Show simple item record

dc.contributor.authorMurley, Alexanderen
dc.contributor.authorCoyle-Gilchrist, Ianen
dc.contributor.authorRouse, Matthewen
dc.contributor.authorJones, Simonen
dc.contributor.authorLi, Winen
dc.contributor.authorWiggins, Julieen
dc.contributor.authorLansdall, Claireen
dc.contributor.authorVázquez Rodríguez, Patriciaen
dc.contributor.authorWilcox, Aliciaen
dc.contributor.authorTsvetanov, Kamen A.en
dc.contributor.authorPatterson, Karalynen
dc.contributor.authorLambon Ralph, Matthewen
dc.contributor.authorRowe, Jamesen
dc.description.abstractThe syndromes caused by frontotemporal lobar degeneration (FTLD) have highly heterogenous and overlapping clinical features. There has been great progress in the refinement of clinical diagnostic criteria in the last decade, but we propose that a better understanding of aetiology, pathophysiology and symptomatic treatments can arise from a transdiagnostic approach to clinical phenotype and brain morphometry. In a cross-sectional epidemiological study, we examined 310 patients with a syndrome likely to be caused by frontotemporal lobar degeneration, including behavioural variant frontotemporal dementia (bvFTD), the non-fluent (nfvPPA), semantic (svPPA) variants of primary progressive aphasia, progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). We also included patients with logopenic primary progressive aphasia (lvPPA) and those who met criteria for PPA but not one of the three subtypes. To date, forty-nine patients have a neuropathological diagnosis. A principal component analysis identified symptom dimensions that broadly recapitulated the core features of the main clinical syndromes. However, the subject-specific scores on these dimensions showed considerable overlap across the diagnostic groups. Sixty-two percent of participants had phenotypic features that met the diagnostic criteria for more than one syndrome. Behavioural disturbance was prevalent in all groups. Forty-four percent of patients with CBS had PSP-like features and thirty percent of patients with PSP had CBS-like features. Many patients with PSP and CBS had language impairments consistent with nfvPPA while patients with bvFTD often had semantic impairments. Using multivariate source-based morphometry on a subset of patients (n=133), we identified patterns of co-varying brain atrophy that were represented across the diagnostic groups. Canonical correlation analysis of clinical and imaging components found three key brain-behaviour relationships that revealed a continuous spectrum across the cohort rather than discrete diagnostic entities. In the forty-six patients with longitudinal follow up (mean 3.6 years) syndromic overlap increased with time. Together, these results show that syndromes associated with FTLD do not form discrete mutually exclusive categories from their clinical features or structural brain changes, but instead exist in a multidimensional spectrum. Patients often manifest diagnostic features of multiple disorders and deficits in behaviour, movement and language domains are not confined to specific diagnostic groups. It is important to recognise individual differences in clinical phenotype, both for clinical management and to understand pathogenic mechanisms. We suggest that the adoption of a transdiagnostic approach to the spectrum of FTLD syndromes provides a useful framework with which to understand disease progression, heterogeneity and treatment.
dc.description.sponsorshipThis work was funded by the Holt Fellowship (AGM), British Academy (KAT, PF160048), Wellcome Trust (JBR, 103838), the PSP Association, the Medical Research Council, the National Institute for Health Research Cambridge Biomedical Research Centre and Cambridge Brain Bank; and the Cambridge Centre for Parkinson Plus.
dc.publisherOxford University Press
dc.rightsAttribution 4.0 International (CC BY)
dc.titleRedefining the multidimensional clinical phenotypes of frontotemporal lobar degeneration syndromesen
prism.publicationNameBrain: a journal of neurologyen
dc.contributor.orcidMurley, Alexander [0000-0003-0813-0670]
dc.contributor.orcidRouse, Matthew [0000-0002-3157-4301]
dc.contributor.orcidJones, Simon [0000-0001-9695-0702]
dc.contributor.orcidTsvetanov, Kamen A. [0000-0002-3178-6363]
dc.contributor.orcidPatterson, Karalyn [0000-0003-1927-7424]
dc.contributor.orcidLambon Ralph, Matthew [0000-0001-5907-2488]
dc.contributor.orcidRowe, James [0000-0001-7216-8679]
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idWELLCOME TRUST (103838/Z/14/Z)
pubs.funder-project-idBritish Academy (pf160048)
pubs.funder-project-idMedical Research Council (MC_U105597119)
cam.orpheus.successTue Jun 16 10:44:39 BST 2020 - The item has an open VoR version.*

Files in this item


This item appears in the following Collection(s)

Show simple item record

Attribution 4.0 International (CC BY)
Except where otherwise noted, this item's licence is described as Attribution 4.0 International (CC BY)