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Review
Predictors of survival in frontotemporal lobar degeneration syndromes
  1. Shadi El-Wahsh1,
  2. Elizabeth C Finger2,
  3. Olivier Piguet3,
  4. Vincent Mok4,
  5. Jonathan D Rohrer5,
  6. Matthew C Kiernan1,3,
  7. Rebekah M Ahmed1,3
  1. 1Department of Neurology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
  2. 2Department of Clinicial Neurological Sciences, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada
  3. 3Brain and Mind Centre, The University of Sydney, Sydney, New South Wales, Australia
  4. 4Gerald Choa Neuroscience Centre, Lui Che Woo Institute of Innovative Medicine, Margaret K.L. Cheung Research Centre for Management of Parkinsonism, Division of Neurology, Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong
  5. 5Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK
  1. Correspondence to Dr Rebekah M Ahmed, The University of Sydney, Sydney, NSW 2050, Australia; rebekahahmed{at}gmail.com

Abstract

After decades of research, large-scale clinical trials in patients diagnosed with frontotemporal lobar degeneration (FTLD) are now underway across multiple centres worldwide. As such, refining the determinants of survival in FTLD represents a timely and important challenge. Specifically, disease outcome measures need greater clarity of definition to enable accurate tracking of therapeutic interventions in both clinical and research settings. Multiple factors potentially determine survival, including the clinical phenotype at presentation; radiological patterns of atrophy including markers on both structural and functional imaging; metabolic factors including eating behaviour and lipid metabolism; biomarkers including both serum and cerebrospinal fluid markers of underlying pathology; as well as genetic factors, including both dominantly inherited genes, but also genetic modifiers. The present review synthesises the effect of these factors on disease survival across the syndromes of frontotemporal dementia, with comparison to amyotrophic lateral sclerosis, progressive supranuclear palsy and corticobasal syndrome. A pathway is presented that outlines the utility of these varied survival factors for future clinical trials and drug development. Given the complexity of the FTLD spectrum, it seems unlikely that any single factor may predict overall survival in individual patients, further suggesting that a precision medicine approach will need to be developed in predicting disease survival in FTLD, to enhance drug target development and future clinical trial methodologies.

  • frontotemporal dementia
  • cognition
  • dementia
  • motor neuron disease

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Footnotes

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  • Correction notice This article has been corrected since it first published. The provenance and peer review statement has been included.

  • Contributors SE-W drafted and wrote and critically appraised the manuscript. EF drafted and wrote and critically appraised the manuscript. OP drafted and wrote and critically appraised the manuscript. VM drafted and wrote and critically appraised the manuscript. JDR drafted and wrote and critically appraised the manuscript. MK drafted and wrote and critically appraised the manuscript. RA drafted and wrote and critically appraised the manuscript.

  • Funding This work was supported in part by funding to Forefront, a collaborative research group dedicated to the study of frontotemporal dementia and motor neurone disease, from the National Health and Medical Research Council of Australia (NHMRC) program grant (#1037746 to OP, MK) and the Australian Research Council Centre of Excellence in Cognition and its Disorders Memory Program (#CE110001021 to OP) and other grants/sources (NHMRC project grant #1003139 to OP), and Royal Australasian College of Physicians, MND Research Institute of Australia. RMA is a NHMRC Early Career Fellow (#1120770). MK was supported by an NHMRC Practitioner Fellowship (#1156093), OP by an NHMRC Senior Research Fellowship (#1103258) and EF by a Physicians Services Incorporated Foundation Mid-career award.

  • Competing interests None declared.

  • Provenance and peer review Commissioned; externally peer reviewed.

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