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Mapping the onset and progression of atrophy in familial frontotemporal lobar degeneration
  1. J C Janssen1,
  2. J M Schott1,
  3. L Cipolotti2,
  4. N C Fox1,
  5. R I Scahill1,
  6. K A Josephs1,
  7. J M Stevens3,4,
  8. M N Rossor1,4
  1. 1Dementia Research Group, Institute of Neurology, London, UK
  2. 2Department of Neuropsychology, National Hospital for Neurology and Neurosurgery, London, UK
  3. 3Department of Clinical Neuroradiology, National Hospital for Neurology and Neurosurgery, London, UK
  4. 4Division of Neuroscience and Psychological Medicine, Faculty of Medicine, Imperial College of Science, Engineering and Medicine, London, UK
  1. Correspondence to:
 Professor M N Rossor
 Dementia Research Group, Institute of Neurology, Queen Square, London WC1N 3BG, UK; m.rossordementia.ion.ucl.ac.uk

Abstract

Background: Frontotemporal lobar degeneration (FTLD) may be inherited as an autosomal dominant disease. Studying patients “at risk” for developing FTLD can provide insights into the earliest onset and evolution of the disease.

Method: We carried out approximately annual clinical, MRI, and neuropsychological assessments on an asymptomatic 51 year old “at risk” family member from a family with FTLD associated with ubiquitin-positive and tau-negative inclusion bodies. We used non-linear (fluid) registration of serial MRI to determine areas undergoing significant regional atrophy at different stages of the disease.

Results: Over the first 26 months of the study, the patient remained asymptomatic, but subsequently developed progressive speech production difficulties, and latterly severe orofacial dyspraxia, dyscalculia, frontal executive impairment, and limb dyspraxia. Regional atrophy was present prior to the onset of symptoms, and was initially centred on the left dorsolateral prefrontal cortex and the left middle frontal gyrus. Latterly, there was increasing asymmetric left frontal and parietal atrophy. Imaging revealed excess and increasing global atrophy throughout the study. Neuropsychological evaluation revealed mild intellectual impairment prior to the onset of these clinical symptoms; frontal executive and left parietal impairment subsequently emerged, culminating in widespread cognitive impairment. Fluid registered MRI allowed the emerging atrophy patterns to be delineated.

Conclusion: We have demonstrated the onset and progressive pattern of in vivo atrophy in familial FTLD using fluid registered MRI and correlated this with the clinical features. Fluid registered MRI may be a useful technique in assessing patterns of focal atrophy in vivo and demonstrating the progression of degenerative diseases.

  • AD, Alzheimer’s disease
  • BBSI, brain boundary shift integral
  • EOD, early onset dementia
  • FTD, frontotemporal dementia
  • FTLD, frontotemporal lobar degeneration
  • MAPT, microtubule associated protein tau
  • NART, National Adult Reading Test
  • PA, progressive non-fluent aphasia
  • TIV, total intracranial volume
  • SD, semantic dementia
  • WAIS-R, Wechsler Adult Intelligence Scale-Revised
  • atrophy
  • fluid registration
  • frontotemporal lobar degeneration
  • MRI
  • presymptomatic
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Footnotes

  • This study was funded by a UK Medical Research Council Program grant G9626876; RIS is supported by the Alzheimer’s Research Trust and latterly by the Medical Research Council; JMS is in receipt of an Alzheimer’s Society Research Fellowship; and NCF is a Medical Research Council Senior Clinical Scientist.

  • Competing interests: none declared

  • Martin Rossor assumed editorship of the Journal of Neurology, Neurosurgery and Psychiatry after submission of this paper and has had no involvement in the review process.

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