Anterior Temporal Lobe Atrophy Research Articles

‘THE MIND IS ITS OWN PLACE’: AMELIORATION OF CLAUSTROPHOBIA IN A PATIENT WITH SEMANTIC DEMENTIA

Specific phobia is defined as marked, persistent and excessive or unreasonable fear when in the presence of, or when anticipating an encounter with, a specific object or situation.1 Here we...

Corticospinal tract degeneration associated with TDP-43 type C pathology and semantic dementia

Four subtypes of frontotemporal lobar degeneration with TDP-43 immunoreactive inclusions have been described (types A-D). Of these four subtypes, motor neuron disease is more commonly associated with type B pathology, but has also been reported with type A pathology. We have noted, however, the unusual occurrence of cases of type C pathology having corticospinal tract degeneration. We aimed to assess the severity of corticospinal tract degeneration in a large cohort of cases with type C (n = 31). Pathological analysis included semi-quantitation of myelin loss of fibres of the corticospinal tract and associated macrophage burden, as well as axonal loss, at the level of the medullary pyramids. We also assessed for motor cortex degeneration and fibre loss of the medial lemniscus/olivocerebellar tract. All cases were subdivided into three groups based on the degree of corticospinal tract degeneration: (i) no corticospinal tract degeneration; (ii) equivocal corticospinal tract degeneration; and (iii) moderate to very severe corticospinal tract degeneration. Clinical, genetic, pathological and imaging comparisons were performed across groups. Eight cases had no corticospinal tract degeneration, and 14 cases had equivocal to mild corticospinal tract degeneration. Nine cases, however, had moderate to very severe corticospinal tract degeneration with myelin and axonal loss. In these nine cases, there was degeneration of the motor cortex without lower motor neuron degeneration or involvement of other brainstem tracts. These cases most commonly presented as semantic dementia, and they had longer disease duration (mean: 15.3 years) compared with the other two groups (10.8 and 9.9 years; P = 0.03). After adjusting for disease duration, severity of corticospinal tract degeneration remained significantly different across groups. Only one case, without corticospinal tract degeneration, was found to have a hexanucleotide repeat expansion in the C9ORF72 gene. All three groups were associated with anterior temporal lobe atrophy on MRI; however, the cases with moderate to severe corticospinal tract degeneration showed right-sided temporal lobe asymmetry and greater involvement of the right temporal lobe and superior motor cortices than the other groups. In contrast, the cases with no or equivocal corticospinal tract degeneration were more likely to show left-sided temporal lobe asymmetry. For comparison, the corticospinal tract was assessed in 86 type A and B cases, and only two cases showed evidence of corticospinal tract degeneration without lower motor neuron degeneration. These findings confirm that there exists a unique association between frontotemporal lobar degeneration with type C pathology and corticospinal tract degeneration, with this entity showing a predilection to involve the right temporal lobe.

Loss of Meaning for “Marriage” in Semantic Dementia

Back to table of contents Previous article Next article LettersFull AccessLoss of Meaning for “Marriage” in Semantic DementiaMario F. Mendez, M.D., Ph.D.Mario F. MendezDept. of Neurology and Psychiatry & Biobehavioral Sciences David Geffen School of Medicine The University of California at Los Angeles V.A. Greater Los Angeles Healthcare CenterSearch for more papers by this author, M.D., Ph.D.Published Online:1 Oct 2012https://doi.org/10.1176/appi.neuropsych.11110351AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Semantic dementia (SD) is a neurodegenerative disorder characterized by the loss of meaning for words, faces, or concepts. We present a rare case of SD in a patient who lost the meaning for the concept of marriage.Case ReportA 68-year-old, right-handed man had a 4-year history of progressive inability to identify words, familiar faces, and concepts. His wife described loss of the meaning of calendar dates such as Valentine's day, his religious events, and gestures and sign language. He responded with a perplexed “What is it?” when confronted with these concepts. His personality had become outgoing, emotionally unaware, rigid in his routines, and inattentive to his self-care. Over the next 2 years, he progressed to inability to recognize foods and smells.Most recently, his loss of concepts extended to the meaning of “marriage.” He understood that his “wife” was a close family member, but did not recognize their relationship as that of a husband and wife, to the point of accepting her living in the same house with another man. When asked about the meaning of “marriage,” he responded with “What is marriage?”On examination, the patient demonstrated semantic deficits. He scored 27/30 on the Mini-Mental State Exam. Language was fluent, with good sentence comprehension, but, on the mini-Boston Naming Test, he failed to name 9 of 15 items, and, when presented with the missed names, was unable to comprehend the words. He had particular difficulty recognizing animate items. On reading, he had difficulty with irregular words and made regularization errors, and, on a face recognition test, he failed to identify 15 of 20 famous faces. The rest of the neurologic examination was intact. Magnetic resonance imaging (MRI) showed severe atrophy of both anterior temporal lobes, most prominent on the right (see Figure 1).FIGURE 1. Coronal and Axial T1-Weighted Images Demonstrating Atrophy in the Anterior Temporal Regions, Most Prominent on the RightDiscussionThis patient has SD with semantic anomia, surface dyslexia, prosopagnosia, difficulty identifying living things, and other semantic deficits. His semantic loss extends to the concept of “marriage.” This loss has fundamentally altered his relationship with his wife in his own home.SD affects the anterior, inferolateral temporal lobes, a “convergence zone” for semantic concepts.1,2 The earliest and most common semantic deficit in SD is semantic anomia,2 or the loss of meaning of words. The deficits in SD, however, extend beyond language, to involve a multimodal loss of the meaning of objects, faces, smells, or more abstract concepts.3 In SD, left temporal involvement particularly affects the semantics of language, and right temporal involvement particularly affects the recognition of faces and living things.4This report describes a patient with SD who lost his sense of the meaning of marriage. His loss of semantic knowledge affected concepts involving interpersonal interactions, customs, and ceremonies. Investigators report that right anterior temporal dysfunction, which was particularly notable in this patient, impairs social concepts,5 and it is possible this region is necessary for concepts of human relationships, such as marriage. Future studies in SD can profitably focus on the organization of semantic knowledge for interpersonal relationships in the brain.Dept. of Neurology and Psychiatry & Biobehavioral Sciences David Geffen School of Medicine The University of California at Los Angeles V.A. Greater Los Angeles Healthcare CenterCorrespondence: M.F. Mendez, M.D., Ph.D.; Neurobehavior Unit (691/116AF), V.A. Greater Los Angeles Healthcare Center, Los Angeles, CA; e-mail: [email protected]eduFunding/Support: This work was supported by Grant #R01AG034499-03.References1 Hodges JR, Mitchell J, Dawson K, et al.: Semantic dementia: demography, familial factors, and survival in a consecutive series of 100 cases. Brain 2010; 133:300–306Crossref, Medline, Google Scholar2 Kertesz A, Jesso S, Harciarek M, et al.: What is semantic dementia?: a cohort study of diagnostic features and clinical boundaries. Arch Neurol 2010; 67:483–489Crossref, Medline, Google Scholar3 Patterson K, Nestor PJ, Rogers TT: Where do you know what you know? the representation of semantic knowledge in the human brain. Nat Rev Neurosci 2007; 8:976–987Crossref, Medline, Google Scholar4 Mendez MF, Kremen SA, Tsai PH, et al.: Interhemispheric differences in knowledge of animals among patients with semantic dementia. Cogn Behav Neurol 2010; 23:240–246Crossref, Medline, Google Scholar5 Zahn R, Moll J, Iyengar V, et al.: Social conceptual impairments in frontotemporal lobar degeneration with right anterior temporal hypometabolism. Brain 2009; 132:604–616Crossref, Medline, Google Scholar FiguresReferencesCited byDetailsCited ByNone Volume 24Issue 4 Fall 2012Pages E56-E57 Metrics PDF download History Published online 1 October 2012 Published in print 1 October 2012

Naming impairment in Alzheimer's disease is associated with left anterior temporal lobe atrophy

There is considerable debate about the neuroanatomic localization of semantic memory, the knowledge of culturally shared elements such as objects, concepts, and people. Two recent meta-analyses of functional imaging studies (fMRI and PET) sought to identify cortical regions involved in semantic processing. Binder and colleagues (Binder et al., 2009) identified several regions of interest, widely distributed throughout the frontal, parietal, and temporal cortices. In contrast, Lambon Ralph and colleagues (2010) focused on the anterior temporal lobe, and found that when the potential for signal loss is accounted for (due, for example, to distortion artifact or field of view restriction), significant regional activation is detected. We set out to determine whether the anterior temporal lobe plays a significant role in picture naming, a task which relies on semantic memory. We examined a relatively large sample of patients with early Alzheimer's disease (N=145), a multifocal disease process typically characterized in the early stages by problems with episodic memory and executive function. Hypothesis-driven analyses based on regions of interest derived from the meta-analyses as well as exploratory analyses across the entire cerebral cortex demonstrated a highly specific correlation between cortical thinning of the left anterior temporal lobe and impaired naming performance. These findings lend further support to theories that include a prominent role for the anterior temporal lobe in tasks that rely on semantic memory.

Asymmetric cortical surface area and morphology changes in mesial temporal lobe epilepsy with hippocampal sclerosis

To date, magnetic resonance imaging (MRI)-based studies of the cerebral cortex in mesial temporal lobe epilepsy (MTLE) have focused primarily on investigating cortical volume and thickness. However, volume is a composite of surface area and thickness, each reflecting distinct neurobiologic and genetic processes. The goal of this study was to investigate cerebral cortex (1) surface area, (2) surface geometric distortion, and (3) thickness in MTLE with hippocampal sclerosis (HS). Seventy patients with "sporadic" unilateral MTLE + HS and 40 healthy controls underwent T(1) -weighted MRI. Processing MR images using an automated cortical surface reconstruction method (FreeSurfer), we quantified cortical surface area, surface geometric distortion (metric distortion), and thickness at each vertex across the entire cortex. Differences between patients and controls were determined using generalized linear models. Separate linear regression models were employed to assess the relationship between cortical surface area and hippocampal volume as well as a series of important clinical features of the condition. We detected an asymmetric reduction in cortical surface area, predominantly in ipsilateral mesial and anterior temporal lobe subregions, of patients with MTLE + HS. Changes in surface geometric features were also evident and closely mirrored surface area patterns. In contrast, cortical thinning appeared dispersed across the cortex bilaterally. The regression models revealed that ipsilateral hippocampal volume was a significant predictor of temporal lobe surface area changes. Our findings indicate that contraction in surface area, rather than cortical thinning, explains ipsilateral mesial and anterior temporal lobe atrophy in patients with MTLE with HS. Furthermore, the alterations in surface geometry indicate folding abnormality involving the same regions. Cortical surface changes may represent sequelae of the disease or deviant cortical development.

Theory of mind impairments in patients with semantic dementia

Semantic dementia is characterized by semantic deficits and behavioural abnormalities that occur in the wake of bilateral inferolateral and predominantly left-sided anterior temporal lobe atrophy. The temporal poles have been shown to be involved in theory of mind, namely the ability to ascribe cognitive and affective mental states to others that regulates social interactions by predicting and interpreting human behaviour. However, very few studies have examined theory of mind in semantic dementia. In this study, we investigated both cognitive and affective theory of mind in a group of patients with semantic dementia, using separate objective and subjective assessment tasks. Results provided objective evidence of an impact of semantic dementia on cognitive and affective theory of mind, consistent with the patients' atrophy in the left temporal lobe and hypometabolism in the temporal lobes and the medial frontal cortex. However, the subjective assessment of theory of mind suggested that awareness of the affective but not cognitive theory of mind deficit persists into the moderate stage of the disease.

Left Anterior Temporal Lobe Sustains Naming in Alzheimers Dementia and Mild Cognitive Impairment

Cognitive decline in degenerative dementia is paralleled by progressive brain atrophy, with the localization of atrophy reflecting specific cognitive impairment. Confrontation naming deficits are frequently observed in dementia across etiologies. In this study we aimed to identify the brain regions underlying this deficit. In patients with clinically diagnosed dementia or mild cognitive impairment (MCI) we investigated the relationship between gray matter volume (GMV) and performance on a standardized confrontation naming test. 268 patients with one of three probable etiologies were included: Alzheimer's Dementia (AD), AD with signs of cerebrovascular pathology, and frontotemporal dementia. Applying voxel-based morphometry using a diffeomorphic registration algorithm we contrasted GMV of patients performing within the normal range with those of patients with pathological performance. Further, differential effects of gray matter atrophy on impaired performance in AD versus MCI of AD type were investigated. Results revealed significantly reduced GMV in the left anterior temporal lobe (ATL) in pathological performers compared to normal performers. The subgroup analysis confined to MCI of AD type and AD patients confirmed this relationship. While left ATL atrophy is known to be implicated in naming deficits in semantic dementia, our data confirm the same in AD and MCI of AD type.

Semantic Diversity Accounts for the “Missing” Word Frequency Effect in Stroke Aphasia: Insights Using a Novel Method to Quantify Contextual Variability in Meaning

Word frequency is a powerful predictor of language processing efficiency in healthy individuals and in computational models. Puzzlingly, frequency effects are often absent in stroke aphasia, challenging the assumption that word frequency influences the behavior of any computational system. To address this conundrum, we investigated divergent effects of frequency in two comprehension-impaired patient groups. Patients with semantic dementia have degraded conceptual knowledge as a consequence of anterior temporal lobe atrophy and show strong frequency effects. Patients with multimodal semantic impairments following stroke (semantic aphasia [SA]), in contrast, show little or no frequency effect. Their deficits arise from impaired control processes that bias activation toward task-relevant aspects of knowledge. We hypothesized that high-frequency words exert greater demands on cognitive control because they are more semantically diverse--they tend to appear in a broader range of linguistic contexts and have more variable meanings. Using latent semantic analysis, we developed a new measure of semantic diversity that reflected the variability of a word's meaning across different context. Frequency, but not diversity, was a significant predictor of comprehension in semantic dementia, whereas diversity was the best predictor of performance in SA. Most importantly, SA patients did show typical frequency effects but only when the influence of diversity was taken into account. These results are consistent with the view that higher-frequency words place higher demands on control processes, so that when control processes are damaged the intrinsic processing advantages associated with higher-frequency words are masked.

Neural basis of music knowledge: evidence from the dementias

The study of patients with semantic dementia has revealed important insights into the cognitive and neural architecture of semantic memory. Patients with semantic dementia are known to have difficulty understanding the meanings of environmental sounds from an early stage but little is known about their knowledge for famous tunes, which might be preserved in some cases. Patients with semantic dementia (n = 13), Alzheimer's disease (n = 14) as well as matched healthy control participants (n = 20) underwent a battery of tests designed to assess knowledge of famous tunes, environmental sounds and famous faces, as well as volumetric magnetic resonance imaging. As a group, patients with semantic dementia were profoundly impaired in the recognition of everyday environmental sounds and famous tunes with consistent performance across testing modalities, which is suggestive of a central semantic deficit. A few notable individuals (n = 3) with semantic dementia demonstrated clear preservation of knowledge of known melodies and famous people. Defects in auditory semantics were mild in patients with Alzheimer's disease. Voxel-based morphometry of magnetic resonance brain images showed that the recognition of famous tunes correlated with the degree of right anterior temporal lobe atrophy, particularly in the temporal pole. This area was segregated from the region found to be involved in the recognition of everyday sounds but overlapped considerably with the area that was correlated with the recognition of famous faces. The three patients with semantic dementia with sparing of musical knowledge had significantly less atrophy of the right temporal pole in comparison to the other patients in the semantic dementia group. These findings highlight the role of the right temporal pole in the processing of known tunes and faces. Overlap in this region might reflect that having a unique identity is a quality that is common to both melodies and people.

Phonological learning in semantic dementia

Patients with semantic dementia (SD) have anterior temporal lobe (ATL) atrophy that gives rise to a highly selective deterioration of semantic knowledge. Despite pronounced anomia and poor comprehension of words and pictures, SD patients have well-formed, fluent speech and normal digit span. Given the intimate connection between phonological STM and word learning revealed by both neuropsychological and developmental studies, SD patients might be expected to show good acquisition of new phonological forms, even though their ability to map these onto meanings is impaired. In contradiction of these predictions, a limited amount of previous research has found poor learning of new phonological forms in SD. In a series of experiments, we examined whether SD patient, GE, could learn novel phonological sequences and, if so, under which circumstances. GE showed normal benefits of phonological knowledge in STM (i.e., normal phonotactic frequency and phonological similarity effects) but reduced support from semantic memory (i.e., poor immediate serial recall for semantically degraded words, characterised by frequent item errors). Next, we demonstrated normal learning of serial order information for repeated lists of single-digit number words using the Hebb paradigm: these items were well-understood allowing them to be repeated without frequent item errors. In contrast, patient GE showed little learning of nonsense syllable sequences using the same Hebb paradigm. Detailed analysis revealed that both GE and the controls showed a tendency to learn their own errors as opposed to the target items. Finally, we showed normal learning of phonological sequences for GE when he was prevented from repeating his errors. These findings confirm that the ATL atrophy in SD disrupts phonological processing for semantically degraded words but leaves the phonological architecture intact. Consequently, when item errors are minimised, phonological STM can support the acquisition of new phoneme sequences in patients with SD.

Does TDP-43 type confer a distinct pattern of atrophy in frontotemporal lobar degeneration?

To determine whether TDP-43 type is associated with distinct patterns of brain atrophy on MRI in subjects with pathologically confirmed frontotemporal lobar degeneration (FTLD). In this case-control study, we identified all subjects with a pathologic diagnosis of FTLD with TDP-43 immunoreactive inclusions (FTLD-TDP) and at least one volumetric head MRI scan (n = 42). In each case we applied published criteria for subclassification of FTLD-TDP into FTLD-TDP types 1-3. Voxel-based morphometry was used to compare subjects with each of the different FTLD-TDP types to age- and gender-matched normal controls (n = 30). We also assessed different pathologic and genetic variants within, and across, the different types. Twenty-two subjects were classified as FTLD-TDP type 1, 9 as type 2, and 11 as type 3. We identified different patterns of atrophy across the types with type 1 showing frontotemporal and parietal atrophy, type 2 predominantly anterior temporal lobe atrophy, and type 3 predominantly posterior frontal atrophy. Within the FTLD-TDP type 1 group, those with a progranulin mutation had significantly more lateral temporal lobe atrophy than those without. All type 2 subjects were diagnosed with semantic dementia. Subjects with a pathologic diagnosis of FTLD with motor neuron degeneration had a similar pattern of atrophy, regardless of whether they were type 1 or type 3. Although there are different patterns of atrophy across the different FTLD-TDP types, it appears that genetic and pathologic factors may also affect the patterns of atrophy.

TDP-43 subtypes are associated with distinct atrophy patterns in frontotemporal dementia

We sought to describe the antemortem clinical and neuroimaging features among patients with frontotemporal lobar degeneration with TDP-43 immunoreactive inclusions (FTLD-TDP). Subjects were recruited from a consecutive series of patients with a primary neuropathologic diagnosis of FTLD-TDP and antemortem MRI. Twenty-eight patients met entry criteria: 9 with type 1, 5 with type 2, and 10 with type 3 FTLD-TDP. Four patients had too sparse FTLD-TDP pathology to be subtyped. Clinical, neuropsychological, and neuroimaging features of these cases were reviewed. Voxel-based morphometry was used to assess regional gray matter atrophy in relation to a group of 50 cognitively normal control subjects. Clinical diagnosis varied between the groups: semantic dementia was only associated with type 1 pathology, whereas progressive nonfluent aphasia and corticobasal syndrome were only associated with type 3. Behavioral variant frontotemporal dementia and frontotemporal dementia with motor neuron disease were seen in type 2 or type 3 pathology. The neuroimaging analysis revealed distinct patterns of atrophy between the pathologic subtypes: type 1 was associated with asymmetric anterior temporal lobe atrophy (either left- or right-predominant) with involvement also of the orbitofrontal lobes and insulae; type 2 with relatively symmetric atrophy of the medial temporal, medial prefrontal, and orbitofrontal-insular cortices; and type 3 with asymmetric atrophy (either left- or right-predominant) involving more dorsal areas including frontal, temporal, and inferior parietal cortices as well as striatum and thalamus. No significant atrophy was seen among patients with too sparse pathology to be subtyped. FTLD-TDP subtypes have distinct clinical and neuroimaging features, highlighting the relevance of FTLD-TDP subtyping to clinicopathologic correlation.

Coordinated and circumlocutory semantic naming errors are related to anterolateral temporal lobes in mild AD, amnestic mild cognitive impairment, and normal aging

Naming difficulties are characteristic of Alzheimer's disease (AD) and, to a lesser extent, of amnestic mild cognitive impairment (aMCI) patients. The association of naming impairment with anterior temporal lobe (ATL) atrophy in Semantic Dementia (SD) could be a tip of the iceberg effect, in which case the atrophy is a marker of more generalized temporal lobe pathology. Alternatively, it could reflect the existence of a functional gradient within the temporal lobes, wherein more anterior regions provide the basis for greater specificity of representation. We tested these two hypotheses in a study of 15 subjects with mild AD, 17 with aMCI, and 16 aged control subjects and showed that coordinate and circumlocutory semantic error production on the Boston Naming Test was weakly correlated with ATL gray matter density, as determined by voxel-based morphometry. Additionally, we investigated whether these errors were benefited by phonemic cues, and similarly to SD, our AD patients had small improvement. Because there is minimal gradient of temporal lobe atrophy in AD or MCI, and, therefore, no basis for a tip of the iceberg effect, these findings support the theory of a modest functional gradient in the temporal lobes, with the ATLs being involved in the naming of more specific objects.

Frontotemporal lobar degeneration with motor neuron disease showing severe and circumscribed atrophy of anterior temporal lobes

Frontotemporal lobar degeneration (FTLD) is characterized by a variety of behavioral and psychiatric symptoms based on the dysfunction of frontal and/or temporal lobes. A 63-year-old Japanese man without a family history of neurological diseases developed progressive symptoms of frontotemporal dementia, followed by motor neuron disease (MND). Brain magnetic resonance images demonstrated severe atrophy in the anterior temporal lobes from early clinical stage. The symptoms got rapidly worsened and the patient died of respiratory failure 1 year 8 months after the disease onset. A postmortem study revealed severe and circumscribed atrophy in the anterior temporal lobes, and histological examination disclosed marked neuronal loss with many neuronal cytoplasmic inclusions which were immunoreactive for ubiquitin antibodies and phosphorylated TAR DNA-binding protein of 43 kDa (TDP-43) antibodies in hippocampal dentate granule cells and amygdalae, as well as a few neuronal cytoplasmic inclusions without dystrophic neurites in the temporal neocortex. This case report showed typical features of FTLD–MND in clinical course and TDP-43 pathology with unusual severity and distribution of cerebral atrophy, suggesting a unique manifestation of FTLD–MND.

The inferior, anterior temporal lobes and semantic memory clarified: Novel evidence from distortion-corrected fMRI

The neural basis of semantic memory generates considerable debate. Semantic dementia results from bilateral anterior temporal lobe (ATL) atrophy and gives rise to a highly specific impairment of semantic memory, suggesting that this region is a critical neural substrate for semantic processing. Recent rTMS experiments with neurologically-intact participants also indicate that the ATL are a necessary substrate for semantic memory. Exactly which regions within the ATL are important for semantic memory are difficult to detect from these methods (because the damage in SD covers a large part of the ATL). Functional neuroimaging might provide important clues about which specific areas exhibit activation that correlates with normal semantic performance. Neuroimaging studies, however, have not consistently found anterior temporal lobe activation in semantic tasks. A recent meta-analysis indicates that this inconsistency may be due to a collection of technical limitations associated with previous studies, including a reduced field-of-view and magnetic susceptibility artefacts associated with standard gradient echo fMRI. We conducted an fMRI study of semantic memory using a combination of techniques which improve sensitivity to ATL activations whilst preserving whole-brain coverage. As expected from SD patients and ATL rTMS experiments, this method revealed bilateral temporal activation extending from the inferior temporal lobe along the fusiform gyrus to the anterior temporal regions, bilaterally. We suggest that the inferior, anterior temporal lobe region makes a crucial contribution to semantic cognition and utilising this version of fMRI will enable further research on the semantic role of the ATL.

Progress in the last decade in our understanding of primary progressive aphasia

Primary progressive aphasia (PPA) is a focal neurodegeneration of the brain affecting the language network. Patients can have isolated language impairment for years without impairment in other areas. PPA is classified as primary progressive nonfluent aphasia (PNFA), semantic dementia (SD), and logopenic aphasia, which have distinct patterns of atrophy on neuroimaging. PNFA and SD are included under frontotemporal lobar degenerations. PNFA patients have effortful speech with agrammatism, which is frequently associated with apraxia of speech and demonstrate atrophy in the left Broca’s area and surrounding region on neuroimaging. Patients with SD have dysnomia with loss of word and object (or face) meaning with asymmetric anterior temporal lobe atrophy. Logopenic aphasics have word finding difficulties with frequent pauses in conversation, intact grammar, and word comprehension but impaired repetition for sentences. The atrophy is predominantly in the left posterior temporal and inferior parietal regions. Recent studies have described several progranulin mutations on chromosome 17 in PNFA. The three clinical syndromes have a less robust relationship to the underlying pathology, which is heterogeneous and includes tauopathy, ubiquitinopathy, Pick’s disease, corticobasal degeneration, progressive supranuclear palsy, and Alzheimer’s disease. Recent studies, however, seem to indicate that a better characterization of the clinical phenotype (apraxic, agrammatic, semantic, logopenic, jargon) increases the predictive value of the underlying pathology. Substantial advances have been made in our understanding of PPAs but developing new biomarkers is essential in making accurate causative diagnoses in individual patients. This is critically important in the development and evaluation of disease-modifying drugs.

Right anterior temporal lobe atrophy and person-based semantic defect: A detailed case study

We report a new case of a right temporal pole variant of frontotemporal dementia (Rtv-FTLD), MD, who presented a slowly progressive deterioration of the recognition of familiar and famous people. We thoroughly investigated MD's face processing and semantic abilities, including a neuroimaging investigation. This analysis revealed a cross-modal person-based deficit together with a more general semantic alteration. However, there was no evidence of impairment in face perception, including holistic processing, or of an abnormal pattern of brain activation in face-sensitive cortical areas. We discuss the nature of face processing in the Rtv-FTLD and the context of a person-based semantic defect.

PO23-TH-02 Components of familiar people identification accessed from face and name in patients with right and left anterior temporal lobe atrophy

PO23-TH-02 Components of familiar people identification accessed from face and name in patients with right and left anterior temporal lobe atrophy

Neurocognitive contributions to verbal fluency deficits in frontotemporal lobar degeneration.

To test the hypothesis that different neurocognitive networks underlie verbal fluency deficits in frontotemporal lobar degeneration (FTLD). Letter ("FAS") and semantic ("animal") fluency tests were administered to patients with a behavioral/dysexecutive disorder (bvFTLD; n = 71), semantic dementia (SemD; n = 21), and progressive nonfluent aphasia (PNFA; n = 26). Tests measuring working memory, naming/lexical retrieval, and semantic knowledge were also obtained. MRI voxel-based morphometry (VBM) studies were obtained on a subset of these patients (bvFTLD, n = 51; PNFA, n = 11; SemD, n = 10). Patients with SemD were disproportionately impaired on the semantic fluency measure. Reduced output on this test was correlated with impaired performance on naming/lexical retrieval tests. VBM analyses related reduced letter and semantic fluency to anterior and inferior left temporal lobe atrophy. Patients with bvFTLD were equally impaired on both fluency tests. Poor performance on both fluency tests was correlated with low scores on working memory and naming/lexical retrieval measures. In this group, MRI-VBM analyses related letter fluency to bilateral frontal atrophy and semantic fluency to left frontal/temporal atrophy. Patients with PNFA were also equally impaired on fluency tests. Reduced semantic fluency output was correlated with reduced performance on naming/lexical retrieval tests. MRI-VBM analyses related semantic fluency to the right frontal lobe and letter fluency to left temporal atrophy. Distinct neurocognitive networks underlie impaired performance on letter and semantic fluency tests in frontotemporal lobar degeneration subgroups.

Relatively preserved knowledge of music in semantic dementia

The brain basis for music knowledge and the effects of disease on music cognition are poorly understood. Here we present evidence for relatively preserved knowledge of music in a musically...