Diagnosis Of Primary Progressive Aphasia Research Articles

Primary progressive aphasias: clinical and genetic heterogeneity and diagnostic difficulties

This systematic review describes primary progressive aphasia (PPA) variants and includes the authors' own clinical observations. Over 20 genes have now been identified, with mutations that are directly involved in the development of the behavioural variant of frontotemporal dementia, as well as other forms of PPA. Pathomorphological markers of Alzheimer's disease were identified in 76% of cases of logopenic PPA, while signs of frontotemporal dementia associated with TDP-43 were identified in 80% of cases of the semantic variant, and those associated with TDP-43/tau were identified in 64% of cases of agrammatic PPA. The clinical diagnosis of PPA is based on a history of long-term, progressive speech disturbances and identifying a particular variant: agrammatic, semantic or logopenic. The primary variant of the speech disorder cannot be identified in approximately 30% of cases. The focus should be on the main and additional clinical signs (presence of agrammatism, object naming, word comprehension, preserved repetition), as well as neuroimaging (presence of asymmetrical frontal and/or temporal lobe atrophy).
 The article also provides key aspects of differential diagnosis of the PPA variants, and puts forth a stepwise diagnostic algorithm. It examines features of PPA progression, with possible development of corticobasal syndrome, illustrated by a clinical case. A dissociation between neuroimaging findings and clinical disease variant is also demonstrated to be possible. Different neuropsychological assessments of patients with aphasia and methods of determining the severity of speech dysfunction are presented. Standardized aphasia assessment tools and the adapted PPA severity scale are provided.

Communication during Covid‐19: Impacts of face coverings on people living with dementia

BackgroundThe compulsory introduction of wearing face coverings and social distancing to curb the spread of Covid‐19 in the United Kingdom has reduced both the quality of auditory information and availability of visual and non‐verbal cues during conversations with others. This is likely to have a greater impact on efficiency and effectiveness of communication for people living with dementia and particularly those with a language‐led dementia: Primary Progressive Aphasia (PPA).MethodTwenty‐four people living with dementia (PLWD), 95 caregivers (on behalf of PLWD) and 38 healthy older controls anonymously reported their experiences of wearing face coverings and the associated impacts on communication via an online survey that ran between December 2020 and April 2021 (age ranges: PLWD 38‐90 years; controls 32‐100 years). The majority of questions were self‐reflective experiences compared to when not wearing face coverings. Mann‐Whitney U tests were used to compare Likert ratings for impact of wearing face coverings on aspects of speaking, listening and holding conversations between PLWD or diagnosis subgroups (27 PPA; 26 Frontotemporal Dementia, FTD; 29 Alzheimer’s disease, AD; 24 Posterior Cortical Atrophy, PCA) and the controls.ResultWearing a face covering made both speaking (80%) and listening (90%) more effortful for the majority of survey respondents and had a greater impact on people living with PPA. Overall PLWD were more likely to require help communicating and those with PPA relied more on non‐verbal strategies (e.g. body language or gestures) than when not wearing a face covering, compared to controls (p=0.001) and other diagnosis subgroups. People with PPA also experienced greater difficulty understanding across diverse everyday listening conditions and most aspects of conversation than controls (p<0.05). People with PCA (p=0.039) also had more difficulty knowing when it was their turn to speak and those with FTD had more difficulty speaking over others (p=0.032), compared to controls. The use of face coverings during the Covid‐19 pandemic also prevented more PLWD from taking part in activities than controls.ConclusionPLWD, and in particular those with a diagnosis of PPA, are particularly susceptible to the negative impacts of the use of face coverings on communication.

Language profile of primary progressive aphasia in a linguistically diverse cohort in India

AbstractBackgroundThe accurate characterization of language and semantic memory deficits is crucial for diagnosis of primary progressive aphasia (PPA). In a linguistically diverse society like India, assessment with linguistically appropriate and culturally relevant tools is essential but challenging. This study aimed at developing language and culture specific tests to diagnose PPA and profile cognitive‐linguistic characteristics of a diverse cohort of PPA in India.MethodBased on typical characteristics of Indian languages: free‐word order, rich system of morphology and case‐marking that are features that differentiate Indian languages from English, a language‐specific assessment battery was developed in seven languages: Hindi, Bengali (Indo‐Aryan languages) and Kannada, Telugu, Malayalam and Tamil (Dravidian languages). In the background of the importance of case‐markers in the syntax of Indian languages, a unique syntax assessment test was specifically developed. To evaluate semantic memory, the Indian Semantic Memory battery was developed using stimuli appropriate for a pan‐Indian cultural context. All patients underwent assessment of language proficiency and comprehensive cognitive evaluation by examiners proficient in the language of testing.Result36 patients with PPA: 22 with semantic variant (svPPA), 12 nonfluent variant (nfvPPA) and 2 logopenic variant (lvPPA) participated. The cohort consisted of proficient speakers of seven Indian languages. A particular difficulty in the appropriate use of case markers on the new test of syntax was revealed in nfvPPA compared to svPPA. Further, the core diagnostic feature of ‘agrammatism’ for PPA in English‐speaking nfvPPA was not as dramatic in Indian patients owing to the morphological richness of Indian languages, leading to reduced contrast between fluent versus non‐fluent aphasia. Consistent with diagnosis, a significant reduction in fluency was demonstrated in nfvPPA (p&lt; 0.006 on fluency tasks). Semantic memory was significantly affected in svPPA as revealed on non‐verbal tasks i.e., word‐picture matching (p&lt;0.02)and semantic association task(p&lt;0.01) of Indian Semantic Battery.ConclusionUsing language and culture specific assessment batteries tailored to the Indian context, a comprehensive clinical characteristics in PPA subtypes were identified. The need to re‐define agrammatism with respect to Indian languages with additional weightage to the use of case markers that assist in identifying the PPA subtype was a novel finding.

Application of Machine Learning to Electroencephalography for the Diagnosis of Primary Progressive Aphasia: A Pilot Study.

Background. Primary progressive aphasia (PPA) is a neurodegenerative syndrome in which diagnosis is usually challenging. Biomarkers are needed for diagnosis and monitoring. In this study, we aimed to evaluate Electroencephalography (EEG) as a biomarker for the diagnosis of PPA. Methods. We conducted a cross-sectional study with 40 PPA patients categorized as non-fluent, semantic, and logopenic variants, and 20 controls. Resting-state EEG with 32 channels was acquired and preprocessed using several procedures (quantitative EEG, wavelet transformation, autoencoders, and graph theory analysis). Seven machine learning algorithms were evaluated (Decision Tree, Elastic Net, Support Vector Machines, Random Forest, K-Nearest Neighbors, Gaussian Naive Bayes, and Multinomial Naive Bayes). Results. Diagnostic capacity to distinguish between PPA and controls was high (accuracy 75%, F1-score 83% for kNN algorithm). The most important features in the classification were derived from network analysis based on graph theory. Conversely, discrimination between PPA variants was lower (Accuracy 58% and F1-score 60% for kNN). Conclusions. The application of ML to resting-state EEG may have a role in the diagnosis of PPA, especially in the differentiation from controls. Future studies with high-density EEG should explore the capacity to distinguish between PPA variants.

Spanish Version of the Mini-Linguistic State Examination for the Diagnosis of Primary Progressive Aphasia.

Primary progressive aphasia (PPA) is a neurodegenerative syndrome with three main clinical variants: non-fluent, semantic, and logopenic. Clinical diagnosis and accurate classification are challenging and often time-consuming. The Mini-Linguistic State Examination (MLSE) has been recently developed as a short language test to specifically assess language in neurodegenerative disorders. Our aim was to adapt and validate the Spanish version of MLSE for PPA diagnosis. Cross-sectional study involving 70 patients with PPA and 42 healthy controls evaluated with the MLSE. Patients were independently diagnosed and classified according to comprehensive cognitive evaluation and advanced neuroimaging. Internal consistency was 0.758. The influence of age and education was very low. The area under the curve for discriminating PPA patients and healthy controls was 0.99. Effect sizes were moderate-large for the discrimination between PPA and healthy controls. Motor speech, phonology, and semantic subscores discriminated between the three clinical variants. A random forest classification model obtained an F1-score of 81%for the three PPA variants. Our study provides a brief and useful language test for PPA diagnosis, with excellent properties for both clinical routine assessment and research purposes.

Primary Progressive Aphasia: Use of Graphical Markers for an Early and Differential Diagnosis.

Primary progressive aphasia (PPA) brings together neurodegenerative pathologies whose main characteristic is to start with a progressive language disorder. PPA diagnosis is often delayed in non-specialised clinical settings. With the technologies’ development, new writing parameters can be extracted, such as the writing pressure on a touch pad. Despite some studies having highlighted differences between patients with typical Alzheimer’s disease (AD) and healthy controls, writing parameters in PPAs are understudied. The objective was to verify if the writing pressure in different linguistic and non-linguistic tasks can differentiate patients with PPA from patients with AD and healthy subjects. Patients with PPA (n = 32), patients with AD (n = 22) and healthy controls (n = 26) were included in this study. They performed a set of handwriting tasks on an iPad® digital tablet, including linguistic, cognitive non-linguistic, and non-cognitive non-linguistic tasks. Average and maximum writing pressures were extracted for each task. We found significant differences in writing pressure, between healthy controls and patients with PPA, and between patients with PPA and AD. However, the classification of performances was dependent on the nature of the tasks. These results suggest that measuring writing pressure in graphical tasks may improve the early diagnosis of PPA, and the differential diagnosis between PPA and AD.

Survival in the Three Common Variants of Primary Progressive Aphasia: A Retrospective Study in a Tertiary Memory Clinic.

Knowledge on the natural history of the three main variants of primary progressive aphasia (PPA) is lacking, particularly regarding mortality. Moreover, advanced stages and end of life issues are rarely discussed with caregivers and families at diagnosis, which can cause more psychological distress. We analyzed data from 83 deceased patients with a diagnosis of PPA. We studied survival in patients with a diagnosis of logopenic variant (lvPPA), semantic variant (svPPA), or non-fluent variant (nfvPPA) and examined causes of death. From medical records, we retrospectively collected data for each patient at several time points spanning five years before the first visit to death. When possible, interviews were performed with proxies of patients to complete missing data. Results showed that survival from symptom onset and diagnosis was significantly longer in svPPA than in lvPPA (p = 0.002) and nfvPPA (p < 0.001). No relevant confounders were associated with survival. Mean survival from symptom onset was 7.6 years for lvPPA, 7.1 years for nfvPPA, and 12 years for svPPA. The most common causes of death were natural cardio-pulmonary arrest and pneumonia. Aspiration pneumonia represented 23% of deaths in nfvPPA. In conclusion, this pilot study found significant differences in survival between the three variants of PPA with svPPA showing the longest and nfvPPA showing more neurologically-related causes of death.

Tonal and orthographic analysis in a Cantonese-speaking individual with nonfluent/agrammatic variant primary progressive aphasia

ABSTRACT Clinical understanding of primary progressive aphasia (PPA) has been established based on English-speaking population. The lack of linguistic diversity in research hinders the diagnosis of PPA in non-English speaking patients. This case report describes the tonal and orthographic deficits of a multilingual native Cantonese-speaking woman with nonfluent/agrammatic variant PPA (nfvPPA) and progressive supranuclear palsy. Our findings suggest that Cantonese-speaking nfvPPA patients exhibit tone production impairments, tone perception deficits at the lexical selection processing, and linguistic dysgraphia errors unique to logographic script writer. These findings suggest that linguistic tailored approaches offer novel and effective tools in identifying non-English speaking PPA individuals.

Description of connected speech across different elicitation tasks in the logopenic variant of primary progressive aphasia.

Despite its importance, in-depth analysis of connected speech is often neglected in the diagnosis of primary progressive aphasia (PPA) - especially for the logopenic variant (lvPPA) for which unreliable differential diagnosis has been documented. Only a few studies have been conducted on this topic in lvPPA. The aim of this study was to describe and compare lexico-semantic and morphosyntactic features of connected speech in participants with lvPPA, in comparison with healthy controls, using three different elicitation tasks (i.e., picture description, story narration and semi-structured interviews). In addition to a number of discourse features, we were particularly interested in the presence or absence of syntactic deficits in this PPA variant in line with recent findings. A prospective group study was conducted to compare lvPPA participants (n = 13) to age- and education-matched healthy controls (n = 13). For each individual, connected speech was obtained using three tasks: (1) The Cookie Theft picture description; (2) Cinderella Story; (3) Topic-directed interview. Production on each task was recorded, transcribed and analysed according to the Quantitative Production Analysis (QPA) protocol, a tool developed by Berndt etal. (2000) for the analysis of sentence production in aphasia. Differences between lvPPA and healthy controls and among elicitation tasks were analysed using repeated measures multilevel mixed-effects regression, separately for each outcome. Four measures were significantly different between lvPPA participants and healthy controls across all elicitation tasks. Specifically, lvPPA participants produced a reduced proportion of open-class words, a higher proportion of verbs, a higher proportion of pronouns and fewer well-formed sentences. For these measures, the difference between lvPPA and healthy controls was consistent among elicitation tasks, except for the proportion of well-formed sentences, where the difference between the two groups was significantly greater in the story narration task than in the other tasks. Across elicitation tasks that used the same analysis protocol (i.e., QPA), a similar pattern of deficits in connected speech emerged in lvPPA patients. Importantly, the findings replicate previous studies, which used different elicitation tasks and analysis protocols. Especially in relation to the documented syntactic deficits, these findings provide implications for differential diagnosis in PPA. What is already known on the subject Connected speech analysis can provide an important contribution to the language assessment for the logopenic variant of primary progressive aphasia (lvPPA). However, only a few studies have been conducted with this population. What this paper adds to existing knowledge This study highlights differences between patients with lvPPA and healthy controls regarding the proportion of open-class words, nouns, verbs and well-formed sentences. What are the potential or actual clinical implications of this work? Importantly, our results highlight syntactic deficits in the same group of individuals with lvPPA, using the same analysis protocol and across various elicitation tasks, which has implications for differential diagnosis.

A case series of verbal semantic processing in primary progressive aphasia: Evidence from the N400 effect

The semantic variant of primary progressive aphasia (PPA) is typically associated with a loss of semantic knowledge. Research on the semantic processing in the other clinical variants of PPA is, however, rather sparse and limited to off-line behavioural studies. This study aimed to investigate verbal semantic processing in patients with the three variants of PPA by the event-related potential technique. The presence, latency, amplitude and/or topographic distribution of the N400 effect may be helpful in the diagnosis of PPA and its clinical variants and it provides temporal information about semantic processing (disturbances) in the three variants of PPA. The N400 effect was studied by a categorical word-priming paradigm and a semantic-anomaly paradigm at sentence level in eight persons with PPA(-plus) and 30 age-matched healthy controls. The mean amplitudes and onset latencies of the N400 effect were compared between each patient and the control group by two methods that are applicable in clinical practice, namely visual inspection and Z-scores. The N400 effect elicited by the categorical-priming paradigm was only present in the two patients with the non-fluent variant of PPA. This effect was absent in the two patients with the semantic variant(-plus), two patients with the logopenic variant(-plus), one patient with the non-fluent variant-plus, and the patient with PPA not otherwise specified. The results of the N400 effect elicited by the semantic-anomaly task at the sentence level were variable, but differences in the presence, mean amplitudes, onset latencies and/or topographic distributions of the effect were found in all patients with PPA(-plus) in comparison with the control group. The results of our study showed that the evaluation of the N400 effect might have an added value in the diagnostic process of PPA in general and in the differentiation of patients with the non-fluent variant from patients with the logopenic and semantic variants. Furthermore, our results indicate the presence of difficulties with retrieving stored semantic knowledge or semantic integration of a word in the preceding context in patients with the three variants of PPA. These findings might help the speech-language pathologist in determining individualized therapy goals and indicate that it might be helpful to focus on verbal semantic processing in language therapy in patients with the three variants of PPA and not only in patients with the semantic variant. What is already known on the subject The semantic variant of PPA is characterized by an impaired object knowledge and single-word comprehension and these functions are relatively spared in the non-fluent and logopenic variants following the guidelines of Gorno-Tempini etal. (2011). Research on the semantic processing in patients with the non-fluent and logopenic variant is, however, rather sparse and limited to off-line behavioural studies. Only four group studies investigated verbal semantic processing by the N400 effect, and these studies indicate disturbances in the three variants of PPA. What this paper adds to existing knowledge Our results indicate the presence of difficulties with retrieving stored semantic knowledge or semantic integration of a word in the preceding context during a semantic-priming paradigm in patients with the semantic and logopenic variants of PPA and during a semantic-anomaly task at the sentence level in patients with the three variants of PPA. What are the potential or actual clinical implications of this work? The results of our study showed that the evaluation of the N400 effect might have an added value in the diagnostic process of PPA in general and in the differentiation of patients with the non-fluent variant from patients with the logopenic and semantic variants. The evaluation of the N400 effect might also help the speech-language pathologist in determining individualized therapy goals and indicate that it might be helpful to focus on verbal semantic processing in language therapy in patients with the three variants of PPA and not only in patients with the semantic variant.

Contribution of the Cognitive Approach to Language Assessment to the Differential Diagnosis of Primary Progressive Aphasia

Diagnosis of primary progressive aphasia (PPA) is essentially based on the identification of progressive impairment of language abilities while other cognitive functions are preserved. The three variants of PPA are characterized by core and supportive clinical features related to the presence or absence of language impairment in different linguistic domains. In this article, we review the cognitive neuropsychological approach to the assessment of PPA and its contribution to the differential diagnosis of the three variants. The main advantage of this assessment approach is that it goes beyond the mere description and classification of clinical syndromes and identifies impaired and preserved cognitive and linguistic components and processes. The article is structured according to the main language domains: spoken production, language comprehension, and written language. Each section includes a brief description of the cognitive processes involved in the assessment tasks, followed by a discussion of typical characteristics for each PPA variant and common pitfalls in the interpretation of the results. In addition, the clinical benefit of the cognitive neuropsychological approach for the behavioral management of PPA is briefly sketched out in the conclusion.

First Symptoms of Primary Progressive Aphasia and Alzheimer's Disease in Brazilian Individuals.

Background: Primary Progressive Aphasia (PPA) is characterized by progressive language impairment due to focal degeneration of brain areas related to linguistic processing. The detection and differential diagnosis of PPA can be difficult with clinical features that may overlap with features of other neurological conditions, such as Alzheimer's disease (AD). The scientific production on PPA in Latin American patients is still scarce. This study investigated the first symptoms in a Brazilian sample of patients with PPA in comparison with AD patients.Method: We compared the first symptoms reported by caregivers of people with PPA (n = 20; semantic variant n = 8, non-fluent variant n = 7, logopenic variant n = 3, and unclassified cases n = 2) and AD (n = 16). Data were collected through the application of a structured questionnaire that was presented in an interview format to the caregiver who knew the patient best.Results: Anomia, paraphasias and motor speech difficulties were the first symptoms capable of differentiating patients with PPA from those with AD, while memory was exclusive of AD. Among the PPA variants, anomia was the initial symptom associated with the semantic variant, while motor speech difficulties were associated with the non-fluent variant. The results are discussed considering the unique cultural and sociodemographic characteristics of this studied population.Conclusion: This study demonstrated that some of the initial symptoms of PPA patients may be unique to clinical variants of PPA and of AD, and their investigation may be useful for the early and differential diagnosis of this population.

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

ABSTRACT 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 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. Application of the dual stream model to PPA

Heterogeneity of repetition abilities in logopenic variant primary progressive aphasia.

ABSTRACT.The differential diagnosis of primary progressive aphasia (PPA) is challenging due to overlapping clinical manifestations of the different variants of the disease. This is particularly true for the logopenic variant of PPA (lvPPA), in which such overlap was reported with regard to impairments in repetition abilities. In this study, four individuals with lvPPA underwent standard neuropsychological and language assessments. The influence of psycholinguistic variables on their performance of in word, nonword and sentence repetition tasks was also specifically explored. Some level of heterogeneity was found in cognitive functions and in language. The four participants showed impairment in sentence repetition in which their performance was negatively affected by semantic reversibility and syntactic complexity. This study supports the heterogeneity of lvPPA with respect to the cognitive and linguistic status of participants. It also shows that sentence repetition is influenced not only by length, but also by semantic reversibility and syntactic complexity, two psycholinguistic variables known to place additional demands on phonological working memory.

Regional correlates of linguistic error types using the Mini Linguistic State Examination (MLSE)

AbstractBackgroundPrimary progressive aphasia is a clinically and pathologically heterogeneous condition. The currently recognised subsyndromes are non‐fluent, fluent and logopenic variants. The MLSE adopts a novel error‐scoring system to classify the PPA syndromes, and has previously been shown to distinguish the syndromic subtypes based on performance in five linguistic domains: motor speech, phonology, semantics, working memory and syntax. Further validity of this method can be achieved with brain MR correlates specific to the MLSE language domains. For instance, shortfalls in semantics would be expected for correlate with atrophy in bilateral anterior temporal gyrus, and errors in motor speech and syntax with regions in the left inferior frontal gyrus.MethodsThe cohort compromised of 105 participants, 61 patients with a root diagnosis of primary progressive aphasia (PNFA, 20; LPA, 24; SD, 17) and 44 matched controls. The MLSE was administrated on all participants who also had 3T MR imaging. Group level analysis was carried out using voxel‐based morphometry and Statistical Parametric Mapping with a region of interest approach.ResultsWe observed a pattern of high sensitivity and specificity for the proposed atrophy patterns (bilateral anterior temporal cortex) associated with semantic errors. Similarly, correlations with atrophy in left inferior frontal and insular regions were observed for deficits in motor speech, phonology and syntax. Regional correlates with working memory deficits were more diffuse.ConclusionsThe results of this study provide evidence that assessment using error types aids classification and differentiation of the profile of PPA patients and conforms with patterns of MR atrophy that would be expected based on previous research.

Validation of the Spanish version of the Mini‐Linguistic State Examination for the diagnosis of primary progressive aphasia

AbstractBackgroundPrimary progressive aphasia (PPA) is a clinical syndrome of neurodegenerative origin with three main clinical variants (nonfluent, semantic, and logopenic). Clinical diagnosis and accurate classification into the three clinical variants is challenging and often time‐consuming. The Mini‐Linguistic State Examination (MLSE) has been recently developed as a short language test specifically designed for language assessment in neurodegenerative disorders. Our aim was to adapt and validate the Spanish version of MLSE for PPA diagnosis.MethodCross‐sectional study involving 70 patients with PPA and 42 healthy controls were evaluated with the MLSE. Patients were independently diagnosed and classified according to a comprehensive cognitive and advanced neuroimaging.ResultInternal consistency was 0.702. Influence of age and education was very low. The area under the curve for discriminating PPA patients and healthy controls was 0.989. Effect sizes were moderate‐large for the discrimination between PPA and healthy controls. In addition, motor speech, phonology and semantics subscores discriminated between the three clinical variants.ConclusionOur study provides a useful and brief language test for the diagnosis of PPA with excellent properties for both clinical routine assessment and research purposes.

Incidental Diagnosis of Primary Progressive Aphasia in the Inpatient Setting: A Note to Raise Clinical Awareness

Purpose The purpose of this report is to raise awareness among medical speech-language pathologists about challenges associated with encountering primary progressive aphasia patients in the acute hospital setting. Method Retrospective medical chart review. Results A 68-year-old woman was hospitalized for hyponatremia, pneumonia, and toxic-metabolic encephalopathy but was also noted to be suffering from chronic verbal difficulty for which medical attention was not sought previously. An interdisciplinary approach to address her verbal difficulty led to the diagnosis and initial management of a neurodegenerative disease characterized primarily by aphasia and apraxia of speech. Conclusion Service implementation lessons learned from this case study in terms of diagnosis and management and patient's illness experience are discussed.

Language and Speech Markers of Primary Progressive Aphasia: A Systematic Review.

Purpose This systematic review aimed to establish language and speech markers to support the clinical diagnosis of primary progressive aphasia (PPA) and its clinical phenotypes. Our first objective was to identify behavioral language and speech markers of early-stage PPA. Our second objective was to identify the electrophysiological correlates of the language and speech characteristics in PPA. Method The databases MEDLINE, Web of Science, and Embase were searched for relevant articles. To identify behavioral markers, the initial subjective complaints and the language and speech deficits detected during the initial diagnostic evaluation were summarized for PPA in general and each clinical variant according to the 2011 consensus diagnostic criteria (nonfluent variant [NFV], semantic variant, and logopenic variant [LV]). To identify electrophysiological markers, the studies in which event-related potentials (ERPs) were elicited by a language or speech paradigm in patients with PPA were included. Results In total, 114 relevant studies were identified, including 110 behavioral studies and only four electrophysiological studies. This review suggests that patients with the semantic variant could be accurately differentiated from the NFV and LV in the initial stages based on the consensus criteria. Nonetheless, the early differentiation between the NFV and LV is not straightforward. In the four electrophysiological studies, differences in the latency, amplitude, and topographical distribution of the semantic N400 component were found between patients with PPA and healthy controls. Conclusions To accurately differentiate the NFV from the LV, it could be important to assess the language and speech degeneration by more specific assessments and by more objective diagnostic methods that offer insights into the language-related processes. Electrophysiological markers of PPA were not identified in this review due to the low number of studies that investigated language-related ERPs. More controlled ERP studies in larger patient cohorts are needed to investigate the diagnostic applicability of language-related ERPs in PPA. Supplemental Material https://doi.org/10.23641/asha.12798080.

Classification and Diagnosis of Primary Progressive Aphasia

I have introduced primary progressive aphasia (PPA) with regard to frontotemporal lobar degeneration (FTLD) and evaluated the following elementary language symptoms for its diagnosis: agrammatism in speech production, apraxia of speech, phonemic paraphasia, naming impairment, impairment of single-word comprehension, and repetition. Furthermore, I have described the clinical symptoms, causative lesions, and pathological findings of three PPA variants -nonfluent/agrammatic, semantic, and logopenic PPA- according to the criteria proposed by Gorno-Tempni et al. (2011).

Qualitative and Quantitative Analyses of Brain 18Fluoro-Deoxy-Glucose Positron Emission Tomography in Primary Progressive Aphasia

Background: A primary progressive aphasia (PPA) diagnosis is generally based on clinical criteria, but often symptoms and signs may overlap in the different forms. Recent data have evidenced that brain ¹⁸fluoro-deoxy-glucose positron emission tomography (¹⁸F-FDG PET) could support the clinical diagnosis, since specific metabolic patterns are described for the different variants. Aims: We further evaluated the usefulness of ¹⁸F-FDG PET, by both visual qualitative (QL) and quantitative (QN) methods in the initial diagnosis of PPA, focusing on the classification of different variants. Moreover, we also analyzed the role of ¹⁸F-FDG PET in clarifying the association of PPA with the early phase of Alzheimer’s disease (AD) or frontotemporal (FTD) dementias. Methods: We consecutively enrolled 35 patients with clinical symptoms of aphasia, suspect of or attributable to PPA. Patients were classified into two groups: 18 cases with clinical symptoms of aphasia but normal neuropsychological tests and an unclear classification of a specific PPA variant (group A) and 17 cases with clinical and neuropsychological signs attributable to PPA with an uncertain differential diagnosis between AD and FTD (group B). All patients underwent brain ¹⁸F-FDG PET/CT, and images were evaluated both by QL and QN, the latter applying an automated analysis program that produced brain regional metabolicmaps and normal age-matched control group comparative analysis (zscore). Results: ¹⁸F-FDG PET showed different patterns of bilateral cortical hypometabolism in the two groups. The combined use of QL and QN permitted to achieved a correct PPA variant diagnosis in 8 of 18 (44.4%) cases of group A and in 14 of 17 (82.3%) of group B, while only QN could support the correct classification of PPA variants in 10 of 18 (55.6%) cases of group A and in 3 of 17 (17.7%) cases of group B in whom the procedure better localized the hypometabolic areas. Conclusions: Brain ¹⁸F-FDG PET had an elevated performance in the early diagnosis of PPA variants and in the advanced PPA AD/FTD classification. QL clarified the development of AD or FTD in advanced PPA cases and supported the differential diagnosis of a PPA variant in a few early cases. QN ¹⁸F-FDG PET evaluation better contributed to the early diagnosis of an unclear metabolic pattern. To correctly identify all cases, patients with diffuse cortical hypometabolism were also included. Larger series are necessary to confirm these data.