest risk.

Topics: Aged; Aniline Compounds; Aphasia, Primary Progressive; Female; Hemorrhage; Humans; Imaging, Three-Dimensional; Magnetic Resonance Imaging; Male; Middle Aged; Neuropsychological Tests; Positron-Emission Tomography; Statistics, Nonparametric; Thiazoles; Tomography, X-Ray Computed

The logopenic variant of primary progressive aphasia (lvPPA) strongly associates with Alzheimer's disease, but can also associate with frontotemporal lobar degeneration. We aimed to assess the frequency of lvPPA in patients with speech and language disorders without β-amyloid deposition, and to perform detailed neuroimaging and genetic testing in such lvPPA patients. Seventy-six patients with a neurodegenerative speech and language disorder and Pittsburgh compound B (PiB) PET imaging demonstrating no β-amyloid deposition were analyzed. Six lvPPA patients (8 %) were identified. All six underwent progranulin (GRN) gene testing. Structural abnormality index maps and Cortex ID analysis were utilized to assess individual patterns of grey matter atrophy on MRI and hypometabolism on 18-F fluorodeoxyglucose (FDG) PET. Statistical parametric mapping was used to perform MRI and FDG-PET group comparisons between those with (GRN-positive) and without (GRN-negative) progranulin mutations. All six lvPPA patients showed left temporoparietal atrophy and hypometabolism. Three patients (50 %) were GRN-positive. Speech, language, and neurological and neuropsychological profiles did not differ between GRN-positive and negative patients, although GRN-positive patients had family histories, were on average 8 years younger, and had lower PiB-PET ratios. All six patients showed similar patterns of atrophy and hypometabolism, although, as a group, GRN-positive patients had more severe abnormalities, particularly in anteromedial temporal lobes. Logopenic PPA accounts for a small minority of neurodegenerative speech and language disorders not associated with β-amyloid deposition. Identification of such patients, however, should prompt testing for GRN mutations, since GRN-positive patients do not have distinctive features, yet account for 50 % of this patient population.

Topics: Age Factors; Aged; Amyloid beta-Peptides; Aniline Compounds; Aphasia, Primary Progressive; Apolipoproteins E; Atrophy; Cerebral Cortex; Female; Fluorodeoxyglucose F18; Humans; Intercellular Signaling Peptides and Proteins; Language Tests; Magnetic Resonance Imaging; Male; Middle Aged; Multimodal Imaging; Mutation; Neuropsychological Tests; Parietal Lobe; Positron-Emission Tomography; Progranulins; Temporal Lobe; Thiazoles; Tomography, X-Ray Computed

To disentangle the clinical heterogeneity of nonsemantic variants of primary progressive aphasia (PPA) and to identify a coherent linguistic-anatomical marker for the logopenic variant of PPA (lv-PPA).. Key speech and language features of 14 cases of lv-PPA and 18 cases of nonfluent/agrammatic variant of PPA were systematically evaluated and scored by an independent rater blinded to diagnosis. Every case underwent a structural MRI and a Pittsburgh compound B (PiB)-PET scan, a putative biomarker of Alzheimer disease. Key speech and language features that showed association with the PiB-PET status were entered into a hierarchical cluster analysis. The linguistic features and patterns of cortical thinning in each resultant cluster were analyzed.. The cluster analysis revealed 3 coherent clinical groups, each of which was linked to a specific PiB-PET status. The first cluster was linked to high PiB retention and characterized by phonologic errors and cortical thinning focused on the left superior temporal gyrus. The second and third clusters were characterized by grammatical production errors and motor speech disorders, respectively, and were associated with low PiB brain retention. A fourth cluster, however, demonstrated nonspecific language deficits and unpredictable PiB-PET status.. These findings suggest that despite the clinical and pathologic heterogeneity of nonsemantic variants, discrete clinical syndromes can be distinguished and linked to specific likelihood of PiB-PET status. Phonologic errors seem to be highly predictive of high amyloid burden in PPA and can provide a specific clinical marker for lv-PPA.

Topics: Aged; Aniline Compounds; Aphasia, Primary Progressive; Articulation Disorders; Cerebral Cortex; Cluster Analysis; Cognition Disorders; Female; Humans; Language Tests; Magnetic Resonance Imaging; Male; Middle Aged; Neurologic Examination; Neuropsychological Tests; Positron-Emission Tomography; Retrospective Studies; Speech; Thiazoles

Apolipoprotein E ε4 (APOE ε4) is a risk factor for β-amyloid deposition in Alzheimer's disease dementia. Its influence on β-amyloid deposition in speech and language disorders, including primary progressive aphasia (PPA), is unclear.. One hundred thirty subjects with PPA or progressive speech apraxia underwent APOE genotyping and Pittsburgh compound B (PiB) PET scanning. The relationship between APOE ε4 and PiB status, as well as severity and regional distribution of PiB, was assessed.. Forty-five subjects had an APOE ε4 allele and 60 subjects were PiB-positive. The odds ratio for a subject with APOE ε4 being PiB-positive compared with a subject without APOE ε4 being PiB-positive was 10.2 (95% confidence interval, 4.4-25.5; P < .0001). The APOE ε4 allele did not influence regional PiB distribution or severity.. APOE ε4 increases the risk of β-amyloid deposition in PPA and progressive speech apraxia but does not influence regional β-amyloid distribution or severity.

Topics: Aged; Aged, 80 and over; Amyloid beta-Peptides; Aniline Compounds; Aphasia, Primary Progressive; Apolipoprotein E4; Apraxias; Brain Mapping; Female; Humans; Male; Middle Aged; Positron-Emission Tomography; Thiazoles

We assessed whether clinical and imaging features of subjects with apraxia of speech (AOS) more severe than aphasia (dominant AOS) are more similar to agrammatic primary progressive aphasia (agPPA) or to primary progressive AOS (PPAOS).. Sixty-seven subjects (PPAOS = 18, dominant AOS = 10, agPPA = 9, age-matched controls = 30) who all had volumetric MRI, diffusion tensor imaging, F18-fluorodeoxyglucose and C11-labeled Pittsburgh compound B (PiB)-PET scanning, as well as neurologic and speech and language assessments, were included in this case-control study. AOS was classified as either type 1, predominated by sound distortions and distorted sound substitutions, or type 2, predominated by syllabically segmented prosodic speech patterns.. The dominant AOS subjects most often had AOS type 2, similar to PPAOS. In contrast, agPPA subjects most often had type 1 (p = 0.01). Both dominant AOS and PPAOS showed focal imaging abnormalities in premotor cortex, whereas agPPA showed widespread involvement affecting premotor, prefrontal, temporal and parietal lobes, caudate, and insula. Only the dominant AOS and PPAOS groups showed midbrain atrophy compared with controls. No differences were observed in PiB binding across all 3 groups, with the majority being PiB negative.. These results suggest that dominant AOS is more similar to PPAOS than agPPA, with dominant AOS and PPAOS exhibiting a clinically distinguishable subtype of progressive AOS compared with agPPA.

Topics: Aged; Aniline Compounds; Aphasia, Broca; Aphasia, Primary Progressive; Brain; Case-Control Studies; Chi-Square Distribution; Diffusion Magnetic Resonance Imaging; Female; Humans; Language Tests; Male; Middle Aged; Neuropsychological Tests; Positron-Emission Tomography; Retrospective Studies; Severity of Illness Index; Speech; Thiazoles

Most subjects with logopenic variant of primary progressive aphasia (lvPPA) have β-amyloid (Aβ) deposition on Pittsburgh Compound B positron emission tomography (PiB-PET), usually affecting prefrontal and temporoparietal cortices, with less occipital involvement.. To assess clinical and imaging features in lvPPA subjects with unusual topographic patterns of Aβ deposition with highest uptake in occipital lobe.. Thirty-three lvPPA subjects with Aβ deposition on PiB-PET were included in this case-control study. Line plots of regional PiB uptake were created, including frontal, temporal, parietal and occipital regions, for each subject. Subjects in which the line sloped downwards in occipital lobe (lvPPA-low), representing low uptake, were separated from those where the line sloped upwards in occipital lobe (lvPPA-high), representing unusually high occipital uptake compared to other regions. Clinical variables, atrophy on MRI, hypometabolism on 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), and presence and distribution of microbleeds and white matter hyperintensities (WMHs) were assessed.. Seventeen subjects (52%) were classified as lvPPA-high. Mean occipital PiB uptake in lvPPA-high was higher than all other regions and higher than all regions in lvPPA-low. The lvPPA-high subjects performed more poorly on cognitive testing, including executive and visuospatial testing, but the two groups did not differ in aphasia severity. Proportion of microbleeds and WMH was higher in lvPPA-high than lvPPA-low. Parietal hypometabolism was greater in lvPPA-high than lvPPA-low.. Unusually high occipital Aβ deposition is associated with widespread cognitive impairment and different imaging findings in lvPPA. These findings help explain clinical heterogeneity in lvPPA and suggest that Aβ influences severity of overall cognitive impairment but not aphasia.

Topics: Aged; Amyloid beta-Peptides; Aniline Compounds; Aphasia, Primary Progressive; Atrophy; Case-Control Studies; Cognition Disorders; Female; Fluorodeoxyglucose F18; Humans; Intracranial Hemorrhages; Male; Middle Aged; Nerve Fibers, Myelinated; Neuroimaging; Neuropsychological Tests; Occipital Lobe; Radionuclide Imaging; Thiazoles

Alzheimer's disease (AD) is found at autopsy in up to one third of patients with primary progressive aphasia (PPA), but clinical features that predict AD pathology in PPA are not well defined. We studied the relationships between language presentation, Abeta amyloidosis, and glucose metabolism in three PPA variants using [11C]-Pittsburgh compound B ([11C]PIB) and [18F]-labeled fluorodeoxyglucose positron emission tomography ([18F]FDG-PET).. Patients meeting PPA criteria (N = 15) were classified as logopenic aphasia (LPA), progressive nonfluent aphasia (PNFA), or semantic dementia (SD) based on language testing. [11C]PIB distribution volume ratios were calculated using Logan graphical analysis (cerebellar reference). [18F]FDG images were normalized to pons. Partial volume correction was applied.. Elevated cortical PIB (by visual inspection) was more common in LPA (4/4 patients) than in PNFA (1/6) and SD (1/5) (p < 0.02). In PIB-positive PPA, PIB uptake was diffuse and indistinguishable from the pattern in matched AD patients (n = 10). FDG patterns were focal and varied by PPA subtype, with left temporoparietal hypometabolism in LPA, left frontal hypometabolism in PNFA, and left anterior temporal hypometabolism in SD. FDG uptake was significant asymmetric (favoring left hypometabolism) in PPA (p < 0.005) but not in AD.. LPA is associated with Abeta amyloidosis, suggesting that subclassification of PPA based on language features can help predict the likelihood of AD pathology. Language phenotype in PPA is closely related to metabolic changes that are focal and anatomically distinct between subtypes, but not to amyloid deposition patterns that are diffuse and similar to AD.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Amyloid beta-Peptides; Analysis of Variance; Aniline Compounds; Aphasia, Primary Progressive; Carbon Isotopes; Dementia; Female; Fluorodeoxyglucose F18; Glucose; Humans; Image Processing, Computer-Assisted; Language; Language Tests; Male; Middle Aged; Positron-Emission Tomography; Thiazoles

A progressive decline in episodic memory affecting activities of daily living is the usual clinical presentation of Alzheimer disease. However, patients presenting with atypical or focal clinical symptoms such as language or visuospatial dysfunction often pose a diagnostic challenge.. To explore the presence and topography of beta amyloid (Abeta) as measured by carbon 11-labeled Pittsburgh Compound B ((11)C-PiB) in patients with atypical presentations of dementia.. At a tertiary referral center for memory disorders, 15 healthy controls, 10 patients with Alzheimer disease, a patient with primary progressive aphasia (PPA), and a patient with posterior cortical atrophy (PCA) underwent (11)C-PiB positron emission tomographic studies. Retention of (11)C-PiB was compared between different groups using statistical parametric mapping.. The topography of cortical (11)C-PiB binding in atypical vs typical Alzheimer disease.. Cortical (11)C-PiB binding was higher in the group with Alzheimer disease and in the patients with PPA and PCA than the controls (P < .001). Both patients with atypical dementia had a similar (11)C-PiB binding pattern to Alzheimer disease although (11)C-PiB retention was higher on the left cerebral hemisphere in the patient with PPA (P < .01) and higher in the occipital cortex in the patient with PCA (P < .01).. The presence of distinctive focal (11)C-PiB retention patterns was demonstrated in 2 patients with atypical onset of dementia. Pittsburgh Compound B has the potential to facilitate differential diagnosis of dementia and identify patients who could benefit from specific therapeutic strategies aimed at beta amyloid reduction.

Topics: Aged; Alzheimer Disease; Amyloid beta-Peptides; Aniline Compounds; Aphasia, Primary Progressive; Atrophy; Brain; Carbon Radioisotopes; Dementia; Female; Humans; Male; Middle Aged; Parietal Lobe; Positron-Emission Tomography; Syndrome; Thiazoles; Tissue Distribution