Temporal Variant Frontotemporal Dementia Research Articles

Symptomatic progression of frontotemporal dementia with the TARDBP I383V variant

ABSTRACT We present a longitudinal description of a man with the TARDBP I383V variant of frontotemporal dementia (FTD). His progressive changes in behavior and language resulted in a diagnosis of the right temporal variant of FTD, also called the semantic behavioral variant (sbvFTD). We also present data from a small series of patients with the TARDBP I383V variant who were enrolled in a nationwide FTD research collaboration (ALLFTD). These data support slowly progressive loss of semantic function. While semantic dementia is infrequently considered genetic, the TARDBP I383V variant seems to be an exception. Longitudinal analyses in larger samples are warranted.

Slowly progressive Right Temporal Variant of Frontotemporal Dementia with ALS2 mutation: A case report

AbstractBackgroundBehavioral variant frontotemporal dementia (bvFTD) is a neurodegenerative disorder characterized by behavioral and personality changes. Findings show variation in the disease progression. Some patients show a rapid progression over a few years, and others show little or no changes over a decade (1) Mutations in the amyotrophic lateral sclerosis 2 (ALS2) gene cause autosomal recessive motor neuron diseases, including juvenile‐onset amyotrophic lateral sclerosis (JALS), and other associated disorders. (2) We present a rare case.MethodWe describe the clinical and imaging features of a man who presented a rare case of Slowly progressive Right Temporal Variant of Frontotemporal Dementia with ALS2 mutation.ResultA 63‐year‐old man presented a 10‐year history of insidious and slowly progressive behavioral changes. He showed reduced emotional responsiveness, with no concern since his wife had received a diagnosis of a malignancy. He followed with disinhibition, and impulsive actions such as excessive shopping with no payment, overspending, and socially inappropriate behavior. He also had a compulsive/ritualized behavior with stereotyped speech, and counting repeatedly steps. His medical family history was unremarkable. The neuropsychological evaluation showed impairment of executive functioning, MMSE 27/30. Neurological examination was normal. Brain MRI frontotemporal atrophy with a marked asymmetry in the right temporal lobe in sagittal, axial, and coronal sequences. CSF biomarkers showed elevated t‐tau with no other changes, and the genetic test showed an ALS2 heterozygous mutation., also counting repeatedly steps.ConclusionThe presence of the C9ORF72 mutation has been shown in slowly progressive FTD, however, other mutations such as ALS2 have not yet been reported with the following phenotype, as in this case (3)

Sporadic behavioral phenotype of Right Temporal Variant of Frontotemporal Dementia: a case report

AbstractBackgroundThere are two subtypes of the right Temporal Variant of Frontotemporal Dementia (rtv‐FTD). Semantic dementia (SMD) phenotype is defined by negative familiar history, word‐finding, anomia, comprehension difficulties, prosopagnosia, and topographagnosia. The behavioral frontotemporal dementia (bvFTD) phenotype is defined by personality changes, inappropriate behaviors, positive family history, and relatively poor performance on neurobehavioral testing with better performance on confrontational naming tests. (1) We present a rare interesting case.MethodWe describe the clinical and imaging features of a man who presented a sporadic behavioral phenotype of rtv‐FTD, showing negative genetic results.ResultA 62‐year‐old man with 8 years of progressive behavioral impairment. He showed personality changes, and compulsive‐like / ritualistic behaviors such as excessive unpurposed accumulation of items, washing hands repeatedly every five minutes, and walking and wandering repeatedly in circles. He also had hiperorality, cravings for sweet foods, social cognition impairment, associated with loss of empathy, and inappropriate social behavior (hypersexuality, verbal aggressivity to unrelated people, and talking bad words to neighbors with no reason). After years he followed with mild to moderate apathy. The neuropsychological evaluation showed impairment of executive functioning, episodic memory impairment, and MMSE 19/30. The neurological exam was unremarkable, and the familiar history was negative. Brain MRI revealed frontotemporal atrophy with a marked asymmetry in the right temporal lobe. The genetic testing was negative, illustrating and sporadic case.ConclusionTheoretically, rtv‐FTD is considered a right variant of semantic phenotype, and the general assumption is that is also a sporadic disorder. Although the behavioral phenotype of rtv‐FTD normally has a genetic basis, showing positive family history, It can be presented as a sporadic disorder with non‐familial variants of FTD, as in this case. (2)

A heterozygous splicing variant IVS9-7A > T in intron 9 of the MAPT gene in a patient with right-temporal variant frontotemporal dementia with atypical 4 repeat tauopathy

Right temporal variant frontotemporal dementia, also called right-predominant semantic dementia, often has an unclear position within the framework of the updated diagnostic criteria for behavioral variant frontotemporal dementia or primary progressive aphasia. Recent studies have suggested that this population may be clinically, neuropathologically, and genetically distinct from those with behavioral variant frontotemporal dementia or left-predominant typical semantic variant primary progressive aphasia. Here we describe a Japanese case of right temporal variant frontotemporal dementia with novel heterozygous MAPT mutation Adenine to Thymidine in intervening sequence (IVS) 9 at position -7 from 3ʹ splicing site of intron 9/exon 10 boundary (MAPT IVS9-7A > T). Postmortem neuropathological analysis revealed a predominant accumulation of 4 repeat tau, especially in the temporal lobe, amygdala, and substantia nigra, but lacked astrocytic plaques or tufted astrocytes. Immunoelectron microscopy of the tau filaments extracted from the brain revealed a ribbon-like structure. Moreover, a cellular MAPT splicing assay confirmed that this novel variant promoted the inclusion of exon 10, resulting in the predominant production of 4 repeat tau. These data strongly suggest that the MAPT IVS9-7 A > T variant found in our case is a novel mutation that stimulates the inclusion of exon 10 through alternative splicing of MAPT transcript and causes predominant 4 repeat tauopathy which clinically presents as right temporal variant frontotemporal dementia.

More extensive hypometabolism and higher mortality risk in patients with right- than left-predominant neurodegeneration of the anterior temporal lobe

BackgroundLeft-predominant neurodegeneration of the anterior temporal lobe (ATL) and the associated syndrome termed semantic variant primary progressive aphasia (svPPA) are well characterized. Less is known about right-predominant neurodegeneration of the ATL, which has been associated with the clinical syndrome named right temporal variant of frontotemporal dementia (rtvFTD). Here, we assessed glucose metabolism across the brain, cognitive performance, and mortality in patients with right-predominant neurodegeneration of the ATL.MethodsPatients with predominant hypometabolism of the ATL on FDG PET (as a measure of neurodegeneration) were retrospectively identified and categorized into those with asymmetrical right, left, or symmetric bilateral involvement (N = 10, 17, and 8). We compared whole-brain, normalized regional glucose metabolism using SPM12, cognitive performance on the CERAD Neuropsychological Assessment Battery, and mortality risk (age- and sex-adjusted Cox proportional hazard model) between groups.ResultsHypometabolism was most pronounced and extensive in patients with right-predominant neurodegeneration of the ATL. Beyond the right temporal lobe, right frontal and left temporal lobes were affected in these patients. Cognitive performance was similarly impaired in all three groups, with predominant naming and hippocampal-dependent memory deficits. Mortality risk was 6.1 times higher in patients with right- than left-predominant ATL neurodegeneration (p < 0.05). Median survival duration after PET was shortest in patients with right- and longest in patients with left-predominant ATL neurodegeneration (5.7 vs 8.3 years after examination).DiscussionMore extensive neurodegeneration and shorter survival duration in patients with right- than left-predominant neurodegeneration of the ATL might indicate that the former consult memory clinics at a later disease stage, when symptoms like naming and episodic memory deficits have already emerged. At the time of diagnosis, the shorter survival duration of patients with right- than left-predominant ATL neurodegeneration should be kept in mind when counseling patients and caregivers.

Prosopagnosia, Other Specific Cognitive Deficits, and Behavioral Symptoms: Comparison between Right Temporal and Behavioral Variant of Frontotemporal Dementia.

Right temporal variant of frontotemporal dementia (rtv-FTD) represents an uncommon and recently described frontotemporal dementia (FTD) entity presenting with symptoms in many ways comparable to those of the frontal or behavioral variant of FTD (bv-FTD). The aims of this study were to explore the timing of cognitive and behavioral symptoms of rtv-FTD, and to compare the distinct cognitive deficits including prosopagnosia and behavioral symptoms of rtv-FTD patients with those observed in bv-FTD patients. We reviewed the records of 105 patients clinically diagnosed with FTD. A total of 7 patients (5 men/2 women) with FTD and marked right temporal atrophy in magnetic resonance imaging (MRI) were detected. Clinical features were compared with those observed in a group of 22 age-matched patients (16 men/6 women) with FTD and predominant frontal lobe atrophy. The main presenting symptoms of rtv-FTD were prosopagnosia, apathy, and episodic memory impairment. In contrast, social awkwardness and compulsive behaviors were dominant in later stages of the disease together with disinhibition and loss of insight with a marked personality change. Although the cognitive and behavioral profiles of patients with right temporal or frontal lobes atrophy present substantial similarities, each subtype has a number of distinct characteristics. It appears that prosopagnosia, obsessive behaviors, and psychotic symptoms are more prominent in rtv-FTD patients.

Semantic and right temporal variant of FTD: Next generation sequencing genetic analysis on a single-center cohort.

Semantic and right temporal variant of frontotemporal dementia (svFTD and rtvFTD) are rare clinical phenotypes in which, in most cases, the underlying pathology is TDP-43 proteinopathy. They are usually sporadic disorders, but recent evidences suggest a higher frequency of genetic mutations for the right temporal versus the semantic variant. However, the genetic basis of these forms is not clear. In this study we performed a genetic screening of a single-center cohort of svFTD and rtvFTD patients, aiming at identifying the associated genetic variants. A panel of 73 dementia candidate genes has been analyzed by NGS target sequencing including both causal and risk/modifier genes in 23 patients (15 svFTD and 8 rtvFTD) and 73 healthy age-matched controls. We first performed a single variant analysis considering rare variants and then a gene-based aggregation analysis to evaluate the cumulative effects of multiple rare variants in a single gene. We found 12 variants in nearly 40% of patients (9/23), described as pathogenic or classified as VUS/likely pathogenic. The overall rate was higher in svFTD than in rtvFTD. Three mutations were located in MAPT gene and single mutations in the following genes: SQSTM1, VCP, PSEN1, TBK1, OPTN, CHCHD10, PRKN, DCTN1. Our study revealed the presence of variants in genes involved in pathways relevant for the pathology, especially autophagy and inflammation. We suggest that molecular analysis should be performed in all svFTD and rtvFTD patients, to better understand the genotype-phenotype correlation and the pathogenetic mechanisms that could drive the clinical phenotypes in FTD.

Clinical, radiologic, and pathologic features of the globular glial tauopathy subtype of frontotemporal lobar degeneration in right temporal variant frontotemporal dementia with salient features of Geschwind syndrome

ABSTRACT Globular Glial Tauopathy (GGT) is a rare form of Frontotemporal Lobar Degeneration (FTLD) consisting of 4-repeat tau globular inclusions in astrocytes and oligodendrocytes. We present the pathological findings of GGT in a previously published case of a 73-year-old woman with behavioral symptoms concerning for right temporal variant frontotemporal dementia with initial and salient features of Geschwind syndrome. Clinically, she lacked motor abnormalities otherwise common in previously published GGT cases. Brain MRI showed focal right anterior temporal atrophy (indistinguishable from five FTLD-TDP cases) and subtle ipsilateral white matter signal abnormalities. Brain autopsy showed GGT type III and Alzheimer’s neuropathologic changes. .

Right Temporal Lobe Variant of Frontotemporal Dementia: Systematic Review.

Frontotemporal dementia corresponds to a heterogenous group of syndromes characterized by progressive changes in behavior and/or language. Approximately 30% of patients with primary progressive aphasia, semantic variant (semantic dementia), present with atrophy in the right cerebral hemisphere, in a rare clinical condition called right temporal variant of frontotemporal dementia (rtvFTD). The objective of the study is to present the main demographic, clinical, neuropsychological, neuroimaging, and pathologic characteristics of rtvFTD patients. A systematic review of the literature was carried out in the PubMed, LILACS, and SCIELO databases between January and March 2022. After the evaluation process, 41 articles were selected, published between 1993 and 2021. We found that rtvFTD presents with severe and progressive prosopagnosia (related to anterior temporal lobe injury) associated with behavioral symptoms-desinibition (51%), apathy (39%), obsessive-compulsive symptoms (37%), changes in eating habits (33%), and depression (28%), which is different from semantic dementia. The most common pathologic pattern is TDP-43, type C. This field of knowledge has few studies (mainly reports and case series) and heterogenous nomenclature, which is a limitation. A multinational longitudinal registry of people with rtvFTD, with standardized assessment and description of symptoms, is necessary to elucidate the characteristics of this entity.

A presumptive association between obsessive compulsions and asymmetric temporal lobe atrophy: a case report

BackgroundThe relatively isolated atrophy of the temporal lobes leads to a clinical radiological pattern, referred to as the temporal variant of frontotemporal dementia. While semantic dementia and behavioral variant frontotemporal dementia are classically related to this syndrome, the logopenic variant of primary progressive aphasia has been less commonly reported. This case report aims to give a pictorial description of a case in which a patient with asymmetric temporal lobe atrophy presented with the logopenic variant of primary progressive aphasia and complex rituals of cleanliness.Case presentationWe report on the case of a 68-year-old, right-handed White woman with complex rituals and progressive speech impairment. The obsessive–compulsive rituals represented an exacerbation of lifelong preoccupations with cleanliness and orderliness that were praised by her relatives. Neuropsychological assessment revealed a striking impairment of language and memory, with relative sparing of tool-use praxis and visuospatial skills. Magnetic resonance imaging and 18fluorodeoxyglucose-positron emission tomography scans showed bilateral asymmetrical temporal lobe atrophy and hypometabolism. A year later, she was still able to entertain conversation for a short while, but her vocabulary and fluency had further declined. Praxis and visuospatial skills remained intact. She did not experience pathological elation, delusions, or hallucinations. The disease followed a relentless progression into a partial Klüver–Bucy syndrome, abulia, and terminal dementia. She died from acute myocardial infarction 8 years after the onset of aphasia. The symptoms and their temporal course supported a diagnosis of logopenic variant of primary progressive aphasia due to asymmetric temporal variant frontotemporal lobar degeneration.ConclusionsThis report gives a pictorial description of a temporal variant of frontotemporal dementia in a patient who presented with worsening of a lifelong obsessive–compulsive disorder and logopenic variant of primary progressive aphasia.

Chapter 24 - Frontotemporal dementia: A unique window on the functional role of the temporal lobes

Frontotemporal dementia (FTD) is an umbrella term covering a plethora of progressive changes in executive functions, motor abilities, behavior, and/or language. Different clinical syndromes have been described in relation to localized atrophy, informing on the functional networks that underlie these specific cognitive, emotional, and behavioral processes. These functional declines are linked with the underlying neurodegeneration of frontal and/or temporal lobes due to diverse molecular pathologies. Initially, the accumulation of misfolded proteins targets specifically susceptible cell assemblies, leading to relatively focal neurodegeneration that later spreads throughout large-scale cortical networks. Here, we discuss the most recent clinical, neuropathological, imaging, and genetics findings in FTD-spectrum syndromes affecting the temporal lobe. We focus on the semantic variant of primary progressive aphasia and its mirror image, the right temporal variant of FTD. Incipient focal atrophy of the left anterior temporal lobe (ATL) manifests with predominant naming, word comprehension, reading, and object semantic deficits, while cases of predominantly right ATL atrophy present with impairments of socioemotional, nonverbal semantic, and person-specific knowledge. Overall, the observations in FTD allow for crucial clinical-anatomic inferences, shedding light on the role of the temporal lobes in both cognition and complex behaviors. The concerted activity of both ATLs is critical to ensure that percepts are translated into concepts, yet important hemispheric differences should be acknowledged. On one hand, the left ATL attributes meaning to linguistic, external stimuli, thus supporting goal-oriented, action-related behaviors (e.g., integrating sounds and letters into words). On the other hand, the right ATL assigns meaning to emotional, visceral stimuli, thus guiding socially relevant behaviors (e.g., integrating body sensations into feelings of familiarity).

Differences in sex distribution between genetic and sporadic FTD

AbstractBackgroundThe reported sex distribution differs between frontotemporal dementia (FTD) cohorts. Possible explanations are the evolving clinical criteria of FTD and its subtypes and the discovery of FTD causal genetic mutations that have resulted in variable findings. Our aim was to determine the sex distribution in a large international retrospective cohort of sporadic and genetic FTD.MethodWe included patients with probable and definite behavioural variant frontotemporal dementia (bvFTD), non‐fluent variant primary progressive aphasia (nfvPPA), semantic variant primary progressive aphasia (svPPA) and right temporal variant frontotemporal dementia (rtvFTD) from the Amsterdam Dementia Cohort, the Montreal Neurological Institute Cohort, the University of Ulm and Technical University of Munich Cohort (part of the German Consortium of Frontotemporal Lobal Degeneration), the Policlinico Milan Cohort and the Sydney FRONTIER Cohort. We compared sex distribution between genetic and sporadic FTD using χ2 tests.ResultA total of 910 subjects were included (56.3% male), of whom 654 had bvFTD, 99 nfvPPA, 117 svPPA and 40 rtvFTD. Of these, 215 had genetic FTD and the sex distribution was equal (51.2% male), which did not differ significantly from sporadic FTD (57.8% male, χ2 p=0.081). In the sporadic bvFTD subgroup, we found a male predominance (61.6% males compared to 52.9% males in the bvFTD genetic group, χ 2 p=0.04). No sex distribution differences between sporadic and genetic cases were found in the other clinical FTD subgroups (all p&gt;0.05).ConclusionDifferences in sex distribution between genetic and sporadic behavioural variant of FTD may provide important clues for its differential pathogenesis and warrants further research.

Differences in Sex Distribution Between Genetic and Sporadic Frontotemporal Dementia.

Background:Reported sex distributions differ between frontotemporal dementia (FTD) cohorts. Possible explanations are the evolving clinical criteria of FTD and its subtypes and the discovery of FTD causal genetic mutations that has resulted in varying demographics.Objective:Our aim was to determine the sex distribution of sporadic and genetic FTD cases and its subtypes in an international cohort.Methods:We included 910 patients with behavioral variant frontotemporal dementia (bvFTD; n = 654), non-fluent variant primary progressive aphasia (nfvPPA; n = 99), semantic variant primary progressive aphasia (svPPA; n = 117), and right temporal variant frontotemporal dementia (rtvFTD; n = 40). We compared sex distribution between genetic and sporadic FTD using χ2-tests.Results:The genetic FTD group consisted of 51.2% males, which did not differ from sporadic FTD (57.8% male, p = 0.08). In the sporadic bvFTD subgroup, males were predominant in contrast to genetic bvFTD (61.6% versus 52.9% males, p = 0.04). In the other clinical FTD subgroups, genetic cases were underrepresented and within the sporadic cases the sex distribution was somewhat equal.Conclusion:The higher male prevalence in sporadic bvFTD may provide important clues for its differential pathogenesis and warrants further research.

Right temporal variant frontotemporal dementia is pathologically heterogeneous: a case-series and a systematic review

Although the right temporal variant frontotemporal dementia (rtvFTD) is characterised by distinct clinical and radiological features, its underlying histopathology remains elusive. Being considered a right-sided variant of semantic variant primary progressive aphasia (svPPA), TDP-43 type C pathology has been linked to the syndrome, but this has not been studied in detail in large cohorts. In this case report and systematic review, we report the autopsy results of five subjects diagnosed with rtvFTD from our cohort and 44 single rtvFTD subjects from the literature. Macroscopic pathological evaluation of the combined results revealed that rtvFTD demonstrated either a frontotemporal or temporal evolution, even if the degeneration started in the right temporal lobe initially. FTLD-TDP type C was the most common underlying pathology in rtvFTD, however, in 64% of rtvFTD, other underlying pathologies than FTLD-TDP type C were present, such as Tau-MAPT and FTLD-TDP type A and B. Additionally, accompanying motor neuron or corticospinal tract degeneration was observed in 28% of rtvFTD patients. Our results show that in contrast to the general assumption, rtvFTD might not be a pure FTLD-TDP type C disorder, unlike its left temporal counterpart svPPA. Large sample size pathological studies are warranted to understand the diverse pathologies of the right and left temporal variants of frontotemporal dementia.

The Right Temporal Variant of Frontotemporal Dementia Is Not Genetically Sporadic: A Case Series.

Background:Right temporal variant frontotemporal dementia (rtvFTD) has been generally considered as a right sided variant of semantic variant primary progressive aphasia (svPPA), which is a genetically sporadic disorder. Recently, we have shown that rtvFTD has a unique clinical syndrome compared to svPPA and behavioral variant frontotemporal dementia.Objective:We challenge the assumption that rtvFTD is a sporadic, non-familial variant of FTD by identifying potential autosomal dominant inheritance and related genes in rtvFTD.Methods:We collected all subjects with a diagnosis of FTD or primary progressive aphasia who had undergone genetic screening (n = 284) and subsequently who had a genetic variant (n = 48) with a diagnosis of rtvFTD (n = 6) in 2 specialized memory clinics.Results:Genetic variants in FTD related genes were found in 33% of genetically screened rtvFTD cases; including MAPT (n = 4), GRN (n = 1), and TARDBP (n = 1) genes, whereas only one svPPA case had a genetic variant in our combined cohorts. Additionally, 4 out of 6 rtvFTD subjects had a strong family history for dementia.Conclusion:Our results demonstrate that rtvFTD, unlike svPPA, is not a pure sporadic, but a heterogeneous potential genetic variant of FTD, and screening for genetic causes for FTD should be performed in patients with rtvFTD.

A clinical-radiological framework of the right temporal variant of frontotemporal dementia.

The concept of the right temporal variant of frontotemporal dementia (rtvFTD) is still equivocal. The syndrome accompanying predominant right anterior temporal atrophy has previously been described as memory loss, prosopagnosia, getting lost and behavioural changes. Accurate detection is challenging, as the clinical syndrome might be confused with either behavioural variant FTD (bvFTD) or Alzheimer’s disease. Furthermore, based on neuroimaging features, the syndrome has been considered a right-sided variant of semantic variant primary progressive aphasia (svPPA). Therefore, we aimed to demarcate the clinical and neuropsychological characteristics of rtvFTD versus svPPA, bvFTD and Alzheimer’s disease. Moreover, we aimed to compare its neuroimaging profile against svPPA, which is associated with predominant left anterior temporal atrophy. Of 619 subjects with a clinical diagnosis of frontotemporal dementia or primary progressive aphasia, we included 70 subjects with a negative amyloid status in whom predominant right temporal lobar atrophy was identified based on blinded visual assessment of their initial brain MRI scans. Clinical symptoms were assessed retrospectively and compared with age- and sex-matched patients with svPPA (n = 70), bvFTD (n = 70) and Alzheimer’s disease (n = 70). Prosopagnosia, episodic memory impairment and behavioural changes such as disinhibition, apathy, compulsiveness and loss of empathy were the most common initial symptoms, whereas during the disease course, patients developed language problems such as word-finding difficulties and anomia. Distinctive symptoms of rtvFTD compared to the other groups included depression, somatic complaints, and motor/mental slowness. Aside from right temporal atrophy, the imaging pattern showed volume loss of the right ventral frontal area and the left temporal lobe, which represented a close mirror image of svPPA. Atrophy of the bilateral temporal poles and the fusiform gyrus were associated with prosopagnosia in rtvFTD. Our results highlight that rtvFTD has a unique clinical presentation. Since current diagnostic criteria do not cover specific symptoms of the rtvFTD, we propose a diagnostic tree to be used to define diagnostic criteria and call for an international validation.

Regional and hemispheric susceptibility of the temporal lobe to FTLD-TDP type C pathology

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.

Right Temporal Variant Frontotemporal Dementia Misdiagnosed as Schizophrenia

Background: Schizophrenia-like presentations of frontotemporal dementia (FTD) are well documented in medical literature, especially during the initial stage of the illness. We present an interesting case of middle-aged white male, who was initially misdiagnosed with major depression at age 50 and then with schizophrenia due to florid psychosis typically seen in Mild Behavioral Impairment (MBI). It was not until over 4-years that a detailed clinical history along with specific investigations confirmed the diagnosis of right temporal variant frontotemporal dementia (rtv-FTD). Methods: The unusual presentation of this case warranted 2-deoxy-2-[fluorine-18]fluoro- D-glucose integrated with computed tomography (FDG-PET) and comprehensive neuropsychological testing to estblish a final diagnosis. Results: The results from neuroimaging and neuropsychological testing supported a diagnosis of rtv-FTD without any evidence for Alzheimer’s dementia. Conclusion: This case illustrates that late-onset atypical psychiatric symptoms should be evaluated for neurocognitive disorders, and the evaluation should include neuroimaging. It is preferable that the neuroimaging findings be personally interpreted by the provider, who therefore needs to be skilled in interpreting neuroimaging studies.

Verbal semantics and the left dorsolateral anterior temporal lobe: a longitudinal case of bilateral temporal degeneration

ABSTRACT Background Semantic variant primary progressive aphasia (svPPA), a clinical syndrome characterized by loss of semantic knowledge, is associated with neurodegeneration that starts in the anterior temporal lobe (ATL) and gradually spreads towards posterior temporal and medial frontal areas. At the earliest stages, atrophy may be predominantly lateralized to either the left or right ATL, leading to different clinical profiles with the greatest impairment of word comprehension or visual/social semantics, respectively. Methods & Procedures We report the in-depth longitudinal investigation of cognitive and neuroanatomical features of JB, an unusual case of ATL neurodegeneration with relative sparing of left lateral ATL regions. Outcomes & Results Over the course of 9 years, neurodegeneration progressed to involve bilateral temporo-lateral and frontal regions, resulting in a relatively symmetric and diffuse frontotemporal atrophy pattern. In parallel, JB developed greater behavioral, cognitive, and language impairments, as well as signs of motor neuron disease at her last evaluation. Episodic memory and socio-emotional processing deficits arose, likely secondary to semantic verbal deficits, while visuospatial processing, executive function, and non-semantic language abilities remained largely unaffected throughout the course of the disease. Conclusions The details of this rare case of early medial more than lateral ATL degeneration are consistent with a bilateral organization of the semantic system and, crucially, with a functional dissociation between medial paralimbic and lateral neocortical temporal regions. Cases of frontotemporal dementia (FTD) such as JB, who initially do not meet current clinical criteria for svPPA and instead present with some features of behavioral variant FTD, highlight the need for specific criteria for the right temporal variant of FTD that we propose could be called semantic variant FTD.

Cardiac responses to viewing facial emotion differentiate frontotemporal dementias.

ObjectiveTo establish proof‐of‐principle for the use of heart rate responses as objective measures of degraded emotional reactivity across the frontotemporal dementia spectrum, and to demonstrate specific relationships between cardiac autonomic responses and anatomical patterns of neurodegeneration.MethodsThirty‐two patients representing all major frontotemporal dementia syndromes and 19 healthy older controls performed an emotion recognition task, viewing dynamic, naturalistic videos of facial emotions while ECG was recorded. Cardiac reactivity was indexed as the increase in interbeat interval at the onset of facial emotions. Gray matter associations of emotional reactivity were assessed using voxel‐based morphometry of patients’ brain MR images.ResultsRelative to healthy controls, all patient groups had impaired emotion identification, whereas cardiac reactivity was attenuated in those groups with predominant fronto‐insular atrophy (behavioral variant frontotemporal dementia and nonfluent primary progressive aphasia), but preserved in syndromes focused on the anterior temporal lobes (right temporal variant frontotemporal dementia and semantic variant primary progressive aphasia). Impaired cardiac reactivity correlated with gray matter atrophy in a fronto‐cingulo‐insular network that overlapped correlates of cognitive emotion processing.InterpretationAutonomic indices of emotional reactivity dissociate from emotion categorization ability, stratifying frontotemporal dementia syndromes and showing promise as novel biomarkers. Attenuated cardiac responses to the emotions of others suggest a core pathophysiological mechanism for emotional blunting and degraded interpersonal reactivity in these diseases.