title: Longitudinal diffusion tensor imaging in frontotemporal dementia.
abstract: OBJECTIVE
  Novel biomarkers for monitoring progression in neurodegenerative conditions are needed. Measurement of microstructural changes in white matter (WM) using diffusion tensor imaging (DTI) may be a useful outcome measure. Here we report trajectories of WM change using serial DTI in a cohort with behavioral variant frontotemporal dementia (bvFTD).
  
  
  METHODS
  Twenty-three patients with bvFTD (12 having genetic mutations), and 18 age-matched control participants were assessed using DTI and neuropsychological batteries at baseline and ~1.3 years later. Baseline and follow-up DTI scans were registered using a groupwise approach. Annualized rates of change for DTI metrics, neuropsychological measures, and whole brain volume were calculated. DTI metric performances were compared, and sample sizes for potential clinical trials were calculated.
  
  
  RESULTS
  In the bvFTD group as a whole, rates of change in fractional anisotropy (FA) and mean diffusivity (MD) within the right paracallosal cingulum were greatest (FA: -6.8%/yr, p < 0.001; MD: 2.9%/yr, p = 0.01). MAPT carriers had the greatest change within left uncinate fasciculus (FA: -7.9%/yr, p < 0.001; MD: 10.9%/yr, p < 0.001); sporadic bvFTD and C9ORF72 carriers had the greatest change within right paracallosal cingulum (sporadic bvFTD, FA: -6.7%/yr, p < 0.001; MD: 3.8%/yr, p = 0.001; C9ORF72, FA: -6.8%/yr, p = 0.004). Sample size estimates using FA change were substantially lower than neuropsychological or whole brain measures of change.
  
  
  CONCLUSIONS
  Serial DTI scans may be useful for measuring disease progression in bvFTD, with particular trajectories of WM damage emerging. Sample size calculations suggest that longitudinal DTI may be a useful biomarker in future clinical trials.
authors.affiliation: Dementia Research Centre, UCL Institute of Neurology, University College London, London, United Kingdom.
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Mahoney
authors.forename: Ivor J A
authors.initials: IJ
authors.lastname: Simpson
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Nicholas
authors.forename: Phillip D
authors.initials: PD
authors.lastname: Fletcher
authors.forename: Laura E
authors.initials: LE
authors.lastname: Downey
authors.forename: Hannah L
authors.initials: HL
authors.lastname: Golden
authors.forename: Camilla N
authors.initials: CN
authors.lastname: Clark
authors.forename: Nicole
authors.initials: N
authors.lastname: Schmitz
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Rohrer
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Schott
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Sebastian
authors.initials: S
authors.lastname: Ourselin
authors.forename: Jason D
authors.initials: JD
authors.lastname: Warren
authors.forename: Nick C
authors.initials: NC
authors.lastname: Fox
mesh_terms: D000368:Aged; D016880:Anisotropy; D001921:Brain / Q000473:pathology*; D016022:Case-Control Studies; D003072:Cognition Disorders / Q000175:diagnosis / Q000209:etiology; D056324:Diffusion Tensor Imaging; D018450:Disease Progression; D005260:Female; D057180:Frontotemporal Dementia / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D012680:Sensitivity and Specificity; D066127:White Matter / Q000473:pathology*