Home-Based Transcranial Direct Current Stimulation in Primary Progressive Aphasia: A Pilot Study.

BACKGROUND: This study aims to determine (a) if home-based anodal transcranial direct current stimulation (a-tDCS) delivered to the left supramarginal gyrus (SMG) coupled with verbal short-term memory/working memory (vSTM/WM) treatment ("RAM", short for "Repeat After Me") is more effective than sham-tDCS in improving vSTM/WM in patients with primary progressive aphasia (PPA), and (b) whether tDCS effects generalize to other language and cognitive abilities. METHODS: Seven PPA participants received home-based a-tDCS and sham-tDCS coupled with RAM treatment in separate conditions in a double-blind design. The treatment task required participants to repeat word spans comprising semantically and phonologically unrelated words in the same and reverse order. The evaluation of treatment effects was carried out using the same tasks as in the treatment but with different items (near-transfer effects) and tasks that were not directly related to the treatment (far-transfer effects). RESULTS: A-tDCS showed (a) a significant effect in improving vSTM abilities, measured by word span backward, and (b) a generalization of this effect to other language abilities, namely, spelling (both real words and pseudowords) and learning (retention and delayed recall). CONCLUSIONS: These preliminary results indicate that vSTM/WM intervention can improve performance in trained vSTM/WM tasks in patients with PPA, especially when augmented with home-based tDCS over the left SMG.

Online speech synthesis using a chronically implanted brain-computer interface in an individual with ALS.

Brain-computer interfaces (BCIs) that reconstruct and synthesize speech using brain activity recorded with intracranial electrodes may pave the way toward novel communication interfaces for people who have lost their ability to speak, or who are at high risk of losing this ability, due to neurological disorders. Here, we report online synthesis of intelligible words using a chronically implanted brain-computer interface (BCI) in a man with impaired articulation due to ALS, participating in a clinical trial (ClinicalTrials.gov, NCT03567213) exploring different strategies for BCI communication. The 3-stage approach reported here relies on recurrent neural networks to identify, decode and synthesize speech from electrocorticographic (ECoG) signals acquired across motor, premotor and somatosensory cortices. We demonstrate a reliable BCI that synthesizes commands freely chosen and spoken by the participant from a vocabulary of 6 keywords previously used for decoding commands to control a communication board. Evaluation of the intelligibility of the synthesized speech indicates that 80% of the words can be correctly recognized by human listeners. Our results show that a speech-impaired individual with ALS can use a chronically implanted BCI to reliably produce synthesized words while preserving the participant's voice profile, and provide further evidence for the stability of ECoG for speech-based BCIs.

Baseline Conceptual-Semantic Impairment Predicts Longitudinal Treatment Effects for Anomia in Primary Progressive Aphasia and Alzheimer's Disease.

Background: An individual's diagnostic subtype may fail to predict the efficacy of a given type of treatment for anomia. Classification by conceptual-semantic impairment may be more informative. Aims: This study examined the effects of conceptual-semantic impairment and diagnostic subtype on anomia treatment effects in primary progressive aphasia (PPA) and Alzheimer's disease (AD). Methods & Procedures: At baseline, the picture and word versions of the Pyramids and Palm Trees and Kissing and Dancing tests were used to measure conceptual-semantic processing. Based on norming that was conducted with unimpaired older adults, participants were classified as being impaired on both the picture and word versions (i.e., modality-general conceptual-semantic impairment), the picture version (Objects or Actions) only (i.e., visual-conceptual impairment), the word version (Nouns or Verbs) only (i.e., lexical-semantic impairment), or neither the picture nor the word version (i.e., no impairment). Following baseline testing, a lexical treatment and a semantic treatment were administered to all participants. The treatment stimuli consisted of nouns and verbs that were consistently named correctly at baseline (Prophylaxis items) and/or nouns and verbs that were consistently named incorrectly at baseline (Remediation items). Naming accuracy was measured at baseline, and it was measured at three, seven, eleven, fourteen, eighteen, and twenty-one months. Outcomes & Results: Compared to baseline naming performance, lexical and semantic treatments both improved naming accuracy for treated Remediation nouns and verbs. For Prophylaxis items, lexical treatment was effective for both nouns and verbs, and semantic treatment was effective for verbs, but the pattern of results was different for nouns -- the effect of semantic treatment was initially nonsignificant or marginally significant, but it was significant beginning at 11 Months, suggesting that the effects of prophylactic semantic treatment may become more apparent as the disorder progresses. Furthermore, the interaction between baseline Conceptual-Semantic Impairment and the Treatment Condition (Lexical vs. Semantic) was significant for verb Prophylaxis items at 3 and 18 Months, and it was significant for noun Prophylaxis items at 14 and 18 Months. Conclusions: The pattern of results suggested that individuals who have modality-general conceptual-semantic impairment at baseline are more likely to benefit from lexical treatment, while individuals who have unimpaired conceptual-semantic processing at baseline are more likely to benefit from semantic treatment as the disorder progresses. In contrast to conceptual-semantic impairment, diagnostic subtype did not typically predict the treatment effects.

Criteria and Indicators for Centers of Clinical Excellence in Stroke Recovery and Rehabilitation: A Global Consensus Facilitated by ISRRA.

BACKGROUND: The aim of the International Stroke Recovery and Rehabilitation Alliance is to create a world where worldwide collaboration brings major breakthroughs for the millions of people living with stroke. A key pillar of this work is to define globally relevant criteria for centers that aspire to deliver excellent clinical rehabilitation and generate exceptional outcomes for patients. OBJECTIVES: This paper presents consensus work conducted with an international group of expert stroke recovery and rehabilitation researchers, clinicians, and people living with stroke to identify and define criteria and measurable indicators for Centers of Clinical Excellence (CoCE) in stroke recovery and rehabilitation. These were intentionally developed to be ambitious and internationally relevant, regardless of a country's development or income status, to drive global improvement in stroke services. METHODS: Criteria and specific measurable indicators for CoCE were collaboratively developed by an international panel of stroke recovery and rehabilitation experts from 10 countries and consumer groups from 5 countries. RESULTS: The criteria and associated indicators, ranked in order of importance, focused upon (i) optimal outcome, (ii) research culture, (iii) working collaboratively with people living with stroke, (iv) knowledge exchange, (v) leadership, (vi) education, and (vii) advocacy. Work is currently underway to user-test the criteria and indicators in 14 rehabilitation centers in 10 different countries. CONCLUSIONS: We anticipate that use of the criteria and indicators could support individual organizations to further develop their services and, more widely, provide a mechanism by which clinical excellence can be articulated and shared to generate global improvements in stroke care.

Verb Frequency and Density Drive Naming Performance in Primary Progressive Aphasia.

Background: Recent work has highlighted the utility of the Boston Naming Test and Hopkins Action Naming Assessment (HANA) for distinguishing between semantic (svPPA), logopenic (lvPPA) and non-fluent agrammatic (nfavPPA) variants of primary progressive aphasia (PPA). Aims: To determine whether item level differences between variants on when naming verbs on the HANA were able to be accounted for using common variables of lexical interest: word frequency, semantic density, concreteness, or valency. We also examined three specific hypotheses: (1) svPPA and lvPPA may result in increased difficulty with decreased semantic density compared to nfavPPA; (2) svPPA may result in increased difficulty with decreased concreteness; and (3) nfavPPA may result in increased difficulty with high syntactic valency. Methods & Procedures: 268 patients with PPA were evaluated using the HANA. A hierarchical Bayesian regression approach was adopted to account for effects of repeated measurement within participants and items. Outcomes & Results: The main effects of variant and verb trait were significant in all models, as was the interaction for frequency, semantic density, and valency. Increasing frequency, semantic density, and concreteness led to better performance, while increasing valency led to poorer performance. Low semantic density contributed to greater difficulty in svPPA and lvPPA, but low concreteness did not uniquely impact verb naming in svPPA. Those with nfavPPA had no particular difficulty as a result of valency. Conclusions: Prior studies have identified the independent effects of frequency and semantic density on verb naming in PPA, which were confirmed by our analyses, and the best predictions of the data were achieved by combining these dimensions. This investigation complements our previous work highlighting the value of the HANA for efficiently demonstrating verb performance in PPA.

Stable Decoding from a Speech BCI Enables Control for an Individual with ALS without Recalibration for 3 Months.

Brain-computer interfaces (BCIs) can be used to control assistive devices by patients with neurological disorders like amyotrophic lateral sclerosis (ALS) that limit speech and movement. For assistive control, it is desirable for BCI systems to be accurate and reliable, preferably with minimal setup time. In this study, a participant with severe dysarthria due to ALS operates computer applications with six intuitive speech commands via a chronic electrocorticographic (ECoG) implant over the ventral sensorimotor cortex. Speech commands are accurately detected and decoded (median accuracy: 90.59%) throughout a 3-month study period without model retraining or recalibration. Use of the BCI does not require exogenous timing cues, enabling the participant to issue self-paced commands at will. These results demonstrate that a chronically implanted ECoG-based speech BCI can reliably control assistive devices over long time periods with only initial model training and calibration, supporting the feasibility of unassisted home use.

When words first fail: Predicting the emergence of primary progressive aphasia variants from unclassifiable anomic performance in early disease.

Background: The majority of patients with primary progressive aphasia (PPA) can be distinguished into one of three variants: semantic, non-fluent/agrammatic, or logopenic. However, many do not meet criteria for any one variant. Aim: To identify aspects of cognitive-linguistic performance that yield an early unclassifiable PPA designation that predicted the later emergence of a given variant. Methods & Procedures: Of 256 individuals with PPA evaluated, 19 initially were unclassifiable and later met criteria for a variant. Receiver operating characteristic curves were used to evaluate the binary ability of a given task to predict eventual classification as a given variant. Tasks with a high area under the curve were examined using regression analyses to determine their ability to predict variant. Outcomes & Results: High mean predictive value was observed for multiple naming assessments targeting nouns and verbs. The Boston Naming Test (BNT) was the only test that, in isolation, resulted in a significant model and high classification accuracy. Conclusions: Although naming impairment is common across PPA variants, very low initial BNT scores emerged as a uniquely accurate basis for predicting eventual semantic variant, and normal BNT scores predicted eventual nonfluent/agrammatic variant. High performance on picture-verb verification was useful in identifying future lvPPA.

Transcranial Direct-Current Stimulation in Subacute Aphasia: A Randomized Controlled Trial.

BACKGROUND: Transcranial direct-current stimulation (tDCS) is a promising adjunct to therapy for chronic aphasia. METHODS: This single-center, randomized, double-blind, sham-controlled efficacy trial tested the hypothesis that anodal tDCS augments language therapy in subacute aphasia. Secondarily, we compared the effect of tDCS on discourse measures and quality of life and compared the effects on naming to previous findings in chronic stroke. Right-handed English speakers with aphasia <3 months after left hemisphere ischemic stroke were included, unless they had prior neurological or psychiatric disease or injury or were taking certain medications (34 excluded; final sample, 58). Participants were randomized 1:1, controlling for age, aphasia type, and severity, to receive 20 minutes of tDCS (1 mA) or sham-tDCS in addition to fifteen 45-minute sessions of naming treatment (plus standard care). The primary outcome variable was change in naming accuracy of untrained pictures pretreatment to 1-week posttreatment. RESULTS: Baseline characteristics were similar between the tDCS (N=30) and sham (N=28) groups: patients were 65 years old, 53% male, and 2 months from stroke onset on average. In intent-to-treat analysis, the adjusted mean change from baseline to 1-week posttreatment in picture naming was 22.3 (95% CI, 13.5-31.2) for tDCS and 18.5 (9.6-27.4) for sham and was not significantly different. Content and efficiency of picture description improved more with tDCS than sham. Groups did not differ in quality of life improvement. No patients were withdrawn due to adverse events. CONCLUSIONS: tDCS did not improve recovery of picture naming but did improve recovery of discourse. Discourse skills are critical to participation. Future research should examine tDCS in a larger sample with richer functional outcomes. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02674490.

Neural regions underlying object and action naming: Complementary evidence from acute stroke and primary progressive aphasia.

Background: Naming impairment is commonly noted in individuals with aphasia. However, object naming receives more attention than action naming. Furthermore, most studies include participants with aphasia due to only one aetiology, commonly stroke. We developed a new assessment, the Hopkins Action Naming Assessment (HANA), to evaluate action naming impairments. Aims: Our aims were to show that the HANA is a useful tool that can (1) identify action naming impairments and (2) be used to investigate the neural substrates underlying naming. We paired the HANA with the Boston Naming Test (BNT) to compare action and object naming. We considered participants with aphasia due to primary progressive aphasia (PPA) or acute left hemisphere stroke to provide a more comprehensive picture of brain-behaviour relationships critical for naming. Behaviourally, we hypothesised that there would be a double dissociation between object and action naming performance. Neuroanatomically, we hypothesised that different neural substrates would be implicated in object vs. action naming and that different lesion-deficit associations would be identified in participants with PPA vs. acute stroke. Methods & Procedures: Participants (N=138 with PPA, N=37 with acute stroke) completed the BNT and HANA. Behavioural performance was compared. A subset of participants (N=31 with PPA, N=37 with acute stroke) provided neuroimaging data. The whole brain was automatically segmented into regions of interest (ROIs). For participants with PPA, the image variables were the ROI volumes, normalised by the brain volume. For participants with acute stroke, the image variables were the percentage of each ROI affected by the lesion. The relationship between ROIs likely to be involved in naming performance was modelled with LASSO regression. Outcomes & Results: Behavioural results showed a double dissociation in performance: in each group, some participants displayed intact performance relative to healthy controls on actions but not objects and/or significantly better performance on actions than objects, while others showed the opposite pattern. These results support the need to assess both objects and actions when evaluating naming deficits. Neuroimaging results identified different regions associated with object vs. action naming, implicating overlapping but distinct networks of regions. Furthermore, results differed for participants with PPA vs. acute stroke, indicating that critical information may be missed when only one aetiology is considered. Conclusions: Overall, the study provides a more comprehensive picture of the neural bases of naming, underscoring the importance of assessing both objects and actions and considering different aetiologies of damage. It demonstrates the utility of the HANA.

Application of the dual stream model to neurodegenerative disease: Evidence from a multivariate classification tool in primary progressive aphasia.

Background: A clinical diagnosis of primary progressive aphasia relies on behavioral characteristics and patterns of atrophy to determine a variant: logopenic; nonfluent/agrammatic; or semantic. The dual stream model (Hickok & Poeppel, 2000; 2004; 2007; 2015) is a contemporary paradigm that has been applied widely to understand brain-behavior relationships; however, applications to neurodegenerative diseases like primary progressive aphasia are limited. Aims: The primary aim of this study is to determine if the dual stream model can be applied to a neurodegenerative disease, such as primary progressive aphasia, using both behavioral and neuroimaging data. Methods & Procedures: We analyzed behavioral and neuroimaging data to apply a multivariate classification tool (support vector machines) to determine if the dual stream model extends to primary progressive aphasia. Sixty-four individuals with primary progressive aphasia were enrolled (26 logopenic variant, 20 nonfluent/agrammatic variant, and 18 semantic variant) and administered four behavioral tasks to assess three linguistic domains (naming, repetition, and semantic knowledge). We used regions of interest from the dual stream model and calculated the cortical volume for gray matter regions and white matter structural volumes and fractional anisotropy. We applied a multivariate classification tool (support vector machines) to distinguish variants based on behavioral performance and patterns of atrophy. Outcomes & Results: Behavioral performance discriminates logopenic from semantic variant and nonfluent/agrammatic from semantic variant. Cortical volume distinguishes all three variants. White matter structural volumes and fractional anisotropy primarily distinguish nonfluent/agrammatic from semantic variant. Regions of interest that contribute to each classification in cortical and white matter analyses demonstrate alignment of logopenic and nonfluent/agrammatic variants to the dorsal stream, while the semantic variant aligns with the ventral stream. Conclusions: A novel implementation of an automated multivariate classification suggests that the dual stream model can be extended to primary progressive aphasia. Variants are distinguished by behavioral and neuroanatomical patterns and align to the dorsal and ventral streams of the dual stream model.

Clinical and neuroimaging characteristics of primary progressive aphasia.

The chapter covers the clinical syndrome of a primary progressive aphasia (PPA), the demographics of this rare neurodegenerative disease, defining clinical and neuroanatomic characteristics of each PPA variant, disease progression, and behavioral features. The chapter begins with a brief introduction that includes references to seminal papers that defined this clinical syndrome and its three variants. The classic PPA subtypes discussed in the chapter are semantic variant PPA (svPPA), nonfluent/agrammatic PPA (nfaPPA), and logopenic variant PPA (lvPPA). The key language and cognitive characteristics, and language tasks that can elicit these language impairments, are detailed. Overlap in the clinical profiles of the PPA variants, which make differential diagnosis challenging, are explained. Disease progression is described, revealing that the PPA variants become more similar over time. Although PPA is language-predominant dementia, there are behavioral manifestations, particularly in svPPA. Changes in behavior in this variant are addressed as well as behavioral changes in nfaPPA and lvPPA that are less well recognized. The patterns of atrophy in the left temporal, parietal, and/or frontal cortices unique to each PPA variant are described. The underlying neuropathologies of the PPA variants are discussed, specifically tauopathies and non-tauopathies associated with svPPA and nfaPPA and Alzheimer's disease pathology in lvPPA.

Task performance to discriminate among variants of primary progressive aphasia.

Primary progressive aphasia can be distinguished into one of three variants: semantic, non-fluent/agrammatic, and logopenic. While a considerable body of work exists characterizing each variant, few prior studies have addressed the problem of optimizing behavioral assessment in a typical outpatient evaluation setting. Our aim is to examine the sensitivity and specificity of a battery of cognitive and linguistic assessments and determine optimal scores for distinguishing patients' subtype based on these instruments. This was a retrospective analysis of outpatient clinical testing of individuals with known or suspected primary progressive aphasia. Evaluations included the National Alzheimer's Coordinating Center frontotemporal lobar degeneration module and additional measures of naming, semantic association, word verification, and picture description. Receiver operating characteristic analysis was used to examine the utility of each task in distinguishing each variant from the others. Logistic regressions were used to examine the combined utility of tasks for distinguishing a given subtype. We examined 435 evaluations of 222 patients retrospectively. The battery was most consistent in distinguishing semantic variant by low scores and non-fluent/agrammatic variant by high scores on a similar subset of tasks. Tasks best distinguishing semantic variant produced a model that correctly classified 86% of cases. Tasks best distinguishing non-fluent/agrammatic variant correctly classified 77% of cases. The battery of tasks was weakest in identifying logopenic variant; only the ratio of sentence reading to sentence repetition performance was identified as a reasonable predictor, and it had predictive accuracy of 67%. Naming assessments were the strongest basis for distinguishing all variants, particularly semantic variant from non-fluent/agrammatic variant. These data illustrate that a number of commonly used assessments perform at chance in distinguishing variant and preliminarily support an abbreviated battery that marginally favors tools not currently included in the frontotemporal lobar degeneration module.

Longitudinal decline in spoken word recognition and object knowledge in primary progressive aphasia.

ABSTRACT: The premise of this study is that spoken word recognition and object knowledge are impaired in semantic variant primary progressive aphasia (PPA) (svPPA) and are spared in logopenic variant (lvPPA) and nonfluent agrammatic primary progressive aphasia (nfaPPA) at disease onset. Over time, however, there may be heterogeneity in these abilities in lvPPA and nfaPPA. We hypothesized that individuals with svPPA would demonstrate poorer performance on baseline spoken word recognition and object knowledge than those with lvPPA and nfaPPA) as documented in the literature, but that rates of decline over time on spoken word recognition and object knowledge would be similar in all 3 PPA variants because these become less distinguishable with disease progression.The aim of this study was to investigate longitudinal patterns of decline in spoken word recognition and object knowledge across PPA variants.Ninety-five individuals with PPA completed the Semantic Word Picture Matching and Semantic Associates tests at baseline to establish expected performance in these areas. Thirty-five individuals completed follow-up testing.The distributions of trichotomized mean rates of decline in object knowledge were similar for lvPPA and svPPA (P = .05). There were weak negative correlations between symptom duration and baseline scores on Semantic Word Picture Matching (r[37] = -0.399, P = .01), and baseline scores on Semantic Associates (r[37] = -0.394, P = .01) in lvPPA.Degradation of spoken word recognition and object knowledge occurs over time in lvPPA. Further investigation of the receptive language deficits in PPA is warranted to characterize language changes that lessen the distinctions between PPA variants with disease progression.

Visuomotor Figure Construction and Visual Figure Delayed Recall and Recognition in Primary Progressive Aphasia.

BACKGROUND: Individuals with primary progressive aphasia (PPA) develop visuospatial deficits over time, and those with logopenic variant (lvPPA) are at greatest risk of developing such deficits. However, not all previous studies of visuospatial deficits in PPA have ensured equivalent duration of disease across variants and few have measured deficits longitudinally. AIMS: The aims of our study were to: 1) investigate differences in baseline visuomotor figure construction, visual figure delayed recall, and figure recognition in PPA variants with similar symptom duration at baseline, and 2) explore patterns of decline in these areas. METHODS & PROCEDURES: Ninety-three individuals with PPA [39 lvPPA, 24 nonfluent agrammatic PPA (nfaPPA), and 30 semantic variant PPA (svPPA)] were administered the Benson Complex Figure Copy, Benson Complex Figure Delay (Recall), and Benson Figure Recognition. Thirty individuals completed this testing 3 to 47 months post baseline. OUTCOME & RESULTS: Participants with lvPPA and svPPA showed lower mean scores than those with nfaPPA on visual figure delayed recall at baseline, even though there were no differences in estimated time from disease onset or correlation with disease severity as reflected by naming performance, F(2, 90) = 5.78, p < .004. Those with nfaPPA performed significantly better than those with lvPPA, Tukey HSD p < .05, and those with svPPA, Tukey HSD p < .01. There were no differences between variants in rate of decline in visuomotor figure construction, visual figure delayed recall, and figure recognition. CONCLUSIONS: These findings revealed relatively spared visuospatial memory in nfaPPA, which may aid in the differential diagnosis of PPA and contribute to designing therapy or compensatory strategies.

Cerebellar neuromodulation improves naming in post-stroke aphasia.

Transcranial direct current stimulation has been shown to increase the efficiency of language therapy in chronic aphasia; however, to date, an optimal stimulation site has not been identified. We investigated whether neuromodulation of the right cerebellum can improve naming skills in chronic aphasia. Using a randomized, double-blind, sham-controlled, within-subject crossover study design, participants received anodal cerebellar stimulation (n = 12) or cathodal cerebellar stimulation (n = 12) + computerized aphasia therapy then sham + computerized aphasia therapy, or the opposite order. There was no significant effect of treatment (cerebellar stimulation versus sham) for trained naming. However, there was a significant order x treatment interaction, indicating that cerebellar stimulation was more effective than sham immediately post-treatment for participants who received cerebellar stimulation in the first phase. There was a significant effect of treatment (cerebellar stimulation versus sham) for untrained naming immediately post-treatment and the significant improvement in untrained naming was maintained at two months post-treatment. Greater gains in naming (relative to sham) were noted for participants receiving cathodal stimulation for both trained and untrained items. Thus, our study provides evidence that repetitive cerebellar transcranial direct stimulation combined with computerized aphasia treatment can improve picture naming in chronic post-stroke aphasia. These findings suggest that the right cerebellum might be an optimal stimulation site for aphasia rehabilitation and this could be an answer to handle heterogeneous participants who vary in their size and site of left hemisphere lesions.

White Matter Hyperintensities Contribute to Language Deficits in Primary Progressive Aphasia.

OBJECTIVE: To determine the contribution of white matter hyperintensities (WMH) to language deficits while accounting for cortical atrophy in individuals with primary progressive aphasia (PPA). METHOD: Forty-three individuals with PPA completed neuropsychological assessments of nonverbal semantics, naming, and sentence repetition plus T2-weighted and fluid-attenuated inversion recovery scans. Using three visual scales, we rated WMH and cerebral ventricle size for both scan types. We used Spearman correlations to evaluate associations between the scales and scans. To test whether visual ratings-particularly of WMH-are associated with language, we compared a base model (including gray matter component scores obtained via principal component analysis, age, and days between assessment and MRI as independent variables) with full models (ie, the base model plus visual ratings) for each language variable. RESULTS: Visual ratings were significantly associated within and between scans and were significantly correlated with age but not with other vascular risk factors. Only the T2 scan ratings were associated with language abilities. Specifically, controlling for other variables, poorer naming was significantly related to larger ventricles (P = 0.033) and greater global (P = 0.033) and periventricular (P = 0.049) WMH. High global WMH (P = 0.034) were also correlated with worse sentence repetition skills. CONCLUSION: Visual ratings of global brain health were associated with language deficits in PPA independent of cortical atrophy and age. While WMH are not unique to PPA, measuring WMH in conjunction with cortical atrophy may elucidate more accurate brain structure-behavior relationships in PPA than cortical atrophy measures alone.

An Efficient Bedside Measure Yields Prognostic Implications for Language Recovery in Acute Stroke Patients.

BACKGROUND: It is estimated that ∼30% of stroke survivors have aphasia, a language disorder resulting from damage to left-hemisphere language networks. In acute care settings, efficient identification of aphasia is critical, but there is a paucity of efficient bedside assessments. OBJECTIVE: To determine whether objective measures on a picture description task administered within 48 hours post stroke (a) predict language recovery, (b) estimate left-hemisphere lesion volume and location, and (c) correlate with other bedside language assessments. METHOD: Behavioral data were scored at acute and chronic time points. Neuroimaging data were used to determine associations between the picture description task, other language assessments, and lesion volume and location. RESULTS: Acute content units, age, and total lesion volume predicted communication recovery; F3,18 = 3.98, P = 0.024; r = 0.40. Significant correlations were found between the picture description task and lesion volume and location. Picture description outcomes were also associated with other clinical language assessments. DISCUSSION: This picture description task quickly predicted the language performance (communication recovery and outcome) for patients who suffered a left-hemisphere stroke. Picture description task measures correlated with damage in the left hemisphere and with other, more time-consuming and cumbersome language assessments that are typically administered acutely at bedside. CONCLUSION: The predictive value of this picture description task and correlations with existing language assessments substantiate the clinical importance of a reliable yet rapid bedside measure for acute stroke patients that can be administered by a variety of health care professionals.

Ethical and Practical Challenges of the Communication and Behavioral Manifestations of Primary Progressive Aphasia.

The communication and behavioral manifestations of primary progressive aphasia (PPA) present ethical and practical challenges for individuals with this clinical syndrome as well as for individuals who are involved closely in their care. In this article, cases representing all three PPA variants (logopenic variant, nonfluent agrammatic, semantic variant) are presented to illustrate commonly encountered situations in which self-determination is at risk in decisions about housing, driving, social interactions, finances, and treatment interventions. Potential approaches, including patient/family education, implementation of safeguards, redirection to meaningful activities, and protections against vulnerability in treatment decisions, are described to preserve autonomy in patients with this neurodegenerative clinical syndrome.

Leukoaraiosis Severity Predicts Rate of Decline in Primary Progressive Aphasia.

BACKGROUND: The rate of decline in language in Primary Progressive Aphasia (PPA) is highly variable and difficult to predict at baseline. The severity of diffuse white matter disease (leukoaraiosis), a marker of overall brain health, may substantially influence the rate of decline. AIMS: To test the hypothesis that leukoaraiosis is associated with a steeper decline in naming in PPA. METHODS AND PROCEDURES: In this longitudinal, observational study, 29 individuals with PPA (all variants) were administered the Boston Naming Test (BNT) at baseline and 1 year later. Two raters evaluated leukoaraiosis on baseline MRI, using the Cardiovascular Health Study scale. We evaluated the effects of leukoaraiosis severity, age, education, and baseline BNT on decline measured by change in BNT accuracy with multivariable linear regression. We also evaluated the effects of these variables on the dichotomized outcome of faster decline in BNT (worst 50%) versus slower decline (best 50%) using logistic regression. RESULTS: Together, leukoaraiosis, age, education, and baseline BNT score predicted change in BNT score (F(3, 25) = 8.12; p=0.0006). Change in BNT score was predicted by severity of leukoaraiosis (t =-3.81; p=0.001) and education (t= -2.45; p=0.022), independently of the other variables. When we dichotomized outcome into upper 50th percentile versus lower 50th percentile (faster decline), faster decline was predicted by all variables together (chi squared = 13.91; p = 0.008). However, only leukoaraiosis independently predicted outcome (OR=2.80; 95%CI: 1.11 to 7.03). For every 1 point increase on the CHS rating scale, there was 2.8 times higher chance of showing faster decline in naming. CONCLUSION: Severity of leukoaraiosis is associated with steeper decline in naming in PPA. This imaging marker can aide in prognosis and planning by caregivers and stratification of participants in clinical trials.

Classification of primary progressive aphasia: challenges and complexities.

Primary progressive aphasia (PPA) is classified into three variants, logopenic variant PPA (lvPPA), nonfluent agrammatic PPA (nfaPPA), and semantic variant PPA (svPPA), based on clinical (syndromic) characteristics with support from neuroimaging and/or underlying neuropathology. Classification of PPA variants provides information valuable to disease management. International consensus criteria are widely employed to identify PPA subtypes; however, classification is complex, and some individuals do not fit neatly into the subtyping scheme. In this review, diagnostic challenges and their implications are discussed, possible explanations for these challenges are explored, and approaches to address PPA classification are considered.