Factors predicting loss of independence and mortality in frontotemporal lobar degeneration

Abstract

Frontotemporal lobar degeneration (FTLD) is a complex clinicopathological concept comprising several fatal neurodegenerative diseases. Clinically, behavioural change, language impairment, semantic memory deficits, motor neuron signs, parkinsonism and apraxia can develop in various orders. 2 Pathologically, tau, transactive response DNAbinding protein 43 kDa and fused in sarcoma are major components of diagnostic lesions of various pathological disease entities. Such clinicopathological complexity may make predicting a longitudinal course difficult in the early stage. On the other hand, most families hope to know the details of the course of a disease and to get practical advice helpful for their life. Researchers also have had a strong interest in this issue. 4 Murley et al used a transdiagnostic approach to survival in an epidemiological cohort in the UK, examining the association between clinical features, independence and survival in 365 patients with FTLD. Clinical diagnoses varied, being behavioural variant frontotemporal dementia (bvFTD), nonfluent variant primary progressive aphasia, semantic variant primary progressive aphasia, progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). They extracted six syndrome dimensions using a principal components analysis of all subjects. Cox proportional hazards regression revealed that a shorter time to death was significantly associated with two syndrome dimensions: one was syndrome dimension 3, which is characterised by the Richardson syndromelike motor phenotype (symmetrical parkinsonism, falls and supranuclear gaze palsy). The other was syndrome dimension 4, which is characterised by asymmetrical parkinsonism, myoclonus and dystonia with cortical features of alien limb syndrome, apraxia and cortical sensory loss. Logistic regression analyses demonstrated that syndrome dimension 1, reflecting behavioural impairment, was the most significant predictor of care home admission. The greatest strength of this study is that all patients who were diagnosed with FTLDrelated syndromes and lived in the UK counties of Cambridgeshire and Norfolk from 2013 to 2014 and from 2017 to 2018 were included. Findings regarding syndrome dimensions defined by not only psychological tests but also concrete symptoms may be useful in the clinical practice of readers. A limitation of this study is the deviation of the proportions of clinical diagnoses: 77% of subjects were diagnosed with PSP, CBS or bvFTD, and indeed PSP and corticobasal degeneration pathologies tended to be frequent in this cohort. Therefore, whether the findings presented in this paper can be generalised to clinical treatment of FTLD remains to be elucidated. Living at home for as long as possible is the dearest wish of people with progressive diseases and their families. Information regarding the prognosis is important in consideration of daily living and life plans. The findings of this study may draw interest from neurological, care and social points of view, and some readers may also consider issues of qualities of care and living environments for patients with FTLD after institutionalisation. 7 Finally, noteworthy is that brain donation and pathological examination are now in progress in an FTLD cohort in this study. Such steady pathological activity combined with clinical assessment, which can be implemented by the voluntary contributions of patients and family, will accumulate findings useful to predict underlying pathogenic processes and longitudinal courses. A ‘gift of hope’ from each patient and family affected is expected to provide clarity for people who have this rare disability, which is still very difficult to deal with in daily life.