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Semantic variant primary progressive aphasia is a clinical syndrome characterized by marked semantic deficits, anterior temporal lobe atrophy and reduced connectivity within a distributed set of regions belonging to the functional network associated with semantic processing. However, to fully depict the clinical signature of semantic variant primary progressive aphasia, it is necessary to also characterize preserved neural networks and linguistic abilities, such as those subserving speech production. In this case-control observational study, we employed whole-brain seed-based connectivity on task-free MRI data of 32 semantic variant primary progressive aphasia patients and 46 healthy controls to investigate the functional connectivity of the speech production network and its relationship with the underlying grey matter. We investigated brain-behaviour correlations with speech fluency measures collected through clinical tests (verbal agility) and connected speech (speech rate and articulation rate). As a control network, we also investigated functional connectivity within the affected semantic network. Patients presented with increased connectivity in the speech production network between left inferior frontal and supramarginal regions, independent of underlying grey matter volume. In semantic variant primary progressive aphasia patients, preserved (verbal agility) and increased (articulation rate) speech fluency measures correlated with increased connectivity between inferior frontal and supramarginal regions. As expected, patients demonstrated decreased functional connectivity in the semantic network (dependent on the underlying grey matter atrophy) associated with average nouns' age of acquisition during connected speech. Collectively, these results provide a compelling model for studying compensation mechanisms in response to disease that might inform the design of future rehabilitation strategies in semantic variant primary progressive aphasia.

The Birch and Swinnerton-Dyer conjecture – which is one of the seven million-dollar Clay Mathematics Institute Millennium Prize Problems – and its generalizations are a significant focus of number theory research. A 2017 article of Jetchev, Skinner and Wan proved a Birch and Swinnerton-Dyer formula at a prime p for certain rational elliptic curves of rank 1. We generalize and adapt that article's arguments to prove an analogous formula for certain modular forms. For newforms f of even weight higher than 2 with Galois representation V containing a Galois-stable lattice T, let W = V / T and let K be an imaginary quadratic field in which the prime p splits. Our main result is that under some conditions, the p-index of the size of the Shafarevich-Tate group of W with respect to the Galois group of K is twice the p-index of a logarithm of the Abel-Jacobi map of a Heegner cycle defined by Bertolini, Darmon and Prasanna. Significant original adaptations we make to the 2017 arguments are (1) a generalized version of a previous calculation of the size of the cokernel of a localization-modulo-torsion map, and (2) a comparison of different Heegner cycles.

Heather R Dial,1,* Holly A Hinshelwood,2,* Stephanie M Grasso,1 H Isabel Hubbard,3 Maria-Luisa Gorno-Tempini,4 Maya L Henry1 1Communication Sciences and Disorders, University of Texas at Austin, Austin, TX, USA; 2Speech Pathology, Wake Forest Baptist Health, Winston-Salem, NC, USA; 3Communication Sciences and Disorders, University of Alberta, Edmonton, AB, Canada; 4Memory and Aging Center, University of California, San Francisco, San Francisco, CA, USA *These authors contributed equally to this work Introduction: Primary progressive aphasia (PPA) is a neurodegenerative disorder characterized by progressive deterioration of speech and language. A growing body of research supports the utility of speech and language intervention in individuals with PPA, although access to these services remains limited. One potential means of increasing treatment accessibility is the delivery of treatment via telemedicine. Evidence supports the use of teletherapy in stroke-induced aphasia, but research examining the application of teletherapy in PPA is limited. In the current study, a non-randomized group comparison design was used to evaluate the feasibility and utility of treatment delivered via teletherapy relative to treatment administered in person for individuals with PPA. Methods: Two treatment protocols were administered as part of a larger study investigating treatment for speech and language deficits in PPA. Participants with semantic (n=10) and logopenic (n=11) PPA received lexical retrieval treatment and individuals with nonfluent/agrammatic PPA (n=10) received video-implemented script training for aphasia designed to promote speech production and fluency. Treatment was administered via teletherapy for approximately half of the participants receiving each intervention. Treatment outcomes and performance on standardized tests were assessed at pre-treatment and post-treatment, as well as 3, 6, and 12 months post-treatment. Results: Overall, both treatment approaches resulted in significant gains for primary outcome measures. Critically, comparison of in-person and teletherapy groups revealed comparable outcomes. Generalization to untrained targets and tasks and maintenance of treatment-induced gains were also comparable for traditional vs teletherapy participants. Conclusion: Overall, treatment outcomes were largely equivalent for individuals receiving treatment via teletherapy vs traditional, in-person delivery. Results support the application of teletherapy for administering restitutive interventions to individuals with mild-to-moderate PPA. Potential implications for using teletherapy in the treatment of cognitive-linguistic and motoric impairments in other disorders and suggestions for administering treatment via telemedicine are discussed. Keywords: PPA, lexical retrieval treatment, script training, telemedicine, telerehabilitation, telepractice

Purpose: This study sought to determine the initial feasibility and benefit of a novel intervention that combines speech-language treatment with counseling treatment for an individual with the nonfluent/agrammatic variant of primary progressive aphasia (PPA).Method: Using a single-case experimental design, we evaluated the utility of modified script training paired with aphasia-modified cognitive behavioral therapy. The study employed a multiple baseline design across scripts for the primary linguistic outcome measure and a mixed methods approach for analyzing counseling outcomes. Psychosocial and communicative functioning scales were administered in conjunction with a phenomenological analysis of semi-structured interviews.Results: The participant completed all study phases and participated in all treatment components. She met the criterion of 90% correct, intelligible scripted words on all trained scripts through 12 months post-treatment. Treatment outcomes were comparable to a comparison cohort that received script training without counseling (Henry et al., 2018). At post-treatment, the participant demonstrated stability or improvement on all measures of psychosocial and communicative functioning, with stability documented on seven out of 11 scales at follow-ups through 12 months post-treatment. A phenomenological analysis revealed pervasive themes of loss and resilience at both time points, and emerging themes of positive self-perception, sense of agency, and emotional attunement following treatment.Conclusions: Results indicate that script training with aphasia-modified cognitive behavioral therapy is a feasible treatment for an individual with the nonfluent/agrammatic variant of PPA, with immediate and lasting benefits to speech-language production and psychosocial functioning. These findings are the first to support the integration of personal adjustment counseling techniques within a speech-language treatment paradigm for PPA.Supplemental Material S1. The VISTA+C participant’s performance on WAB-R subtests at each study time point.Supplemental Material S2. Linguistic parameters used for balancing the trained and untrained scripts of the VISTA+C participant.Supplemental Material S3. Participant's script characteristics. Supplemental Material S4. Script rate details. Supplemental Material S5. Sample dyadic aphasia-modified CBT exchange between patient and clinician. Schaffer, K. M., Evans, W. S., Dutcher, C. D., Philburn, C., & Henry, M. L. (2021). Embedding aphasia-modified cognitive behavioral therapy in script training for primary progressive aphasia: A single-case pilot study. American Journal of Speech-Language Pathology. Advance online publication. https://doi.org/10.1044/2021_AJSLP-20-00361

espanolTodos los docentes en general viven de cierta manera preocupados, especialmente los del area de las matematicas, por generar en sus educandos el desarrollo de las competencias argumentativas, propositivas e interpretativas. La manera memoristica en que algunas fabricas de cuadernos han promocionado la tablas de multiplicar han hecho por muchas generaciones que los propositos de las areas se vean truncados a mi parecer por el mal uso de esta estrategia de mercadeo. El Metodo “Maya” nacio desde hace aproximadamente 10 anos, los mismos que tiene mi hijo Juan Jose, buscando realizar un aporte social y educativo a la comunidad; innovando desde la didactica y las estrategias de aprendizaje significativo, propio de la teoria constructivista que sostiene que el conocimiento no se descubre, sino que por el contrario lo construye el individuo a partir de su propia forma de ser, pensar e interpreta la informacion. El proposito de este ejercicio es llamar la atencion sobre la necesidad de disminuir la posibilidad de no naturalizar el conocimiento memoristico sobre el aprendizaje de las tablas de multiplicar. El metodo “Maya” insiste en aplicar ciertas propiedades de la multiplicacion de numeros naturales y otras estrategias metodologicas, permitiendo que, al manejar el algoritmo de la multiplicacion, basta con conocer “de memoria” el producto de 15 numeros naturales por los digitos no nulos, haciendo mas atractivo el aprendizaje de las llamadas tablas de multiplicar. La utilidad de este metodo estriba en que es la puerta de entrada al calculo mental y al desarrollo de habilidades y competencias en matematicas. EnglishEvery teachers in general live worried in a certain way, especially those of the area of mathematics, to generate in their students the development of competencies: argumentative, propositional and interpretative competences. The memoristic way in which some notebook factories have promoted the multiplication tables, have originated during the generations that the purposes of the areas are truncated in my point of view by the bad using of this marketing strategy. The “Maya” Method was born 10 years ago, the same age than my son Juan Jose, trying to do an educational and social contribution to the community; innovating since the didactics and the significant learning strategies, typical of the constructivist theory which holds that maintains that the knowledge is not discovered, but on the contrary; Knowledge is built from their own way of being, thinking and interpreting information. I pretend to diminish the possibility of not naturalizing the memoristic knowledge about learning the multiplication tables. The “Maya” method insists on applying certain properties of the multiplication of natural numbers and other methodological strategies, letting that, when handling the multiplication algorithm, it is enough to know “from memory” the product of 15 natural numbers by the non-null digits, making more attractive the learning of the named multiplication tables. The usefulness of this method is that it is the gateway to mental calculation and the development of skills and competences in mathematics.

Intrinsic connectivity networks (ICNs) identified through task-free fMRI (tf-fMRI) offer the opportunity to investigate human brain circuits involved in language processes without requiring participants to perform challenging cognitive tasks. In this study, we assessed the ability of tf-fMRI to isolate reproducible networks critical for specific language functions and often damaged in primary progressive aphasia (PPA). First, we performed whole-brain seed-based correlation analyses on tf-fMRI data to identify ICNs anchored in regions known for articulatory, phonological, and semantic processes in healthy male and female controls (HCs). We then evaluated the reproducibility of these ICNs in an independent cohort of HCs, and recapitulated their functional relevance with a post hoc meta-analysis on task-based fMRI. Last, we investigated whether atrophy in these ICNs could inform the differential diagnosis of nonfluent/agrammatic, semantic, and logopenic PPA variants. The identified ICNs included a dorsal articulatory-phonological network involving inferior frontal and supramarginal regions; a ventral semantic network involving anterior middle temporal and angular gyri; a speech perception network involving superior temporal and sensorimotor regions; and a network between posterior inferior temporal and intraparietal regions likely linking visual, phonological, and attentional processes for written language. These ICNs were highly reproducible across independent groups and revealed areas consistent with those emerging from task-based meta-analysis. By comparing ICNs' spatial distribution in HCs with patients' atrophy patterns, we identified ICNs associated with each PPA variant. Our findings demonstrate the potential use of tf-fMRI to investigate the functional status of language networks in patients for whom activation studies can be methodologically challenging.SIGNIFICANCE STATEMENT We showed that a single, short, task-free fMRI acquisition is able to identify four reproducible and relatively segregated intrinsic left-dominant networks associated with articulatory, phonological, semantic, and multimodal orthography-to-phonology processes, in HCs. We also showed that these intrinsic networks relate to syndrome-specific atrophy patterns in primary progressive aphasia. Collectively, our results support the application of task-free fMRI in future research to study functionality of language circuits in patients for whom tasked-based activation studies might be methodologically challenging.

Purpose: Diagnosis and classification of primary progressive aphasia (PPA) requires confirmation of specific speech and language symptoms, highlighting the important role of speech-language pathologists in the evaluation process. The purpose of this case report is to inform speech-language pathologists regarding current practices for diagnostic assessment in PPA, describing standard approaches as well as complementary, state-of-the-art procedures that may improve diagnostic precision.Method: We describe the diagnostic evaluation of a 49-year-old woman with complaints of progressive word-finding difficulty. She completed standard neurological, neuropsychological, and speech-language evaluations, as well as magnetic resonance and positron emission tomography imaging of her brain. In addition, a history of developmental speech, language, and learning abilities was obtained, as well as genetic testing and assessment of cerebrospinal fluid biomarkers. We discuss the evaluation results in the context of the most current research related to PPA diagnosis.Conclusion: Detailed behavioral assessment, thorough intake of symptom history and neurodevelopmental differences, multimodal neuroimaging, and comprehensive examination of genes and biomarkers are of paramount importance for detecting and characterizing PPA, with ramifications for early behavioral and/or pharmacological intervention.Supplemental Material S1. Supplemental methods. Europa, E., Iaccarino, L., Perry, D. C., Weis, E., Welch, A. E., Rabinovici, G. D., Miller, B. L., Gorno-Tempini, M. L., & Henry, M. L. (2020). Diagnostic assessment in primary progressive aphasia: An illustrative case example. American Journal of Speech-Language Pathology. Advance online publication. https://doi.org/10.1044/2020_AJSLP-20-00007

In n-dimensional affine space over the field Z / 3 Z , a cap is given by a set of points no three of which are in a line, and the cap set problem asks for the largest possible size of an arbitrary cap. The solution to the cap set problem is known for n at most 6. In this paper, we define and apply standard diagrams. These pictures interpret a well-known technique for solving the cap set problem in a new way, allowing conclusions to be derived more easily and intuitively than before. We use standard diagrams to find caps in dimensions up to and including 4 systematically. We prove the apparently new result that in dimension 4, up to isomorphism there are exactly 20 size-18 caps, which we give explicitly. This article is the first of a series. In later articles, we plan to use the methods and results of this paper to investigate dimensions 5 and higher. The eventual goal is to solve the cap set problem in dimension 7, the first unsolved case.

Objective: To characterize in vivo signatures of pathological diagnosis in a large cohort of patients with primary progressive aphasia (PPA) variants defined by current diagnostic classification. Methods: Extensive clinical, cognitive, neuroimaging, and neuropathological data were collected from 69 patients with sporadic PPA, divided into 29 semantic (svPPA), 25 nonfluent (nfvPPA), 11 logopenic (lvPPA), and 4 mixed PPA. Patterns of gray matter (GM) and white matter (WM) atrophy at presentation were assessed and tested as predictors of pathological diagnosis using support vector machine (SVM) algorithms. Results: A clinical diagnosis of PPA was associated with frontotemporal lobar degeneration (FTLD) with transactive response DNA-binding protein (TDP) inclusions in 40.5%, FTLD-tau in 40.5%, and Alzheimer disease (AD) pathology in 19% of cases. Each variant was associated with 1 typical pathology; 24 of 29 (83%) svPPA showed FTLD-TDP type C, 22 of 25 (88%) nfvPPA showed FTLD-tau, and all 11 lvPPA had AD. Within FTLD-tau, 4R-tau pathology was commonly associated with nfvPPA, whereas Pick disease was observed in a minority of subjects across all variants except for lvPPA. Compared with pathologically typical cases, svPPA-tau showed significant extrapyramidal signs, greater executive impairment, and severe striatal and frontal GM and WM atrophy. nfvPPA-TDP patients lacked general motor symptoms or significant WM atrophy. Combining GM and WM volumes, SVM analysis showed 92.7% accuracy to distinguish FTLD-tau and FTLD-TDP pathologies across variants. Interpretation: Each PPA clinical variant is associated with a typical and most frequent cognitive, neuroimaging, and neuropathological profile. Specific clinical and early anatomical features may suggest rare and atypical pathological diagnosis in vivo. Ann Neurol 2017;81:430–443.

The non-fluent/agrammatic variant of primary progressive aphasia (nfvPPA) presents with a gradual decline in grammar and motor speech resulting from selective degeneration of speech-language regions in the brain. There has been considerable progress in identifying treatment approaches to remediate language deficits in other primary progressive aphasia variants; however, interventions for the core deficits in nfvPPA have yet to be systematically investigated. Further, the neural mechanisms that support behavioural restitution in the context of neurodegeneration are not well understood. We examined the immediate and long-term benefits of video implemented script training for aphasia (VISTA) in 10 individuals with nfvPPA. The treatment approach involved repeated rehearsal of individualized scripts via structured treatment with a clinician as well as intensive home practice with an audiovisual model using 'speech entrainment'. We evaluated accuracy of script production as well as overall intelligibility and grammaticality for trained and untrained scripts. These measures and standardized test scores were collected at post-treatment and 3-, 6-, and 12-month follow-up visits. Treatment resulted in significant improvement in production of correct, intelligible scripted words for trained topics, a reduction in grammatical errors for trained topics, and an overall increase in intelligibility for trained as well as untrained topics at post-treatment. Follow-up testing revealed maintenance of gains for trained scripts up to 1 year post-treatment on the primary outcome measure. Performance on untrained scripts and standardized tests remained relatively stable during the follow-up period, indicating that treatment helped to stabilize speech and language despite disease progression. To identify neural predictors of responsiveness to intervention, we examined treatment effect sizes relative to grey matter volumes in regions of interest derived from a previously identified speech production network. Regions of significant atrophy within this network included bilateral inferior frontal cortices and supplementary motor area as well as left striatum. Volumes in a left middle/inferior temporal region of interest were significantly correlated with the magnitude of treatment effects. This region, which was relatively spared anatomically in nfvPPA patients, has been implicated in syntactic production as well as visuo-motor facilitation of speech. This is the first group study to document the benefits of behavioural intervention that targets both linguistic and motoric deficits in nfvPPA. Findings indicate that behavioural intervention may result in lasting and generalized improvement of communicative function in individuals with neurodegenerative disease and that the integrity of spared regions within the speech-language network may be an important predictor of treatment response.

The bound of uniform strong primeness of the ring Mn(R) of n by n matrices over the unitary ring R is denoted mn(R). The concepts of uniform, right and left strong primeness for matrix rings are re-interpreted in terms of bilinear equations and multiplication of vectors. These interpretations are used to prove new results. Bounds of strong primeness of unitary rings R are linked to the bounds for Mn(R). The bound m2(D) is investigated for division rings D. Results by van den Berg (1998) and Beidar and Wisbauer (2004) linking uniform strong primeness to the existence of certain, possibly nonassociative, division algebras are generalised from fields to division rings. The result mn(D)≤2n−1 of van den Berg (1998) for division rings is extended to mnn′(R)≤(2n−1)mn′(R) for general unitary rings. In the case of formally real fields F, it is improved to mn(F)≤2n−2 for integers n>1 and mn(F)≤2n−4 for even n>2. This improvement, used in conjunction with a generalisation of an algebraic–topological proof of Hopf's theorem on real division algebras, yields m2k+1(R)=m2k+2(R)=2k+1. Bounds on mn(R) for other n are also obtained.

Highlights ► Patterns of cell loss in lvPPA remain asymmetrical over time. ► More anterior left hemisphere areas become involved over time. ► Right hemisphere regions become affected that mirror early left hemisphere change. ► Left hemisphere atrophy rates are greater than right hemisphere. ► Over time patients with lvPPA develop single word level processing deficits., The logopenic variant of primary progressive aphasia (PPA) is characterised by impaired sentence repetition and word retrieval difficulties. Post mortem studies, amyloid imaging and CSF tau/Aβ measurements suggest Alzheimer’s disease (AD) pathology as the underlying cause. Relatively little is known about patterns of progression in patients with the logopenic variant of PPA. 21 patients (3 with post mortem confirmation of AD and 5 with positive amyloid PIB-PET scans) were studied with longitudinal T1-weighted MR imaging (mean interscan interval 1.2 years) using volumetric analysis and voxel-based morphometry (VBM). Baseline imaging showed asymmetrical (left greater than right) involvement of the posterior superior temporal and inferior parietal lobes as well as posterior cingulate and medial temporal lobes. The whole brain rate of volume loss was 2.0% per year with a greater rate of left hemisphere atrophy (2.3%/year) than right hemisphere (1.6%/year). Longitudinal VBM analysis showed increasing involvement of other areas in the left hemisphere (temporal, parietal, frontal and caudate) and atrophy of areas in the right hemisphere that had been involved earlier in the disease in the left hemisphere, particularly posterior cingulate/precuneus. With disease progression there was worsening of anomia, sentence repetition and sentence comprehension but consistent with the spread of imaging changes also deficits in single word comprehension, single word repetition and verbal memory. This study shows that the logopenic variant of PPA remains an asymmetrical disease, with spread through the left hemisphere language network but also involvement to a lesser degree of regions in the right hemisphere that mirror the earlier left hemisphere changes.

Syntactic processing deficits are highly variable in individuals with primary progressive aphasia. Damage to left inferior frontal cortex has been associated with syntactic deficits in primary progressive aphasia in a number of structural and functional neuroimaging studies. However, a contrasting picture of a broader syntactic network has emerged from neuropsychological studies in other aphasic cohorts, and functional imaging studies in healthy controls. To reconcile these findings, we used functional magnetic resonance imaging to investigate the functional neuroanatomy of syntactic comprehension in 51 individuals with primary progressive aphasia, composed of all clinical variants and a range of degrees of syntactic processing impairment. We used trial-by-trial reaction time as a proxy for syntactic processing load, to determine which regions were modulated by syntactic processing in each patient, and how the set of regions recruited was related to whether syntactic processing was ultimately successful or unsuccessful. Relationships between functional abnormalities and patterns of cortical atrophy were also investigated. We found that the individual degree of syntactic comprehension impairment was predicted by left frontal atrophy, but also by functional disruption of a broader syntactic processing network, comprising left posterior frontal cortex, left posterior temporal cortex, and the left intraparietal sulcus and adjacent regions. These regions were modulated by syntactic processing in healthy controls and in patients with primary progressive aphasia with relatively spared syntax, but they were modulated to a lesser extent or not at all in primary progressive aphasia patients whose syntax was relatively impaired. Our findings suggest that syntactic comprehension deficits in primary progressive aphasia reflect not only structural and functional changes in left frontal cortex, but also disruption of a wider syntactic processing network.

ImportanceWe provide novel evidence of specific clinical and neuroimaging features that may help for the in vivo prediction of underlying pathology in patients with nonfluent/agrammatic primary progressive aphasia (nfvPPA) and progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD) proved by autopsy.ObjectiveTo characterize the neurological, cognitive, and neuroimaging features of patients with nfvPPA-in whom either PSP or CBD was eventually confirmed at autopsy-at initial presentation and at 1-year follow-up.Design, setting, and participantsA prospective longitudinal clinical-pathological study was conducted in a tertiary research clinic that specialized in cognitive disorders. Fourteen patients were evaluated between January 2002 and December 2014. Inclusion criteria for the study were a clinical diagnosis of nfvPPA; the availability of speech, language, and cognitive testing for at least 1 evaluation; magnetic resonance imaging within 6 months of initial evaluation; and a postmortem pathological diagnosis of PSP or CBD. Ten matched healthy control participants were also included.Main outcomes and measuresClinical, cognitive, and neuroimaging longitudinal data were analyzed to characterize the whole nfvPPA-4-repeat-tau group and identify differences between nfvPPA-PSP and nfvPPA-CBD both at presentation and longitudinally.ResultsPatient groups did not differ significantly in age, sex, or handedness (nfvPPA-PSP group: median [interquartile range (IQR)] age, 74 [67-76] years; 1 of 5 male [20%]; 1 of 5 left-handed [20%]; and nfvPPA-CBD group: mean [IQR] age, 65 [54-81] years; 3 of 9 male [33%]; 0 left-handed). Motor speech impairment and left frontal white matter atrophy were the most prominent common features. At presentation, dysarthria (Motor Speech Examination median [IQR] score: nfvPPA-PSP, 4 [2-7]; nfvPPA-CBD, 0 [0-4]; P = .02), depression (Geriatric Depression Scale median [IQR] score: nfvPPA-PSP, 19 [3-28]; nfvPPA-CBD, 4 [0-16]; P = .04), and relatively selective white matter atrophy were typical of the nfvPPA-PSP group, while greater gray matter atrophy and a trend toward greater sentence comprehension deficits (median [IQR] sentence comprehension correct: nfvPPA-PSP, 98% [80-100]; nfvPPA-CBD, 81% [65-98]; P = .08) were found in the nfvPPA-CBD group. At follow-up after 1 year, we observed no significant differences in any speech or language measures. Furthermore, atrophy in patients with PSP progressed within the subcortical/brainstem motor system generating greater oculomotors deficits and swallowing difficulty; atrophy in patients with CBD spread anteriorly in prefrontal regions consistent with their greater working memory impairment and development of behavioral symptoms.Conclusions and relevanceIn patients presenting with nfvPPA, presence of early severe dysarthria, relatively selective white matter atrophy at presentation, and a greater rate of change in the brainstem measured by longitudinal imaging may be useful for differentiating underlying PSP from CBD pathology during life.

ObjectiveTo evaluate the effect of amyloid imaging on clinical decision making.MethodsWe conducted a retrospective analysis of 140 cognitively impaired patients (mean age 65.0 years, 46% primary β-amyloid (Aβ) diagnosis, mean Mini-Mental State Examination 22.3) who underwent amyloid (Pittsburgh compound B [PiB]) PET as part of observational research studies and were evaluated clinically before and after the scan. One hundred thirty-four concurrently underwent fluorodeoxyglucose (FDG)-PET. We assessed for changes between the pre- and post-PET clinical diagnosis (from Aβ to non-Aβ diagnosis or vice versa) and Alzheimer disease treatment plan. The association between PiB/FDG results and changes in management was evaluated using χ(2) and multivariate logistic regression. Postmortem diagnosis was available for 24 patients (17%).ResultsConcordance between scan results and baseline diagnosis was high (PiB 84%, FDG 82%). The primary diagnosis changed after PET in 13/140 patients (9%) overall but in 5/13 (38%) patients considered pre-PET diagnostic dilemmas. When examined independently, discordant PiB and discordant FDG were both associated with diagnostic change (unadjusted p < 0.0001). However, when examined together in a multivariate logistic regression, only discordant PiB remained significant (adjusted p = 0.00013). Changes in treatment were associated with discordant PiB in patients with non-Aβ diagnoses (adjusted p = 0.028), while FDG had no effect on therapy. Both PiB (96%) and FDG (91%) showed high agreement with autopsy diagnosis.ConclusionsPET had a moderate effect on clinical outcomes. Discordant PiB had a greater effect than discordant FDG, and influence on diagnosis was greater than on treatment. Prospective studies are needed to better characterize the clinical role of amyloid PET.

The neural organization of semantic memory remains much debated. A 'distributed-only' view contends that semantic knowledge is represented within spatially distant, modality-selective primary and association cortices. Observations in semantic variant primary progressive aphasia have inspired an alternative model featuring the anterior temporal lobe as an amodal hub that supports semantic knowledge by linking distributed modality-selective regions. Direct evidence has been lacking, however, to support intrinsic functional interactions between an anterior temporal lobe hub and upstream sensory regions in humans. Here, we examined the neural networks supporting semantic knowledge by performing a multimodal brain imaging study in healthy subjects and patients with semantic variant primary progressive aphasia. In healthy subjects, the anterior temporal lobe showed intrinsic connectivity to an array of modality-selective primary and association cortices. Patients showed focal anterior temporal lobe degeneration but also reduced physiological integrity throughout distributed modality-selective regions connected with the anterior temporal lobe in healthy controls. Physiological deficits outside the anterior temporal lobe correlated with scores on semantic tasks and with anterior temporal subregion atrophy, following domain-specific and connectivity-based predictions. The findings provide a neurophysiological basis for the theory that semantic processing is orchestrated through interactions between a critical anterior temporal lobe hub and modality-selective processing nodes.

Many patients with primary progressive aphasia (PPA) are impaired in syntactic production. Because most previous studies of expressive syntax in PPA have relied on quantitative analysis of connected speech samples, which is a relatively unconstrained task, it is not well understood which specific syntactic structures are most challenging for these patients. We used an elicited syntactic production task to identify which syntactic structures pose difficulties for 31 patients with three variants of PPA: non-fluent/agrammatic, semantic and logopenic. Neurodegenerative and healthy age-matched participants were included as controls. As expected, non-fluent/agrammatic patients made the most syntactic errors. The structures that resulted in the most errors were constructions involving third person singular present agreement, and constructions involving embedded clauses. Deficits on this elicited production task were associated with atrophy of the left posterior inferior frontal gyrus.