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John R Hodges - One of the best experts on this subject based on the ideXlab platform.
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Energy expenditure in Frontotemporal Dementia: a behavioural and imaging study
Brain, 2016Co-Authors: Rebekah M. Ahmed, Olivier Piguet, Matthew C Kiernan, Ramon Landin-romero, Tinh-hai Collet, Agatha A. Van Der Klaauw, Emma Devenney, Elana Henning, I. Sadaf Farooqi, John R HodgesAbstract:Abnormal eating behaviour and metabolic parameters including insulin resistance, dyslipidaemia and body mass index are increasingly recognized as important components of neurodegenerative disease and may contribute to survival. It has previously been established that behavioural variant Frontotemporal Dementia is associated with abnormal eating behaviour characterized by increased sweet preference. In this study, it was hypothesized that behavioural variant Frontotemporal Dementia might also be associated with altered energy expenditure. A cohort of 19 patients with behavioural variant Frontotemporal Dementia, 13 with Alzheimer’s disease and 16 (age- and sex-matched) healthy control subjects were studied using Actiheart devices (CamNtech) to assess resting and stressed heart rate. Actiheart devices were fitted for 7 days to measure sleeping heart rate, activity levels, and resting, active and total energy expenditure. Using high resolution structural magnetic resonance imaging the neural correlates of increased resting heart rate were investigated including cortical thickness and region of interest analyses. In behavioural variant Frontotemporal Dementia, resting ( P = 0.001), stressed ( P = 0.037) and sleeping heart rate ( P = 0.038) were increased compared to control subjects, and resting heart rate ( P = 0.020) compared to Alzheimer disease patients. Behavioural variant Frontotemporal Dementia was associated with decreased activity levels compared to controls ( P = 0.002) and increased resting energy expenditure ( P = 0.045) and total energy expenditure ( P = 0.035). Increased resting heart rate correlated with behavioural (Cambridge Behavioural Inventory) and cognitive measures (Addenbrooke’s Cognitive Examination). Increased resting heart rate in behavioural variant Frontotemporal Dementia correlated with atrophy involving the mesial temporal cortex, insula, and amygdala, regions previously suggested to be involved exclusively in social and emotion processing in Frontotemporal Dementia. These neural correlates overlap the network involved in eating behaviour in Frontotemporal Dementia, suggesting a complex interaction between eating behaviour, autonomic function and energy homeostasis. As such the present study suggests that increased heart rate and autonomic changes are prevalent in behavioural variant Frontotemporal Dementia, and are associated with changes in energy expenditure. An understanding of these changes and neural correlates may have potential relevance to disease progression and prognosis. * Abbreviations : ALS : amyotrophic lateral sclerosis BMI : body mass index bvFTD : behavioural variant Frontotemporal Dementia FTD : Frontotemporal Dementia RMSSD : root mean squared of successive differences
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Grey and white matter brain network changes in Frontotemporal Dementia subtypes
Translational Neuroscience, 2013Co-Authors: Tim Nguyen, Claire O’callaghan, Samrah Ahmed, Maxime Bertoux, John R Hodges, Michael HornbergerAbstract:Background Frontotemporal Dementia (FTD) comprises of three clinical syndromes, behavioural-variant Frontotemporal Dementia (bvFTD), semantic Dementia (SV-PPA), and progressive nonfluent aphasia (NFV-PPA) with unique underlying neuroanatomical deficits. To date, however, grey matter structural differences and their connecting white matter tracts in this network have been mostly characterised in comparison to controls, whereas within FTD subtype comparisons in the same patients have not been explored.
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In vivo and post-mortem memory circuit integrity in Frontotemporal Dementia and Alzheimer's disease.
Brain : a journal of neurology, 2012Co-Authors: Michael Hornberger, Stephanie Wong, Olivier Piguet, Jillian Kril, Muireann Irish, John R Hodges, Glenda HallidayAbstract:Behavioural variant Frontotemporal Dementia can present with episodic memory deficits as severe as those in Alzheimer's disease. Little is known of the integrity of grey matter areas and white matter tracts of the Papez memory circuit in these diseases. The integrity of the Papez circuit (hippocampus, fornix, mammillary bodies, anterior thalamus, cingulate cortex) was investigated in vivo and at post-mortem in behavioural variant Frontotemporal Dementia and Alzheimer's disease cohorts using voxel-based morphometry, diffusion tensor imaging and manual volumetric tracing. Our findings indicate that behavioural variant Frontotemporal Dementia and Alzheimer's disease show similar degrees of hippocampal atrophy in vivo, but patients with behavioural variant Frontotemporal Dementia show greater hippocampal atrophy at post-mortem, with the Frontotemporal lobar degeneration with TDP-43 inclusions subtype being particularly affected. Cingulate cortex findings show an expected atrophy pattern with behavioural variant Frontotemporal Dementia being affected more anteriorly and Alzheimer's disease showing more posterior atrophy. More importantly, subcortical Papez circuit regions (fornix and anterior thalamus) were affected in behavioural variant Frontotemporal Dementia only, with atrophy in these regions determining the degree of amnesia in behavioural variant Frontotemporal Dementia. Hippocampal atrophy does not appear to be an efficient diagnostic marker for underlying behavioural variant Frontotemporal Dementia or Alzheimer's disease pathology, although for behavioural variant Frontotemporal Dementia, episodic memory deficits in conjunction with marked hippocampal atrophy emerge as potential biomarkers for Frontotemporal lobar degeneration with TDP-43 inclusions pathology. Sub-regions of the Papez circuit were differentially affected in behavioural variant Frontotemporal Dementia and Alzheimer's disease with subcortical regions determining the degree of episodic memory deficits in behavioural variant Frontotemporal Dementia. Subcortical atrophy should be taken into account when establishing whether the severe amnesia observed in a patient is likely to be due to behavioural variant Frontotemporal Dementia or Alzheimer's disease pathology.
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In vivo and post-mortem memory circuit integrity in Frontotemporal Dementia and Alzheimer's disease.
Brain, 2012Co-Authors: Michael Hornberger, Stephanie Wong, Olivier Piguet, Jillian Kril, Muireann Irish, John R Hodges, Glenda M HallidayAbstract:Behavioural variant Frontotemporal Dementia can present with episodic memory deficits as severe as those in Alzheimer’s disease. Little is known of the integrity of grey matter areas and white matter tracts of the Papez memory circuit in these diseases. The integrity of the Papez circuit (hippocampus, fornix, mammillary bodies, anterior thalamus, cingulate cortex) was investigated in vivo and at post-mortem in behavioural variant Frontotemporal Dementia and Alzheimer’s disease cohorts using voxel-based morphometry, diffusion tensor imaging and manual volumetric tracing. Our findings indicate that behavioural variant Frontotemporal Dementia and Alzheimer’s disease show similar degrees of hippocampal atrophy in vivo , but patients with behavioural variant Frontotemporal Dementia show greater hippocampal atrophy at post-mortem , with the Frontotemporal lobar degeneration with TDP-43 inclusions subtype being particularly affected. Cingulate cortex findings show an expected atrophy pattern with behavioural variant Frontotemporal Dementia being affected more anteriorly and Alzheimer’s disease showing more posterior atrophy. More importantly, subcortical Papez circuit regions (fornix and anterior thalamus) were affected in behavioural variant Frontotemporal Dementia only, with atrophy in these regions determining the degree of amnesia in behavioural variant Frontotemporal Dementia. Hippocampal atrophy does not appear to be an efficient diagnostic marker for underlying behavioural variant Frontotemporal Dementia or Alzheimer’s disease pathology, although for behavioural variant Frontotemporal Dementia, episodic memory deficits in conjunction with marked hippocampal atrophy emerge as potential biomarkers for Frontotemporal lobar degeneration with TDP-43 inclusions pathology. Sub-regions of the Papez circuit were differentially affected in behavioural variant Frontotemporal Dementia and Alzheimer’s disease with subcortical regions determining the degree of episodic memory deficits in behavioural variant Frontotemporal Dementia. Subcortical atrophy should be taken into account when establishing whether the severe amnesia observed in a patient is likely to be due to behavioural variant Frontotemporal Dementia or Alzheimer’s disease pathology. * Abbreviations : DTI : diffusion tensor imaging FTD : Frontotemporal Dementia FTLD : Frontotemporal lobar Dementia VBM : voxel-based morphometry
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motor neuron dysfunction in Frontotemporal Dementia
Brain, 2011Co-Authors: James R Burrell, Matthew C Kiernan, Steve Vucic, John R HodgesAbstract:Frontotemporal Dementia and motor neuron disease share clinical, genetic and pathological characteristics. Motor neuron disease develops in a proportion of patients with Frontotemporal Dementia, but the incidence, severity and functional significance of motor system dysfunction in patients with Frontotemporal Dementia has not been determined. Neurophysiological biomarkers have been developed to document motor system dysfunction including: short-interval intracortical inhibition, a marker of corticospinal motor neuron dysfunction and the neurophysiological index, a marker of lower motor neuron dysfunction. The present study performed detailed clinical and neurophysiological assessments on 108 participants including 40 consecutive patients with Frontotemporal Dementia, 42 age- and gender-matched patients with motor neuron disease and 26 control subjects. Of the 40 patients with Frontotemporal Dementia, 12.5% had concomitant motor neuron disease. A further 27.3% of the patients with Frontotemporal Dementia had clinical evidence of minor motor system dysfunction such as occasional fasciculations, mild wasting or weakness. Biomarkers of motor system function were abnormal in Frontotemporal Dementia. Average short-interval intracortical inhibition was reduced in Frontotemporal Dementia (4.3 ± 1.7%) compared with controls (9.1 ± 1.1%, P < 0.05). Short-interval intracortical inhibition was particularly reduced in the progressive non-fluent aphasia subgroup, but was normal in patients with behavioural variant Frontotemporal Dementia and semantic Dementia. The neurophysiological index was reduced in Frontotemporal Dementia (1.1) compared with controls (1.9, P < 0.001), indicating a degree of lower motor neuron dysfunction, although remained relatively preserved when compared with motor neuron disease (0.7, P < 0.05). Motor system dysfunction in Frontotemporal Dementia may result from pathological involvement of the primary motor cortex, with secondary degeneration of lower motor neurons in the brainstem and anterior horn of the spinal cord. * Abbreviations : ALSFRS-R : Amyotrophic Lateral Sclerosis Functional Rating Score – Revised FTD : Frontotemporal Dementia FUS : fused in sacrcoma MND : motor neuron disease MRCSS : Medical Research Council Sum Score PNFA : progressive non-fluent aphasia TDP-43 : TAR DNA-binding protein 43
Bruce L. Miller - One of the best experts on this subject based on the ideXlab platform.
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Young-onset Frontotemporal Dementia in a homozygous tau R406W mutation carrier.
Annals of Clinical and Translational Neurology, 2015Co-Authors: Ana C. Sias, Anna Karydas, Jamie Fong, Peter Pressman, Theodore P. Zanto, Mary De May, Giovanni Coppola, Daniel H. Geschwind, Bruce L. MillerAbstract:Microtubule-associated protein tau mutations result in 10-20% of cases of genetic Frontotemporal lobar degeneration. Tau mutation carriers typically develop behavioral variant Frontotemporal Dementia with or without parkinsonism. Unlike most Frontotemporal Dementia gene mutations, heterozygous R406W tau mutation carriers most often develop clinical Alzheimer's disease. We report a homozygous tau R406W mutation carrier with behavioral variant Frontotemporal Dementia who developed symptoms 20 years before mean family symptom onset. Voxel-based morphometry showed frontoinsular, frontal, and mesial temporal cortical atrophy. Homozygous tau R406W mutations appear to accelerate symptom onset and drive a behavioral variant Frontotemporal Dementia syndrome.
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Psychosis in Frontotemporal Dementia
Journal of Alzheimer's Disease, 2014Co-Authors: Shunichiro Shinagawa, Shinichiro Nakajima, Eric Plitman, Ariel Graff-guerrero, Masaru Mimura, Kazuhiko Nakayama, Bruce L. MillerAbstract:Frontotemporal Dementia (FTD) is a neurodegenerative disorder, associated with a progressive decline in behavior caused by focal degeneration of the frontal lobes. Psychosis was an underestimated symptom of FTD, however, recent genetic research has revealed a high prevalence of psychosis in certain genetic groups. The primary objective of this work is to review the literature on psychosis in FTD and to propose directions for future research, with reference to findings on psychosis in schizophrenia. A search was performed using PubMed, MEDLINE, and EMBASE. Search terms included "Frontotemporal Dementia", "psychosis", "schizophreni*", "psychotic symptoms", "hallucinations", and "delusions", and it identified 122 articles. Results revealed: 1) prevalence is approximately 10%, 2) TDP-43 type B and FUS pathologies might have relatively high frequency of psychosis, 3) psychosis in FTD is higher with genetic mutations of C9ORF72 and GRN, 4) imaging researches did not achieve conclusive results, and 5) no treatment for psychosis in FTD is currently available. A limitation of this systematic review is that it includes a small number of studies specifically examining psychosis in FTD. It is suggested that a possible overlap exists between FTD and schizophrenia. This potential overlap indicates a vulnerability to psychosis due to brain systems and pathways shared by these disorders.
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Patterns of striatal degeneration in Frontotemporal Dementia.
Alzheimer Disease & Associated Disorders, 2013Co-Authors: Cathra Halabi, Bruce L. Miller, Anasheh Halabi, David Dean, Pei-ning Wang, Adam L. Boxer, John Q. Trojanowski, Stephen J. Dearmond, Joel H. Kramer, William W. SeeleyAbstract:Behavioral variant Frontotemporal Dementia and semantic Dementia have been associated with striatal degeneration, but few studies have delineated striatal subregion volumes in vivo or related them to the clinical phenotype. We traced caudate, putamen, and nucleus accumbens on magnetic resonance images to quantify volumes of these structures in behavioral variant Frontotemporal Dementia, semantic Dementia, Alzheimer disease, and healthy controls (n=12 per group). We further related these striatal volumes to clinical deficits and neuropathologic findings in a subset of patients. Behavioral variant Frontotemporal Dementia and semantic Dementia showed significant overall striatal atrophy compared with controls. Moreover, behavioral variant Frontotemporal Dementia showed panstriatal degeneration, whereas semantic Dementia featured a more focal pattern involving putamen and accumbens. Right-sided striatal atrophy, especially in the putamen, correlated with the overall behavioral symptom severity and with specific behavioral domains. At autopsy, patients with behavioral variant Frontotemporal Dementia and semantic Dementia showed striking and severe tau or TAR DNA-binding protein of 43 kDa pathology, especially in ventral parts of the striatum. These results demonstrate that ventral striatum degeneration is a prominent shared feature in behavioral variant Frontotemporal Dementia and semantic Dementia and may contribute to the social-emotional deficits common to both disorders.
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divergent network connectivity changes in behavioural variant Frontotemporal Dementia and alzheimer s disease
Brain, 2010Co-Authors: Juan Zhou, Bruce L. Miller, Joel H. Kramer, Michael D Greicius, Efstathios D Gennatas, Matthew E Growdon, Jung Y Jang, Gil D Rabinovici, Michael W Weiner, William W. SeeleyAbstract:Resting-state or intrinsic connectivity network functional magnetic resonance imaging provides a new tool for mapping large-scale neural network function and dysfunction. Recently, we showed that behavioural variant Frontotemporal Dementia and Alzheimer's disease cause atrophy within two major networks, an anterior 'Salience Network' (atrophied in behavioural variant Frontotemporal Dementia) and a posterior 'Default Mode Network' (atrophied in Alzheimer's disease). These networks exhibit an anti-correlated relationship with each other in the healthy brain. The two diseases also feature divergent symptom-deficit profiles, with behavioural variant Frontotemporal Dementia undermining social-emotional function and preserving or enhancing visuospatial skills, and Alzheimer's disease showing the inverse pattern. We hypothesized that these disorders would exert opposing connectivity effects within the Salience Network (disrupted in behavioural variant Frontotemporal Dementia but enhanced in Alzheimer's disease) and the Default Mode Network (disrupted in Alzheimer's disease but enhanced in behavioural variant Frontotemporal Dementia). With task-free functional magnetic resonance imaging, we tested these ideas in behavioural variant Frontotemporal Dementia, Alzheimer's disease and healthy age-matched controls (n = 12 per group), using independent component analyses to generate group-level network contrasts. As predicted, behavioural variant Frontotemporal Dementia attenuated Salience Network connectivity, most notably in frontoinsular, cingulate, striatal, thalamic and brainstem nodes, but enhanced connectivity within the Default Mode Network. Alzheimer's disease, in contrast, reduced Default Mode Network connectivity to posterior hippocampus, medial cingulo-parieto-occipital regions and the dorsal raphe nucleus, but intensified Salience Network connectivity. Specific regions of connectivity disruption within each targeted network predicted intrinsic connectivity enhancement within the reciprocal network. In behavioural variant Frontotemporal Dementia, clinical severity correlated with loss of right frontoinsular Salience Network connectivity and with biparietal Default Mode Network connectivity enhancement. Based on these results, we explored whether a combined index of Salience Network and Default Mode Network connectivity might discriminate between the three groups. Linear discriminant analysis achieved 92% clinical classification accuracy, including 100% separation of behavioural variant Frontotemporal Dementia and Alzheimer's disease. Patients whose clinical diagnoses were supported by molecular imaging, genetics, or pathology showed 100% separation using this method, including four diagnostically equivocal 'test' patients not used to train the algorithm. Overall, the findings suggest that behavioural variant Frontotemporal Dementia and Alzheimer's disease lead to divergent network connectivity patterns, consistent with known reciprocal network interactions and the strength and deficit profiles of the two disorders. Further developed, intrinsic connectivity network signatures may provide simple, inexpensive, and non-invasive biomarkers for Dementia differential diagnosis and disease monitoring.
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distinctive neuropsychological patterns in Frontotemporal Dementia semantic Dementia and alzheimer disease
Cognitive and Behavioral Neurology, 2003Co-Authors: Joel H. Kramer, Jennifer Jurik, Sharon J Sha, Katherine P Rankin, Howard J Rosen, Julene K Johnson, Bruce L. MillerAbstract:AbstractObjectiveTo assess the ability of a brief neuropsychological bedside screening battery to discriminate between Alzheimer disease, Frontotemporal Dementia, and semantic Dementia.MethodsSubjects were 21 patients with Frontotemporal Dementia, 14 patients with semantic Dementia, and 30 patients
William W. Seeley - One of the best experts on this subject based on the ideXlab platform.
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Behavioral Variant Frontotemporal Dementia.
CONTINUUM: Lifelong Learning in Neurology, 2019Co-Authors: William W. SeeleyAbstract:ABSTRACTPURPOSE OF REVIEWThis article describes the clinical, anatomic, genetic, and pathologic features of behavioral variant Frontotemporal Dementia (bvFTD) and discusses strategies to improve diagnostic accuracy, emphasizing common pitfalls to avoid. Key aspects of management and the future of di
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Cerebrospinal fluid biomarkers predict Frontotemporal Dementia trajectory
Annals of Clinical and Translational Neurology, 2018Co-Authors: Peter A. Ljubenkov, Adam M. Staffaroni, Julio C. Rojas, Isabel E. Allen, Ping Wang, Hilary W. Heuer, Anna Karydas, John Kornak, Yann Cobigo, William W. SeeleyAbstract:Author(s): Ljubenkov, Peter A; Staffaroni, Adam M; Rojas, Julio C; Allen, Isabel E; Wang, Ping; Heuer, Hilary; Karydas, Anna; Kornak, John; Cobigo, Yann; Seeley, William W; Grinberg, Lea T; Spina, Salvatore; Fagan, Anne M; Jerome, Gina; Knopman, David; Boeve, Brad F; Dickerson, Bradford C; Kramer, Joel; Miller, Bruce; Boxer, Adam L; Rosen, Howard J | Abstract: Objective:The prognostic value of cerebrospinal fluid neurofilament light chain, total tau, phosphorylated tau181, and amyloid beta1-42 was examined in Frontotemporal Dementia subtypes. Methods:We compared baseline biomarkers between 49 controls, 40 patients with behavioral variant Frontotemporal Dementia, 24 with semantic variant primary progressive aphasia, and 26 with nonfluent variant primary progressive aphasia. Linear mixed effect models were used to assess the value of baseline biomarkers in predicting clinical and radiographic change in patient cohorts over multiple yearly follow up visits. Results:Neurofilament light chain concentrations were lowest in controls. Elevated baseline neurofilament light chain predicted faster worsening in clinical severity, Frontotemporal volume and Frontotemporal fractional anisotropy in patients with behavioral variant Frontotemporal Dementia and nonfluent variant primary progressive aphasia. High total tau similarly predicted faster progression in nonfluent variant primary progressive aphasia. In behavioral variant Frontotemporal Dementia, higher phosphorylated tau181 predicted faster clinical progression whereas lower amyloid beta1-42 predicted faster volumetric and fractional anisotropy reduction. Neurofilament light chain and phosphorylated tau181 were of greater predictive value in patients with tau pathology as compared to TDP-43 pathology. Baseline neurofilament light chain correlated with baseline clinical severity and Frontotemporal volume in behavioral variant Frontotemporal Dementia. Baseline total tau correlated with baseline clinical severity in semantic variant primary progressive aphasia. Interpretation:High cerebrospinal fluid neurofilament light chain predicts more aggressive disease in behavioral variant Frontotemporal Dementia and nonfluent variant primary progressive aphasia. Total tau, phosphorylated tau181, and amyloid beta1-42 also predict some measures of disease aggressiveness in Frontotemporal Dementia.
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Schizophrenia as a mimic of behavioral variant Frontotemporal Dementia
Neurocase, 2016Co-Authors: Cora J. Kerssens, William W. Seeley, Welmoed A. Krudop, Niels D. Prins, Bart N.m. Van Berckel, Annemieke J.m. Rozemuller, Philip Scheltens, Max L. Stek, Yolande A.l. PijnenburgAbstract:Recently, the diagnostic criteria for the behavioral variant of Frontotemporal Dementia were revised. Although these criteria offer a relatively high sensitivity, their specificity is yet unknown. We describe a 54-year-old woman fulfilling criteria for both late-onset schizophrenia and probable behavioral variant Frontotemporal Dementia. Following an initial presentation with psychosis, she developed progressive apathy, compulsiveness, and executive dysfunction. Moreover, bilateral Frontotemporal hypometabolism was seen on [(18)F]fludeoxyglucose-positron emission tomography. A post-mortem diagnosis of schizophrenia was established, given the clinical picture combined with the pathological exclusion of a neurodegenerative cause. Our case suggests that patients with other brain disorders may meet the current diagnostic criteria for probable Frontotemporal Dementia. Further clinicopathological validation of these criteria is needed to determine their exact specificity.
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Patterns of striatal degeneration in Frontotemporal Dementia.
Alzheimer Disease & Associated Disorders, 2013Co-Authors: Cathra Halabi, Bruce L. Miller, Anasheh Halabi, David Dean, Pei-ning Wang, Adam L. Boxer, John Q. Trojanowski, Stephen J. Dearmond, Joel H. Kramer, William W. SeeleyAbstract:Behavioral variant Frontotemporal Dementia and semantic Dementia have been associated with striatal degeneration, but few studies have delineated striatal subregion volumes in vivo or related them to the clinical phenotype. We traced caudate, putamen, and nucleus accumbens on magnetic resonance images to quantify volumes of these structures in behavioral variant Frontotemporal Dementia, semantic Dementia, Alzheimer disease, and healthy controls (n=12 per group). We further related these striatal volumes to clinical deficits and neuropathologic findings in a subset of patients. Behavioral variant Frontotemporal Dementia and semantic Dementia showed significant overall striatal atrophy compared with controls. Moreover, behavioral variant Frontotemporal Dementia showed panstriatal degeneration, whereas semantic Dementia featured a more focal pattern involving putamen and accumbens. Right-sided striatal atrophy, especially in the putamen, correlated with the overall behavioral symptom severity and with specific behavioral domains. At autopsy, patients with behavioral variant Frontotemporal Dementia and semantic Dementia showed striking and severe tau or TAR DNA-binding protein of 43 kDa pathology, especially in ventral parts of the striatum. These results demonstrate that ventral striatum degeneration is a prominent shared feature in behavioral variant Frontotemporal Dementia and semantic Dementia and may contribute to the social-emotional deficits common to both disorders.
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Anterior insula degeneration in Frontotemporal Dementia
Brain Structure and Function, 2010Co-Authors: William W. SeeleyAbstract:The human anterior insula is anatomically and functionally heterogeneous, containing key nodes within distributed speech–language and viscero-autonomic/social–emotional networks. The Frontotemporal Dementias selectively target these large-scale systems, leading to at least three distinct clinical syndromes. Examining these disorders, researchers have begun to dissect functions which rely on specific insular nodes and networks. In the behavioral variant of Frontotemporal Dementia, early-stage frontoinsular degeneration begets progressive “Salience Network” breakdown that leaves patients unable to model the emotional impact of their own actions or inactions. Ongoing studies seek to clarify local microcircuit- and cellular-level factors that confer selective frontoinsular vulnerability. The search for Frontotemporal Dementia treatments will depend on a rich understanding of insular biology and could help clarify specialized human language, social, and emotional functions.
Michael Hornberger - One of the best experts on this subject based on the ideXlab platform.
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Grey and white matter brain network changes in Frontotemporal Dementia subtypes
Translational Neuroscience, 2013Co-Authors: Tim Nguyen, Claire O’callaghan, Samrah Ahmed, Maxime Bertoux, John R Hodges, Michael HornbergerAbstract:Background Frontotemporal Dementia (FTD) comprises of three clinical syndromes, behavioural-variant Frontotemporal Dementia (bvFTD), semantic Dementia (SV-PPA), and progressive nonfluent aphasia (NFV-PPA) with unique underlying neuroanatomical deficits. To date, however, grey matter structural differences and their connecting white matter tracts in this network have been mostly characterised in comparison to controls, whereas within FTD subtype comparisons in the same patients have not been explored.
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In vivo and post-mortem memory circuit integrity in Frontotemporal Dementia and Alzheimer's disease.
Brain : a journal of neurology, 2012Co-Authors: Michael Hornberger, Stephanie Wong, Olivier Piguet, Jillian Kril, Muireann Irish, John R Hodges, Glenda HallidayAbstract:Behavioural variant Frontotemporal Dementia can present with episodic memory deficits as severe as those in Alzheimer's disease. Little is known of the integrity of grey matter areas and white matter tracts of the Papez memory circuit in these diseases. The integrity of the Papez circuit (hippocampus, fornix, mammillary bodies, anterior thalamus, cingulate cortex) was investigated in vivo and at post-mortem in behavioural variant Frontotemporal Dementia and Alzheimer's disease cohorts using voxel-based morphometry, diffusion tensor imaging and manual volumetric tracing. Our findings indicate that behavioural variant Frontotemporal Dementia and Alzheimer's disease show similar degrees of hippocampal atrophy in vivo, but patients with behavioural variant Frontotemporal Dementia show greater hippocampal atrophy at post-mortem, with the Frontotemporal lobar degeneration with TDP-43 inclusions subtype being particularly affected. Cingulate cortex findings show an expected atrophy pattern with behavioural variant Frontotemporal Dementia being affected more anteriorly and Alzheimer's disease showing more posterior atrophy. More importantly, subcortical Papez circuit regions (fornix and anterior thalamus) were affected in behavioural variant Frontotemporal Dementia only, with atrophy in these regions determining the degree of amnesia in behavioural variant Frontotemporal Dementia. Hippocampal atrophy does not appear to be an efficient diagnostic marker for underlying behavioural variant Frontotemporal Dementia or Alzheimer's disease pathology, although for behavioural variant Frontotemporal Dementia, episodic memory deficits in conjunction with marked hippocampal atrophy emerge as potential biomarkers for Frontotemporal lobar degeneration with TDP-43 inclusions pathology. Sub-regions of the Papez circuit were differentially affected in behavioural variant Frontotemporal Dementia and Alzheimer's disease with subcortical regions determining the degree of episodic memory deficits in behavioural variant Frontotemporal Dementia. Subcortical atrophy should be taken into account when establishing whether the severe amnesia observed in a patient is likely to be due to behavioural variant Frontotemporal Dementia or Alzheimer's disease pathology.
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In vivo and post-mortem memory circuit integrity in Frontotemporal Dementia and Alzheimer's disease.
Brain, 2012Co-Authors: Michael Hornberger, Stephanie Wong, Olivier Piguet, Jillian Kril, Muireann Irish, John R Hodges, Glenda M HallidayAbstract:Behavioural variant Frontotemporal Dementia can present with episodic memory deficits as severe as those in Alzheimer’s disease. Little is known of the integrity of grey matter areas and white matter tracts of the Papez memory circuit in these diseases. The integrity of the Papez circuit (hippocampus, fornix, mammillary bodies, anterior thalamus, cingulate cortex) was investigated in vivo and at post-mortem in behavioural variant Frontotemporal Dementia and Alzheimer’s disease cohorts using voxel-based morphometry, diffusion tensor imaging and manual volumetric tracing. Our findings indicate that behavioural variant Frontotemporal Dementia and Alzheimer’s disease show similar degrees of hippocampal atrophy in vivo , but patients with behavioural variant Frontotemporal Dementia show greater hippocampal atrophy at post-mortem , with the Frontotemporal lobar degeneration with TDP-43 inclusions subtype being particularly affected. Cingulate cortex findings show an expected atrophy pattern with behavioural variant Frontotemporal Dementia being affected more anteriorly and Alzheimer’s disease showing more posterior atrophy. More importantly, subcortical Papez circuit regions (fornix and anterior thalamus) were affected in behavioural variant Frontotemporal Dementia only, with atrophy in these regions determining the degree of amnesia in behavioural variant Frontotemporal Dementia. Hippocampal atrophy does not appear to be an efficient diagnostic marker for underlying behavioural variant Frontotemporal Dementia or Alzheimer’s disease pathology, although for behavioural variant Frontotemporal Dementia, episodic memory deficits in conjunction with marked hippocampal atrophy emerge as potential biomarkers for Frontotemporal lobar degeneration with TDP-43 inclusions pathology. Sub-regions of the Papez circuit were differentially affected in behavioural variant Frontotemporal Dementia and Alzheimer’s disease with subcortical regions determining the degree of episodic memory deficits in behavioural variant Frontotemporal Dementia. Subcortical atrophy should be taken into account when establishing whether the severe amnesia observed in a patient is likely to be due to behavioural variant Frontotemporal Dementia or Alzheimer’s disease pathology. * Abbreviations : DTI : diffusion tensor imaging FTD : Frontotemporal Dementia FTLD : Frontotemporal lobar Dementia VBM : voxel-based morphometry
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episodic memory in Frontotemporal Dementia a critical review
Brain, 2012Co-Authors: Olivier Piguet, Michael HornbergerAbstract:This review offers a critical appraisal of the literature on episodic memory performance in Frontotemporal Dementia. Historically, description of patients diagnosed with what was then known as Pick's disease included the presence of memory deficits and an underlying amnestic syndrome was noted in some of these patients. Over the last 20 years, however, the clinical view has been that episodic memory processing is relatively intact in the Frontotemporal Dementia syndrome. In particular, patients with the subtypes of behavioural variant Frontotemporal Dementia and progressive non-fluent aphasia are reported to perform within normal limits on standard memory tests. In the third clinical presentation of Frontotemporal Dementia, semantic Dementia, relatively intact episodic memory against a significantly impaired semantic memory was regarded as the hallmark. This position was instrumental in the development of clinical diagnostic criteria for Frontotemporal Dementia in which amnesia was explicitly listed as an exclusion criterion for the disease. The relative intactness of episodic memory, therefore, appeared to be a useful diagnostic marker to distinguish early Frontotemporal Dementia from Alzheimer's disease, in which early episodic memory disturbance remains the most common clinical feature. We argue that recent evidence questions the validity of preserved episodic memory in Frontotemporal Dementia, particularly in behavioural variant Frontotemporal Dementia. In semantic Dementia, a complex picture emerges with preservation of some components of episodic memory, notably recognition-based visual memory and recall of recent autobiographical events. We propose a critical synthesis of recent neuropsychological evidence on retrograde and anterograde memory in light of neuroimaging and neuropathological findings, demonstrating involvement of medial temporal structures in Frontotemporal Dementia, structures known to be critical for episodic memory processing. We further argue that the multifactorial nature of most memory tests commonly used clinically fail to capture the memory deficits in Frontotemporal Dementia and that sensitive assessment tools of memory are needed. Together, recent clinical and experimental findings and the historical evidence represent a strong case for a re-evaluation of the importance of memory disturbance in the clinical diagnosis of Frontotemporal Dementia. * Abbreviations : FTD : Frontotemporal Dementia PNFA : progressive non-fluent aphasia
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Episodic memory in Frontotemporal Dementia: a critical review.
Brain : a journal of neurology, 2012Co-Authors: Michael Hornberger, Olivier PiguetAbstract:This review offers a critical appraisal of the literature on episodic memory performance in Frontotemporal Dementia. Historically, description of patients diagnosed with what was then known as Pick's disease included the presence of memory deficits and an underlying amnestic syndrome was noted in some of these patients. Over the last 20 years, however, the clinical view has been that episodic memory processing is relatively intact in the Frontotemporal Dementia syndrome. In particular, patients with the subtypes of behavioural variant Frontotemporal Dementia and progressive non-fluent aphasia are reported to perform within normal limits on standard memory tests. In the third clinical presentation of Frontotemporal Dementia, semantic Dementia, relatively intact episodic memory against a significantly impaired semantic memory was regarded as the hallmark. This position was instrumental in the development of clinical diagnostic criteria for Frontotemporal Dementia in which amnesia was explicitly listed as an exclusion criterion for the disease. The relative intactness of episodic memory, therefore, appeared to be a useful diagnostic marker to distinguish early Frontotemporal Dementia from Alzheimer's disease, in which early episodic memory disturbance remains the most common clinical feature. We argue that recent evidence questions the validity of preserved episodic memory in Frontotemporal Dementia, particularly in behavioural variant Frontotemporal Dementia. In semantic Dementia, a complex picture emerges with preservation of some components of episodic memory, notably recognition-based visual memory and recall of recent autobiographical events. We propose a critical synthesis of recent neuropsychological evidence on retrograde and anterograde memory in light of neuroimaging and neuropathological findings, demonstrating involvement of medial temporal structures in Frontotemporal Dementia, structures known to be critical for episodic memory processing. We further argue that the multifactorial nature of most memory tests commonly used clinically fail to capture the memory deficits in Frontotemporal Dementia and that sensitive assessment tools of memory are needed. Together, recent clinical and experimental findings and the historical evidence represent a strong case for a re-evaluation of the importance of memory disturbance in the clinical diagnosis of Frontotemporal Dementia.
Olivier Piguet - One of the best experts on this subject based on the ideXlab platform.
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Energy expenditure in Frontotemporal Dementia: a behavioural and imaging study
Brain, 2016Co-Authors: Rebekah M. Ahmed, Olivier Piguet, Matthew C Kiernan, Ramon Landin-romero, Tinh-hai Collet, Agatha A. Van Der Klaauw, Emma Devenney, Elana Henning, I. Sadaf Farooqi, John R HodgesAbstract:Abnormal eating behaviour and metabolic parameters including insulin resistance, dyslipidaemia and body mass index are increasingly recognized as important components of neurodegenerative disease and may contribute to survival. It has previously been established that behavioural variant Frontotemporal Dementia is associated with abnormal eating behaviour characterized by increased sweet preference. In this study, it was hypothesized that behavioural variant Frontotemporal Dementia might also be associated with altered energy expenditure. A cohort of 19 patients with behavioural variant Frontotemporal Dementia, 13 with Alzheimer’s disease and 16 (age- and sex-matched) healthy control subjects were studied using Actiheart devices (CamNtech) to assess resting and stressed heart rate. Actiheart devices were fitted for 7 days to measure sleeping heart rate, activity levels, and resting, active and total energy expenditure. Using high resolution structural magnetic resonance imaging the neural correlates of increased resting heart rate were investigated including cortical thickness and region of interest analyses. In behavioural variant Frontotemporal Dementia, resting ( P = 0.001), stressed ( P = 0.037) and sleeping heart rate ( P = 0.038) were increased compared to control subjects, and resting heart rate ( P = 0.020) compared to Alzheimer disease patients. Behavioural variant Frontotemporal Dementia was associated with decreased activity levels compared to controls ( P = 0.002) and increased resting energy expenditure ( P = 0.045) and total energy expenditure ( P = 0.035). Increased resting heart rate correlated with behavioural (Cambridge Behavioural Inventory) and cognitive measures (Addenbrooke’s Cognitive Examination). Increased resting heart rate in behavioural variant Frontotemporal Dementia correlated with atrophy involving the mesial temporal cortex, insula, and amygdala, regions previously suggested to be involved exclusively in social and emotion processing in Frontotemporal Dementia. These neural correlates overlap the network involved in eating behaviour in Frontotemporal Dementia, suggesting a complex interaction between eating behaviour, autonomic function and energy homeostasis. As such the present study suggests that increased heart rate and autonomic changes are prevalent in behavioural variant Frontotemporal Dementia, and are associated with changes in energy expenditure. An understanding of these changes and neural correlates may have potential relevance to disease progression and prognosis. * Abbreviations : ALS : amyotrophic lateral sclerosis BMI : body mass index bvFTD : behavioural variant Frontotemporal Dementia FTD : Frontotemporal Dementia RMSSD : root mean squared of successive differences
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In vivo and post-mortem memory circuit integrity in Frontotemporal Dementia and Alzheimer's disease.
Brain : a journal of neurology, 2012Co-Authors: Michael Hornberger, Stephanie Wong, Olivier Piguet, Jillian Kril, Muireann Irish, John R Hodges, Glenda HallidayAbstract:Behavioural variant Frontotemporal Dementia can present with episodic memory deficits as severe as those in Alzheimer's disease. Little is known of the integrity of grey matter areas and white matter tracts of the Papez memory circuit in these diseases. The integrity of the Papez circuit (hippocampus, fornix, mammillary bodies, anterior thalamus, cingulate cortex) was investigated in vivo and at post-mortem in behavioural variant Frontotemporal Dementia and Alzheimer's disease cohorts using voxel-based morphometry, diffusion tensor imaging and manual volumetric tracing. Our findings indicate that behavioural variant Frontotemporal Dementia and Alzheimer's disease show similar degrees of hippocampal atrophy in vivo, but patients with behavioural variant Frontotemporal Dementia show greater hippocampal atrophy at post-mortem, with the Frontotemporal lobar degeneration with TDP-43 inclusions subtype being particularly affected. Cingulate cortex findings show an expected atrophy pattern with behavioural variant Frontotemporal Dementia being affected more anteriorly and Alzheimer's disease showing more posterior atrophy. More importantly, subcortical Papez circuit regions (fornix and anterior thalamus) were affected in behavioural variant Frontotemporal Dementia only, with atrophy in these regions determining the degree of amnesia in behavioural variant Frontotemporal Dementia. Hippocampal atrophy does not appear to be an efficient diagnostic marker for underlying behavioural variant Frontotemporal Dementia or Alzheimer's disease pathology, although for behavioural variant Frontotemporal Dementia, episodic memory deficits in conjunction with marked hippocampal atrophy emerge as potential biomarkers for Frontotemporal lobar degeneration with TDP-43 inclusions pathology. Sub-regions of the Papez circuit were differentially affected in behavioural variant Frontotemporal Dementia and Alzheimer's disease with subcortical regions determining the degree of episodic memory deficits in behavioural variant Frontotemporal Dementia. Subcortical atrophy should be taken into account when establishing whether the severe amnesia observed in a patient is likely to be due to behavioural variant Frontotemporal Dementia or Alzheimer's disease pathology.
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In vivo and post-mortem memory circuit integrity in Frontotemporal Dementia and Alzheimer's disease.
Brain, 2012Co-Authors: Michael Hornberger, Stephanie Wong, Olivier Piguet, Jillian Kril, Muireann Irish, John R Hodges, Glenda M HallidayAbstract:Behavioural variant Frontotemporal Dementia can present with episodic memory deficits as severe as those in Alzheimer’s disease. Little is known of the integrity of grey matter areas and white matter tracts of the Papez memory circuit in these diseases. The integrity of the Papez circuit (hippocampus, fornix, mammillary bodies, anterior thalamus, cingulate cortex) was investigated in vivo and at post-mortem in behavioural variant Frontotemporal Dementia and Alzheimer’s disease cohorts using voxel-based morphometry, diffusion tensor imaging and manual volumetric tracing. Our findings indicate that behavioural variant Frontotemporal Dementia and Alzheimer’s disease show similar degrees of hippocampal atrophy in vivo , but patients with behavioural variant Frontotemporal Dementia show greater hippocampal atrophy at post-mortem , with the Frontotemporal lobar degeneration with TDP-43 inclusions subtype being particularly affected. Cingulate cortex findings show an expected atrophy pattern with behavioural variant Frontotemporal Dementia being affected more anteriorly and Alzheimer’s disease showing more posterior atrophy. More importantly, subcortical Papez circuit regions (fornix and anterior thalamus) were affected in behavioural variant Frontotemporal Dementia only, with atrophy in these regions determining the degree of amnesia in behavioural variant Frontotemporal Dementia. Hippocampal atrophy does not appear to be an efficient diagnostic marker for underlying behavioural variant Frontotemporal Dementia or Alzheimer’s disease pathology, although for behavioural variant Frontotemporal Dementia, episodic memory deficits in conjunction with marked hippocampal atrophy emerge as potential biomarkers for Frontotemporal lobar degeneration with TDP-43 inclusions pathology. Sub-regions of the Papez circuit were differentially affected in behavioural variant Frontotemporal Dementia and Alzheimer’s disease with subcortical regions determining the degree of episodic memory deficits in behavioural variant Frontotemporal Dementia. Subcortical atrophy should be taken into account when establishing whether the severe amnesia observed in a patient is likely to be due to behavioural variant Frontotemporal Dementia or Alzheimer’s disease pathology. * Abbreviations : DTI : diffusion tensor imaging FTD : Frontotemporal Dementia FTLD : Frontotemporal lobar Dementia VBM : voxel-based morphometry
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episodic memory in Frontotemporal Dementia a critical review
Brain, 2012Co-Authors: Olivier Piguet, Michael HornbergerAbstract:This review offers a critical appraisal of the literature on episodic memory performance in Frontotemporal Dementia. Historically, description of patients diagnosed with what was then known as Pick's disease included the presence of memory deficits and an underlying amnestic syndrome was noted in some of these patients. Over the last 20 years, however, the clinical view has been that episodic memory processing is relatively intact in the Frontotemporal Dementia syndrome. In particular, patients with the subtypes of behavioural variant Frontotemporal Dementia and progressive non-fluent aphasia are reported to perform within normal limits on standard memory tests. In the third clinical presentation of Frontotemporal Dementia, semantic Dementia, relatively intact episodic memory against a significantly impaired semantic memory was regarded as the hallmark. This position was instrumental in the development of clinical diagnostic criteria for Frontotemporal Dementia in which amnesia was explicitly listed as an exclusion criterion for the disease. The relative intactness of episodic memory, therefore, appeared to be a useful diagnostic marker to distinguish early Frontotemporal Dementia from Alzheimer's disease, in which early episodic memory disturbance remains the most common clinical feature. We argue that recent evidence questions the validity of preserved episodic memory in Frontotemporal Dementia, particularly in behavioural variant Frontotemporal Dementia. In semantic Dementia, a complex picture emerges with preservation of some components of episodic memory, notably recognition-based visual memory and recall of recent autobiographical events. We propose a critical synthesis of recent neuropsychological evidence on retrograde and anterograde memory in light of neuroimaging and neuropathological findings, demonstrating involvement of medial temporal structures in Frontotemporal Dementia, structures known to be critical for episodic memory processing. We further argue that the multifactorial nature of most memory tests commonly used clinically fail to capture the memory deficits in Frontotemporal Dementia and that sensitive assessment tools of memory are needed. Together, recent clinical and experimental findings and the historical evidence represent a strong case for a re-evaluation of the importance of memory disturbance in the clinical diagnosis of Frontotemporal Dementia. * Abbreviations : FTD : Frontotemporal Dementia PNFA : progressive non-fluent aphasia
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Episodic memory in Frontotemporal Dementia: a critical review.
Brain : a journal of neurology, 2012Co-Authors: Michael Hornberger, Olivier PiguetAbstract:This review offers a critical appraisal of the literature on episodic memory performance in Frontotemporal Dementia. Historically, description of patients diagnosed with what was then known as Pick's disease included the presence of memory deficits and an underlying amnestic syndrome was noted in some of these patients. Over the last 20 years, however, the clinical view has been that episodic memory processing is relatively intact in the Frontotemporal Dementia syndrome. In particular, patients with the subtypes of behavioural variant Frontotemporal Dementia and progressive non-fluent aphasia are reported to perform within normal limits on standard memory tests. In the third clinical presentation of Frontotemporal Dementia, semantic Dementia, relatively intact episodic memory against a significantly impaired semantic memory was regarded as the hallmark. This position was instrumental in the development of clinical diagnostic criteria for Frontotemporal Dementia in which amnesia was explicitly listed as an exclusion criterion for the disease. The relative intactness of episodic memory, therefore, appeared to be a useful diagnostic marker to distinguish early Frontotemporal Dementia from Alzheimer's disease, in which early episodic memory disturbance remains the most common clinical feature. We argue that recent evidence questions the validity of preserved episodic memory in Frontotemporal Dementia, particularly in behavioural variant Frontotemporal Dementia. In semantic Dementia, a complex picture emerges with preservation of some components of episodic memory, notably recognition-based visual memory and recall of recent autobiographical events. We propose a critical synthesis of recent neuropsychological evidence on retrograde and anterograde memory in light of neuroimaging and neuropathological findings, demonstrating involvement of medial temporal structures in Frontotemporal Dementia, structures known to be critical for episodic memory processing. We further argue that the multifactorial nature of most memory tests commonly used clinically fail to capture the memory deficits in Frontotemporal Dementia and that sensitive assessment tools of memory are needed. Together, recent clinical and experimental findings and the historical evidence represent a strong case for a re-evaluation of the importance of memory disturbance in the clinical diagnosis of Frontotemporal Dementia.
