title: Structural and functional brain connectivity in presymptomatic familial frontotemporal dementia.
abstract: OBJECTIVE
  We aimed to investigate whether cognitive deficits and structural and functional connectivity changes can be detected before symptom onset in a large cohort of carriers of microtubule-associated protein tau and progranulin mutations.
  
  
  METHODS
  In this case-control study, 75 healthy individuals (aged 20-70 years) with 50% risk for frontotemporal dementia (FTD) underwent DNA screening, neuropsychological assessment, and structural and functional MRI. We used voxel-based morphometry and tract-based spatial statistics for voxelwise analyses of gray matter volume and diffusion tensor imaging measures. Using resting-state fMRI scans, we assessed whole-brain functional connectivity to frontoinsula, anterior midcingulate cortex (aMCC), and posterior cingulate cortex.
  
  
  RESULTS
  Although carriers (n = 37) and noncarriers (n = 38) had similar neuropsychological performance, worse performance on Stroop III, Ekman faces, and Happé cartoons correlated with higher age in carriers, but not controls. Reduced fractional anisotropy and increased radial diffusivity throughout frontotemporal white matter tracts were found in carriers and correlated with higher age. Reductions in functional aMCC connectivity were found in carriers compared with controls, and connectivity between frontoinsula and aMCC seeds and several brain regions significantly decreased with higher age in carriers but not controls. We found no significant differences or age correlations in posterior cingulate cortex connectivity. No differences in regional gray matter volume were found.
  
  
  CONCLUSIONS
  This study convincingly demonstrates that alterations in structural and functional connectivity develop before the first symptoms of FTD arise. These findings suggest that diffusion tensor imaging and resting-state fMRI may have the potential to become sensitive biomarkers for early FTD in future clinical trials.
authors: Department of Neurology, Erasmus Medical Center, Rotterdam, the Netherlands.
authors: Elise G P
authors: EG
authors: Dopper
authors: Serge A R B
authors: SA
authors: Rombouts
authors: Lize C
authors: LC
authors: Jiskoot
authors: Tom den
authors: Td
authors: Heijer
authors: J Roos A
authors: JR
authors: de Graaf
authors: Inge de
authors: Id
authors: Koning
authors: Anke R
authors: AR
authors: Hammerschlag
authors: Harro
authors: H
authors: Seelaar
authors: William W
authors: WW
authors: Seeley
authors: Ilya M
authors: IM
authors: Veer
authors: Mark A
authors: MA
authors: van Buchem
authors: Patrizia
authors: P
authors: Rizzu
authors: John C
authors: JC
authors: van Swieten
mesh_terms: D000328:Adult; D000368:Aged; D001923:Brain Chemistry / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism / Q000473:pathology; D057180:Frontotemporal Dementia / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009415:Nerve Net / Q000473:pathology* / Q000503:physiopathology*; D012306:Risk; D013329:Structure-Activity Relationship
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