title: White matter disease contributes to apathy and disinhibition in behavioral variant frontotemporal dementia.
abstract: OBJECTIVE
  To relate changes in fractional anisotropy associated with behavioral variant frontotemporal dementia to measures of apathy and disinhibition.
  
  
  BACKGROUND
  Apathy and disinhibition are the 2 most common behavioral features of behavioral variant frontotemporal dementia, and these symptoms are associated with accelerated patient decline and caregiver stress. However, little is known about how white matter disease contributes to these symptoms.
  
  
  METHODS
  We collected neuropsychiatric data, volumetric magnetic resonance imaging, and diffusion-weighted imaging in 11 patients who met published criteria for behavioral variant frontotemporal dementia and had an autopsy-validated cerebrospinal fluid profile consistent with frontotemporal lobar degeneration. We also collected imaging data on 34 healthy seniors for analyses defining regions of disease in the patients. We calculated and analyzed fractional anisotropy with a white matter tract-specific method. This approach uses anatomically guided data reduction to increase sensitivity, and localizes results within canonically defined tracts. We used nonparametric, cluster-based statistical analysis to relate fractional anisotropy to neuropsychiatric measures of apathy and disinhibition.
  
  
  RESULTS
  The patients with behavioral variant frontotemporal dementia had widespread reductions in fractional anisotropy in anterior portions of frontal and temporal white matter, compared to the controls. Fractional anisotropy correlated with apathy in the left uncinate fasciculus and with disinhibition in the right corona radiata.
  
  
  CONCLUSIONS
  In patients with behavioral variant frontotemporal dementia, apathy and disinhibition are associated with distinct regions of white matter disease. The implicated fiber tracts likely support frontotemporal networks that are involved in goal-directed behavior.
authors.affiliation: *Penn Frontotemporal Degeneration Center, Department of Neurology †Penn Image Computing and Science Laboratory, Department of Radiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania ‡Centre for Medical Image Computing, Department of Computer Science, University College London, London, United Kingdom.
authors.forename: John P
authors.initials: JP
authors.lastname: Powers
authors.forename: Lauren
authors.initials: L
authors.lastname: Massimo
authors.forename: Corey T
authors.initials: CT
authors.lastname: McMillan
authors.forename: Paul A
authors.initials: PA
authors.lastname: Yushkevich
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: James C
authors.initials: JC
authors.lastname: Gee
authors.forename: Murray
authors.initials: M
authors.lastname: Grossman
mesh_terms: D000368:Aged; D057565:Apathy; D001526:Behavioral Symptoms / Q000209:etiology; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D057180:Frontotemporal Dementia / Q000473:pathology / Q000523:psychology*; D057174:Frontotemporal Lobar Degeneration / Q000473:pathology / Q000523:psychology*; D006801:Humans; D007266:Inhibition, Psychological; D056784:Leukoencephalopathies / Q000473:pathology / Q000523:psychology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D066127:White Matter / Q000473:pathology*