Dissertations / Theses on the topic 'Frontotemporal dementia'
To see the other types of publications on this topic, follow the link: Frontotemporal dementia.
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 dissertations / theses for your research on the topic 'Frontotemporal dementia.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse dissertations / theses on a wide variety of disciplines and organise your bibliography correctly.
1
Sampson, Elizabeth Lesley. "Longitudinal studies in frontotemporal dementia." Thesis, University College London (University of London), 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.406422.
Full text
2
Rascovsky, Katya. "Neuropsychological aspects of frontotemporal dementia /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2005. http://wwwlib.umi.com/cr/ucsd/fullcit?p3167837.
Full text
3
Graham, A. J. "Learning and memory in frontotemporal dementia." Thesis, University of Cambridge, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.599590.
Full text
4
Yancopoulou, Despina. "Neuropathological and genetic studies on frontotemporal dementia." Thesis, University of Cambridge, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.614974.
Full text
5
Orr, Miranda Ethel. "Mouse and stem cell models of frontotemporal dementia." Diss., Montana State University, 2012. http://etd.lib.montana.edu/etd/2012/orr/OrrM0512.pdf.
Full textAbstract:
Alzheimer's disease (AD) is the most prevalent brain disease in the United States, and an escalating health concern. AD patient brains acquire hallmark protein aggregates, referred to as senile A beta plaques and neurofibrillary tangles (NFTs), that coincide with brain cell loss and dementia. A subset of AD patients carry mutant genes. Our understanding of AD largely relies on model systems that express these gene variants. Mice engineered to express AD-mutant human genes develop A beta plaques, but fail to develop the tau-containing NFTs or cell loss. Mutant tau variants are required to induce NFTs and neuronal loss in mice, but AD patients carry normal tau genes. The inability of mouse tau to become a pathogenic protein in the presence of AD-mutant gene variants, and the general insufficiency of the current systems to recapitulate AD, inspired the research described here. To determine if species differences between mouse and human tau inhibit the progression of AD in mice, I utilized a well-characterized mouse model of a related disease, frontotemporal dementia (FTD). FTD mice carry mutant human tau and develop NFTs and cell loss. I ablated mouse tau in FTD mice and looked for signs of more severe pathology. I compared the FTD mice, with and without mouse tau, to FTD mice with and without wild type human tau to investigate potential tau species-specific differences. My studies indicated that wild type tau, mouse or human, dampened the pathological effects of FTD tau implying a general, not mouse-specific, effect of normal tau protein. Our data suggest that unknown factors, distinct from endogenous mouse tau, contribute to the inability of mice to model AD. The recent interest in patient-specific stem cell (SC) models to study disease necessitates a thorough evaluation of their ability to recapitulate key characteristics of disease, reproducibility, and longevity. I generated and characterized brain SC cultures from FTD fetal mice and compared them to those generated from mice with normal human tau. Significant genotype associated differences were discovered in the SC system and later verified in adult mice to reinforce the potential of patient-specific SC models to study disease.
6
Rizzu, Patrizia. "Mutations in frontotemporal dementia linking tau to neurodegeneration." [S.l.] : Rotterdam : [The Author] ; Erasmus University [Host], 2002. http://hdl.handle.net/1765/12093.
Full text
7
Urwin, H. N. "Cellular models of CHMP2B mutations in frontotemporal dementia." Thesis, University College London (University of London), 2010. http://discovery.ucl.ac.uk/19564/.
Full textAbstract:
Mutations in the charged multivesicular body protein 2B gene (CHMP2B) cause frontotemporal dementia termed frontotemporal dementia linked to chromosome 3 (FTD-3) in a large Danish pedigree and also in an unrelated Belgian familial FTD patient. Genetic analyses on the Danish pedigree and the role of CHMP2B mutations in frontotemporal dementia are reported. The clinicopathological spectrum of FTD-3 and other FTD subtypes is also described. CHMP2B is a component of the endosomal sorting complex required for transport (ESCRT-III), which is required for formation and function of the multivesicular body (MVB), an endosomal structure that fuses with the lysosome to degrade endocytosed proteins. Cellular models of CHMP2B mutations showed an enlarged late endosomal phenotype and an abnormal pattern of ubiquitination. Functional studies demonstrated a specific disruption of endosome-lysosome fusion but not sorting of endocytosed receptors by the MVB. Investigations into the mechanism of impaired fusion suggested impaired recruitment of the GTPase Rab7, known to be necessary for vesicular fusion, onto endosomes in CHMP2B mutant cells. Studies of patient tissue revealed a novel endosomal pathology in CHMP2B mutation-positive patient brains and also abnormal endosomes in patient fibroblasts. These data indicate that defects in endosomal fusion events can lead to neurodegeneration and suggest a potential pathogenic mechanism for CHMP2B mutations.
8
Suhonen, N. M. (Noora Maria). "Cognitive and behavioral characteristics of frontotemporal lobar degeneration." Doctoral thesis, Oulun yliopisto, 2017. http://urn.fi/urn:isbn:9789526216102.
Full textAbstract:
Abstract Frontotemporal lobar degeneration (FTLD) is the second commonest cause of dementia after Alzheimer’s disease (AD) in patients <65 years. Its most frequent clinical subtype is behavioral variant frontotemporal dementia (bvFTD) characterized by behavioral change and executive deficits. FTLD also encompasses two variants of primary progressive aphasia (PPA) characterized by language deficits. The majority of familial FTLD cases are linked to the C9ORF72 expansion mutation. As both cognitive and behavioral changes are core diagnostic features of FTLD, neuropsychological assessment is vital. However, neuropsychological literature is inconclusive regarding the most functional measures for detecting FTLD. Current knowledge on the cognitive profile of patients with the C9ORF72 expansion is scarce. The aims of this thesis were threefold: (1) to identify the cognitive measures that optimally serve the differential diagnosis of FTLD, (2) to characterize the neuropsychological profile of C9ORF72 expansion; and (3) to examine the utility of the Modified Frontal Behavioral Inventory (FBI-mod) in differentiating FTLD, AD, and mild cognitive impairment (MCI). The participants comprised FTLD, AD, and MCI patients diagnosed in the University Hospitals of Oulu and Kuopio. The patients underwent a detailed neuropsychological assessment including the CERAD neuropsychological battery (CERAD-NB) and the FBI-mod. While bvFTD was characterized by verbal fluency, working memory, and verbal comprehension deficits relative to AD, AD was associated with greater episodic memory impairments. The poorer delayed recall in AD was further evident on the memory tests of the CERAD-NB; however, its overall utility in the differentiation between FTLD and AD was limited. The C9ORF72 expansion carriers showed more severe executive deficits than non-carriers. The C9ORF72 expansion may further be associated with slowly progressing FTLD. On the FBI-mod, bvFTD was linked to amplified behavioral symptoms relative to AD, MCI, and PPA. Findings highlight the importance of incorporating a broad cognitive battery in the neuropsychological evaluation of FTLD. Though the clinical phenotype of C9ORF72 expansion appears broad, executive impairment likely is a core feature of bvFTD patients with the expansion. The use of the FBI-mod is recommended as a structured measure for behavioral symptoms of bvFTDTiivistelmä Otsa-ohimolohkorappeumat on Alzheimerin taudin (AT) jälkeen yleisin työikäisten dementiaa aiheuttava sairausryhmä. Sen yleisin alamuoto on otsalohkodementia, jonka ensioireita ovat käyttäytymisen muutokset ja toiminnanohjauksen ongelmat. Sairausryhmään kuuluu myös kaksi kielellisin oirein ilmenevää alatyyppiä. C9ORF72-toistojaksomutaation on todettu selittävän suurimman osan perinnöllisistä tapauksista. Kognitiivisten ja käyttäytymiseen liittyvien muutosten arvioiminen on keskeinen osa taudin diagnostiikkaa. Tutkimustiedon perusteella on epäselvää, mitkä neuropsykologiset menetelmät soveltuvat parhaiten otsa-ohimolohkorappeumien tunnistamiseen. Tieto C9ORF72-mutaation kantajien kognitiivisesta profiilista on niukkaa. Tutkimuksen tavoitteena oli löytää neuropsykologisia menetelmiä, joista on hyötyä otsa-ohimolohkorappeumien erotusdiagnostiikassa ja selvittää C9ORF72-mutaation kantajien neuropsykologisia erityispiirteitä. Lisäksi haluttiin tutkia käytösoireita kartoittavan FBI-mod -läheiskyselyn hyödyllisyyttä otsa-ohimolohkorappeumien, AT:n ja lievän kognitiivisen heikentymän (MCI) erottamisessa. Aineisto koostui Oulun ja Kuopion yliopistosairaaloissa diagnosoiduista otsa-ohimolohkorappeuma-, AT- ja MCI-potilaista, joille oli tehty CERAD-tehtäväsarja, laaja neuropsykologinen tutkimus sekä FBI-mod. Otsalohkodementiaa sairastavat suoriutuivat AT-potilaita heikommin sanasujuvuutta, työmuistia ja kielellistä käsityskykyä arvioivissa tehtävissä, kun taas tapahtumamuisti oli heikompi AT:a sairastavilla. Myös CERAD-tehtäväsarjassa AT-potilaat suoriutuivat heikommin viivästetyn mieleenpalautuksen tehtävissä, mutta kokonaisuutena tehtäväsarjan kyky erotella otsa-ohimolohkorappeumaa ja AT:a sairastavat oli rajallinen. C9ORF72-mutaation kantajilla toiminnanohjauksen ongelmat olivat vaikeampia kuin ei-kantajilla. Lisäksi havaittiin, että C9ORF72-mutaatioon liittyvä sairaus voi edetä hyvin hitaasti. FBI-mod erotteli hyvin otsalohkodementiaa sairastavat AT- ja MCI-potilaista sekä otsa-ohimolohkorappeumien kielellistä muotoa sairastavista. Tulokset korostavat laajan neuropsykologisen tutkimuksen merkitystä otsa-ohimolohkorappeumien diagnostiikassa. Vaikka C9ORF72-mutaation kliininen kuva on vaihteleva, ovat toiminnanohjauksen ongelmat keskeinen osa taudinkuvaa. FBI-mod -kyselyn käyttö on suositeltavaa otsalohkodementiaan liittyvien käytösoireiden strukturoidussa arvioinnissa
9
Haussmann, Robert, Marek Wysocki, Moritz D. Brandt, Andreas Hermann, and Markus Donix. "MAPT mutation associated with frontotemporal dementia and parkinsonism (FTDP-17)." Cambridge University Press, 2017. https://tud.qucosa.de/id/qucosa%3A70705.
Full textAbstract:
We present a 56-year-old patient suffering from frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17). The history included a three-generation pedigree and the patient was found to be a mutation carrier. The diagnosis was hindered by late appearance of the hypokinetic movement disorder. For clinicians, it is important to consider rare neurodegenerative disease variants in early-onset familial dementia syndromes with behavioral, cognitive, and motor symptoms
10
Bradley, Paul. "The family experience of frontotemporal dementia : a qualitative study." Thesis, University of Birmingham, 2009. http://etheses.bham.ac.uk//id/eprint/403/.
Full textAbstract:
Overview This thesis is submitted in partial fulfilment for the requirements of the degree of Doctor of Clinical Psychology at the School of Psychology, University of Birmingham. It comprises of a research and a clinical volume. Volume I Volume I is the research component of the thesis. It consists of two papers, the first of which is a review of the literature that uses ‘Theory of Mind’ (ToM) tasks with people with frontal-variant frontotemporal dementia (fvFTD). All the research identified is systematically appraised in terms of the methodology and the quality of the published reports. The evidence indicates that ToM is impaired in people with fvFTD; however more robust findings were evident from research which comprehensively measured neuropsychological functioning and used established and well known ToM tests. More recent research has diversified into exploring other aspects of social cognition, such as emotional processing and empathy, and their relationships with ToM. The nominated journal for this review paper is ‘Neuropsychologia’. The second paper is a qualitative research project that explores the experiences of family members of people living with fvFTD. The research questions were: How does the development of fvFTD in a working age person affect the family experience of living with that person, and how might mental health services respond to the needs of those family members? Individual in-depth interviews were carried out with six relatives (including partners, a sibling, and an adult child), and Interpretative Phenomenological Analysis (IPA) was used to analyse the data resulting in the emergence of four main themes. The findings demonstrate how family caregivers of people with fvFTD have to contend with specific behavioural challenges and personality changes associated with the condition. The study also indicates that knowledge about fvFTD is lacking in both carers and professionals alike, causing uncertainty and long periods waiting for a diagnosis, which adds to the burden of care for these people. Services need to be developed to cater for specific individual needs and awareness needs to be raised in all health care services. The nominated journal for this research paper is ‘Dementia: The International Journal of Social Research and Practice’. Volume II Volume II is the clinical component of the thesis, which consists of five clinical practice reports (CPRs) that describe and evaluate clinical work carried out during clinical placements throughout the training course. The first CPR ‘Psychological Models’ formulates the case of an 18-year-old woman with anxiety symptoms from a systemic and a cognitive perspective. The second CPR ‘Small Scale Service-Related Research Project’ is a qualitative evaluation of a drop-in service for young people leaving care. The third CPR ‘Single Case Experimental Design’ evaluates the intervention designed to support a woman with a moderate learning disability and behaviour that challenged services. The fourth CPR ‘Case Study’ details the neuropsychological assessment of an 81-year-old man with memory problems. The fifth CPR was presented orally and it describes the use of Cognitive Analytic Therapy with a woman presenting with anxiety following treatment for breast cancer. The abstract is included here only.
11
Kipps, Christopher Myles William. "Insights into frontotemporal dementia : an imaging and neuropsychological study." Thesis, University of Cambridge, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.611105.
Full text
12
Marshall, Charles R. "Physiology and neuroanatomy of emotional reactivity in frontotemporal dementia." Thesis, University College London (University of London), 2018. http://discovery.ucl.ac.uk/10053086/.
Full textAbstract:
The frontotemporal dementias (FTD) are a heterogeneous group of neurodegenerative diseases that cause variable profiles of fronto-insulo-temporal network disintegration. Loss of empathy and dysfunctional social interaction are a leading features of FTD and major determinants of care burden, but remain poorly understood and difficult to measure with conventional neuropsychological instruments. Building on a large body of work in the healthy brain showing that embodied responses are important components of emotional responses and empathy, I performed a series of experiments to examine the extent to which the induction and decoding of somatic physiological responses to the emotions of others are degraded in FTD, and to define the underlying neuroanatomical changes responsible for these deficits. I systematically studied a range of modalities across the entire syndromic spectrum of FTD, including daily life emotional sensitivity, the cognitive categorisation of emotions, interoceptive accuracy, automatic facial mimicry, autonomic responses, and structural and functional neuroanatomy to deconstruct aberrant emotional reactivity in these diseases. My results provide proof of principle for the utility of physiological measures in deconstructing complex socioemotional symptoms and suggest that these warrant further investigation as clinical biomarkers in FTD. Chapter 3: Using a heartbeat counting task, I found that interoceptive accuracy is impaired in semantic variant primary progressive aphasia, but correlates with sensitivity to the emotions of others across FTD syndromes. Voxel based morphometry demonstrated that impaired interoceptive accuracy correlates with grey matter volume in anterior cingulate, insula and amygdala. Chapter 4: Using facial electromyography to index automatic imitation, I showed that mimicry of emotional facial expressions is impaired in the behavioural and right temporal variants of FTD. Automatic imitation predicted correct identification of facial emotions in healthy controls and syndromes focussed on the frontal lobes and insula, but not in syndromes focussed on the temporal lobes, suggesting that automatic imitation aids emotion recognition only when social concepts and semantic stores are intact. Voxel based morphometry replicated previously identified neuroanatomical correlates of emotion identification ability, while automatic imitation was associated with grey matter volume in a visuomotor network including primary visual and motor cortices, visual motion area (MT/V5) and supplementary motor cortex. Chapter 5: By recording heart rate during viewing of facial emotions, I showed that the normal cardiac reactivity to emotion is impaired in FTD syndromes with fronto-insular atrophy (behavioural variant FTD and nonfluent variant primary progressive aphasia) but not in syndromes focussed on the temporal lobes (right temporal variant FTD and semantic variant primary progressive aphasia). Unlike automatic imitation, cardiac reactivity dissociated from emotion identification ability. Voxel based morphometry revealed grey matter correlates of cardiac reactivity in anterior cingulate, insula and orbitofrontal cortex. Chapter 6: Subjects viewed videos of facial emotions during fMRI scanning, with concomitant recording of heart rate and pupil size. I identified syndromic profiles of reduced activity in posterior face responsive regions including posterior superior temporal sulcus and fusiform face area. Emotion identification ability was predicted by activity in more anterior areas including anterior cingulate, insula, inferior frontal gyrus and temporal pole. Autonomic reactivity related to activity in both components of the central autonomic control network and regions responsible for processing the sensory properties of the stimuli.
13
Ryan, Sarah. "Modelling C9orf72-linked frontotemporal dementia and amyotrophic lateral sclerosis." Thesis, University of Manchester, 2015. https://www.research.manchester.ac.uk/portal/en/theses/modelling-c9orf72linked-frontotemporal-dementia-and-amyotrophic-lateral-sclerosis(92740fce-3f4a-43cc-afed-b0f40f71ed03).html.
Full textAbstract:
Frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) are neurodegenerative diseases with considerable clinical, genetic and pathological overlap. A GGGGCC hexanucleotide repeat expansion in a non-coding region of C9orf72 on chromosome 9 is the major cause of both FTLD and ALS. An understanding of the mechanisms through which the expansion leads to neurodegeneration will therefore be vital for development of novel therapeutics. There are 3 possible mechanisms through which the GGGGCC expansion may cause toxicity: (i) through haploinsufficiency of C9orf72, (ii) repetitive RNA transcripts arising from the expansion may be toxic or (iii) translation of the expansion may produce toxic peptides. Whilst the expansion is located in a non-coding region of the gene, long GC-rich RNA transcripts may be translated in the absence of an ATG start codon, through a process known as repeat-associated non-ATG translation (RAN-translation). 5 distinct dipeptide repeat proteins (DPRs) have been found to arise from the expansion through RAN-translation of the sense and antisense strands in all frames: poly-GA, -GR, -PR, -AP and –GP. All 5 DPRs have been shown to aggregate in patient tissue, indicating that they may play a role in C9FTLD/ALS pathogenesis. This project aimed to generate a series of models to investigate the mechanisms of neurodegeneration in C9FTLD/ALS, using C. elegans and cell culture. A transgenic worm strain which does not express the C. elegans orthologue of C9orf72 was first characterised. No impairments were observed in motility or life-span, demonstrating that loss of C9orf72 function does not cause an ALS-like phenotype in C. elegans. When considered alongside recent literature, this finding suggests that toxic gain of function mechanisms may be more important in C9FTLD/ALS pathogenesis. The impact of DPRs on cellular function was next investigated. Constructs were generated containing alternative codon sequences for each of the 5 DPRs, to express each peptide in the absence of the repetitive GGGGCC RNA sequences found in disease. A step-wise cloning strategy was employed to progressively increase repeat-length in these constructs until physiologically-relevant lengths of > 1000 repeats were obtained. DPRs were then expressed in HeLa cells, in order to assess the individual effects of each peptide on cellular function. Poly-GA formed large, star-shaped cytoplasmic inclusions which co-localised with ubiquilin-2 and p62, closely resembling the inclusions observed in patient tissue. This implies a potential role of proteasome dysfunction in C9FTLD/ALS. Conversely, the alanine-rich DPRs, poly-GR and –PR, translocated to the nucleolus, where poly-GR in particular caused nucleolar stress. Furthermore, nucleolar poly-GR caused loss of Cajal bodies from the nucleus, and a loss or mislocalisation of survival motor neuron protein (SMN). This is of particular interest to C9ALS, since loss of SMN is selectively toxic to motor neurons. Furthermore, loss of Cajal bodies and nucleolar stress are likely to cause defects in RNA processing, which may contribute to neurotoxicity.
14
Rytty, R. (Riikka). "Resting-state functional MRI in behavioral variant of frontotemporal dementia." Doctoral thesis, Oulun yliopisto, 2016. http://urn.fi/urn:isbn:9789526211336.
Full textAbstract:
Abstract Frontotemporal lobar degeneration (FTLD) is the second most common neurodegenerative disease leading to early-onset dementia with an estimated worldwide prevalence of 10 to 30 cases per 100000 individuals in the age group of 46 to 65 years. Behavioral variant frontotemporal dementia (bvFTD) is the most common FTLD subtype. It is characterized by a progressive deterioration of behavior and personality as well as executive dysfunction. In Finland, almost 50 % of familial FTLD cases are attributable to the C9ORF72 mutation. bvFTD is associated with a characteristic pattern of brain atrophy detectable in structural MRI. However, these changes are typically not visible in the early stages of the disease. Resting-state functional MRI (RS-fMRI) is being increasingly used to evaluate changes in functional connectivity within neuronal networks in the brain but only a few RS-fMRI investigations of bvFTD patients have been published with inconsistent results. The object of this thesis was to investigate functional connectivity changes detected in the salience (SLN) and default mode networks (DMN) in bvFTD. Another aim was to clarify the role of other cognitive resting-state networks in this disease. A cohort of 26 bvFTD patients was studied, with 8 of these patients carrying the C9ORF72 expansion. Connectivity changes were detected in multiple clinically relevant cognitive networks. Decreased functional connectivity was observed in the SLN, which is associated with guiding of behavior. Increased activity was present in the DMN and the dorsal attention network (DAN). In C9ORF72 associated bvFTD, there was an abnormal linkage detected between the DMN and the thalamus. Currently, fMRI is generally used as a research tool and in a group setting. Different study methods have been used in the literature and also in the studies of this thesis, the analysis procedures differed to some extent. The variety of analysis methods may explain the heterogeneity in fMRI findings in bvFTD patients. There is a need for standardization of the fMRI methodology, larger study groups and also in the future the methodology should be improved so that single patient analysis would provide results to allow a confident diagnosis of this diseaseTiivistelmä Otsa-ohimolohkorappeuma (Frontotemporal lobar degeneration, FTLD) on toiseksi yleisin etenevä dementiaan johtava sairaus, joka ilmaantuu usein jo työikäisenä. Otsalohkodementia on otsa-ohimolohkorappeuman yleisin alamuoto, jonka oireisto painottuu persoonan ja käyttäytymisen muutoksiin sekä toiminnan ohjauksen ongelmiin. Suomessa C9ORF72-toistojaksomutaatio selittää lähes 50 % perinnöllisistä otsa-ohimolohkorappeumista. Aivojen rakenteellisella magneettikuvauksella (MK) voidaan havaita rakenteellisia muutoksia, jotka ilmaantuvat kuitenkin vasta taudin edettyä vaikeampaan vaiheeseen. Aivojen lepotilan toiminnallinen magneettikuvaus (TMK) mahdollistaa aivojen hermoverkkojen toiminnan eli konnektiviteetin kartoituksen. Aiemmin TMK:a on tutkittu esim. Alzheimerin taudissa. Otsalohkodementiassa TMK:sta on julkaistu ainoastaan yksittäisiä tutkimuksia ja tulokset ovat olleet osin ristiriitaisia. Väitöskirjatutkimuksen tarkoituksena on ollut selvittää valve-lepotilan hermoverkossa ja olennaisen tunnistavassa hermoverkossa tapahtuvia muutoksia otsalohkodementiaa sairastavilla potilailla. Toisena tavoitteena on ollut tutkia muissa kognitiivisissa hermoverkoissa tapahtuvia muutoksia. Otsalohkodementiaa sairastaville potilaille (n= 26) sekä ikä- ja sukupuolivakioiduille kontrolleille on tehty kliininen tutkimus ja rakenteellinen sekä toiminnallinen aivojen magneettikuvaus. Kahdeksalla potilaalla todettiin C9ORF72-toistojaksomutaatio. Useiden kognitiivisten hermoverkkojen toiminnassa havaittiin muutoksia, jotka korreloivat potilaiden kliinisiin oireisiin. Alentunutta konnektiviteettia todettiin olennaisen tunnistavassa hermoverkossa, joka osallistuu käyttäytymisen säätelyyn. Lisääntynyttä konnektiviteettia esiintyi valve-lepotilan hermoverkossa ja tarkkaavaisuus hermoverkossa. Potilailla, joilla on C9ORF72-mutaatio, havaittiin epänormaali yhteys valve-lepotilan hermoverkon ja talamuksen välillä. TMK:ta käytetään tällä hetkellä lähinnä tutkimustyökaluna. Analyysityökaluissa on ollut vaihtelevuutta eri julkaisuissa ja osin myös tämän väitöskirjan osatöissä. Julkaistut TMK-löydökset otsalohkodementiassa ovat osin ristiriitaisia ja se saattaa selittyä erilaisilla analyysimenetelmillä. Metodologiaa tulisi standardisoida ja lisäksi tarvitaan suurempia potilasryhmiä ja menetelmien kehittämistä, jotta TMK:n käyttö yksilötason kliinisessä diagnostiikassa olisi jatkossa mahdollista
15
Ferrari, R. "Genetic analysis of frontotemporal dementia and progressive supra nuclear palsy." Thesis, University College London (University of London), 2014. http://discovery.ucl.ac.uk/1429248/.
Full textAbstract:
Genome-wide association study (GWAS) is an effective method for mapping genetic variants underlying common and complex diseases. This thesis describes the investigation of the disorders, frontotemporal dementia (FTD) and progressive supranuclear palsy (PSP). FTD affects the frontal/temporal lobes and presents behavioural changes (bvFTD), cognitive decline or language dysfunction (primary progressive aphasia [PPA]), whilst PSP affects predominantly the brain stem resulting in loss of balance, falls, and parkinsonian signatures. Beside recent advancements in the understanding of the clinical and neuropathological characteristics as well as the genetics associated with these diseases, their underlying pathogenic mechanisms are still unclear. The main aims of the work in this thesis were to perform a complete GWAS on clinical FTD and a follow up targeted study of new loci identified in the recent PSP-GWAS in a cohort of ~100 pathologically confirmed PSP cases. By completing these projects the main expected outcomes were to: 1 – Identify novel risk loci associated with FTD, and; 2 – Identify SNPs and haplotypes associated with increased risk of developing PSP and genetic variants possibly affecting expression and/or splicing of transcription elements relevant to PSP.
16
Borger, Eva. "New intracellular mechanisms involved in Alzheimer's disease and frontotemporal dementia." Thesis, University of St Andrews, 2012. http://hdl.handle.net/10023/3092.
Full textAbstract:
Dementia causes an increasing social and economic burden worldwide, demanding action regarding its diagnosis, treatment and everyday management. Recent years have seen many advances in neurodegeneration research, but the search for new truly disease modifying therapies for Alzheimer's disease (AD) and frontotemporal dementia (FTD) has so far not been successful. This is mainly due to a lack of understanding of the precise intracellular events that lead up to neuronal dysfunction in early and in late stages of the disease. This thesis describes the approaches taken to extend the current knowledge about the intracellular effects of neuronal amyloid-beta and the signalling pathways causing neuronal death or disturbed synaptic function in dementia. Endophilin-1(Ep-1), amyloid-binding alcohol dehydrogenase (ABAD), peroxiredoxin-2 (Prx-2) and the EF-hand domain family, member D2 (EFHD2) have been found to be elevated in the human brain with dementia and in mouse models for frontotemporal lobar degeneration (FTLD) or AD. The expression of these proteins as well as the expression of c-Jun N-terminal kinase (JNK), c-Jun and APP were analysed by western blotting and real-time PCR in human brains affected by AD or FTLD as well as in mouse models for AD. This provided a new insight into the regulation of these proteins in relation to each other in the ageing brain and uncovered a new potential link between elevated levels of EFHD2, Prx-2 and APP in FTLD. By studying the effects of the overexpression of Ep-1 in neurons, this research has led to a better understanding of its role in JNK-activation. It furthermore verified a protective role for Prx-2 against neurotoxicity and pointed towards a new function for Prx-2 in the regulation of JNK-signalling. The analysis of the effect of increased levels of EFHD2 uncovered for the first time its involvement in the PI3K-signalling cascade in neuronal cells. The current work has therefore contributed to the knowledge about the cellular processes that are affected by Ep-1, Prx-2 and EFHD2 in different types of dementia and will greatly benefit future research into their actions in the neuronal network.
17
Long, Zhe. "Frontotemporal Dementia-Motor Neuron Disease: disease continuum or distinct entity?" Thesis, University of Sydney, 2020. https://hdl.handle.net/2123/23012.
Full textAbstract:
Frontotemporal dementia-motor neuron disease (FTD-MND) is a rare disease characterised by the simultaneous occurrence of FTD and MND. Clinical, pathological, and genetic investigations have highlighted the association between FTD and MND, but much remains unclear. The experimental studies of this thesis comprehensively and systematically investigate the natural history of cognition and behaviour in FTD-MND and explore whether FTD-MND is distinct from well-recognised FTD phenotypes using clinical, neuropsychological and multimodal neuroimaging analyses. Results arising from two separate studies (Chapters 3 and 4) reveal that the majority of FTD-MND presents with variable combinations of behaviour, language and motor deficits initially, and fulfil FTD-MND diagnosis within 24 months from symptom onset. Heterogenous deficits persist even after meeting FTD-MND diagnostic criteria. Clinical heterogeneity in FTD-MND, highlighted by using a data-driven approach, may reflect variable white matter tract involvement. Language impairment in FTD-MND is highly prevalent, and more mixed than in FTD language phenotypes. The frequency and severity of behavioural and language deficits in FTD-MND lie between that of FTD phenotypes. Over time (Chapter 5), cognition and language deficits progress more rapidly in FTD-MND than bvFTD. Progression in FTD-MND may be driven by left inferior frontal gyrus and anterior temporal lobe involvemeny. Survival in FTD-MND is much shorter than in FTD, despite a similar age at onset. Motor neuron dysfunction may be highly specific for frontotemporal lobar degeneration TAR DNA binding protein 43 kDa (FTLD-TDP, Chapter 6), but the current FTLD-TDP pathological staging scheme may not correlate with clinical progression. These findings demonstrate that FTD-MND is distinct from, rather than simply a later clinical stage of, FTD.
18
Peters, Frédéric, Daniela Perani, Karl Herholz, Vjera Holthoff, Bettina Beuthien-Baumann, Sandro Sorbi, Alberto Pupi, et al. "Orbitofrontal Dysfunction Related to Both Apathy and Disinhibition in Frontotemporal Dementia." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-135825.
Full textAbstract:
Orbitofrontal metabolic impairment is characteristic of the frontal variant of frontotemporal dementia (fv-FTD), as are early changes in emotional and social conduct. Two main types of behavioral disturbances have been distinguished in fv-FTD patients: apathetic and disinhibited manifestations. In this study, we searched for relationships between brain metabolism and presence of apathetic or disinhibited behavior. Metabolic activity and behavioral data were collected in 41 fv-FTD patients from European PET centers. A conjunction analysis of the PET data showed an expected impairment of metabolic activity in the anterior cingulate, ventromedial and orbital prefrontal cortex, the dorsolateral prefrontal cortex and the left anterior insula in fv-FTD subjects compared to matched controls. A correlation was observed between disinhibition scores on the Neuropsychiatric Inventory scale and a cluster of voxels located in the posterior orbitofrontal cortex (6, 28, –24). Comparison of brain activity between apathetic and nonapathetic fv-FTD patients from two centers also revealed a specific involvement of the posterior orbitofrontal cortex in apathetic subjects (4, 22, –22). The results confirm that the main cerebral metabolic impairment in fv-FTD patients affects areas specializing in emotional evaluation and demonstrate that decreased orbitofrontal activity is related to both disinhibited and apathetic syndromes in fv-FTDDieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich
19
Chen, Yu. "Cerebellar contributions to cognitive changes in frontotemporal dementias." Thesis, The University of Sydney, 2020. https://hdl.handle.net/2123/21825.
Full textAbstract:
Mounting evidence indicates that the impact of cerebellar damage extends beyond motor function, and also affects cognition. Frontotemporal dementia (FTD) is associated with heterogeneous patterns of cortical atrophy, primarily affecting the frontal and/or temporal lobes. Previous research has also found cerebellar changes in FTD. The cognitive role of the cerebellum in FTD, however, remains unclear. This thesis, therefore, examines cerebellar contributions to cognitive changes using a combination of behavioural and neuroimaging approaches in the three main FTD subtypes, each with distinct clinical cognitive profiles: behavioural-variant FTD (bvFTD), semantic dementia (SD), and progressive nonfluent aphasia (PNFA). The results from this thesis demonstrated that the cerebellum is affected in all the three FTD subtypes, with syndrome-specific patterns of cerebellar changes across subtypes (Chapters 2, 4-6). These cerebellar changes are associated with cognitive performance in FTD. Novel evidence of an independent cerebellar contribution and an interaction between the cerebellum and the cerebrum, and their relations with cognition in FTD subtypes are also reported (Chapters 4-7). Importantly, cerebellar atrophy progresses over time and is associated with cognitive decline with disease progression (Chapter 6). The expansion of GGGGCC hexanucleotide repeat in the non-coding intronic region of the chromosome 9 open reading frame 72 gene (C9orf72) is the most common genetic cause of familial FTD. Comparison between FTD patients with and without C9orf72 gene expansion revealed distinct patterns of cerebellar grey matter atrophy between groups, and this cerebellar atrophy is differentially associated with cognitive performance (Chapter 7). Together, the results of this thesis uncover syndrome-specific cerebellar changes across FTD syndromes, which in turn relate to discrete cognitive dysfunctions. These findings extend the understanding of the cerebellum and point to its involvement across an array of processes beyond the domain of motor function. From a clinical perspective, these novel findings bring new insights into the mechanisms mediating FTD symptomatology, and have important implications for disease management, intervention and wellbeing for both patients and carers.
20
Peters, Frédéric, Daniela Perani, Karl Herholz, Vjera Holthoff, Bettina Beuthien-Baumann, Sandro Sorbi, Alberto Pupi, et al. "Orbitofrontal Dysfunction Related to Both Apathy and Disinhibition in Frontotemporal Dementia." Karger, 2006. https://tud.qucosa.de/id/qucosa%3A27680.
Full textAbstract:
Orbitofrontal metabolic impairment is characteristic of the frontal variant of frontotemporal dementia (fv-FTD), as are early changes in emotional and social conduct. Two main types of behavioral disturbances have been distinguished in fv-FTD patients: apathetic and disinhibited manifestations. In this study, we searched for relationships between brain metabolism and presence of apathetic or disinhibited behavior. Metabolic activity and behavioral data were collected in 41 fv-FTD patients from European PET centers. A conjunction analysis of the PET data showed an expected impairment of metabolic activity in the anterior cingulate, ventromedial and orbital prefrontal cortex, the dorsolateral prefrontal cortex and the left anterior insula in fv-FTD subjects compared to matched controls. A correlation was observed between disinhibition scores on the Neuropsychiatric Inventory scale and a cluster of voxels located in the posterior orbitofrontal cortex (6, 28, –24). Comparison of brain activity between apathetic and nonapathetic fv-FTD patients from two centers also revealed a specific involvement of the posterior orbitofrontal cortex in apathetic subjects (4, 22, –22). The results confirm that the main cerebral metabolic impairment in fv-FTD patients affects areas specializing in emotional evaluation and demonstrate that decreased orbitofrontal activity is related to both disinhibited and apathetic syndromes in fv-FTD.Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.
21
Dols, Icardo Oriol 1987. "Assessing the genetic overlap in amyotrophic lateral sclerosis and frontotemporal dementia." Doctoral thesis, Universitat Pompeu Fabra, 2016. http://hdl.handle.net/10803/523545.
Full textAbstract:
There are overwhelming evidences that amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are part of a clinical, pathological and genetic continuum. The C9orf72 repeat expansion is the most common genetic defect among ALS/FTD patients. Besides, the use of next generation sequencing technologies has launched a new era in the study of human diseases. These approaches have unraveled an unprecedented amount of genes associated with both ALS and FTD. This work focuses on the study of the genetic overlap in the ALS/FTD spectrum. In this context, we have studied the C9orf72 expansion mutation in ALS and FTD patients. Also, we have assessed the role of CHCHD10 and TUBA4A, two genes recently found to cause ALS, in Spanish patients with ALS and/or FTD. Finally, we have performed whole-exome sequencing in ALS/FTD patients without the C9orf72 expansion mutation to study the genetic profile of these cases free from the most common genetic defect related to these neurodegenerative disorders.Una gran quantitat d’evidències suggereixen que l’esclerosi lateral amiotròfica (ELA) i la demència frontotemporal (DFT) formen part d’un contínuum clínic, patològic i genètic. L’expansió d’un hexanucleòtid al gen C9orf72 és l’alteració genètica més freqüent en els pacients amb ELA/DFT. L’ús de les tecnologies d’ultraseqüenciació ha iniciat una nova era en l’estudi de les malalties humanes. Aquests mètodes han permès el descobriment d’una gran quantitat de gens associats a l’ELA i la DFT. Aquesta tesi se centra en estudiar el contínuum genètic en l’espectre ELA/DFT. Així doncs, s’ha estudiat el paper de l’expansió de l’hexanucleòtid a C9orf72 en pacients amb ELA i DFT. També s’ha estudiat el rol dels gens CHCHD10 i TUBA4A, dos gens que recentment s’ha demostrat que causen ELA, en pacients espanyols amb ELA i/o DFT. Finalment, l’exoma de pacients amb ELA/DFT no portadors de l’expansió a C9orf72 s’ha seqüenciat per tal d’estudiar el component genètic associat a l’espectre ELA/DFT lliures de l’alteració genètica més comuna.
22
Rigg, Zoe M. "Exploring the emotional impact and adjustment in frontotemporal dementia family carers." Thesis, Canterbury Christ Church University, 2016. http://create.canterbury.ac.uk/15160/.
Full textAbstract:
Behavioural variant frontotemporal dementia (bv-FTD) is a rare form of the condition which manifests in personality and behavioural changes. Literature has indicated that this is a particularly challenging condition for family carers. Research has begun to explore the qualitative experiences of this group of carers, but is limited to date. The current study aimed to further explore these experiences with an emphasis on how these carers learn to adjust and accept their situation. Grounded theory methodology was adopted to analyse semi-structured interviews with 12 spousal carers (2 were male). A theoretical model is proposed to describe the carer journey and cyclical adjustment process within the progressive context of bv-FTD. This model implies that early stages in the process, including pre-investigation, as well as a number of mediating factors, including the carer’s own past experiences, influence the adjustment process. There is a continuous cycle of adjustment for these carers. These findings add to the existing research base by considering different stages of the adjustment process and linking themes together for a better understanding of the experiences.
23
Ingelson, Martin. "Molecular aspects of tau proteins in Alzheimer's disease and frontotemporal dementia /." Stockholm, 2001. http://diss.kib.ki.se/2001/91-628-4904-2/.
Full text
24
Downey, L. E. "Defining the neuropsychological and neuroimaging phenotype of behavioural variant frontotemporal dementia." Thesis, University College London (University of London), 2014. http://discovery.ucl.ac.uk/1437738/.
Full textAbstract:
Frontotemporal dementia (FTD) is the second most common cause of early-onset dementia after Alzheimer’s disease (AD). There exists a paucity of quantifiable, sensitive, and specific biomarkers to detect this disease and track its manifestation and progression. The primary aim of this thesis was to develop and investigate new biomarkers for FTD, and focused on the examination of neuropsychological biomarkers in the behavioural variant of FTD (bvFTD) and their neuroanaotmical correlates. Chapters 4 and 5 explored social cognition in patients with FTD and the neural correlates of this behaviour. bvFTD patients displayed gross dysfunction in the perception of sarcasm and the ability to understand basic social signals, and this mapped onto a larger social cognition neural network that has previously been defined in the literature. These findings delineate a brain network substrate for the social impairment that characterises FTD syndromes. In Chapters 6 and 7, I explored the executive functions of task switching, reaction time, and neural timing in patients with FTD. Results indicated several dissociable executive capacities, which mapped onto discrete neural areas as part of a larger executive function network, suggesting that structures implicated in aspects of executive functioning can be targeted by FTD and may underpin aspects of the bvFTD phenotype. In the final Chapter, I devised a novel battery to examine the bases of psychosis in FTD patients with the C9ORF72 mutation, which demonstrated a specific and unique impairment in the ability to interpret somatosensory proprioceptive information in these patients, which may represent a candidate mechanism for psychosis. The studies described in this thesis contribute to the growing interest in characterising and understanding the neuropsychological phenotypes of bvFTD. Improved understanding of the anatomical associations of neuropsycholgical performance in this patient population could potentially facilitate earlier and more accurate diagnosis and symptom management.
25
Mathieson, Danielle Ilene, and Danielle Ilene Mathieson. "Developing and Characterizing a TDP-43 Drosophila Model of Frontotemporal Dementia." Thesis, The University of Arizona, 2017. http://hdl.handle.net/10150/625083.
Full textAbstract:
Frontotemporal Dementia (FTD) is a progressive neurodegenerative disease that is
characterized by intraneuronal protein aggregates. In 45% of FTD cases, these intracellular
inclusions contain TAR-DNA binding protein (TDP-43). Though many animal models of
FTD exist, none have been generated in Drosophila melanogaster through TDP-43
overexpression that recapitulate learning and memory deficits found in late stages of the
disease. In an attempt to develop such a model, we overexpressed TDP-43 and disease-associated
mutant variants in the mushroom bodies of the fly. Their learning and memory
was tested using a courtship assay that measures conditioned decreases in male courtship
behavior after experience with an unreceptive female. Subsequent courtship behavior with
a receptive female was also measured. TDP-43 expressing flies did not show significant
differences from controls in their courtship behavior with the unreceptive female, but all
genotypes and ages showed a reduction in courtship when paired with the receptive
female. Differences in courtship behavior between flies that subsequently mated with the
receptive female and those that did not were also found. This suggests that genetic
background of the transgenic flies and the behavior of the receptive female have profound
effects on the courtship behavior of male Drosophila.
26
Katzeff, Jared. "Understanding immune pathways altered in frontotemporal dementia and amyotrophic lateral sclerosis." Thesis, The University of Sydney, 2021. https://hdl.handle.net/2123/25450.
Full textAbstract:
Frontotemporal dementia (FTD) is a neurodegenerative disease characterised by behaviour and language alterations. The major subtype is behavioural variant FTD (bvFTD). Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease characterised by muscle wasting. FTD and ALS are considered to be on the same disease spectrum, because of overlapping genetic, pathological and clinical traits. Increasing evidence suggests that neuroinflammation is a key aspect of both bvFTD and ALS pathogenesis. Currently, there are no definitive biomarkers for diagnosing either disease. The aims of this project were to understand immune pathways altered in FTD and ALS, and to identify proteins that can be used to develop biomarkers for the two diseases. We used multimodal techniques in molecular biology and proteomics to assess mRNA and protein changes in serum and brain tissues. A proteomics analysis identified 23 proteins altered in bvFTD and 14 proteins altered in ALS, with many of these proteins relating to innate immunity and calcium-related functions. A cytokine screen identified two cytokines (GRO- and IL-18) that were altered in both serum and brain tissue samples. Finally, expression analysis of brain tissues revealed that ABCA4 and ABCA13 were altered in FTD, both of which correlated strongly with microglial marker expression. This study represents the first proteomics side-by-side comparison of serum changes in FTD and ALS, providing new insights into under-recognised perturbed pathways and an avenue for biomarker development for FTD and ALS.
27
O'Connor, Claire Marie. "Understanding behaviour and function in frontotemporal dementia: developing better intervention approaches." Thesis, The University of Sydney, 2017. http://hdl.handle.net/2123/16899.
Full textAbstract:
Frontotemporal dementia (FTD) is the second most common younger onset dementia after Alzheimer’s disease, and comprises three primary clinical variants: behavioural variant (bvFTD), and two language variants divided according to the pattern of language deterioration: non-fluent primary progressive aphasia (nfvPPA) and semantic variant primary progressive aphasia (svPPA). FTD is associated with marked behavioural symptoms and impairments to everyday function in activities of daily living, which are both included as markers of disease progression in clinical and in research settings. Despite this, the relationship between these two significant variables remains unknown. The relationship between behavioural symptoms and functional impairments in FTD is addressed in this thesis. Further to this, the implications of these symptoms are explored in the context of providing a tailored non-pharmacological intervention to an FTD cohort. In order to achieve these objectives, a series of five studies were undertaken. The first study investigated the relationship between behavioural changes, cognitive symptoms, and functional disability in the primary progressive aphasias. This study showed similar functional abilities in people with svPPA and nfvPPA, but differing patterns of behavioural symptoms, and different factors contributing to their functional impairments. The second study explored the longitudinal relationship between behaviour and function in bvFTD and svPPA. While bvFTD was more functionally impaired, both groups shared overlapping baseline behavioural symptoms. Apathy was a strong contributor to functional decline in both groups, whereas stereotypical behaviours only contributed for bvFTD. The third study built on these findings by identifying four distinct behavioural phenotypes of bvFTD (based on levels of apathy and disinhibition), with differing patterns of functional decline and brain atrophy. The final two studies pertained to the implementation of the Tailored Activity Program (TAP) with a cohort of people with FTD and their carers. TAP is an occupational therapy based intervention that involves working collaboratively with carers and using tailored activities to engage the person with dementia. The feasibility and acceptability of this intervention is described, highlighting the importance for further and rigorous intervention trials in FTD. Finally, two case studies are presented, which demonstrate the applicability of TAP for people with FTD. The studies presented in this thesis shed light on the role of behavioural symptoms in the functional impairments seen in FTD, and provide support for the use of TAP as an intervention approach for people with FTD. These outcomes provide important data to contribute to the development of better management and intervention approaches within the FTD spectrum.
28
Kmetzsch, Virgilio. "Multimodal analysis of neuroimaging and transcriptomic data in genetic frontotemporal dementia." Electronic Thesis or Diss., Sorbonne université, 2022. https://accesdistant.sorbonne-universite.fr/login?url=https://theses-intra.sorbonne-universite.fr/2022SORUS279.pdf.
Full textAbstract:
La démence frontotemporale (DFT) représente le deuxième type de démence le plus fréquent chez les adultes de moins de 65 ans. Il n’existe aucun traitement capable de guérir cette maladie. Dans ce contexte, il est essentiel d’identifier des biomarqueurs capables d’évaluer la progression de la maladie. Cette thèse a deux objectifs. Premièrement, analyser les profils d’expression des microARNs circulants prélevés dans le plasma sanguin de participants, afin d’identifier si l’expression de certains microARNs est corrélée au statut mutationnel et à la progression de la maladie. Deuxièmement, proposer des méthodes pour intégrer des données transversales de type microARN et de neuroimagerie pour estimer la progression de la maladie. Nous avons mené trois études. D’abord, nous avons analysé des échantillons de plasma provenant de porteurs d’une expansion dans le gène C9orf72. Ensuite, nous avons testé toutes les signatures de microARNs identifiées dans la littérature comme biomarqueurs potentiels de la DFT ou de la sclérose latérale amyotrophique (SLA), dans deux cohortes indépendantes. Enfin, dans notre troisième étude, nous avons proposé une nouvelle méthode, utilisant un autoencodeur variationnel multimodal supervisé, qui estime à partir d’échantillons de petite taille un score de progression de la maladie en fonction de données transversales d’expression de microARNs et de neuroimagerie. Les travaux menés dans cette thèse interdisciplinaire ont montré qu’il est possible d’utiliser des biomarqueurs non invasifs, tels que les microARNs circulants et l’imagerie par résonance magnétique, pour évaluer la progression de maladies neurodégénératives rares telles que la DFT et la SLAFrontotemporal dementia (FTD) represents the second most common type of dementia in adults under the age of 65. Currently, there are no treatments that can cure this condition. In this context, it is essential that biomarkers capable of assessing disease progression are identified. This thesis has two objectives. First, to analyze the expression patterns of microRNAs taken from blood samples of patients, asymptomatic individuals who have certain genetic mutations causing FTD, and controls, to identify whether the expressions of some microRNAs correlate with mutation status and disease progression. Second, this work aims at proposing methods for integrating cross-sectional data from microRNAs and neuroimaging to estimate disease progression. We conducted three studies. Initially, we focused on plasma samples from C9orf72 expansion carriers. We identified four microRNAs whose expressions correlated with the clinical status of the participants. Next, we tested all microRNA signatures identified in the literature as potential biomarkers of FTD or amyotrophic lateral sclerosis (ALS), in two groups of individuals. Finally, in our third work, we proposed a new approach, using a supervised multimodal variational autoencoder, that estimates a disease progression score from cross-sectional microRNA expression and neuroimaging datasets with small sample sizes. The work conducted in this interdisciplinary thesis showed that it is possible to use non-invasive biomarkers, such as circulating microRNAs and magnetic resonance imaging, to assess the progression of rare neurodegenerative diseases such as FTD and ALS
29
Silva, Thais Bento Lima da. "Validação da escala de estadiamento e progressão da demência frontotemporal (FTD-FRS)." Universidade de São Paulo, 2018. http://www.teses.usp.br/teses/disponiveis/5/5138/tde-09052018-111153/.
Full textAbstract:
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 DFTIntroduction: 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
30
Skoglund, Lena. "Molecular Mechanisms of Frontotemporal Lobar Degeneration." Doctoral thesis, Uppsala universitet, Institutionen för folkhälso- och vårdvetenskap, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-9550.
Full textAbstract:
The aim of this thesis was to identify genetic factors involved in frontotemporal lobar degeneration (FTLD), a neurodegenerative disorder clinically characterised by a progressive change in personality, behaviour and language. FTLD is a genetically complex disorder and a positive family history is found in up to 40% of the cases. In 10-20% of the familial cases the disease can be explained by mutations in the gene encoding the microtubule associated protein tau (MAPT). In the first study we describe the clinical and neuropathological features of a Finnish family with FTLD caused by a mutation in MAPT. We also provide evidence that the pathogenic mechanism of this mutation is through altered splicing of MAPT transcripts. Recently, mutations in the gene encoding progranulin (PGRN) were identified as a major cause of FTLD. In the second study we describe a Swedish family with FTLD caused by a frameshift mutation in PGRN. We provide a clinical and neuropathological description of the family, as well as evidence that the pathogenicity of this mutation is through nonsense-mediated decay of the mutant mRNA transcripts and PGRN haploinsufficiency. In the third study we describe a novel PGRN splice site mutation and a previously described PGRN frameshift mutation, found in a mutation screen of 51 FTLD patients. We describe the clinical and neuropathological characteristics of the mutation carriers and demonstrate that haploinsufficiency is the pathogenic mechanism of the two mutations. In the fourth study we investigate the prevalence of PGRN and MAPT gene dosage alterations in 39 patients with FTLD. No gene dosage alterations were identified, indicating that variations in copy number of the PGRN and MAPT genes are not a common cause of disease, at least not in this FTLD patient collection.
31
Suárez, Calvet Marc. "Degeneració lobular frontotemporal: estudi clínic, neuropatològic i de biomarcadors." Doctoral thesis, Universitat Autònoma de Barcelona, 2016. http://hdl.handle.net/10803/398996.
Full textAbstract:
La present tesi té com a objectiu estudiar des de diferents punts de vista la degeneració lobular frontotemporal (FTLD), una malaltia neurodegenerativa que es caracteritza per la pèrdua neuronal focal en els lòbuls frontals i temporals. Aquesta malaltia és molt heterogènia des del punt de vista clínic, neuropatològic i genètic, com també en els mecanismes patogènics. Aquesta heterogeneïtat fa que sovint el diagnòstic no sigui fàcil i que la seva classificació nosològica i la recerca en els seus mecanismes sigui especialment complexa. En aquesta tesi s’aborda aquesta heterogeneïtat estudiant diferents aspectes de la FTLD.
Primer, s’estudia la FTLD des de un punt de vista clínic: s’avaluen els nous criteris de la variant conductual d’aquesta malaltia (bvFTD) en la cohort de pacients seguits a la Unitat de Memòria de l'hospital de la Santa Creu i Sant Pau. Des del punt de vista genètic, es caracteritzen aspectes clínics i radiològics específics dels casos de FTLD que presenten una expansió de la repetició d’hexanucleòtids en el gen C9orf72. Seguidament, des del punt de vista dels biomarcadors, es mesura en sang i líquid cefaloraquidi la proteïna TDP-43 i la seva forma fosforilada (pTDP-43). En l’últim capítol, s’aprofundeix en els mecanismes moleculars de la patogènia de la FTLD amb dipòsits de proteïnes FUS i FET (FTLD-FET), s’estudien la metilació en les arginines presents en aquests proteïnes i com aquest canvi postraduccional regula el transport citoplasma-nucli de la proteïna FUS. Finalment, es realitza un estudi neuropatològic a on es comparen les diferències en el patró de metilació de la proteïna FUS entre la FTLD-FET i la esclerosi lateral amiotròfica amb mutacions en el gen de FUS (ALS-FUS). Aquest estudi afegeix una nova diferència entre la FTLD-FET i la ALS-FUS, tot i que ambdues comparteixen els dipòsits de la proteïna FUS.The aim of the present thesis is to study frontotemporal lobar degeneration (FTLD), a neurodegenerative disease characterised by a focal neural loss in the frontal and the temporal lobes, from different perspectives. FTLD is a very heterogeneous disease either from the clinical or the neuropathological, genetic and pathogenic perspectives. This heterogeneity makes its diagnosis challenging and its nosologic classification and pathogenesis research especially puzzling. In the present thesis, this heterogeneity is addressed through studying FTLD from different angles. First, FTLD is investigated from a clinical viewpoint: the most recent clinical criteria about the behavioural variant of FTLD (bvFTD) are evaluated through the cohort of patients followed in the Memory Unit of Hospital de la Santa Creu i Sant Pau. From a genetic perspective, specific clinical and radiological features of the FTLD patients carrying a hexanucleotide repeat expansion in the C9orf72 gene are defined. Next, and from a biomarkers angle, TDP-43 protein and its phosphorylated form (pTDP-43) are measured in blood and in cerebrospinal fluid (CSF). In the last chapter, the molecular pathogenic mechanisms of FTLD with FUS- and FET-positive inclusions (FTLD-FET) are scrutinized, in order to study the methylation pattern of the arginines present in FUS protein and how this posttranslational modification regulates the cytoplasmic-nuclear transport. Finally, a neuropathological study is performed by means of the comparison of the differences in FUS methylation pattern between FTLD-FET and amyotrophic lateral sclerosis with FUS mutations (ALS-FUS). This study provides further evidence of the differences between FTLD-FET and ALS-FUS, despite the fact that both diseases share the deposition of the protein FUS.
32
Elfgren, Christina I. "Aspects of frontal and medial temporal brain functions neuropsychological and functional imaging studies in normals and in frontotemporal dementia /." Lund : Dept. of Psychology, University of Lund, and Dept. of Psychogeriatrics, University Hospital, 1997. http://books.google.com/books?id=EuZqAAAAMAAJ.
Full text
33
Froelich, Fabre Susanne. "Genetic studies of frontotemporal dementia : with particular emphasis on the tau gene /." Stockholm, 2001. http://diss.kib.ki.se/2001/91-628-4714-7/.
Full text
34
Heyanka, Daniel. "Lateralized and Overall Olfactory Identification Ability in Frontotemporal Dementia and Alzheimer's Disease." NSUWorks, 2010. http://nsuworks.nova.edu/cps_stuetd/38.
Full textAbstract:
This research involves an examination of the olfactory ability of individuals with Frontotemporal Dementia, Alzheimer's disease, and geriatric individuals with cognitive complaints owing to Major Depressive Disorder or Generalized Anxiety Disorder. The purpose of this study was to determine if olfactory differences were useful in differentiating between demented and non-demented individuals. Due to the pathway of the olfactory tract, it can be expected that there would be equal olfactory deficits in those diagnosed with Frontotemporal Dementia and Alzheimer's disease, and that these deficits would be worse than those found in geriatric individuals with Major Depressive Disorder or Generalized Anxiety Disorder. Five hypotheses were investigated. The first utilized an ANCOVA and found that the olfaction of the demented group was worse than that of the non-demented, psychiatric group. The second utilized a series of Discriminant Function Analyses and F-tests and determined that olfaction best classified demented and non-demented individuals. The third implemented a Mixed Model ANOVA to assess for lateralized smell deficits within the demented group and between the demented and non-demented groups and found no main effects of lateralization or interaction effects. The fourth hypothesis investigated the relationship between smell and commonly used neuropsychological tests in a Frontotemporal Dementia sample, and found that there was no difference between the relationship of tests measuring the frontal and temporal lobes to those measuring other cerebral areas. The fifth hypothesis replicated Hypothesis 4 in an Alzheimer's disease sample and found that there was a significant difference between the relationship of tests measuring the frontal and temporal lobes to those measuring other cerebral areas. Primarily, this study demonstrated that dementia patients present with significantly more olfactory deficits than a psychiatric sample with subjective cognitive complaints. Additionally, olfaction correctly distinguished the Dementia Group from the Psychiatric Group with 81.6% accuracy, 90.2% sensitivity and 67.6% specificity. Alone, these classification statistics are quite impressive, appearing equivalent, or possibly superior to the classification statistics of commonly used neuropsychological tests of memory, executive functioning, and visuospatial ability. This study concluded that adding an olfactory measure to an assessment battery provides clinically relevant data, and enhances the diagnostic accuracy of the battery. However, though this study found the Alberta Smell Test was a valuable addition to a test battery, the absence of lateralized findings demonstrated the unirhinal format, by which the Alberta Smell Test is administered, does not provide diagnostically relevant information above and beyond the information a clinician will gain from birhinal assessment.
35
Roche, Lauren. "Frontotemporal dementia and primary progressive aphasia caregivers: coping, caregiving appraisals and wellbeing." Thesis, The University of Sydney, 2014. http://hdl.handle.net/2123/13367.
Full textAbstract:
Frontotemporal Lobar Degeneration (FTLD) is a neurodegenerative disease with younger-onset, characterised by behavioural and/or language decline known as frontotemporal dementia (FTD) and primary progressive aphasia (PPA) respectively. Those caregiving for persons with FTD and PPA arguably appraise their caregiving role and adopt coping strategies unique to the syndrome. The aim of this thesis was to investigate the appraisals, coping strategies and psychological wellbeing of FTD/PPA caregivers. A systematic review (Study 1) found no caregiver or care-recipient characteristics were reliably predictive of dementia caregivers’ adoption of solution-focused, emotional support/acceptance-based or dysfunctional coping strategies. Study 2 found the effect of care-recipients’ care needs on FTD caregivers’ wellbeing depended on caregiver appraisals of strain. Use of dysfunctional coping strategies and fewer financial resources contributed to high levels of caregiver strain, which in turn predicted reduced QoL. Caregivers’ use of dysfunctional coping as a response to their strain increased levels of depression, while problem-focused coping strategies increased their QoL. Study 3 found PPA severity was not predictive of caregiver satisfaction or psychological wellbeing. Caregivers’ appraisal of satisfaction was not related to coping strategies, caregiver depression and positive affect, nor did satisfaction act as a mediator of PPA severity and psychological wellbeing. Rather, problem-focused coping uniquely predicted reduced caregiver depression. Younger PPA caregivers were at risk of adopting more dysfunctional coping strategies. This thesis highlights that the coping strategies adopted by FTD and PPA caregivers influence their caregiving appraisals and psychological wellbeing. As coping strategies are amenable to change and were central to the psychological wellbeing of both FTD and PPA caregivers, coping strategies ought to be a focus of intervention in this population.
36
Liu, Lulu. "Temporal cognition: subjective time and its connection with memory in frontotemporal dementia." Thesis, The University of Sydney, 2022. https://hdl.handle.net/2123/27780.
Full textAbstract:
Although ubiquitous and central to everyday life, how humans apprehend, experience, and mentally navigate time remains poorly understood. This thesis aimed to explore subjective time in healthy ageing, as well as pathological ageing, frontotemporal dementia (FTD), namely, behavioural-variant frontotemporal dementia (bvFTD), semantic dementia (SD) and progressive nonfluent aphasia (PNFA), to determine profiles and neural correlates of subjective time in older adults and dementia syndromes, and to reveal how subjective time alterations potentially relate to everyday memory impairments across syndromes.
Employing multiple time perception tasks, Chapters 3 and 4 reveal compromised subjective time in healthy ageing and bvFTD but intact performance in language variants of FTD (a combination of SD and PNFA). Time perception in FTD relates to grey matter density decrease in predominantly frontoinsular brain regions and the basal ganglia (i.e., putamen and caudate), as well as decreased functional connectivity of the frontoparietal network and salience network. Furthermore, Chapter 5 demonstrates past- and future-oriented memory disturbances in both Alzheimer’s disease (AD) and bvFTD, rather than SD and PNFA, with neuroimaging analyses suggesting the role of the orbitofrontal cortex in everyday memory across past and future contexts in dementia. Taken together, these findings provide novel insights on the complex nature of time perception across healthy ageing and pathological ageing, with the potential to inform the characterisation and management of FTD.
37
Skibinski, Gaia. "Mutations in the ESCRTIII endosomal complex protein CHMP2B associate with frontotemporal dementia." Thesis, University College London (University of London), 2005. http://discovery.ucl.ac.uk/1446676/.
Full textAbstract:
Frontotemporal dementia (FTD) is a common cause of early onset progressive dementia. FTD is genetically heterogeneous with loci identified at several genomic regions including chromosome 17 and chromosome 9, An autosomal dominant form of FTD had previously been linked to the pericentromeric region of chromosome 3 (FTD3) in a large Danish family. The dementia starts with subtle personality and behaviour changes. The work presented in this thesis aimed to identify the mutant gene causing FTD3. Haplotype analysis was used to narrow the disease locus to between flanking markers, D3S3581 and D3S3690, which span a physical distance of 15.5Mb. Sequence analysis of candidate genes within the disease haplotype identified a mutation in the 3' acceptor splice site of exon 6 of charged multi vesicular body protein 2B (CHMP2B) that segregated with affected FTD3 family members only. This mutation was shown to disrupt RNA processing of CHMP2B resulting in the formation of two aberrant splice variants: Intron5 and CHMP2B?10. The former was the inclusion of the whole of intron 5 into the mRNA whilst the latter was the loss of 10 base pairs at the start of exon 6. Overexpression of the aberrant CHMP2B isoforms in an in vitro cell model showed disruption of the cellular localisation of CHMP2B and the endosomal pathway. Previous work carried out on Vps2, the yeast ortholog of CHMP2B, identified it as one of four proteins that make up the endosomal sorting complex required for transport III (ESCRTIII) complex. The ESCRTIII complex assembles on the endosomal membrane and functions in the formation of multivesicular bodies (MVBs) and the sorting of proteins for degradation, recycling or storage. The identification of mutations in CHMP2B in FTD adds to the growing body of evidence in the literature that supports endosomal dysfunction as an underlying mechanism of neurodegeneration. The work in this study allows diagnostic testing for FTD3 family members and has provided new clues for the understanding of neurodegeneration in FTD and other neurodegenerative diseases.
38
Lima-Silva, Thais Bento. "Funcionalidade e desempenho cognitivo na demência frontotemporal variante comportamental." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/5/5138/tde-25032013-164625/.
Full textAbstract:
Lima-Silva TB. Funcionalidade e desempenho cognitivo na demência frontotemporal variante comportamental. [Dissertação]. São Paulo: Faculdade de Medicina, Universidade de São Paulo, 2012. Resumo Introdução: Existem poucos estudos sobre alterações funcionais na Demência Frontotemporal variante comportamental (DFTvc). Subtipos de demência menos estudados, como a DFTvc, vêm ganhando destaque, por também apresentarem importância epidemiológica. Objetivou-se no presente estudo: 1. Caracterizar o desempenho funcional e cognitivo de pacientes com diagnóstico prévio de DFTvc, atendidos em ambulatórios de Neurologia e Psiquiatria e compará-los a pacientes com Doença de Alzheimer (DA) e controles saudáveis; 2. Examinar a correlação entre o desempenho em escalas funcionais (DAFS-BR, DAD e PFAQ) e o desempenho cognitivo; 3. Avaliar a acurácia diagnóstica da DAFS-BR para a detecção da DFTvc e da DA. Métodos: Participaram 96 indivíduos com idade igual ou superior a 45 anos, com escolaridade formal acima de dois anos. Destes, 31 haviam recebido o diagnóstico de DFTvc, 31 de DA e 34 eram adultos saudáveis pareados aos pacientes com DFTvc e DA para idade e escolaridade. Foram aplicados: questionário sociodemográfico e de variáveis clínicas; Escala de Depressão Geriátrica (Geriatric Depression Scale - GDS) de 15 itens, Escala de Ansiedade Geriátrica (Geriatric Anxiety Inventory - GAI), Addenbrooke Cognitive Examination-Revised (ACE-R) que engloba as questões do Mini Exame do Estado Mental (MEEM), Executive Interview (EXIT-25), Direct Assessment of Functional Status (DAFS-BR). O protocolo dos acompanhantes conteve a Escala Cornell de Depressão em Demência, Pfeffer Functional Activities Questionnaire (PFAQ), Disability Assessment for Dementia (DAD), Inventário Neuropsiquiátrico (NPI) e a Escala de Avaliação Clínica da Demência (CDR). Resultados: Pôde-se observar que o grupo com DFTvc apresentou pior desempenho em Alimentação na DAFS-BR e nos domínios de Iniciação e Planejamento/Organização na DAD, comparado aos idosos com DA, sugerindo que a dependência na DFTvc é mais acentuada. A pontuação mais elevada na PFAQ, sugeriu que a dependência na DFTvc é mais acentuada. Foram encontradas correlações significativas entre o desempenho cognitivo e funcional. Os dados de acurácia para a DAFS-BR sugeriram que a escala pode auxiliar na identificação das demências, apresentando limitações no diagnóstico diferencial entre os subtipos. Considerações finais: Os resultados apresentados sugerem que indivíduos com DFTvc apresentam maior prejuízo funcional, quando comparados com participantes com DA e adultos saudáveis. Os resultados apresentados destacaram a importância da avaliação funcional de pacientes com suspeita de DFTvc, devido à relevância destas alterações para o diagnóstico e manejo clínico deste subtipo de demência.Summary Introduction: There are but a few research studies on functional impairment in behavioral variant Frontotemporal Dementia. Less studied dementia subtypes, such as bvFTD, have been gaining prominence due to their epidemiological significance. The objectives of the present research were to: 1. Characterize the functional and cognitive performance of patients previously diagnosed with bvFTD treated at outpatient clinics of Neurology and Psychiatry, and compare their performance with that of patients with AD and normal controls; 2. Examine the correlation between performance in the functional scales (DAFS-BR, DAD e PFAQ) and cognitive performance; and 3. Evaluate the diagnostic accuracy of the DAFS-BR for detecting bvFTD and AD. Methodology: The sample consisted of 96 individuals aged 45 or older, with at least two years of formal education. Of these, 31 had been diagnosed with bvFTD, 31 with AD, and 34 were healthy adults paired with the patients with bvFTD and AD for age and education. The following instruments were used: sociodemographic and clinical questionnaire; 15-item Geriatric Depression Scale (GDS); Geriatric Anxiety Inventory (GAI); Addenbrooke Cognitive Examination-Revised (ACE-R), which includes the questions of the Mini Mental State Examination (MMSE); Executive Interview (EXIT-25); and the Direct Assessment of Functional Status Revised (DAFS-BR). The protocol for caregivers included the Cornell Scale for Depression in Dementia, Pfeffer Functional Activities Questionnaire (PFAQ), Disability Assessment for Dementia (DAD), Neuropsychiatric Inventory (NPI) and the Clinical Dementia Rating scale (CDR). Results: Individuals in the bvFTD group had lower performance in the ´Eating skills´ item of the DAFS-BR, and in ´Initiation´ and in ´Planning/Organization´ in the DAD, suggesting a higher level of dependence in bvFTD, and Higher scores in the PFAQ suggested that dependence in bvFTD is more pronounced. Significant correlations were found between cognitive and functional performances. The accuracy data for the DAFS-BR indicated that the scale can help identify dementia however, it has limitations in the differential diagnosis among subtypes. Final Considerations: The results suggest that individuals with bvFTD display greater functional impairment when compared to individuals with AD and to healthy adults. These results highlight the importance of assessing functionality status among patients suspected to have bvFTD. These deficits are relevant for the diagnosis and clinical management of this subtype of dementia.
39
Kaivorinne, A. L. (Anna-Lotta). "Frontotemporal lobar degeneration in Finland:molecular genetics and clinical aspects." Doctoral thesis, Oulun yliopisto, 2012. http://urn.fi/urn:isbn:9789526200132.
Full textAbstract:
Abstract Frontotemporal lobar degeneration (FTLD) is the second most common neurodegenerative disease leading to early-onset dementia (< 65 years), next to Alzheimer’s disease. FTLD is substantially a genetic disorder with up to 50% of cases having a positive family history. Mutations in the genes microtubule-associated protein tau (MAPT) and progranulin (PGRN) account for about 10–20% of all cases of FTLD. Hexanucleotide repeat expansion mutation within the gene C9ORF72 has recently been identified as the major cause of FTLD, FTLD with amyotrophic lateral sclerosis (ALS) and pure ALS. During this study, hexanucleotide repeat expansion within the C9ORF72 gene was shown to explain nearly 50% of familial and 30% of all FTLD cases in the Finnish population. Otherwise, the genetic background of Finnish FTLD is largely unknown. The object of the present work was to disentangle the genetic aetiology of FTLD in the Finnish population. We studied a cohort of patients with a clinical diagnosis of FTLD from the province of Northern Ostrobothnia, Finland. Sequencing analysis of the genes MAPT, charged multi-vesicular body protein 2B (CHMP2B) and TAR DNA binding protein (TARDBP) were performed and the MAPT haplotypes were analysed. Correlations between genotype and phenotype were studied in patients with C9ORF72 repeat expansion mutation. C9ORF72 expansion mutation explained nearly 30% of cases of FTLD in our cohort. Concomitant ALS and positive family history of the disease increased the possibility of carrying expanded C9ORF72. The clinical phenotype of C9ORF72 expansion carriers varied at presentation: both behavioural and language variants were detected with or without ALS. The behavioural presentations included prominent psychotic features, although psychiatric presentations were not overrepresented in expansion carriers. No pathogenic mutations were identified in the MAPT, CHMP2B and TARDBP genes in our series of FTLD patients. The H2 MAPT haplotype was associated with FTLD in the series. Our findings emphasise the importance of C9ORF72 expansion mutation in FTLD. While mutations in MAPT and PGRN cause a significant proportion of cases of FTLD worldwide, they seem to be rare causes of FTLD in the Finnish population. Besides being infrequent in other populations, mutations in CHMP2B and TARDBP are rare causes of FTLD in the Finnish population as well. Our findings have clinical implications for recognising phenotypic features characteristic of expanded C9ORF72 as well as for genetic counselling of Finnish patients with FTLD. Even though a considerable proportion of our cases of familial FTLD is caused by the C9ORF72 expansion, over 50 % of our familial cases are without a molecular genetic diagnosis, suggesting that there are other unidentified causal genes to be foundTiivistelmä Otsa-ohimolohkorappeumat on toiseksi yleisin työikäisten dementiaa aiheuttava etenevä aivojen rappeumasairaus. Toisinaan otsa-ohimolohkorappeumat esiintyvät yhdessä liikehermorappeuman, amyotrofisen lateraaliskleroosin (ALS), kanssa. Perinnöllisillä tekijöillä on todennäköisesti keskeinen merkitys taudin taustalla. Mutaatiot microtubule-associated protein tau (MAPT)- ja progranulin (PGRN) geeneissä aiheuttavat yhteensä 10–20 % otsa-ohimolohkorappeumista maailmalla. C9ORF72-geenissä sijaitsevan toistojaksomonistuman on vastikään todettu olevan yleisin otsa-ohimolohkorappeumia ja ALS:a aiheuttava mutaatio. Mutaatio on erityisen yleinen suomalaisessa väestössä selittäen lähes 50 % suvuittaisista ja 30 % kaikista otsa-ohimolohkorappeumista. Oireyhtymän perinnöllisyys on muutoin huonosti tunnettu suomalaisessa väestössä. Tutkimuksen tavoitteena oli selvittää otsa-ohimolohkorappeumien geneettisiä syitä aineistossa, joka koostui vuosina 1999–2010 Oulun yliopistollisessa sairaalassa tutkituista potilaista. Tutkimuksessa selvitettiin MAPT-, charged multi-vesicular body protein 2B (CHMP2B)- ja TAR DNA-binding protein (TARDBP) geenien mutaatioiden esiintyvyyttä ja määritettiin MAPT-geenin haplotyypit. Lisäksi tutkittiin taudin kliinisiä erityispiirteitä C9ORF72-mutaation kantajilla. C9ORF72-mutaatio selitti lähes 30 % otsa-ohimolohkorappeumista aineistossamme. Tutkimuksessa havaittiin, että suvuittain esiintyvä tautimuoto ja ALS yhdistyneenä otsa-ohimolohkorappeumaan liittyivät merkittävästi C9ORF72-mutaatioon. Monistuman kantajien fenotyyppi oli moninainen – ensioireina oli sekä käytösongelmia että kielellisiä vaikeuksia. Vaikka C9ORF72-mutaation kantajilla on kuvattu runsaasti psykoottisia oireita, psykoottiset oireet eivät olleet selvästi yliedustettuna mutaation kantajilla aineistossamme. Tutkimuksessa ei löydetty tautia aiheuttavia mutaatioita MAPT-, CHMP2B- tai TARDBP-geeneistä. Havaitsimme kuitenkin tilastollisesti merkittävän yhteyden MAPT-geenin H2-haplotyypin ja otsa-ohimolohkorappeumien välillä. Tuloksemme antavat uutta tietoa C9ORF72-mutaation kantajien kliinisistä erityispiirteistä. MAPT-geenin mutaatioiden merkitys otsa-ohimolohkorappeumien synnyssä ei näyttäisi olevan suomalaisessa väestössä niin merkittävä kuin muissa väestöissä. CHMP2B- ja TARDBP-mutaatiot ovat harvinainen oireyhtymän syy myös suomalaisessa väestössä. Tuloksiamme voidaan hyödyntää suomalaisten otsa-ohimolohkorappeumapotilaiden perinnöllisessä neuvonnassa. Huomattavista edistysaskelista huolimatta yli puolet suvuittain esiintyvistä tautitapauksistamme on vailla geneettistä diagnoosia, mikä antaa aihetta jatkotutkimuksille
40
Mioshi, Eneida. "Activities of daily living, behaviour and cognition in frontotemporal dementia : an integrated approach." Thesis, University of Cambridge, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608417.
Full text
41
Balendra, Rubika. "Molecular mechanisms and therapeutic strategies in C9orf72 amyotrophic lateral sclerosis and frontotemporal dementia." Thesis, University College London (University of London), 2017. http://discovery.ucl.ac.uk/10040362/.
Full textAbstract:
Background A hexanucleotide expansion in C9orf72 is a common cause of the fatal neurodegenerative disorders amyotrophic lateral sclerosis and frontotemporal dementia. We have found evidence in a Drosophila model that neurotoxicity is mediated by dipeptide repeat (DPR) proteins generated by repeat-associated non-ATG translation. Here we aimed to evaluate in models of amyotrophic lateral sclerosis and frontotemporal dementia caused by the C9orf72 mutation (C9FTD/ALS) whether DPR proteins cause nucleolar dysfunction and whether small molecules that bind C9orf72 G-quadruplex repeat RNA reduce disease phenotypes. Methods We assessed nucleolar function in Drosophila models. Nucleolar volume was measured with immunofluorescence and confocal microscopy, using automated image analysis. Human induced pluripotent stem cells (iPSCs) from patients with C9orf72-ALS and from healthy controls were taken through neural induction and patterning to derive spinal motor neuron populations. Disease phenotypes were measured with fluorescence in-situ hybridisation for the typical RNA foci seen in C9orf72-ALS patients and an immunoassay for DPRs. Small molecules binding to C9orf72-repeat RNA were applied to the human iPSC-derived spinal motor neurons and fed to C9orf72 Drosophila to evaluate rescue of disease phenotypes. Findings The DPR poly-GR led to increased nucleolar volumes in Drosophila brain. The DPR poly-GA also led to increased nucleolar volume, but to a much lesser extent. Small molecules binding to G-quadruplex GGGGCC RNA showed efficacy in C9orf72 patient-derived neurons and in C9orf72 Drosophila. Interpretation Emerging evidence suggests that nucleolar dysfunction is a key mechanism in C9FTD/ALS. We have shown that DPR proteins lead to nucleolar dysfunction in C9orf72 Drosophila and in C9FTLD patient frontal cortex. The high prevalence of C9orf72-ALS makes use of targeted therapies a compelling strategy. Evidence for amelioration of C9orf72 phenotypes in patient-derived neurons and in Drosophila suggests that targeting G-quadruplex GGGGCC repeat RNA is a potential strategy for treating disease, which requires further optimisation and validation.
42
Menden, Kevin [Verfasser]. "Computational methods and analyses to dissect the pathogenesis of Frontotemporal Dementia / Kevin Menden." Tübingen : Universitätsbibliothek Tübingen, 2021. http://d-nb.info/1236994043/34.
Full text
43
Coad, Bethany. "Neurocognitive networks for social cognition : insights from diffusion weighted imaging and frontotemporal dementia." Thesis, Cardiff University, 2017. http://orca.cf.ac.uk/111503/.
Full textAbstract:
Empathy is a complex and multicomponent social cognitive function. It is underpinned by large-scale neurocognitive networks, the precise cognitive and neural structure of which remains debated. Despite this, relatively little work has considered the cognitive or neural components of empathy at the network-level. Here I present work using diffusion weighted magnetic resonance imaging (DWI) in healthy adults, and cognitive and behavioural assessment in a relatively rare form of dementia, the behavioural variant of frontotemporal dementia (bvFTD). Using these methods I explore: (a) the relationship between the microstructural properties of white matter tracts that mediate connectivity between distinct neurocognitive networks and separable cognitive components of empathic cognition (b) the cognitive and behavioural consequences of perturbation to neurocognitive networks in dementia. BvFTD is of interest here as it appears to preferentially target neural networks that support socioemotional processing. In chapters 2 and 3, evidence regarding the white matter structures that are affected by bvFTD guides investigations of the relationship between the microstructural properties of specific white matter tracts and social cognitive functioning in the healthy adult brain. In these chapters, I show that, in young healthy adults, two white matter pathways, sensitive to early changes in bvFTD, the Uncinate fasciculus (UF) and the cingulum bundle (CB), are related to individual differences in two components of empathic functioning, respectively: facial emotion decoding and mentalising. In chapter 4 I show the dissociation of performance on tasks assessing these cognitive functions in an individual with early bvFTD. I highlight the sensitivity and potential clinical utility of tasks assessing literary fiction-based mentalising. In Chapter 5 I present a detailed qualitative description of social cognitive change in frontotemporal dementia (FTD), from the perspective of family members. I consider what such detailed descriptions of everyday behaviour may tell us about the cognitive underpinnings of complex social behaviour. The findings of this thesis further our understanding of the dissociable neurocognitive networks that support empathic functioning, including their structural underpinnings and the behavioural consequences of their perturbation. In the general discussion, I consider the implications of this work for our understanding of social cognitive functioning and bvFTD.
44
Rounding, Natalie. "Zebrafish C9orf72 loss-of-function models of Amyotrophic Lateral Sclerosis and Frontotemporal Dementia." Thesis, University of Sheffield, 2018. http://etheses.whiterose.ac.uk/19832/.
Full text
45
Agresta, A. M. "PROTEOMIC INVESTIGATION ON NASU-HAKOLA DISEASE: SHEDDING LIGHT ON FRONTOTEMPORAL TREM2-BASED DEMENTIA." Doctoral thesis, Università degli Studi di Milano, 2018. http://hdl.handle.net/2434/543128.
Full textAbstract:
La malattia di Nasu-Hakola (NHD), nota anche come osteodisplasia lipomembranosa policistica con leucoencefalopatia sclerosante (PLOSL), è una patologia sistemica ereditaria recessiva caratterizzata da demenza presenile frontotemporale e lesioni ossee. Le basi genetiche che determinano la patologia sono correlate ad un difetto strutturale di due geni, TREM2 e DAP12, che codificano per due subunità del recettore transmembrana di un complesso di segnalazione espresso dalle cellule della microglia e dagli osteoclasti. Ad oggi, studi molecolari o proteomici di questa malattia sono assenti o scarsi, infatti in letteratura sono riportati solo studi cognitivo-comportamentali e genetici di singoli pazienti. Con l’obiettivo di ottenere maggiori informazioni circa l'insorgenza e/o la progressione dell’NHD, lo scopo di questo progetto di dottorato è stato quello di caratterizzare il proteoma linfoblastoide di un'intera famiglia in cui due membri hanno manifestato un fenotipo NHD.
Il progetto è stato focalizzato sull'analisi proteomica della linea cellulare linfoblastoide (LCL) ottenuta da 7 soggetti: due omozigoti (Ho), quattro eterozigoti (He) ed un wildtype (Wt). L'approccio proteomico utilizzato è gel-free e basato sulla tecnologia MudPIT (Multidimensional Protein Identification Technology) che si avvale della combinazione di micro-cromatografia liquida bidimensionale e spettrometria di massa tandem ad alta risoluzione. L'identificazione delle sequenze peptidiche e delle relative proteine è stata ottenuta tramite un software (Bioworks) basato sull'algoritmo SEQUEST per l’interpretazione degli spettri di massa acquisiti. Le liste proteiche sono state sottoposte all'analisi bioinformatica mediante software sviluppati in laboratorio (MAProMa, Multidimensional Algorithm Protein Map) e/o disponibili in rete, allo scopo di evidenziare gli andamenti di espressione proteica e le vie metaboliche coinvolte nell'insorgenza e/o progressione dell’NHD. Lo studio ha permesso di identificare circa 3000 proteine distinte all'interno dei tre gruppi analizzati e circa 400 proteine sono state identificate come peculiari di ciascuna categoria (Ho, He, Wt). In particolare, i dati hanno evidenziato la presenza di proteine differenzialmente espresse associate a processi correlabili alla neurodegenerazione. Inoltre, le reti proteiche hanno messo in rilievo alcune via molecolari che potrebbero essere coinvolte nell'insorgenza o nella progressione di questo raro disordine frontotemporale. Pertanto, la piattaforma MudPIT, completamente automatizzata, ha dimostrato la sua efficacia nello studio dei profili di espressione proteica di pazienti affetti da NHD e si può candidare come valida piattaforma per lo studio di altre demenze frontotemporali legate a TREM2. Infatti, questo approccio ha consentito di generare, per la prima volta, il profilo proteico più completo delle cellule linfoblastoidi appartenenti a soggetti Nasu-Hakola e di caratterizzare le vie metaboliche coinvolte nelle alterazioni funzionali di questa patologia.Nasu-Hakola Disease (NHD), also known as Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy (PLOSL), is a recessively inherited systemic leucodystrophy disorder characterized by a combination of frontotemporal presenile dementia and lytic bone lesions. It is known that NHD is genetically related to a structural defect of TREM2 and DAP12 genes that encode for different subunits of the membrane receptor signalling complex expressed by microglia and osteoclast cells. To date, molecular or proteomic studies about this disorder are absent or scarce, and only case reports based on neuropsychological and genetic tests have been reported. In light of this, to obtain in depth knowledges about the onset and/or progression of the NHD, the aim of this PhD project was to characterize the Lymphoblastoid proteome of an entire family in which two members manifested a NHD phenotype, through an innovative proteomic approach. The project was focused on the proteomic analysis of Lymphoblastoid cell lines (LCLs) obtained from 7 kin subjects: two homozygote (Ho), four heterozygote (He) and one wild type (Wt). Gel-free proteomic approach, based on MudPIT (Multidimensional Protein Identification Technology), was applied for the analysis of the whole protein extract. The identification of peptide sequences and their assigned proteins was obtained through an automated protein discovery software (Bioworks) based on SEQUEST algorithm for data handling of mass spectra. Protein lists were submitted to bioinformatics analysis by means of a home-made software (MAProMa, Multidimensional Algorithm Protein Map) and available on-line tools, in order to highlight the protein expression trends and the most involved pathways in the NHD onset and/or progression. The application of a gel-free proteomic approach on NHD subjects allowed to identify about 3000 distinct proteins within the three analysed groups and about 400 proteins were identified as peculiar of each category (Ho, He, Wt). Of note, data showed the presence of differentially expressed proteins associated to neurodegenerative processes. Moreover, the protein networks highlighted some molecular pathways that could be involved in the onset or progression of this rare frontotemporal disorder. Therefore, the fully automated MudPIT platform has demonstrated its effectiveness in the study of the protein expression profiles of NHD patients and could be a valid platform for the investigation of other TREM2-based frontotemporal dementias. This approach allowed to generate, for the first time, the whole protein profile of Lymphoblastoid cells from Nasu-Hakola subjects and to characterize the metabolic pathways involved in functional alterations of this pathology.
46
Lindau, Maria. "Clinical differentiation between frontotemporal dementia and Alzheimer's disease : psychometric, behavioral, neuroimaging and neurophysiological information /." Stockholm, 2002. http://diss.kib.ki.se/2002/91-7349-430-5/.
Full text
47
Green, Sophie. "The neural basis of disorders of social knowledge : Major Depressive Disorder and Frontotemporal Dementia." Thesis, University of Manchester, 2011. https://www.research.manchester.ac.uk/portal/en/theses/the-neural-basis-of-disorders-of-social-knowledge-major-depressive-disorder-and-frontotemporal-dementia(c5d16402-8a89-4143-b5fd-16c6fb386485).html.
Full textAbstract:
A fronto-temporo-mesolimbic integration model of moral cognition proposed that the experience of self- and other-blaming feelings is dependent upon integration of different forms of representations including: 1) differentiated conceptual representations about social behaviours served by the anterior temporal lobe, 2) sequential representations about the consequences of social actions in the ventral frontal lobes, and 3) motivational state representations in mesolimbic regions. Here, I use this model to investigate overgeneral forms of self-blaming feelings, such as self-contempt in remitted Major Depressive Disorder (MDD), and inappropriate social behaviour of patients with Frontotemporal Lobar Degeneration (FTLD). Individuals with remitted MDD demonstrated an increased proneness to experience overgeneral self-blaming feelings (self-contempt bias). This was associated with decreased conceptual differentiation when evaluating one's own social behaviour relative to that of others, combined with the tendency to find one's own behaviours more unpleasant than that of other people. An fMRI study revealed that compared to a control group, people with remitted MDD exhibited decreased functional connectivity across a fronto-temporo-limbic network that was selective for self-blaming relative to other-blaming feelings. These findings provide a neural mechanism for self-blaming biases, thereby helping to understand vulnerability to MDD. In the FTLD study, we demonstrated a double dissociation between deficits in conceptual and sequential social knowledge in patients with Semantic (SD) and Frontotemporal Dementia (FTD) respectively. This could partly explain the inappropriate social behaviours occurring in both of these groups. These results shed new light on the basis of self-blaming biases in MDD and inappropriate social behaviour in FTLD, and provide a platform for future investigations of these disorders from this perspective.
48
Bung, Manuela Alexandra. "A quantitative approach to analysing conversational turn-taking in Alzheimer's disease and frontotemporal dementia." Thesis, University of Southampton, 2016. https://eprints.soton.ac.uk/413463/.
Full textAbstract:
Communicating and understanding words require a wide range of cognitive resources involving phonological, lexical, semantic and perceptual processing. Disturbance in these domains is associated with pathology in temporal and/or frontal cortical areas. The subsequent abnormal breakdown in fluent speech can be observed in frontotemporal dementia or Alzheimer’s disease, in which brain atrophy in these areas is common. Organization and interaction during a conversation depend, additionally, on the ability to plan and exchange information. Such executive resources are required for structuring, planning, monitoring and organizing speech output, and are impaired when critical networks in dorsolateral prefrontal brain regions become disrupted. The aim of this study was to identify speech parameters, to characterise and describe the subgroups of dementia which could be used to improve the correct identification of dementia types at an early stage of the disease. Our analysis was based on the interactional organization of conversations and overlapping behaviour. As a new approach in speech analysis of dementia, we aimed to develop a method to quantify traditionally qualitative measurements. We carried out two studies: In the first we recorded conversations elicited using a map task in healthy subjects paired with a familiar or an unfamiliar partner. We aimed to identify candidate parameters for characterising conversational behaviour and to investigate the existence of a Familiarity effect. Twenty-four conversations were recorded: twelve between familiar pairs and twelve between unfamiliar pairs. Conversations were analysed for overlap behaviour in the categories Confirmations, Predictions, Full Turn-Taking, Failed Turn-Taking, Failed Turn-Taking Completed and Others. In the second we recorded nine Alzheimer’s disease patients and three frontotemporal dementia patients using the same methodology of pairing, conversation stimulation and analysis as for the healthy subjects. The familiar partner was a family member or carer and the unfamiliar was a research assistant. For the patients recording sessions were repeated every three to eight months over a period of a year. Analysis showed that the chosen experimental design and the parameters describing planning and executive abilities in speech are promising in terms of supporting our main research question on the subject of finding characteristic conversational behaviour in subtypes of dementia. We also found indicators for the Familiarity effect in healthy and dementia speech. The case studies, which we conducted for three FTD patients, allowed providing an insight in to certain turn-taking behaviour by using examples of the transcripts. Again, we found that Familiarity is a promising indicator in conjunction with the categorical analysis for characterising FTD speech. We demonstrated changes in the underlying structure of Alzheimer’s disease and frontotemporal dementia speech with respect to the frequency of overlaps and outlined speech strategies of the patients to bypass cognitive limitations over time.
49
Burson, Kathy C. "Early Detection of Decline in Executive Functioning in Alzheimer's, Frontotemporal, and Lewy Body Dementia." Thesis, Fielding Graduate University, 2022. http://pqdtopen.proquest.com/#viewpdf?dispub=28409892.
Full textAbstract:
Cognitive deficits associated with an aging population have been the focus of clinical research interest as an increasing number of people survive into older age. These research interests have determined that there is a need to accurately detect the onset of cognitive changes that show the beginning of a dementia syndrome and to differentiate among disorders with distinct etiologies and sites of pathology. Impairment in executive functions has been recognized as one cognitive feature in which changes and deficits have been reported in various types of neurodegenerative disorders. Mild cognitive impairment is often viewed as a transitional stage between normal aging and Alzheimer’s disease (AD), frontotemporal lobe dementia (FTD), and Lewy body dementia (LBD). Neuropsychological evaluations can assist in detecting the onset of cognitive executive functioning changes and decline in the early stages of dementia disorders. The purpose of this study was to determine if there is a change in executive functioning profiles in subjects who initially have no dementia but later receive a diagnosis of neurodegenerative disorders of Alzheimer’s, frontotemporal lobe, and Lewy body dementias. Possible early executive functioning indicators might be found that could then be used to identify at-risk individuals before a formal diagnosis is made. Strategic interventions could then be provided to lessen the effects of these disorders. Early intervention allows more time for individuals to gain access to strategies and plan for changes that may occur throughout the process of these disorders. It also provides information for further study. The aim of this study was to test the hypothesis that once a subject has been diagnosed with dementia a detectable change has occurred in executive functioning measures. Participants were 34 persons between the ages of 61-89 who had been given a series of neuropsychological tests of executive functioning. Individuals who met criteria for AD, LBD, and FTD disorders were included in this sample, and their scores from baseline evaluation to initial diagnosis of AD, LBD, and FTD were analyzed to determine changes in executive functioning measures. The executive functioning tests included verbal associative fluency retrieval of animal and vegetable exemplars, Trail Making Part B, and Digit Span Backward from the Wechsler Memory Scale-Revised (WMR-R). Analysis included changes in executive functioning measures when the diagnosis of AD, LBD, or FTD was made after a change from the initial diagnosis of no dementia. The results of this study are that patients performed similarly across different measures, with the exception of the Trails B subtest, which indicated a significant difference. This subtest difference emerged between the initial evaluation and the first diagnosis of AD, LBD, or FTD.
50
Hutchings, Rosalind. "Cognitive and neural mechanisms of face processing in frontotemporal dementia and primary progressive aphasia." Thesis, The University of Sydney, 2018. http://hdl.handle.net/2123/18881.
Full textAbstract:
Face processing is an integral part of human social communication, relying on complex neural and cognitive networks. While the role of posterior (i.e., occipitotemporal) brain regions in face processing has been examined extensively, the contribution of anterior (i.e., frontotemporal) brain regions is less clear. Of relevance here, is the profile of frontal and temporal brain atrophy in frontotemporal dementia (FTD) and primary progressive aphasia (PPA) including, behavioural-variant FTD, semantic dementia, progressive nonfluent aphasia and logopenic progressive aphasia. A review of the literature demonstrates variable degrees of face processing impairment across these four syndromes, but with little investigation into the mechanisms underlying this impairment. The experimental studies of this thesis therefore employ novel experimental tasks in combination with neuroimaging to systematically assess face processing in FTD and PPA. Results arising from three separate studies demonstrate that behavioural-variant FTD and semantic dementia patients attend to and encode relevant facial cues, although an interaction between ‘late’ and ‘early’ face processing is evident (Chapters 3-5). Novel evidence of a widespread deficit affecting facial identity and expression processing in progressive nonfluent aphasia and logopenic progressive aphasia, moderated by cognitive ability, is also reported (Chapter 6). Together, findings demonstrate an interaction between anterior and posterior brain regions supporting face processing. Identification of the mechanisms contributing to overt deficits in FTD and PPA permits improved symptom characterisation. In addition, the investigations presented here provide a unique approach for clarifying the brain networks underlying complex behaviour and the functional, cognitive and social outcomes when disrupted.