TITLE

Clinical and neuroanatomical signatures of tissue pathology in frontotemporal lobar degeneration

AUTHOR(S)
Rohrer, Jonathan D.; Lashley, Tammaryn; Schott, Jonathan M.; Warren, Jane E.; Mead, Simon; Isaacs, Adrian M.; Beck, Jonathan; Hardy, John; de Silva, Rohan; Warrington, Elizabeth; Troakes, Claire; Al-Sarraj, Safa; King, Andrew; Borroni, Barbara; Clarkson, Matthew J.; Ourselin, Sebastien; Holton, Janice L.; Fox, Nick C.; Revesz, Tamas; Rossor, Martin N.
PUB. DATE
September 2011
SOURCE
Brain: A Journal of Neurology;Sep2011, Vol. 134 Issue 9, p2565
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Relating clinical symptoms to neuroanatomical profiles of brain damage and ultimately to tissue pathology is a key challenge in the field of neurodegenerative disease and particularly relevant to the heterogeneous disorders that comprise the frontotemporal lobar degeneration spectrum. Here we present a retrospective analysis of clinical, neuropsychological and neuroimaging (volumetric and voxel-based morphometric) features in a pathologically ascertained cohort of 95 cases of frontotemporal lobar degeneration classified according to contemporary neuropathological criteria. Forty-eight cases (51%) had TDP-43 pathology, 42 (44%) had tau pathology and five (5%) had fused-in-sarcoma pathology. Certain relatively specific clinicopathological associations were identified. Semantic dementia was predominantly associated with TDP-43 type C pathology; frontotemporal dementia and motoneuron disease with TDP-43 type B pathology; young-onset behavioural variant frontotemporal dementia with FUS pathology; and the progressive supranuclear palsy syndrome with progressive supranuclear palsy pathology. Progressive non-fluent aphasia was most commonly associated with tau pathology. However, the most common clinical syndrome (behavioural variant frontotemporal dementia) was pathologically heterogeneous; while pathologically proven Pick's disease and corticobasal degeneration were clinically heterogeneous, and TDP-43 type A pathology was associated with similar clinical features in cases with and without progranulin mutations. Volumetric magnetic resonance imaging, voxel-based morphometry and cluster analyses of the pathological groups here suggested a neuroanatomical framework underpinning this clinical and pathological diversity. Frontotemporal lobar degeneration-associated pathologies segregated based on their cerebral atrophy profiles, according to the following scheme: asymmetric, relatively localized (predominantly temporal lobe) atrophy (TDP-43 type C); relatively symmetric, relatively localized (predominantly temporal lobe) atrophy (microtubule-associated protein tau mutations); strongly asymmetric, distributed atrophy (Pick's disease); relatively symmetric, predominantly extratemporal atrophy (corticobasal degeneration, fused-in-sarcoma pathology). TDP-43 type A pathology was associated with substantial individual variation; however, within this group progranulin mutations were associated with strongly asymmetric, distributed hemispheric atrophy. We interpret the findings in terms of emerging network models of neurodegenerative disease: the neuroanatomical specificity of particular frontotemporal lobar degeneration pathologies may depend on an interaction of disease-specific and network-specific factors.
ACCESSION #
65458140

 

Related Articles

  • Frontotemporal lobar degeneration: current knowledge and future challenges. Cerami, Chiara; Scarpini, Elio; Cappa, Stefano; Galimberti, Daniela // Journal of Neurology;Nov2012, Vol. 259 Issue 11, p2278 

    Frontotemporal lobar degeneration (FTLD) is one of the most frequent neurodegenerative disorders with a presenile onset. It presents with a spectrum of clinical manifestations, ranging from behavioral and executive impairment to language disorders and motor dysfunction. New diagnostic criteria...

  • Simple motor stereotypies are not specific features of behavioural frontotemporal dementia. Cagnin, Annachiara; Formentin, Chiara; Pompanin, Sara; Zarantonello, Giulia; Jelcic, Nela; Venneri, Annalena; Ermani, Mario // Journal of Neurology, Neurosurgery & Psychiatry;Aug2014, Vol. 85 Issue 8, p943 

    A letter to the editor is presented in response to the article "Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia" by K Rascovsky et al. in 2011 issue.

  • Alzheimer Disease. Cummings, Jeffrey L.; Cole, Greg // JAMA: Journal of the American Medical Association;5/8/2002, Vol. 287 Issue 18, p2335 

    Focuses on alzheimer disease, a progressive neurodegenerative disorder. Incidence, prevalence, and economic impact; Clinical diagnosis; Pathology; Molecular genetics and pathogenesis; Treatments, including cholinesterase inhibitors.

  • Globular glial-like inclusions in a patient with advanced Alzheimer's disease. Gelpi, Ellen; Cullel, Francesc; Navarro-Otano, Judith; Lladó, Albert // Acta Neuropathologica;Jul2013, Vol. 126 Issue 1, p155 

    A letter to the editor is presented in response to the article "Globular glial tauopathies (GGT) presenting with motor neuron disease or frontotemporal dementia: an emerging group of 4-repeat tauopathies," by Z. Ahmed and colleagues in the 2011 issue.

  • Frontotemporal dementia and primary progressive aphasia, a review. Kirshner, Howard S. // Neuropsychiatric Disease & Treatment;2014, Vol. 10, p1045 

    Frontotemporal dementias are neurodegenerative diseases in which symptoms of frontal and/or temporal lobe disease are the first signs of the illness, and as the diseases progress, they resemble a focal left hemisphere process such as stroke or traumatic brain injury, even more than a...

  • Therapeutic and diagnostic challenges for frontotemporal dementia. D'Alton, Simon; Lewis, Jada // Frontiers in Aging Neuroscience;Aug2014, Vol. 6, p1 

    In the search for therapeutic modifiers, frontotemporal dementia (FTD) has traditionally been overshadowed by other conditions such as Alzheimer's disease (AD). A clinically and pathologically diverse condition, FTD has been galvanized by a number of recent discoveries such as novel genetic...

  • The behavioral variant of frontotemporal dementia: linking neuropathology to social cognition. Cerami, Chiara; Cappa, Stefano // Neurological Sciences;Aug2013, Vol. 34 Issue 8, p1267 

    The behavioral variant of frontotemporal dementia (bvFTD) is one of the most frequent neurodegenerative disorders with a presenile onset. It is characterized by a long phase of subclinical behavioral changes and social conduct disorders, associated with a progressive modification of personality....

  • Frontotemporal dementia-amyotrophic lateral sclerosis syndrome locus on chromosome 16p12.1-q12.2: genetic, clinical and neuropathological analysis. Dobson-Stone, Carol; Luty, Agnes; Thompson, Elizabeth; Blumbergs, Peter; Brooks, William; Short, Cathy; Field, Colin; Panegyres, Peter; Hecker, Jane; Solski, Jennifer; Blair, Ian; Fullerton, Janice; Halliday, Glenda; Schofield, Peter; Kwok, John // Acta Neuropathologica;Apr2013, Vol. 125 Issue 4, p523 

    Numerous families exhibiting both frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) have been described, and although many of these have been shown to harbour a repeat expansion in C9ORF72, several C9ORF72-negative FTD-ALS families remain. We performed neuropathological and...

  • C9ORF72 hexanucleotide repeats in behavioral and motor neuron disease: clinical heterogeneity and pathological diversity. Yokoyama, Jennifer S.; Sirkis, Daniel W.; Miller, Bruce L. // American Journal of Neurodegenerative Disease;2014, Vol. 3 Issue 1, p1 

    Hexanucleotide repeat expansion in C9ORF72 is the most common genetic cause of frontotemporal dementia (FTD), a predominantly behavioral disease, and amyotrophic lateral sclerosis (ALS), a disease of motor neurons. The primary objectives of this review are to highlight the clinical heterogeneity...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics