Academic literature on the topic 'Semantic variant primary progressive aphasia'

Individuals with primary progressive aphasia (PPA) show selective breakdown in regions within the proposed dorsal (articulatory–phonological) and ventral (lexical–semantic) pathways involved in language processing. Phonological STM impairment, which has been attributed to selective damage to dorsal pathway structures, is considered to be a distinctive feature of the logopenic variant of PPA. By contrast, phonological abilities are considered to be relatively spared in the semantic variant and are largely unexplored in the nonfluent/agrammatic variant. Comprehensive assessment of phonological ability in the three variants of PPA has not been undertaken. We investigated phonological processing skills in a group of participants with PPA as well as healthy controls, with the goal of identifying whether patterns of performance support the dorsal versus ventral functional–anatomical framework and to discern whether phonological ability differs among PPA subtypes. We also explored the neural bases of phonological performance using voxel-based morphometry. Phonological performance was impaired in patients with damage to dorsal pathway structures (nonfluent/agrammatic and logopenic variants), with logopenic participants demonstrating particular difficulty on tasks involving nonwords. Binary logistic regression revealed that select phonological tasks predicted diagnostic group membership in the less fluent variants of PPA with a high degree of accuracy, particularly in conjunction with a motor speech measure. Brain–behavior correlations indicated a significant association between the integrity of gray matter in frontal and temporoparietal regions of the left hemisphere and phonological skill. Findings confirm the critical role of dorsal stream structures in phonological processing and demonstrate unique patterns of impaired phonological processing in logopenic and nonfluent/agrammatic variants of PPA.

Abstract Speech-language pathologists are increasingly treating patients with progressive disorders, including primary progressive aphasia (PPA). For many years, two variants of PPA were recognized: a nonfluent type—progressive nonfluent aphasia (PNFA)—and a fluent form—semantic dementia (SD). In 2004, a third variant—logopenic progressive aphasia (LPA)—was described. This article will review clinical symptoms, neuroimaging correlates, and the neuropathologies that are typically associated with PNFA, SD, and LPA. Case studies are included to further illustrate the characteristics of each of these three PPA variants.

Primary progressive aphasia (PPA) corresponds to the gradual degeneration of language which can occur as nonfluent/agrammatic PPA, semantic variant PPA or logopenic variant PPA. We describe the clinical evolution of a patient with PPA presenting jargon aphasia as a late feature. At the onset of the disease (ten years ago) the patient showed anomia and executive deficits, followed later on by phonemic paraphasias and neologisms, deficits in verbal short-term memory, naming, verbal and semantic fluency. At recent follow-up the patient developed an unintelligible jargon with both semantic and neologistic errors, as well as with severe deficit of comprehension which precluded any further neuropsychological assessment. Compared to healthy controls, FDG-PET showed a hypometabolism in the left angular and middle temporal gyri, precuneus, caudate, posterior cingulate, middle frontal gyrus, and bilaterally in the superior temporal and inferior frontal gyri. The clinical and neuroimaging profile seems to support the hypothesis that the patient developed a late feature of logopenic variant PPA characterized by jargonaphasia and associated with superior temporal and parietal dysfunction.

Primary progressive aphasia (PPA) is classified into three variants, logopenic variant PPA (lvPPA), nonfluent agrammatic PPA (nfaPPA), and semantic variant PPA (svPPA), based on clinical (syndromic) characteristics with support from neuroimaging and/or underlying neuropathology. Classification of PPA variants provides information valuable to disease management. International consensus criteria are widely employed to identify PPA subtypes; however, classification is complex, and some individuals do not fit neatly into the subtyping scheme. In this review, diagnostic challenges and their implications are discussed, possible explanations for these challenges are explored, and approaches to address PPA classification are considered.

Abstract Despite epidemiological and genetic data linking semantic dementia to inflammation, the topography of neuroinflammation in semantic dementia, also known as the semantic variant of primary progressive aphasia, remains unclear. The pathology starts at the tip of the left temporal lobe where, in addition to cortical atrophy, a strong signal appears with the tau PET tracer 18F-flortaucipir, even though the disease is not typically associated with tau but with TDP-43 protein aggregates. Here, we characterized the topography of inflammation in semantic variant primary progressive aphasia using high-resolution PET and the tracer 11C-PBR28 as a marker of microglial activation. We also tested the hypothesis that inflammation, by providing non-specific binding targets, could explain the 18F-flortaucipir signal in semantic variant primary progressive aphasia. Eight amyloid-PET-negative patients with semantic variant primary progressive aphasia underwent 11C-PBR28 and 18F-flortaucipir PET. Healthy controls underwent 11C-PBR28 PET (n = 12) or 18F-flortaucipir PET (n = 12). Inflammation in PET with 11C-PBR28 was analysed using Logan graphical analysis with a metabolite-corrected arterial input function. 18F-flortaucipir standardized uptake value ratios were calculated using the cerebellum as the reference region. Since monoamine oxidase B receptors are expressed by astrocytes in affected tissue, selegiline was administered to one patient with semantic variant primary progressive aphasia before repeating 18F-flortaucipir scanning to test whether monoamine oxidase B inhibition blocked flortaucipir binding, which it did not. While 11C-PBR28 uptake was mostly cortical, 18F-flortaucipir uptake was greatest in the white matter. The uptake of both tracers was increased in the left temporal lobe and in the right temporal pole, as well as in regions adjoining the left temporal pole such as insula and orbitofrontal cortex. However, peak uptake of 18F-flortaucipir localized to the left temporal pole, the epicentre of pathology, while the peak of inflammation 11C-PBR28 uptake localized to a more posterior, mid-temporal region and left insula and orbitofrontal cortex, in the periphery of the damage core. Neuroinflammation, greatest in the areas of progression of the pathological process in semantic variant primary progressive aphasia, should be further studied as a possible therapeutic target to slow disease progression.

The goal of this article is to outline the utility of both language and non-language testing in making a diagnosis of logopenic, nonfluent/agrammatic, and semantic variant primary progressive aphasias PPA as well as delineate important behavioral and speech features that can be detected via clinical observation. We review speech/language presentations, non-language cognitive domains, and behavioral manifestations associated with each disorder. Patients with logopenic variant PPA evidence non-language cognitive impairments that include acalculia, phonological working memory deficits, and mild/variable difficulties with memory and visuospatial functions. In contrast, patients with nonfluent/agrammatic variant PPA display non-language impairments in executive functions, and show relative preservation of memory and visuospatial functions. Finally, semantic variant patients display behavioral changes in social comportment as well as non-language difficulties with category fluency and arithmetic facts; they display relative preservation, if not enhancement, of visuospatial functions. In summary, broad neural networks that support both language and non-language functions are affected in PPA syndromes, thus a comprehensive assessment of additional neuropsychological domains may aid in solidifying and subtyping PPA diagnoses.

Primary progressive aphasia is a neurodegenerative disorder that was recently classified into three types: fluent (semantic), nonfluent, and logopenic. The logopenic variant is the least common one and is closely related to Alzheimer's disease in comparison to the other two variants that are closely related to frontotemporal dementia. We report the case of a middle-aged woman who presented to our center with progressive aphasia that was undiagnosed for two years. The patient's neurological evaluation including positron emission tomography is consistent with a logopenic variant of primary progressive aphasia.

AbstractObjectives: The aim of this study was to identify whether the three main primary progressive aphasia (PPA) variants would show differential profiles on measures of visuospatial cognition. We hypothesized that the logopenic variant would have the most difficulty across tasks requiring visuospatial and visual memory abilities. Methods: PPA patients (n=156), diagnosed using current criteria, and controls were tested on a battery of tests tapping different aspects of visuospatial cognition. We compared the groups on an overall visuospatial factor; construction, immediate recall, delayed recall, and executive functioning composites; and on individual tests. Cross-sectional and longitudinal comparisons were made, adjusted for disease severity, age, and education. Results: The logopenic variant had significantly lower scores on the visuospatial factor and the most impaired scores on all composites. The nonfluent variant had significant difficulty on all visuospatial composites except the delayed recall, which differentiated them from the logopenic variant. In contrast, the semantic variants performed poorly only on delayed recall of visual information. The logopenic and nonfluent variants showed decline in figure copying performance over time, whereas in the semantic variant, this skill was remarkably preserved. Conclusions: This extensive examination of performance on visuospatial tasks in the PPA variants solidifies some previous findings, for example, delayed recall of visual stimuli adds value in differential diagnosis between logopenic variant PPA and nonfluent variant PPA variants, and illuminates the possibility of common mechanisms that underlie both linguistic and non-linguistic deficits in the variants. Furthermore, this is the first study that has investigated visuospatial functioning over time in the PPA variants. (JINS, 2018, 24, 259–268)

Primary progressive aphasia (PPA) includes a group of neurodegenerative disorders that are characterized by progressive deterioration of language functions, while other cognitive functions, at least at the onset of the disease, are relatively spared. There are three basic subtypes of PPA: the nonfluent progressive aphasia (nvPPA), the semantic variant of a primary progressive aphasia (svPPA), and the logopenic progressive aphasia (lvPPA). The semantic variant of a PPA can also be found in the literature under the term of semantic dementia. It is clinically manifested by progressive deterioration of semantic knowledge, fluent aphasia, impaired naming and comprehension, prosopagnosia and surface dyslexia and dysgraphia (in languages with irregular orthography). As the disease progresses, other cognitive changes can be observed. The main cause of the disorder is progressive bilateral atrophy of the anterior temporal lobes, which is more manifested in the left hemisphere. The literature is modest in terms of the use of specific treatment methods in the rehabilitation of these patients. Since speech and language disorders are the most conspicuous symptom, at least at the beginning of the disease, the role of speech therapists in the assessment and restitution of speechlanguage and communication skills is also indisputable.

Background: Primary progressive aphasia (PPA) is a clinical dementia syndrome characterized by impairments in language. The presence of Alzheimer disease (AD) neuropathology has been observed in approximately 40% of PPA cases. Cross-sectional and longitudinal features of cortical atrophy in PPA are emerging but less is known about the integrity of subcortical structures, particularly the thalamus. As a major relay station in the brain, the thalamus is implicated in language functioning given its reciprocal connections with perisylvian regions in the cortex. High-dimensional brain mapping was used to characterize thalamic morphology in individuals with and without non-semantic PPA. Further, shape differences were compared between PPA participants with suspected AD pathology (PPAAβ +) and those without suspected AD pathology (PPAAβ -) as determined by amyloid PET scans. The relationship between shape and specific language deficits were also investigated. Method: Thalamic integrity was examined in 57 PPA participants relative to cognitively healthy controls (N=44) with similar demographics. MR scans were acquired using high-resolution T1-weighted MPRAGE volumes following the ADNI protocol. Thalamic shape features were estimated using Large Deformation Diffeomorphic Metric Mapping. Thalamic nuclei of interest included mediodorsal, pulvinar, and anterior regions. General linear models compared differences in thalamic shape between groups. Pearson models characterized relationships between thalamic nuclei and language function. Results: After controlling for whole brain volume, thalamic volume did not differ between groups [F(1, 99)=0.80, p=0.80]. However, PPA participants exhibited significant bilateral inward shape deformation in dorsal and ventral regions that extended in an anterior to posterior fashion, and unilateral outward deformation in medial and lateral regions only in the left thalamus relative to controls [F(9, 91)=5.75, p<0.001, Wilk's Λ=0.64]. There were no shape differences between PPAAβ + and PPAAβ – groups. Pearson models revealed significant correlations between confrontation naming and shape deformation in the left pulvinar (r=0.59, p<0.01) and left anterior (r=0.55, p<0.01) thalamic nuclei for the PPAAβ + group only, such that lower language scores reflected greater localized volume loss. Conclusions: In the absence of volumetric differences, shape measures were able to capture unique aspects of localized morphologic differences in PPA that corresponded to worse naming performance only in those with suspected AD pathology. Thalamic changes appear to be a contributing and unrecognized component to the presentation and language characterization of PPA.

Introdução: No Brasil há carência de instrumentos validados para a análise do curso da Demência Frontotemporal (DFT). Dessa forma, torna-se relevante a validação da Escala de Estadiamento e Progressão da Demência Frontotemporal (FTD-FRS). Em nosso meio, as escalas de estadiamento das demências, como a Clinical Dementia Rating (CDR), foram elaboradas para graduar a doença de Alzheimer (DA) e não incluem os sintomas específicos da DFT. Objetivos: 1. Realizar a tradução, adaptação transcultural e validação da FTD-FRS para o contexto brasileiro. 2. Avaliar a capacidade da FTD-FRS detectar alterações em pacientes com DFTvc, afasia progressiva primária (APP) e DA após 12 meses da avaliação inicial, em comparação com a escala CDR para DLFT, e com a CDR original. Métodos: Participaram do estudo 101 indivíduos com idade igual ou superior a 40 anos, com escolaridade formal acima de dois anos, sendo 31 pacientes com diagnóstico de DFT variante comportamental (DFTvc), doze pacientes com afasia progressiva primária (APP), 28 pacientes com doença de Alzheimer (DA), oito com comprometimento cognitivo leve (CCL) e 22 controles normais (CN). Foram entrevistados os familiares ou cuidadores que tinham contato frequente com o paciente. Os pacientes com DA, e com os subtipos de DFT foram pareados quanto à gravidade da doença, segundo a CDR. Resultados: Foi realizado o processo de adaptação transcultural da FTD-FRS. Consistiu em: tradução, retrotradução (realizadas por tradutores independentes), discussão com especialistas sobre a versão em português e equivalência com a versão original, e desenvolvimento da versão final. A consistência interna da FTD-FRS, estimada pelo alfa de Cronbach foi 0,975, e o coeficiente de correlação intra-classe, para a estabilidade no teste e reteste em seis meses foi de 0,977. A análise fatorial revelou a existência de quatro fatores que se correlacionaram significativamente com os domínios da CDR-DLFT. Os pacientes com DFTvc apresentaram progressão mais rápida em 12 meses do que os demais subtipos de demência na FTD-FRS, na CDR-DLFT e na CDR-original. Considerações finais: A FTD-FRS tem propriedades psicométricas adequadas para seu uso clínico no Brasil. Este instrumento pode auxiliar na caracterização de sintomas clínicos relevantes para o diagnóstico e estadiamento da DFT. Também pode documentar os resultados relacionados à intervenção terapêutica. Este estudo fornece aos clínicos e pesquisadores um instrumento válido para estadiamento e acompanhamentode de pacientes diagnosticados com DFT
Introduction: In Brazil there is a shortage of validated instruments for the analysis of the course of Frontotemporal Dementia (FTD). Thus, the validation of the Frontotemporal Dementia Staging and Progression Scale (FTD-FRS) becomes relevant. In our setting, dementia staging scales, such as the Clinical Dementia Rating (CDR), were designed to stage Alzheimer\'s disease (AD) and did not include the specific symptoms of FTD. Objectives: 1. To perform the translation, cross-cultural adaptation and validation of the FTD-FRS for the Brazilian context. 2. Evaluate the ability of the FTD-FRS to detect changes in patients with bvFTD, primary progressive aphasia (PPA) and AD after 12 months of the initial evaluation, compared to the CDR scale for FTLD, and with the original CDR. Methods: A total of 101 individuals aged 40 years and older, with formal schooling above two years of age, were included in the study. Twenty-one patients were diagnosed with bvFTD, twelve patients with PPA, 28 AD, eight with mild cognitive impairment (MCI) and 22 normal controls (NC). Family members or caregivers who had frequent contact with the patient were interviewed. Patients with AD and with FTD subtypes were matched for disease severity, according to CDR. Results: The process of cross-cultural adaptation of the FTD-FRS was carried out. It consisted of: translation, back-translation (carried out by independent translators), discussion with experts about the Portuguese version and equivalence with the original version, and development of the final version. The internal consistency of the FTD-FRS, estimated by the Cronbach\'s alpha was 0.975, and the intra-class correlation coefficient for the test and retest stability at six months was 0.977. Factor analysis revealed the existence of four factors that correlated significantly with the CDR-DLFT domains. Patients with bvFTD showed faster progression at 12 months than the other dementia subtypes in the FTD-FRS, CDR-DLFT and CDR-original version scales. Final considerations: FTD-FRS has psychometric properties suitable for clinical use in Brazil. This instrument may aid in the characterization of clinical symptoms relevant to the diagnosis and staging of FTD. It can also document the results related to therapeutic interventions. This study provides clinicians and researchers with a valid instrument for staging and follow-up of patients diagnosed with FTD

For two decades, researchers and clinicians have been using the diagnostic criteria for FTD to generally diagnose a patient as suffering from PPA and the criteria of Neary et al. (1998) to further specify the diagnosis as progressive nonfluent aphasia or semantic dementia. However, there were a number of PPA cases that could not be classified according to the criteria of Neary and colleagues, which led to a revision of the diagnostic clinical and research criteria for PPA by Gorno-Tempini et al. (2011). The revised criteria encompass three PPA variants (svPPA, nfvPPA, and lvPPA) with three stages characterized by increasing evidence: clinical diagnosis, imaging-supported diagnosis, and diagnosis with definite pathology. As compared to the previous diagnostic criteria, more emphasis is placed on imaging markers as supportive features. These imaging criteria were however proposed based on a purely qualitative evaluation of the literature and have not been validated so far. The aim of this thesis was to quantitatively evaluate the validity of the new diagnostic imaging criteria for PPA variants using anatomical likelihood meta-analyses (study 1) and to investigate the usefulness of these imaging criteria for the individual diagnosis of PPA patients in clinical routine using support vector machine classification (study 2).

L’augmentation de la prévalence des démences est un problème majeur d’intérêt international. À la différence du vieillissement normal, la démence désigne l’affaiblissement progressif de l’ensemble des fonctions intellectuelles : mémoire, attention, jugement, capacité de raisonnement et les perturbations de conduite qui en résultent. Mondialement, on estime que 35,6 millions de personnes sont atteintes de démence et on dénombre 7,7 millions de nouveaux cas chaque année (WHO, 2012). Dans ce contexte, la détection précoce, prédiction et dissociation des différents syndromes démentiels sont d’un intérêt primordial, en particulier à des fins de traitement. Au cours de la dernière décennie, la littérature scientifique a montré, grâce à l’apport des outils de neuroimagerie, une association entre les troubles de la mémoire épisodique observés chez les patients atteints de maladie d’Alzheimer (MA) et l’atrophie hippocampique qu’on retrouve également chez la majorité d’entre eux (Petersen et al., 2000). Toutefois, plusieurs études portant sur la variante sémantique de l’aphasie primaire progressive (vsAPP), anciennement appelée la démence sémantique (Gorno-Tempini et al., 2011), retrouvent un patron d’atrophie semblable à celui retrouvé dans la MA en ce qui concerne l’hippocampe (Chan et al., 2001; Davies, Graham, Xuereb, Williams, & Hodges, 2004; Duval et al., 2012; Galton et al., 2001; Gorno-Tempini et al., 2004; Hornberger & Piguet, 2012; Nestor, Fryer, & Hodges, 2006; Pleizier et al., 2012; Schroeter & Neumann, 2011). Or, au niveau cognitif, ces patients démontrent plutôt une détérioration de la mémoire sémantique et n’ont généralement pas de trouble majeur au niveau de la mémoire épisodique, du moins durant les premières phases de la maladie (Gorno-Tempini et al., 2011). Il s’avère donc primordial de comparer et de préciser nos connaissances par rapport à l’implication de l’hippocampe dans ces deux pathologies afin d’orienter leurs diagnostics cliniques respectifs et de mieux diriger les méthodes d’intervention disponibles. Une étude récente a montré, chez des participants en santé, que des parties différentes de l’hippocampe sont impliquées dans le réseau de la mémoire épisodique comparativement à celui de la mémoire sémantique (La Joie et al., 2014). La partie antérieure de l’hippocampe serait impliquée dans la mémoire sémantique, tandis que la partie postérieure de cette structure serait plutôt associée à la mémoire épisodique. Notre hypothèse générale est donc que des parties différentes de l’hippocampe sont touchées dans les deux maladies en raison de leurs connexions distinctes avec les deux systèmes soutenant la mémoire épisodique et sémantique respectivement, et qu’ainsi la partie antérieure de l’hippocampe est plus touchée dans la vsAPP et la partie postérieure est plus touchée dans la MA. Le premier article de la thèse visait à identifier et comparer le patron d’atrophie cérébrale associé à la vsAPP et la MA à travers une méta-analyse basée sur des études anatomiques antérieures, et à caractériser plus précisément le volume de l’hippocampe sous un axe antéro-postérieur dans les deux maladies. Les résultats de l’étude ont confirmé la signature d’atrophie cérébrale classique observée dans les deux maladies, mais également l’hypothèse que l’hippocampe est touché de façon bilatérale dans la MA et la vsAPP. Par contre, dans la vsAPP, l’atrophie est limitée à la partie antérieure de la structure tandis qu’une atrophie plus globale a été observée dans la MA. De plus, lorsque les deux groupes ont été directement comparés, une atrophie plus prononcée de la partie postérieure a été observée dans le groupe MA versus vsAPP. Le deuxième article de la thèse visait à investiguer l’effet de la vsAPP sur les patrons de connectivité fonctionnelle de l’hippocampe antérieur versus postérieur. Les résultats ont montré deux patrons différents de connectivité fonctionnelle, entre l’hippocampe antérieur versus postérieur et le reste du cerveau, chez les contrôles. De plus, une réduction de la connectivité dans l’hippocampe antérieur a été observée chez le groupe vsAPP, et une connectivité fonctionnelle comparable à celle des contrôles a été trouvée dans l’hippocampe postérieur. Globalement, nos résultats confirment que l’atrophie de l’hippocampe est présente, mais de façon différentielle, dans la MA et la vsAPP. Nos résultats soutiennent également l’hypothèse que les syndromes neurodégénératifs comme la MA et la vsAPP n’impliquent pas seulement des atrophies focales, mais découlent plutôt d’une déconnexion entre diverses régions anatomiques, et que les symptômes cliniques sont causés par cette scission dans les réseaux neuronaux qui supportent des fonctions cognitives comme la mémoire sémantique et épisodique.
The increase in the prevalence of dementia is a major international concern. Unlike normal aging, dementia refers to the progressive weakening of all intellectual functions: memory, attention, judgment, reasoning ability, and the resulting behavioral changes. Globally, it is estimated that 35.6 million people are affected by dementia, and 7.7 million of new cases are reported each year (WHO, 2012). In this context, early detection, prediction and dissociation of these different syndromes are of primary interest, particularly for treatment purposes. Over the past decade, the scientific literature has shown, with the help of neuroimaging tools, an association between the episodic memory impairments observed in patients with Alzheimer's disease (AD) and the hippocampal atrophy found in the majority of these patients (Petersen et al., 2000). However, several studies regarding the semantic variant of primary progressive aphasia (svPPA), previously known as semantic dementia (Gorno- Tempini et al., 2011), find a similar hippocampal atrophy pattern to that found in AD patients (Brambati et al., 2009; Chan et al., 2001; Davies et al., 2004; Desgranges et al., 2007; Galton et al., 2001; Nestor et al., 2006). However, from a cognitive perspective, these patients rather demonstrate a deterioration of semantic memory and do not generally show episodic memory impairments, at least during the beginning of the disease (Gorno-Tempini et al., 2011). It is therefore essential to compare and clarify our knowledge regarding the involvement of the hippocampus in these two pathologies in order to guide their respective clinical diagnoses and available intervention methods. A recent study has shown, in healthy participants, that different parts of the hippocampus are involved in the episodic versus semantic memory networks (La Joie et al., 2014). The anterior part of the hippocampus would be involved in semantic memory, whereas the posterior part of this structure would be associated to episodic memory. Our general hypothesis is that different parts of the hippocampus are affected in both diseases, because of their distinct connections to the two systems supporting episodic and semantic memory, and thus that the anterior part of the hippocampus would be impaired in svPPA whereas the posterior part would be impaired in AD. The first article of the thesis aimed to identify and compare the pattern of cerebral atrophy associated with svPPA and AD through a meta-analysis based on previous anatomical studies, and to further characterize the volume of the hippocampus under an antero-posterior axis in both diseases. The results of the study confirmed the hypothesis that, in addition to the classical signature of cerebral atrophy observed in both diseases, the hippocampus is affected bilaterally in AD and svPPA. In svPPA, however, the atrophy is limited to the anterior part of the structure whereas a more general atrophy was observed in AD. In addition, when both groups were directly compared, a more pronounced posterior atrophy was observed in the AD versus svPPA group. The second article of the thesis aimed to investigate the impact of AD and svPPA on the functional connectivity patterns of the anterior versus posterior hippocampus. The results showed two different patterns of functional connectivity, between the anterior and posterior hippocampus and the rest of the brain, in controls. A reduction in functional connectivity in the anterior hippocampus was observed in svPPA, whereas a comparable functional connectivity pattern to that of controls was observed in the posterior hippocampus. Overall, our results confirm that atrophy of the hippocampus is present, but affects different parts of the structure, in both diseases. Our results also support the hypothesis that neurodegenerative syndromes such as AD and svPPA do not only implicate focal atrophies, but rather derive from a disconnection between various anatomical regions, and that clinical symptoms are caused by this rupture in the neural networks supporting cognitive functions such as semantic and episodic memory.

Frontotemporal dementia (FTD) is an uncommon but important form of degenerative disease characterized by clinical syndromes that result from degeneration of the frontal and temporal lobes. FTD is divided based on clinical presentation into behavioral variant FTD (bvFTD), semantic dementia, and progressive nonfluent/agrammatic aphasia. Several recent studies have advanced our knowledge of the genetics of FTD, with the three most common FTD genes being microtubule-associated protein tau (MAPT) and progranulin (GRN), and a noncoding repeat expansion in C9ORF72. Tau and TDP-43 are the most common pathologies associated with FTD. No pharmacological therapies are currently approved for use in FTD.

This chapter comprises 16 case histories that illustrate methods of assessment described in the rest of this book and the use of the Addenbrooke’s Cognitive Examination (ACE)-III. Each case begins with a brief history from the patient and observations by the family followed by findings on cognitive examination focusing on the profile shown on the ACE-III, the results of imaging investigations, and a discussion of the diagnosis and its differential, with a final summary of the principal conclusions, indicating whether the services of a neuropsychologist are required or not. The cases present important common conditions (such as mild cognitive impairment, Alzheimer’s disease in the mild and moderate stages, behavioural variant frontotemporal dementia, progressive non-fluent aphasia, semantic dementia, corticobasal degeneration, progressive supranuclear palsy, and Huntington’s disease) as well as interesting neuropsychological syndromes (such as prosopagnosia, amnestic stoke, and transient epileptic amnesia).

Frontotemporal dementia (FTD) is the second most common form of dementia in persons younger than 65 years after Alzheimer’s disease. The FTD spectrum is characterized by clinical, molecular and genetic heterogeneity. Core features of FTD are behavioural and language manifestations and the clinical spectrum of FTD currently includes a behavioural variant, progressive nonfluent aphasia and semantic dementia. The most common behavioural features are disinhibition, apathy, loss of empathy, hyperorality and perseveration. Neuroimaging usually demonstrates focal atrophy and hypometabolism in the anterior part of the frontal and temporal lobes. A careful history and neuropsychological examination, and judicious use of neuroimaging, can help distinguish FTD from other common forms of dementia, especially Alzheimer’s disease, vascular dementia, and dementia with Lewy bodies. Although no specific pharmacological treatments for FTD exists, symptom management with serotonin reuptake inhibitors and non pharmacological interventions have been shown to be beneficial.

Language, speech, and semantic knowledge are fundamental cognitive functions critical for human communication and knowledge of the world. Language comprehension and production involve core areas in the left temporoparietal cortex and inferior frontal gyrus that participate in separate but interacting networks for semantic and syntactic processing. Voice and speech production are controlled by separate corticobulbar systems that are hierarchically organized. Semantic knowledge about world objects and their action primarily involves ventrolateral portions of the anterior temporal lobe. Disturbances of these processes manifest with different forms of primary progressive aphasia, apraxia of speech, or semantic variant primary progressive aphasia.

Dementia is the term used to describe progressive impairment of thinking and memory that interferes with daily function. Dementia is not a specific disorder; rather, it is a condition with many causes. Alzheimer’s disease is the most common cause of dementia. Other common causes of dementia include vascular dementia, dementia with Lewy bodies, primary progressive aphasia which comes in the logopenic, semantic, and nonfluent/agrammatic variants, behavioral variant frontotemporal dementia, and normal pressure hydrocephalus. Primary care providers are able to diagnose most straightforward cases of dementia, whereas specialists such as neuropsychologists, neurologists, psychiatrists, and geriatricians may be needed when the diagnosis is not straightforward.

Dementia is the term used to describe progressive impairment of thinking and memory that interferes with daily function. Dementia is not a specific disorder; rather, it is a condition with many causes. Alzheimer’s disease is the most common cause of dementia. Other common causes of dementia include vascular dementia, dementia with Lewy bodies, primary progressive aphasia which comes in the logopenic, semantic, and nonfluent/agrammatic variants, behavioral variant frontotemporal dementia, and normal pressure hydrocephalus. Primary care providers are able to diagnose most straightforward cases of dementia, whereas specialists such as neuropsychologists, neurologists, psychiatrists, and geriatricians may be needed when the diagnosis is not straightforward.

In addition to Alzheimer’s disease, other brain disorders of aging that affect thinking and memory include vascular dementia, dementia with Lewy bodies, Parkinson’s disease dementia, behavioral variant frontotemporal dementia, primary progressive aphasia that has logpenic, semantic, and non-fluent agrammatic variants, and normal pressure hydrocephalus. Each produces characteristic changes in thinking, memory, language, behavior, and/or movement that allow you and the doctor to know when to consider them as possible causes of your loved one’s dementia. Note that the dementia of every individual is unique, so the symptoms and signs that they will manifest are all different. However, when dementias reach the moderate to severe stage, most dementias looks similar, despite having different causes.

In addition to Alzheimer’s disease, other brain disorders of aging that affect thinking and memory include vascular dementia, dementia with Lewy bodies, Parkinson’s disease dementia, behavioral variant frontotemporal dementia, primary progressive aphasia that has logpenic, semantic, and non-fluent agrammatic variants, and normal pressure hydrocephalus. Each produces characteristic changes in thinking, memory, language, behavior, and/or movement that allow you and the doctor to know when to consider them as possible causes of your loved one’s dementia. Note that the dementia of every individual is unique, so the symptoms and signs that they will manifest are all different. However, when dementias reach the moderate to severe stage, most dementias looks similar, despite having different causes.

Frontotemporal dementia describes a group of insidious and slowly progressive clinical syndromes that are due to frontal and/or temporal lobe dysfunction including a behavioral variant, a semantic variant, and a non-fluent aphasia variant. The diagnosis is reached through a careful, detailed history and a neurological and neuropsychological examination. Imaging techniques can help support the diagnosis and identify unique patterns of brain atrophy. Various underlying neuropathologies have been described and are related to protein misfolding implicating primarily tau or TAR DNA-binding protein 43. In its familial form, FTD can result from mutations in MAPT, PGRN, or C9orf72. Treatment currently focuses on a multidisciplinary approach involving patient and caregiver education, and social support through day care center and support groups. Pharmacological treatment is mainly symptomatic although disease-modifying therapies are being studied.

Frontotemporal dementia (FTD) is a family of neurodegenerative diseases and syndromes that most commonly involve the frontal and temporal lobes, producing dramatic alterations of personality, behavior, language, and other cognitive abilities (McKhann et al., 2001). Age of onset tends to be younger than in Alzheimer’s disease (AD), with most patients becoming symptomatic in the sixth decade of life. Although population-based epidemiologic studies of FTD have found a prevalence of approximately 5–10 per 100,000 in patients 50 years of age and older, autopsy-based case series have found that approximately 5% to15% of people with dementia have FTD, a discrepancy suggesting that many cases go undiagnosed during life (Rosso et al., 2003). Recent advances in clinicopathologic correlation have revealed that a number of neurologic conditions previously conceived of as independent disease entities such as progressive supranuclear palsy (PSP), corticobasilar degeneration (CBD), and hippocampal sclerosis dementia are in many cases better classified in the FTD family (McKhann et al., 2001; Blass et al., 2004). Many patients with FTD develop other neurologic syndromes as well, including parkinsonism and amyotrophic lateral sclerosis (ALS). FTD is actually a group of clinical syndromes with overlapping neuropathologies. The clinical expression of the disease relates primarily to the anatomic location of disease involvement rather than the neuropathologic subtype; there are many such subtypes. Clinical variants are most distinct early in the disease course, when the degree of anatomic involvement may be limited to discrete regions. As the disease spreads through the brain, many patients have symptoms that become complex and take on char acteristics of other variants. The first clinical FTD variant is one in which behavioral abnormalities and personality changes dominate the clinical presentation. This syndrome is usually associated with disease involvement of the frontal and anterior temporal lobes. In addition, there are two language presentations: primary progressive aphasia and semantic dementia (McKhann et al., 2001). The neurologic syndromes of PSP, CBD, and ALS with dementia are familiar to the neurologist because of their neurologic symptoms; it is noteworthy that patients with any of the previously mentioned syndromes routinely develop the psychiatric symptoms reviewed below.

This chapter emphasizes the value of preliminary observations in making a provisional diagnosis of dementia. Significant aspects of the history are detailed, such as head injury or brain hemorrhage that could lead to hydrocephalus or superficial siderosis. Diagnostic clues are given that facilitate identification of the posterior cortical variant of Alzheimer’s disease, characterized by progressive decline in visuospatial, visuoperceptual, literacy, and praxic skills. Emphasized is the importance of temporal pattern of disease, manifesting as episodic confusion and dementia progressing over a period of months. Further clues are outlined to facilitate identification of frontotemporal dementia variants, including semantic dementia, the behavioral variant, progressive nonfluent aphasia, and logopenic aphasia. The value of physical examination is stressed as it may disclose an underlying structural lesion.