Article Text

PDF
086
THE EVOLUTION OF FRONTOTEMPORAL DEMENTIA DUE TO THE MAPT MUTATION: A SEVENTEEN YEAR NATURAL HISTORY STUDY
  1. Colin Mahoney,
  2. T Yeatman,
  3. JD Rohrer,
  4. E Manning,
  5. KK Leung,
  6. MN Rossor,
  7. JD Warren,
  8. N Fox
  1. University College London

    Abstract

    Introduction Frontotemporal Dementia (FTD) is a common cause of early–onset dementia. A high proportion of cases are due to autosomal dominant mutations. Understanding the natural history of these disorders will be important in the development of diagnostic biomarkers and future disease modifying therapies. However, natural history studies in FTD are lacking. Here we present longitudinal clinical, neuropsychological and neuroimaging data on two members of a family followed over 17 years.

    Methods 13 assessments were carried out during follow–up. Assessments included volumetric MRI, clinical and neuropsychological assessments. Volumetric MRI underwent whole–brain and hippocampal segmentation. Consecutive whole brain and hippocampal regions underwent affine registration and volume change was calculated using the boundary shift integral. Rates of whole brain and hippocampal change were calculated. Patterns of atrophy were visualised using voxel–based morphometry.

    Results Genetic testing confirmed a mutation in MAPT (exon 10+16 mutation) in one sibling who manifested symptoms 11 years after initial assessment. Neuropsychological changes were only detected one year after clinical onset with a decline in episodic memory and naming. However, increased rates of whole brain atrophy were evident as early as the ten years from onset (carrier=1.1%/year, non–carrier 0.1%). On average rates of hippocampal atrophy were disproportionate (2.9%/year) compared to whole brain atrophy (0.6%/year). Rates of atrophy had a non–linear profile. VBM analysis confirmed atrophy of bilateral anterior and medial temporal lobes.

    Discussion This natural history study demonstrates that atrophy in MAPT mutations may be detectable up to a decade in advance of clinical onset. Hippocampal atrophy may be a more sensitive disease biomarker in MAPT associated FTD. Non–linear rates of atrophy may suggest disease evolution has multiple phases.

    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE
    • PARKINSON'S DISEASE
    • STROKE

    Statistics from Altmetric.com

    Request permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.