Progressive Loss Of Semantic Knowledge Research Articles

Characterizing a Language Phenotype of Dementia with Lewy Bodies: A Clinicopathological Series (P13-6.009)

<h3>Objective:</h3> We report on three individuals with semantic variant primary progressive aphasia (svPPA) whose post-mortem pathology was consistent with diffuse neocortical Lewy body disease (LBD). We believe this is a heretofore unrecognized phenotype of LBD. <h3>Background:</h3> The present conception of primary dementias pairs clinical syndromes with neuropathologies, proven on necropsy or indirectly implicated by biomarkers. Each pairing is a clinicopathological entity. There is an increasing focus in the field of neurodegenerative disease to better characterize clinicopathological disorders, so as to target research and treatment approaches. SvPPA clinically manifests with progressive loss of semantic knowledge and is commonly associated with TDP-43 type C proteinopathy as well as Alzheimer’s(AD) and other tau pathologies. We report on three instances of svPPA associated with LBD pathology. We believe this is the first such report in the literature. <h3>Design/Methods:</h3> Our institution’s brain bank was queried for clinicopathological cases with a clinical diagnosis of svPPA and neuropathologic diagnosis of LBD. Three cases met the international consensus criteria for svPPA and were included in this study. <h3>Results:</h3> Three males aged 60–76 satisfied our inclusion criteria. Two subjects had significant temporal atrophy, and one had substantia nigral pallor. DAT scan was available in one subject, which was a negative study. All subjects fit the neuropathological consensus criteria for LBD with a diffuse neocortical distribution. In addition, all subjects had moderate vascular pathology and AD pathology (2-high ADNC, 1-intermediate). One case was also found with limbic associated Stage 1 TDP-43 proteinopathy. <h3>Conclusions:</h3> Here we propose a novel language variant of Lewy body disease. Although rare, LBD should be included as a differential diagnosis in individuals with svPPA. In the future, characterizing phenotypes of LBD will assist in more precise targeting of research and treatment strategies. <b>Disclosure:</b> Dr. Merhi has nothing to disclose. Anna C Sullivan has nothing to disclose. Miss Bhavaraju has nothing to disclose. Dr. Walker has nothing to disclose. Dr. Bieniek has nothing to disclose. Dr. Abdullah has nothing to disclose. Dr. Salardini has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Biogen. The institution of Dr. Salardini has received research support from NIH/NIA. The institution of Dr. Salardini has received research support from Taylor Family. Dr. Salardini has received publishing royalties from a publication relating to health care. Dr. Rini has nothing to disclose. An immediate family member of Dr. Parker has received personal compensation for serving as an employee of Rochal Industries, Rochal Parners. An immediate family member of Dr. Parker has received personal compensation in the range of $5,000-$9,999 for serving as an officer or member of the Board of Directors for Sanara Med Tech. An immediate family member of Dr. Parker has stock in Sanara Med Tech. An immediate family member of Dr. Parker has stock in Rochal Industries. An immediate family member of Dr. Parker has stock in Rochal Parnters. The institution of Dr. Parker has received research support from Texas Alzheimer’s Research and Care Consortium. The institution of an immediate family member of Dr. Parker has received research support from Rochal Industries. An immediate family member of Dr. Parker has received intellectual property interests from a discovery or technology relating to health care. An immediate family member of Dr. Parker has received publishing royalties from a publication relating to health care. Dr. Parker has received personal compensation in the range of $500-$4,999 for serving as a Grand Rounds Speaker with Univ of Texas Tyler. An immediate family member of Dr. Parker has received personal compensation in the range of $0-$499 for serving as a NIH Review Committees Member with NIH. An immediate family member of Dr. Parker has a non-compensated relationship as a Chairwoman of the Board - Ann Salamone with BioMed SA that is relevant to AAN interests or activities.

The Importance of Being Familiar: The Role of Semantic Knowledge in the Activation of Emotions and Factual Knowledge from Music in the Semantic Variant of Primary Progressive Aphasia.

The role of semantic knowledge in emotion recognition remains poorly understood. The semantic variant of primary progressive aphasia (svPPA) is a degenerative disorder characterized by progressive loss of semantic knowledge, while other cognitive abilities remain spared, at least in the early stages of the disease. The syndrome is therefore a reliable clinical model of semantic impairment allowing for testing the propositions made in theoretical models of emotion recognition. The main goal of this study was to investigate the role of semantic memory in the recognition of basic emotions conveyed by music in individuals with svPPA. The performance of 9 individuals with svPPA was compared to that of 32 control participants in tasks designed to investigate the ability: a) to differentiate between familiar and non-familiar musical excerpts, b) to associate semantic concepts to musical excerpts, and c) to recognize basic emotions conveyed by music. Results revealed that individuals with svPPA showed preserved abilities to recognize familiar musical excerpts but impaired performance on the two other tasks. Moreover, recognition of basic emotions and association of musical excerpts with semantic concepts was significantly better for familiar than non-familiar musical excerpts in participants with svPPA. Results of this study have important implications for theoretical models of emotion recognition and music processing. They suggest that impairment of semantic memory in svPPA affects both the activation of emotions and factual knowledge from music and that this impairment is modulated by familiarity with musical tunes.

Errorless Learning Therapy in Semantic Variant of Primary Progressive Aphasia.

The semantic variant of primary progressive aphasia (svPPA) is characterized by a progressive loss of semantic knowledge impairing the ability to name and to recognize the meaning of words. We aimed to evaluate the immediate and short-term effect of errorless learning speech therapy on the naming and recognition of commonly used words in patients with svPPA. Eight participants diagnosed with svPPA received 16 sessions of intensive errorless learning speech therapy. Naming and word comprehension tasks were evaluated at baseline, immediately postintervention, and at follow-up after 1, 3, and 6 months. These evaluations were performed using two item sets (a trained list and an untrained list). In the naming tasks, patients showed a significant improvement in trained items immediately after the intervention, but that improvement decayed progressively when therapy ended. No improvements were found either in trained comprehension or in untrained tasks. Errorless learning therapy could improve naming ability in patients with svPPA. This effect may be due to the relative preservation of episodic memory, but the benefit is not maintained over time, presumably because there is no consolidation.

Multimodal semantic battery to monitor progressive loss of concepts in the semantic variant of primary progressive aphasia (svPPA): an innovative proposal

ABSTRACT Semantic variant primary progressive aphasia (svPPA) is a rare neurodegenerative disease characterized by a progressive loss of semantic knowledge. Patients with svPPA show anomia, impaired word comprehension, poor object recognition, and difficulties in retrieving semantic information. svPPA is also a unique “natural” model that allows clinicians and cognitive neuroscientists to study the organization of semantic memory because only semantic knowledge is affected in the initial period of the disease, with relative sparing of other cognitive domains. In the clinical practice, semantic memory is commonly tested only with verbal tests. The aim of the present study was to preliminary test a new Multimodal Semantic Battery developed in our laboratory, which comprised 11 subtests designed to assess the semantic knowledge of multiple items via all input modalities. The battery was administered twice, over four years, to a patient diagnosed with svPPA. We found that when extensively tested with multiple tests, in some cases, he was still able to recall semantic features of the items that otherwise would not have emerged with standard semantic tests. These results are discussed for the clinical practice: monitoring semantic memory through all modalities in a practical and reliable way could be useful for both clinicians and experimental researchers to better investigate the breakdown of semantic knowledge.

Genetic variation across RNA metabolism and cell death gene networks is implicated in the semantic variant of primary progressive aphasia

The semantic variant of primary progressive aphasia (svPPA) is a clinical syndrome characterized by neurodegeneration and progressive loss of semantic knowledge. Unlike many other forms of frontotemporal lobar degeneration (FTLD), svPPA has a highly consistent underlying pathology composed of TDP-43 (a regulator of RNA and DNA transcription metabolism). Previous genetic studies of svPPA are limited by small sample sizes and a paucity of common risk variants. Despite this, svPPA’s relatively homogenous clinicopathologic phenotype makes it an ideal investigative model to examine genetic processes that may drive neurodegenerative disease. In this study, we used GWAS metadata, tissue samples from pathologically confirmed frontotemporal lobar degeneration, and in silico techniques to identify and characterize protein interaction networks associated with svPPA risk. We identified 64 svPPA risk genes that interact at the protein level. The protein pathways represented in this svPPA gene network are critical regulators of RNA metabolism and cell death, such as SMAD proteins and NOTCH1. Many of the genes in this network are involved in TDP-43 metabolism. Contrary to the conventional notion that svPPA is a clinical syndrome with few genetic risk factors, our analyses show that svPPA risk is complex and polygenic in nature. Risk for svPPA is likely driven by multiple common variants in genes interacting with TDP-43, along with cell death,x` working in combination to promote neurodegeneration.

Characteristic clinical presentations and CSF biomarker features in patients with semantic dementia

Background: Semantic dementia (SD) is a neurodegenerative disorder clinically characterized by progressive loss of semantic knowledge. Neuroimaging feature of SD is atrophic change of the anterior temporal lobe often with left-side predominance. However, patients with right-side predominant atrophy have been also described.

Quest for the best: Effects of errorless and active encoding on word re-learning in semantic dementia

Semantic dementia is a neurocognitive disorder characterised by a steady and progressive loss of semantic knowledge in the presence of relatively preserved other cognitive skills. Recent treatment studies have proven that language rehabilitation aimed at anomia in semantic dementia can be successful. The objective of this study was to examine the separate and interactive effects of errorless vs. errorful and active vs. passive learning approaches to anomia and their effects on naming and comprehension of treated items, as well as maintenance and generalisation of treatment gains. Seven participants with semantic dementia re-learned two sets of words (one for which participants retained auditory comprehension, and one for which they did not) in each of four different treatment methods based on those approaches. Errorless learning proved more successful than errorful learning in restoring lexical representations in all but one participant while there was no interaction between effects of errorless and active approaches on treatment success. Maintenance of treatment gains showed an advantage for errorless learning at one but not three months post-treatment, although all overall gains were maintained to a significant degree at both time points. Effects of both treatment and maintenance were stronger for items for which participants showed preserved auditory comprehension. The results are discussed in a framework of progressive language disorders and applicability of errorless methods to language rehabilitation in semantic dementia.

Category-specific deficits in semantic dementia Links between perception and semantic knowledge

The nature of knowledge and its relationship with the perceptual processes are among the most central issues in the study of human cognition. Should knowledge be abstract, then semantic memory and perception should be relatively independent. On the contrary, if knowledge is sensory-dependent, then memory and perception should be very close. The first view is supported by the multiple system approach of memory, whereas the second view is supported by the single-store memory theories. One way to study these links is through the category-specific impairment and the sensory-functional theory (SFT). Category-specific impairment is generally observed for living items compared to artefacts. The SFT explains this deficit by defining living items as essentially based on perception. In the abstract view of knowledge, a living deficit should be related to a deficit in processing sensory knowledge. On the opposite, the sensory-dependent view states that this deficit results from perception impairment. This article focuses on the relations between knowledge and perception in semantic dementia (SD). SD is characterized by a progressive loss of semantic knowledge, making it particularly interesting to study. This article first focuses on the SFT, to explain the category-specific impairment. The issue of perceptual processing in SD is then reviewed from the lowest level (senses) to the highest level of perception (multimodal integration). The data demonstrated normal perception for these patients. However, visual integration appeared to be impaired for existing knowledge. This result is discussed in relation with a possible involvement of the anterior temporal lobes. These regions are known to be the most vulnerable in SD. Recently these regions have also been shown to be involved in the multimodal integration. Taken together, these data suggest that perception and knowledge could be linked and partially explained by the SFT. Finally, the data support the sensory-dependent approaches of memory.

Semantische Demenz

Semantic dementia (SD) is a relatively rare primary degenerative brain disease, often with onset before the age of 65, which belongs to the group of frontotemporal lobar degenerations. The central characteristic of SD is a progressive loss of semantic knowledge with manifestation in aphasia as well as impaired face and object recognition. A reliable discrimination of SD from other neurodegenerative conditions, in particular from Alzheimer's disease, may be a challenge for neurologists as well as neuropsychologists. In the first place, a sound knowledge base is expected from the expert in order to minimize false diagnoses. To illustrate this, a detailed case history of a 55-year old patient is presented who was referred for an independent medical and neuropsychological examination for disability benefits. The referral question was Pick's disease. However, the clinical manifestation as well as the results of a comprehensive neuropsychological evaluation clearly indicated the diagnosis of SD with neuroimaging and neuropsychological evidence of marked right temporal lobe atrophy. The case history highlights a number of problems inherent in current practice of dementia assessment. For differential diagnosis of dementing conditions, a thorough neuropsychological assessment appears to be indispensable.

Démence sémantique : réflexions d’un groupe de travail pour des critères de diagnostic en français et la constitution d’une cohorte de patients

Semantic dementia (SD) is a syndrome of progressive loss of semantic knowledge for objects and people. International criteria propose that SD be included in the frontotemporal lobar degeneration syndromes, with progressive non-fluent aphasia and frontotemporal dementia (FTD). However, several related syndromes have been defined that clinically and conceptually share both similarities and differences with SD: fluent progressive aphasia, progressive prosopagnosia, temporal variant of FTD. In order to establish a French consensus for the diagnosis and modalities of evaluation and follow-up of SD, a working group, composed of neurologists, neuropsychologists and speech-therapists, was established by the Groupe de réflexion sur les évaluations cognitives (GRECO). New criteria were elaborated, based on clinical, neuropsychological, and imaging data. They define typical and atypical forms of SD. A diagnosis of typical SD relies on an isolated and progressive loss of semantic knowledge, attested by a deficit of word comprehension and a deficit of objects and/or people identification, with imaging showing temporal atrophy and/or hypometabolism. SD is atypical if the deficit of semantic knowledge is present only within a single modality (verbal versus visual), or if non-semantic deficits (mild and not present at onset) and/or neurological signs, are associated with the semantic loss.

Progressive knowledge loss: A longitudinal case study

The evolution of the progressive loss of semantic knowledge of a patient, VZ, with lesions mainly affecting the infero-medial temporal lobes, was followed for two years. At the beginning of the study VZ's performance was mainly characterized by a category-specific deficit for living things and a modality-specific deficit for perceptual attribute knowledge. As time went on, VZ's disorder affected all categories by changing the relationship between category and attribute knowledge. Data show that dissociations may change in the course of progressive cognitive breakdown, depending on both degeneration stage and task demands. VZ's performance is discussed in the light of the most influential theoretical accounts. Methodological suggestions regarding longitudinal studies of degenerative patients are also put forward.

Neural correlates of semantic and behavioural deficits in frontotemporal dementia

Patients with frontotemporal dementia (FTD) can present with the clinical syndrome of semantic dementia due to a progressive loss of semantic knowledge or a neuropsychiatric syndrome characterised by aberrant social behaviours although frequently both co-exist. It has been assumed that the former is underpinned by damage to the temporal lobes and the latter, predominantly, by damage to the frontal lobes. Using the technique of voxel-based morphometry, we studied a group of FTD cases ( n = 18) with a range of cognitive and neuropsychiatric features to correlate loss of semantic knowledge (as measured by the sum of two semantic tests) and aberrant behaviour (as measured by the neuropsychiatric inventory, NPI) with regional loss of grey matter volume. Semantic breakdown correlated with extensive loss of grey matter volume throughout the left anterior temporal lobe and less significantly with right temporal pole and subcallosal gyrus. Aberrant behaviour correlated with loss of grey matter volume in the dorso-mesial frontal lobe—paracingulate region, Brodmann areas 6/8/9—more so on the right. The frontal paracingulate correlation suggests that damage to this region may significantly contribute to the genesis of the behavioural syndrome seen in FTD.