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Focal anterior temporal lobe degeneration often preferentially affects the left or right hemisphere. While patients with left-predominant anterior temporal lobe atrophy show severe anomia and verbal semantic deficits and meet criteria for semantic variant primary progressive aphasia and semantic dementia, patients with early right anterior temporal lobe atrophy are more difficult to diagnose as their symptoms are less well understood. Focal right anterior temporal lobe atrophy is associated with prominent emotional and behavioural changes, and patients often meet, or go on to meet, criteria for behavioural variant frontotemporal dementia. Uncertainty around early symptoms and absence of an overarching clinico-anatomical framework continue to hinder proper diagnosis and care of patients with right anterior temporal lobe disease. Here, we examine a large, well-characterized, longitudinal cohort of patients with right anterior temporal lobe-predominant degeneration and propose new criteria and nosology. We identified individuals from our database with a clinical diagnosis of behavioural variant frontotemporal dementia or semantic variant primary progressive aphasia and a structural MRI (n = 478). On the basis of neuroimaging criteria, we defined three patient groups: right anterior temporal lobe-predominant atrophy with relative sparing of the frontal lobes (n = 46), frontal-predominant atrophy with relative sparing of the right anterior temporal lobe (n = 79) and left-predominant anterior temporal lobe-predominant atrophy with relative sparing of the frontal lobes (n = 75). We compared the clinical, neuropsychological, genetic and pathological profiles of these groups. In the right anterior temporal lobe-predominant group, the earliest symptoms were loss of empathy (27%), person-specific semantic impairment (23%) and complex compulsions and rigid thought process (18%). On testing, this group exhibited greater impairments in Emotional Theory of Mind, recognition of famous people (from names and faces) and facial affect naming (despite preserved face perception) than the frontal- and left-predominant anterior temporal lobe-predominant groups. The clinical symptoms in the first 3 years of the disease alone were highly sensitive (81%) and specific (84%) differentiating right anterior temporal lobe-predominant from frontal-predominant groups. Frontotemporal lobar degeneration-transactive response DNA binding protein (84%) was the most common pathology of the right anterior temporal lobe-predominant group. Right anterior temporal lobe-predominant degeneration is characterized by early loss of empathy and person-specific knowledge, deficits that are caused by progressive decline in semantic memory for concepts of socioemotional relevance. Guided by our results, we outline new diagnostic criteria and propose the name, ‘semantic behavioural variant frontotemporal dementia’, which highlights the underlying cognitive mechanism and the predominant symptomatology. These diagnostic criteria will facilitate early identification and care of patients with early, focal right anterior temporal lobe degeneration as well as in vivo prediction of frontotemporal lobar degeneration-transactive response DNA binding protein pathology.

Naming of nouns and verbs can be selectively impaired in neurological disorders, but the specificity of the neural and cognitive correlates of such dissociation remains unclear. Functional imaging and stroke research sought to identify cortical regions selectively recruited for nouns versus verbs, yet findings are inconsistent. The present study investigated this issue in neurodegenerative diseases known to selectively affect different brain networks, thus providing new critical evidence of network specificity. We examined naming performances on nouns and verbs in 146 patients with different neurodegenerative syndromes (Primary Progressive Aphasia - PPA, Alzheimer's disease - AD, and behavioral variant Frontotemporal Dementia - FTD) and 30 healthy adults. We then correlated naming scores with MRI-derived cortical thickness values as well as with performances in semantic and syntactic tasks, across all subjects. Results indicated that patients with the semantic variant PPA named significantly fewer nouns than verbs. Instead, nonfluent/agrammatic PPA patients named fewer verbs than nouns. Across all subjects, performance on nouns (adjusted for verbs) specifically correlated with cortical atrophy in left anterior temporal regions, and performance on verbs (adjusted for nouns) with atrophy in left inferior and middle frontal, inferior parietal and posterior temporal regions. Furthermore, lower lexical-semantic abilities correlated with deficits in naming both nouns and verbs, while lower syntactic abilities only correlated with naming verbs. Our results show that different neural and cognitive mechanisms underlie naming of specific grammatical categories in neurodegenerative diseases. Importantly, our findings showed that verb processing depends on a widespread perisylvian networks, suggesting that some regions might be involved in processing different types of action knowledge. These findings have important implications for early differential diagnosis of neurodegenerative disorders.

Purpose Diagnosis and classification of primary progressive aphasia (PPA) requires confirmation of specific speech and language symptoms, highlighting the important role of speech-language pathologists in the evaluation process. The purpose of this case report is to inform speech-language pathologists regarding current practices for diagnostic assessment in PPA, describing standard approaches as well as complementary, state-of-the-art procedures that may improve diagnostic precision. Method We describe the diagnostic evaluation of a 49-year-old woman with complaints of progressive word-finding difficulty. She completed standard neurological, neuropsychological, and speech-language evaluations, as well as magnetic resonance and positron emission tomography imaging of her brain. In addition, a history of developmental speech, language, and learning abilities was obtained, as well as genetic testing and assessment of cerebrospinal fluid biomarkers. We discuss the evaluation results in the context of the most current research related to PPA diagnosis. Conclusion Detailed behavioral assessment, thorough intake of symptom history and neurodevelopmental differences, multimodal neuroimaging, and comprehensive examination of genes and biomarkers are of paramount importance for detecting and characterizing PPA, with ramifications for early behavioral and/or pharmacological intervention. Supplemental Material https://doi.org/10.23641/asha.12771113

It has been proposed that focal anterior temporal lobe (ATL) degeneration is a specific, unitary FTLD-TDP-related disease that initially preferentially affects the left or right hemisphere. Patients with early left ATL (lATL) atrophy show severe anomia and verbal semantic deficits and meet criteria for semantic variant primary progressive aphasia (svPPA) and semantic dementia, prompting appropriate neurological care. There is less consensus regarding the symptoms in right ATL (rATL) predominant cases, who most often present with behavioral and emotional changes leading to a misdiagnosis of a psychiatric disorder, and later of behavioral variant frontotemporal dementia (bvFTD). Uncertainties regarding early symptoms and lack of an overarching framework continues to hinder proper diagnosis and care of patients with rATL disease. Here, we present symptom chronology, cognitive and socioemotional profiles of a large, well-characterized, longitudinally followed cohort of patients with rATL-predominant degeneration and propose new criteria and nosology for the syndrome.We identified individuals with a clinical diagnosis of bvFTD or svPPA and a structural MRI (n=478). Based on neuroimaging criteria, we identified three groups: patients with rATL-predominant atrophy with relative sparing of the frontal lobes (n=46), patients with frontal-predominant atrophy with relative sparing of the rATL (n=79), and patients with lATL-predominant atrophy with relative sparing of the frontal lobes (n=75). Seventy-eight patients had undergone autopsy. We analyzed patients’ clinical, neuropsychological, genetic, anatomical, and pathological profiles.In the rATL-predominant group, the earliest symptoms were loss of empathy (27%), person-specific semantic impairment (23%), and complex compulsions and rigid thought process (18%). On testing, this group exhibited greater impairments in emotional theory of mind, identifying famous people from names and face, and facial affect naming (despite preserved face perception) than the lATL- and frontal-predominant groups. The clinical features were highly sensitive (81%) and specific (84%) in differentiating rATL from bvFTD in the first three years of the disease. FTLD-TDP (84%) was the most common pathology.Our results suggest that rATL-predominant degeneration is characterized by early loss of empathy and person-specific knowledge, deficits that are caused by progressive loss of semantic memory for concepts of social-emotional relevance. Although this syndrome exists along a clinical, anatomical, and pathological continuum with svPPA, patients present with progressive behavioral changes. To facilitate early identification and care in clinical and research settings, we propose specific diagnostic criteria and the term “emotional semantic variant frontotemporal dementia” to distinguish this syndrome from other forms of frontotemporal dementia.

Highlights • Anterior temporal lobe (ATL) degeneration is most often caused by FTLD-TDP type C pathology. • Cases can present with predominantly left (60%) or right (40%) ATL atrophy. • Within ATLs, medial regions are more vulnerable than lateral ones. • The observed spectrum of clinical phenotypes is driven by atrophy lateralization. • Left and right temporal variants of FTD should be considered the same disease., Post-mortem studies show that focal anterior temporal lobe (ATL) neurodegeneration is most often caused by frontotemporal lobar degeneration TDP-43 type C pathology. Clinically, these patients are described with different terms, such as semantic variant primary progressive aphasia (svPPA), semantic dementia (SD), or right temporal variant frontotemporal dementia (FTD) depending on whether the predominant symptoms affect language, semantic knowledge for object or people, or socio-emotional behaviors. ATL atrophy presents with various degrees of lateralization, with right-sided cases considered rarer even though estimation of their prevalence is hampered by the paucity of studies on well-characterized, pathology-proven cohorts. Moreover, it is not clear whether left and right variants show a similar distribution of atrophy within the ATL cross-sectionally and longitudinally. Here we study the largest cohort to-date of pathology-proven TDP-43-C cases diagnosed during life as svPPA, SD or right temporal variant FTD. We analyzed clinical, cognitive, and neuroimaging data from 30 cases, a subset of which was followed longitudinally. Guided by recent structural and functional parcellation studies, we constructed four bilateral ATL regions of interest (ROIs). The computation of an atrophy lateralization index allowed the comparison of atrophy patterns between the two hemispheres. This led to an automatic, imaging-based classification of the cases as left-predominant or right-predominant. We then compared the two groups in terms of regional atrophy patterns within the ATL ROIs (cross-sectionally) and atrophy progression (longitudinally). Results showed that 40% of pathology proven cases of TDP-43-C diagnosed with a temporal variant presented with right-lateralized atrophy. Moreover, the findings of our ATL ROI analysis indicated that, irrespective of atrophy lateralization, atrophy distribution within both ATLs follows a medial-to-lateral gradient. Finally, in both left and right cases, atrophy appeared to progress to the contralateral ATL, and from the anterior temporal pole to posterior temporal and orbitofrontal regions. Taken together, our findings indicate that incipient right predominant ATL atrophy is common in TDP-43-C pathology, and that distribution of damage within the ATLs appears to be the same in left- and right- sided variants. Thus, regardless of differences in clinical phenotype and atrophy lateralization, both temporal variants of FTD should be viewed as a spectrum presentation of the same disease.