Logopenic Variant Research Articles

Multiclass prediction of different dementia syndromes based on multi-centric volumetric MRI imaging

IntroductionDementia syndromes can be difficult to diagnose. We aimed at building a classifier for multiple dementia syndromes using magnetic resonance imaging (MRI). MethodsAtlas-based volumetry was performed on T1-weighted MRI data of 426 patients and 51 controls from the multi-centric German Research Consortium of Frontotemporal Lobar Degeneration including patients with behavioral variant frontotemporal dementia, Alzheimer’s disease, the three subtypes of primary progressive aphasia, i.e., semantic, logopenic and nonfluent-agrammatic variant, and the atypical parkinsonian syndromes progressive supranuclear palsy and corticobasal syndrome. Support vector machine classification was used to classify each patient group against controls (binary classification) and all seven diagnostic groups against each other in a multi-syndrome classifier (multiclass classification). ResultsThe binary classification models reached high prediction accuracies between 71 and 95% with a chance level of 50%. Feature importance reflected disease-specific atrophy patterns. The multi-syndrome model reached accuracies of more than three times higher than chance level but was far from 100%. Multi-syndrome model performance was not homogenous across dementia syndromes, with better performance in syndromes characterized by regionally specific atrophy patterns. Whereas diseases generally could be classified vs controls more correctly with increasing severity and duration, differentiation between diseases was optimal in disease-specific windows of severity and duration. DiscussionResults suggest that automated methods applied to MR imaging data can support physicians in diagnosis of dementia syndromes. It is particularly relevant for orphan diseases beside frequent syndromes such as Alzheimer’s disease.

The Discourse Profile in Corticobasal Syndrome: A Comprehensive Clinical and Biomarker Approach.

The aim of this study was to characterize the oral discourse of CBS patients and to verify whether measures obtained during a semi-spontaneous speech production could differentiate CBS patients from controls. A second goal was to compare the performance of patients with CBS probably due to Alzheimer's disease (CBS-AD) pathology and CBS not related to AD (CBS-non-AD) in the same measures, based on the brain metabolic status (FDG-PET) and in the presence of amyloid deposition (amyloid-PET). Results showed that CBS patients were significantly different from controls in speech rate, lexical level, informativeness, and syntactic complexity. Discursive measures did not differentiate CBS-AD from CBS-non-AD. However, CBS-AD displayed more lexical-semantic impairments than controls, a profile that is frequently reported in patients with clinical AD and the logopenic variant of primary progressive aphasia (lvPPA). CBS-non-AD presented mainly with impairments related to motor speech disorders and syntactic complexity, as seen in the non-fluent variant of PPA.

Executive functions in primary progressive aphasia: A meta-analysis.

Executive functions (EFs) refer to a set of cognitive processes, specifically shifting, inhibition, updating of working memory, and are involved in the cognitive control of behavior. Conflicting results have been reported regarding impairments of EFs in Primary Progressive Aphasia (PPA). We performed a multi-level meta-analysis to confirm whether deficits of EFs exist in this population, focusing on a common EFs composite, and the components shifting, inhibition and updating separately. We included 141 studies that report on 294EFs tasks. The overall mean weighted effect size was large (d=-1,28), indicating poorer EFs in PPA as compared to age-matched cognitively healthy controls. Differences between effect sizes of the EFs components were not significant, indicating all components are affected similarly. Overall, moderator analysis revealed that PPA variant and disease duration were significant moderators of performance, while task modality and years of education were not. The non-fluent/agrammatic PPA and the logopenic PPA variants were similarly affected, but the semantic variant was affected to a lesser extent. We discuss implications for clinical and research settings, and future research.

Automated Analysis of Written Language in the Three Variants of Primary Progressive Aphasia.

Despite the important role of written language in everyday life, abnormalities in functional written communication have been sparsely investigated in PPA. We developed a Python program which uses a language parser and quantifies content units (CU) and total utterances in language samples. The program was used to analyze written descriptions of the WAB Picnic scene, based on a pre-defined CU corpus, from a cohort with 95 participants (20 controls, 28 nonfluent variant Primary Progressive Aphasia (nfvPPA), 30 logopenic variant (lvPPA), 17 semantic variant (svPPA)). We then compared written functional communication between the three PPA variants and controls. We analyzed the measurements in relation to aphasia severity (Progressive Aphasia Severity Scale Sum of Boxes (PASS SoB) and Clinical Dementia Rating Supplemental Language (CDR-L) scores), and dementia severity (Clinical Dementia Rating Sum of Boxes (CDR SoB)). The reliability of the automated analysis was high as compared to manual scoring of 239 samples (99.6%). One-way ANOVAs revealed patients with lvPPA and svPPA wrote fewer CU than controls (mean+/-SD 11.97+/-7.87 and 10+/-4.5, vs 18.5+/-9.32) (F(3, 91)=[4.897], p=0.003). There was a trend towards a decrease in CU in nfvPPA (13.89+/-6.33) (p=0.144). Patients with all PPA subtypes (nfvPPA mean+/-SD 34.64+/-18.89; lvPPA 38+/-24.54; svPPA 28.88+/-20.36) wrote fewer total utterances than controls (61.7+/-27.86) (F(3, 91)=[7.778], p<0.001). The CU/utterance ratio was higher in nfvPPA and svPPA than in controls and lvPPA (0.42+/-0.14 and 0.43+/0.22 vs 0.3+/-0.05 and 0.32+/-0.12 respectively) (F(3, 91)=[5.592], p=0.001). Considering all PPA samples, regression analysis showed a decrease in CU relative to an increase in PASS SoB (R=0.24, p=0.04), CDR-L (R=0.22, p=0.06), and CDR SoB (R=0.34, p=0.004). As expected, we found impairments in informative written language in patients with PPA. Automated CU analysis is a tool that can improve assessment of functional written communication, and may be an objective tool to track aphasia progression. More studies are required to assess individual changes over time and whether these findings could be extrapolated to other forms of cognitive impairment.

Characterization of the logopenic variant of Primary Progressive Aphasia: A systematic review and meta-analysis.

The linguistic and anatomical variability of the logopenic variant of Primary Progressive Aphasia (lv-PPA) as defined by current diagnostic criteria has been the topic of an intense debate. The present review and meta-analysis aims at characterizing the profile of lv-PPA, by a comprehensive analysis of the available literature on the neuropsychological, neuroimaging, electrophysiological, pathological, and genetic features of lv-PPA. We conducted a systematic bibliographic search, leading to the inclusion of 207 papers. Of them, 12 were used for the Anatomical Likelihood Estimation meta-analysis on grey matter revealed by magnetic resonance imaging data. The results suggest that the current guidelines outline a relatively consistent syndrome, characterized by a core set of linguistic and, to a lesser extent, non-linguistic deficits, mirroring the involvement of left temporal and parietal regions typically affected by Alzheimer Disease pathology. Variations of the lv-PPA profile are discussed in terms of heterogeneity of the neuropsychological instruments and the diagnostic criteria adopted.

Sentence repetition span in primary progressive aphasia and Alzheimer's disease: Insights from preliminary results

Primary Progressive Aphasia (PPA) is a neurocognitive disorder ascribed to cortical atrophy impacting language abilities. It is widely classified into three main variants, logopenic PPA (lvPPA), the semantic variant of PPA (svPPA), and the non-fluent PPA (nfvPPA), showing different impairment patterns across variants. However, in the early phases of PPA, it is not always easy to dissociate different PPA variants and distinguish PPA from other neurodegenerative disorders. One characteristic language symptom that seems to be a distinguishing factor of PPA, especially the logopenic variant, is impaired sentence repetition. Nonetheless, studies examining sentence repetition in PPA, and Alzheimer's disease (AD) more broadly, have resulted in mixed findings. To better understand the working memory-intensive nature of sentence repetition deficits, we designed a sentence repetition span task. We seek to understand (i) whether three diagnostic groups (lvPPA, svPPA, and AD) encounter greater sentence repetition difficulties than the controls, and (ii) whether using a span task design, in which the number of content words increases as the span length increases, would help dissociate PPA variants from AD type dementia. In this study, we administered a sentence repetition span task to four groups of French-speaking individuals with lvPPA (n = 14), svPPA (n = 5), and with AD (n = 13), and their age-matched healthy controls (n = 61). The results showed that all three diagnostic groups (lvPPA, svPPA, and AD) performed equally poorly compared to the controls on the repetition span task virtually in all measures (i.e., sentence span, the number of content words, and the number of omission and substitution errors). One intriguing finding was that the lvPPA group produced an exalted number of phonological errors during repeating sentences, while this type of error was somewhat moderate in the svPPA group and only minimal in the AD group. We conclude that the sentence repetition difficulty in PPA and AD should be modulated by working memory capacity, as our participants undoubtedly demonstrated greater difficulty as the span length increased. However, we note that working memory-intensive sentence repetition deficits based on the number of content words might not reveal critical diagnostic differences between the neurodegenerative groups.

Verb Frequency and Density Drive Naming Performance in Primary Progressive Aphasia

ABSTRACT 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.

Escala Barcelona para la apraxia bucofonatoria: instrumento de evaluación cuantitativo

IntroductionCurrently there is no tool to quantify buccophonatory apraxia to stratify, compare and monitor patients longitudinally in an objective manner. Our aim in this study is to create a quantitative scale for buccophonatory apraxia and evaluate it in patients with the non-fluent/grammatical variant of Primary Progressive Aphasia (nfvPPA) and other neurodegenerative diseases that occur with speech and/or language problems. MethodsThe scale was designed based on useful elements in the assessment of buccophonatory apraxia and the total was quantified in seconds. The scale was administered to 64 participants with diagnoses of: nfvPPA, semantic variant of Primary Progressive Aphasia (svPPA), logopenic variant of Primary Progressive Aphasia (lvPPA), Huntington's disease, Parkinson's disease, as well as a group of healthy controls. ResultsPatients showed a significantly higher score compared to controls. The group nfvPPA had the highest mean score on the scale (429seconds±278). The scale was useful to differentiate vnfPPA from svPPA and Parkinson's disease (area under curve [AUC] of 0.956 and 0.989 respectively), but less to differentiate it from Huntington's disease (AUC=0.67) and lvPPA. There was a statistically significant relationship between total score and disease severity in nfvPPA (p<0.029). ConclusionsThe Barcelona scale for buccophonatory apraxia could be useful to quantitatively evaluate buccophonatory apraxia in different neurodegenerative diseases, and compare patients, especially in nfvPPA.

Towards a more cognitive evaluation of progressive aphasias?

This scientific commentary refers to 'Unclassified fluent variants of primary progressive aphasia: distinction from semantic and logopenic variants' by Watanabe et al. (https://doi.org/10.1093/braincomms/fcac015).

Barcelona scale for buccophonatory apraxia: Quantitative assessment tool

IntroductionCurrently there is no tool to quantify buccophonatory apraxia to stratify, compare and monitor patients longitudinally in an objective manner. Our aim in this study is to create a quantitative scale for buccophonatory apraxia and evaluate it in patients with the non-fluent/grammatical variant of primary progressive aphasia (nfvPPA) and other neurodegenerative diseases that occur with speech and/or language problems. MethodsThe scale was designed based on useful elements in the assessment of buccophonatory apraxia and the total was quantified in seconds. The scale was administered to 64 participants with diagnoses of: nfvPPA, semantic variant of primary progressive aphasia (svPPA), logopenic variant of primary progressive aphasia (lvPPA), Huntington’s disease, Parkinson’s disease, as well as a group of healthy controls. ResultsPatients showed a significantly higher score compared to controls. The nfvPPA group had the highest mean score on the scale (429 seconds ± 278). The scale was useful to differentiate vnfPPA from svPPA and Parkinson’s disease (area under curve [AUC] of 0.956 and 0.989, respectively), but less to differentiate it from Huntington’s disease (AUC = 0.67) and lvPPA. There was a statistically significant relationship between total score and disease severity in nfvPPA (P < .029). ConclusionsThe Barcelona scale for buccophonatory apraxia could be useful to quantitatively evaluate buccophonatory apraxia in different neurodegenerative diseases, and compare patients, especially in nfvPPA.

Comorbid Neurodegeneration in Primary Progressive Aphasia: Clinicopathological Correlations in a Single-Center Study.

Introduction Primary progressive aphasia (PPA) is a clinically variable syndrome manifesting as slow progressive loss of speech and language with multiple underlying neurodegenerative pathologies. Materials and Methods We included data from nine PPA patients with available autopsies. We then retrospectively reviewed all available medical records, neuropsychology, and MRI results to confirm the corresponding subtypes of PPA and compared them with postmortem neuropathological results. Results Clinical presentations corresponded to the nonfluent/agrammatic variant in six cases, the semantic variant in one case, the logopenic variant in one case, and the mixed variant (concomitant nonfluent/agrammatic plus semantic variant) in one case. Patients with a broader clinical presentation, i.e., combining manifestations of one PPA subtype and symptoms of another PPA variant, had autopsy comorbidities showing multiple neurodegenerative disorders. Of the nine subjects enrolled in the study, Alzheimer's disease (AD) was found in eight cases; however, in only one case, AD was detected as an isolated neuropathological substrate of PPA. In eight brain samples, different comorbid neuropathologies were detected: three cases with comorbid AD and dementia with Lewy bodies, two cases with comorbid AD and TDP-43 pathology, one case with comorbid AD and complex tauopathies, and one case with comorbid AD with both tau and TDP-43 deposits. Finally, one case had comorbid tau and TDP-43 pathology but without comorbid AD pathology. Conclusions Our observation suggests that PPA cases could be more heterogeneous in their etiology than previously thought and underlying neurodegenerative comorbidities should be considered in routine practice, especially if the clinical presentation of PPA is atypical.

Multimodality Imaging in Primary Progressive Aphasia.

Primary progressive aphasia is a clinically and neuropathologically heterogeneous group of progressive neurodegenerative disorders, characterized by language-predominant impairment and commonly associated with atrophy of the dominant language hemisphere. While this clinical entity has been recognized dating back to the 19th century, important advances have been made in defining our current understanding of primary progressive aphasia, with 3 recognized subtypes to date: logopenic variant, semantic variant, and nonfluent/agrammatic variant. Given the ongoing progress in our understanding of the neurobiology and genomics of these rare neurodegenerative conditions, accurate imaging diagnoses are of the utmost importance and carry implications for future therapeutic triaging. This review covers the diverse spectrum of primary progressive aphasia and its multimodal imaging features, including structural, functional, and molecular neuroimaging findings; it also highlights currently recognized diagnostic criteria, clinical presentations, histopathologic biomarkers, and treatment options of these 3 primary progressive aphasia subtypes.

Speech disorders in primary progressive aphasia (PPA)

Introduction : Primary progressive aphasia (PPA) is a group of neurodegenerative disorders whose main feature is speech and language dysfunction. There are three main forms of PPA - non-fluent variant - agrammatic (nfvPPA), semantic variant (svPPA) and logopenic variant (lvPPA). These include the canonical syndromes currently recognized by consensus diagnostic criteria.&#x0D; . Material and method : An overview of language disorders in primary progressive aphasia is presented. The impact on the conversation process and the patient's quality of life assessment was evaluated. The work was based on scientific publications posted on the scientific platform PubMed.&#x0D; Results : In order to diagnose PPA, criteria must be met, i.e., language difficulties are the main feature of the clinical picture, language difficulties are the main cause of disability in daily life, and that aphasia is the most significant disorder in the initial period of the disease.&#x0D; Conclusions : PPA significantly affects both the production and comprehension of speech. It affects the idea, content, construction and delivery of the patient's speech. In addition, it causes significant difficulties in the repetition of speech, both full sentences and words alone.&#x0D; Keywords : "speech disorders", "aphasia", "dysarthria", "primary progressive aphasia".&#x0D;

Understanding the multidimensional cognitive deficits of logopenic variant primary progressive aphasia.

The logopenic variant of primary progressive aphasia is characterized by early deficits in language production and phonological short-term memory, attributed to left-lateralized temporoparietal, inferior parietal and posterior temporal neurodegeneration. Despite patients primarily complaining of language difficulties, emerging evidence points to performance deficits in non-linguistic domains. Temporoparietal cortex, and functional brain networks anchored to this region, are implicated as putative neural substrates of non-linguistic cognitive deficits in logopenic variant primary progressive aphasia, suggesting that degeneration of a shared set of brain regions may result in co-occurring linguistic and non-linguistic dysfunction early in the disease course. Here, we provide a Review aimed at broadening the understanding of logopenic variant primary progressive aphasia beyond the lens of an exclusive language disorder. By considering behavioural and neuroimaging research on non-linguistic dysfunction in logopenic variant primary progressive aphasia, we propose that a significant portion of multidimensional cognitive features can be explained by degeneration of temporal/inferior parietal cortices and connected regions. Drawing on insights from normative cognitive neuroscience, we propose that these regions underpin a combination of domain-general and domain-selective cognitive processes, whose disruption results in multifaceted cognitive deficits including aphasia. This account explains the common emergence of linguistic and non-linguistic cognitive difficulties in logopenic variant primary progressive aphasia, and predicts phenotypic diversification associated with progression of pathology in posterior neocortex.

Neuroanatomical Correlates of Semantic Features of Narrative Speech in Semantic and Logopenic Variants of Primary Progressive Aphasia.

The semantic variant of a primary progressive aphasia (svPPA) is characterized by progressive disruption of semantic knowledge. This study aimed to compare the semantic features of words produced during a narrative speech in svPPA and the logopenic variant of PPA (lvPPA) and to explore their neuroanatomical correlates. Six patients with svPPA and sixteen with lvPPA underwent narrative speech tasks. For all the content words, a semantic depth index (SDI) was determined based on the taxonomic structure of a large lexical database. Study participants underwent an MRI examination. Cortical thickness measures were extracted according to the Desikan atlas. Correlations were computed between SDI and the thickness of cortical regions. Mean SDI was lower for svPPA than for lvPPA. Correlation analyses showed a positive association between the SDI and the cortical thickness of the bilateral temporal pole, parahippocampal and entorhinal cortices, and left middle and superior temporal cortices. Disruption of semantic knowledge observed in svPPA leads to the production of generic terms in narrative speech, and the SDI may be useful for quantifying the level of semantic impairment. The measure was associated with the cortical thickness of brain regions associated with semantic memory.

Utility of the Addenbrooke’s Cognitive Examination III online calculator to differentiate the primary progressive aphasia variants

The Addenbrooke’s Cognitive Examination III is a brief cognitive screening tool that is widely used for the detection and monitoring of dementia. Recent findings suggest that the three variants of primary progressive aphasia can be distinguished based on their distinct profiles on the five subdomain scores of this test. Here, we investigated the utility of the Addenbrooke’s Cognitive Examination III to differentiate the primary progressive aphasia variants based on their item-by-item performance profiles on this test. From these results, we created an interactive primary progressive aphasia Addenbrooke’s Cognitive Examination III calculator which predicts the variant based on a patient’s unique item-by-item profile. Twenty-eight logopenic variant, 25 non-fluent variant and 37 semantic variant primary progressive aphasia patients and 104 healthy controls completed the Addenbrooke’s Cognitive Examination III at first clinical presentation. Multinomial regression analyses were conducted to establish performance profiles among groups, and R Shiny from RStudio was used to create the interactive Addenbrooke’s Cognitive Examination III diagnostic calculator. To verify its accuracy, probability values of the regression model were derived based on a 5-fold cross-validation of cases. The calculator’s accuracy was then verified in an independent sample of 17 logopenic, 19 non-fluent and 13 semantic variant primary progressive aphasia patients and 68 Alzheimer’s disease patients who had completed the Addenbrooke’s Cognitive Examination III (or an older version of this test: Revised) and had in vivo amyloid-PET imaging and/or brain autopsy pathological confirmation. Cross-validation of cases in the calculator model revealed different rates of sensitivity in classifying variants: semantic = 100%, non-fluent = 80.6% and logopenic = 79.9%; healthy controls were distinguished from primary progressive aphasia patients with 100% sensitivity. Verification of in vivo amyloid and/or autopsy-confirmed patients showed that the calculator correctly classified 10/13 (77%) semantic variant, 3/19 (16%) non-fluent variant and 4/17 (24%) logopenic variant patients. Importantly, for patients who were not classified, diagnostic probability values mostly pointed toward the correct clinical diagnosis. Furthermore, misclassified diagnoses of the primary progressive aphasia cohort were rare (1/49; 2%). Although 22 of the 68 Alzheimer’s disease patients (32%) were misclassified with primary progressive aphasia, 19/22 were misclassified with the logopenic variant (i.e. falling within the same neuropathological entity). The Addenbrooke’s Cognitive Examination III primary progressive aphasia diagnostic calculator demonstrates sound accuracy in differentiating the variants based on an item-by-item Addenbrooke’s Cognitive Examination III profile. This calculator represents a new frontier in using data-driven approaches to differentiate the primary progressive aphasia variants.

Logogenic Primary Progressive Aphasia or Alzheimer Disease: Contribution of Acoustic Markers in Early Differential Diagnosis.

The logopenic variant of Primary Progressive Aphasia (lvPPA), a syndromic disorder centered on language impairment, often presents variable underlying neurodegenerative pathologies such as Alzheimer Disease (AD). Actual language assessment tests and lumbar puncture, focused on AD diagnosis, cannot precisely distinguish the symptoms, or predict their progression at onset time. We analyzed acoustic markers, aiming to discriminate lvPPA and AD as well as the influence of AD biomarkers on acoustic profiles at the beginning of the disease. We recruited people with AD (n = 8) and with lvPPA (n = 8), with cerebrospinal fluid biomarker profiles determined by lumbar puncture. The participants performed a sentence repetition task that allows assessing potential lvPPA phonological loop deficits. We found that temporal and prosodic markers significantly differentiate the lvPPA and AD group at an early stage of the disease. Biomarker and acoustic profile comparisons discriminated the two lvPPA subgroups according to their biomarkers. For lvPPA with AD biomarkers, acoustic profile equivalent to an atypical AD form with a specific alteration of the phonological loop is shown. However, lvPPA without AD biomarkers has an acoustic profile approximating the one for DLFT. Therefore, these results allow us to classify lvPPA differentially from AD based on acoustic markers from a sentence repetition task. Furthermore, our results suggest that acoustic analysis would constitute a clinically efficient alternative to refused lumbar punctures. It offers the possibility to facilitate early, specific, and accessible neurodegenerative diagnosis and may ease early care with speech therapy, preventing the progression of symptoms.

18F-FDG PET Imaging in Neurodegenerative Dementing Disorders: Insights into Subtype Classification, Emerging Disease Categories, and Mixed Dementia with Copathologies.

Since the invention of 18F-FDG as a neurochemical tracer in the 1970s, 18F-FDG PET has been used extensively for dementia research and clinical applications. FDG, a glucose analog, is transported into the brain via glucose transporters and metabolized in a concerted process involving astrocytes and neurons. Although the exact cellular mechanisms of glucose consumption are still under investigation, 18F-FDG PET can sensitively detect altered neuronal activity due to neurodegeneration. Various neurodegenerative disorders affect different areas of the brain, which can be depicted as altered 18F-FDG uptake by PET. The spatial patterns and severity of such changes can be reproducibly visualized by statistical mapping technology, which has become widely available in the clinic. The differentiation of 3 major neurodegenerative disorders by 18F-FDG PET, Alzheimer disease (AD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB), has become standard practice. As the nosology of FTD evolves, frontotemporal lobar degeneration, the umbrella term for pathology affecting the frontal and temporal lobes, has been subclassified clinically into behavioral variant FTD; primary progressive aphasia with 3 subtypes, semantic, nonfluent, and logopenic variants; and movement disorders including progressive supranuclear palsy and corticobasal degeneration. Each of these subtypes is associated with differential 18F-FDG PET findings. The discovery of new pathologic markers and clinicopathologic correlations via larger autopsy series have led to newly recognized or redefined disease categories, such as limbic-predominant age-related TDP-43 encephalopathy, hippocampus sclerosis, primary age-related tauopathy, and argyrophilic grain disease, which have become a focus of investigations by molecular imaging. These findings need to be integrated into the modern interpretation of 18F-FDG PET. Recent pathologic investigations also have revealed a high prevalence, particularly in the elderly, of mixed dementia with overlapping and coexisting pathologies. The interpretation of 18F-FDG PET is evolving from a traditional dichotomous diagnosis of AD versus FTD (or DLB) to a determination of the most predominant underlying pathology that would best explain the patient's symptoms, for the purpose of care guidance. 18F-FDG PET is a relatively low cost and widely available imaging modality that can help assess various neurodegenerative disorders in a single test and remains the workhorse in clinical dementia evaluation.

Linguistic characteristics of different types of aphasia: A computer-assisted qualitative analysis using T-LAB

Aphasic disorders are observed in patients with both vascular and neurodegenerative pathology. Although spontaneous speech in the various forms of aphasia has some features that are identifiable on a purely linguistic level, diagnosing the type of aphasia critically relies on the support of clinical and neuroimaging data. To identify some core characteristics of different types of fluent aphasias (i.e., disorders of speech production due to lesions in the posterior regions of the left perisylvian areas not associated with articulatory deficits or apraxia of speech) in spontaneous speech using T-LAB computer-assisted qualitative analyses. This is a mixed-method software that allows exploring narratives by highlighting their key features using linguistic, statistical and graphical tools. We collected samples of spontaneous speech (narratives) from 34 fluent aphasic Italian speakers (i.e.,11 post-stroke aphasic patients, 17 with the logopenic variant of Primary Progressive Aphasia and 6 with the semantic variant) during the description of the Cookie Theft Picture of the Boston Diagnostic Aphasia Examination. Thirty-four healthy control subjects were asked to complete the same task. Analyses of the entire corpus (all of the narratives), specific metadata introduction and tagging were performed by two raters and any conflicts were resolved by a third rater. T-LAB analysis revealed statistically significant differences between both aphasic patients and healthy controls and between vascular and degenerative patients. Although the main distinction emerged between post-stroke and neurodegenerative aphasias, important differences also emerged between the individuals with the logopenic variant and the semantic variant. These findings underline the potential usefulness of a computer-assisted analysis of speech production to identify the core linguistic characteristics of different aphasic disorders, independently of any clinical support.

Differential linguistic features of verbal fluency in behavioral variant frontotemporal dementia and primary progressive aphasia

Frontotemporal dementia (FTD) is an early-onset neurodegenerative disorder with a heterogeneous clinical presentation. Verbal fluency is regularly used as a sensitive measure of language ability, semantic memory, and executive functioning, but qualitative changes in verbal fluency in FTD are currently overlooked. This retrospective study examined qualitative, linguistic features of verbal fluency in 137 patients with behavioral variant (bv)FTD (n = 50), or primary progressive aphasia (PPA) [25 non-fluent variant (nfvPPA), 27 semantic variant (svPPA), and 34 logopenic variant (lvPPA)] and 25 control participants. Between-group differences in clustering, switching, lexical frequency (LF), age of acquisition (AoA), neighborhood density (ND), and word length (WL) were examined in the category and letter fluency with analysis of variance adjusted for age, sex, and the total number of words. Associations with other cognitive functions were explored with linear regression analysis. The results showed that the verbal fluency performance of patients with svPPA could be distinguished from controls and other patient groups by fewer and smaller clusters, more switches, higher LF, and lower AoA (all p < 0.05). Patients with lvPPA specifically produced words with higher ND than the other patient groups (p < 0.05). Patients with bvFTD produced longer words than the PPA groups (p < 0.05). Clustering, switching, LF, AoA, and ND—but not WL—were differentially predicted by measures of language, memory, and executive functioning (range standardized regression coefficient 0.25–0.41). In addition to the total number of words, qualitative linguistic features differ between subtypes of FTD. These features provide additional information on lexical processing and semantic memory that may aid the differential diagnosis of FTD.