Redefining the multidimensional clinical phenotypes of frontotemporal lobar degeneration syndromes.

摘要: The syndromes caused by frontotemporal lobar degeneration have highly heterogeneous and overlapping clinical features. There has been great progress in the refinement of diagnostic criteria past decade, but we propose that a better understanding aetiology, pathophysiology symptomatic treatments can arise from transdiagnostic approach to phenotype brain morphometry. In cross-sectional epidemiological study, examined 310 patients with syndrome likely be degeneration, including behavioural variant dementia, non-fluent, semantic variants primary progressive aphasia (PPA), supranuclear palsy corticobasal syndrome. We included logopenic PPA those who met for not specific subtype. To date, 49 neuropathological diagnosis. A principal component analysis identified symptom dimensions broadly recapitulated core features main syndromes. However, subject-specific scores on these showed considerable overlap across groups. Sixty-two per cent participants had phenotypic more than one Behavioural disturbance was prevalent all Forty-four palsy-like 30% syndrome-like Many language impairments consistent non-fluent while dementia often impairments. Using multivariate source-based morphometry subset (n = 133), patterns covarying atrophy were represented Canonical correlation imaging components found three key brain-behaviour relationships, continuous spectrum cohort rather discrete entities. 46 follow-up (mean 3.6 years) syndromic increased time. Together, results show associated do form mutually exclusive categories their or structural changes, instead exist multidimensional spectrum. Patients manifest multiple disorders deficits behaviour, movement domains are confined It is important recognize individual differences phenotype, both management understand pathogenic mechanisms. suggest provides useful framework which disease progression, heterogeneity target future higher proportion patients.