title: Effects of the coexistence of late-life depression and mild cognitive impairment on white matter microstructure.
abstract: OBJECTIVE
  Late-life depression (LLD) and amnestic mild cognitive impairment (aMCI) are associated with white matter (WM) disruptions of the fronto-limbic and interhemispheric tracts implicated in mood regulation and episodic memory functions. This work investigates the extent of these WM abnormalities in patients LLD and aMCI when these diseases occur alone and when they coexist.
  
  
  METHODS
  Eighty-four subjects separated into cognitively normal (n=33), LLD (n=20), aMCI (n=18), and comorbid aMCI and LLD (n=13) completed Diffusion Tensor Imaging (DTI) scans. Tract-based spatial statistics was employed to skeletonize multiple DTI indices of the cingulum, corpus callosum, fornix and uncinate fasciculus. Analysis of covariance and post-hoc tests compared group differences. Multiple linear regressions were performed between DTI and behavioral measures for the whole sample and within individual patient groups.
  
  
  RESULTS
  Divergent microstructural disruptions were identified in LLD- and aMCI-only groups, whereas the comorbid group showed widespread abnormalities especially in the hippocampal cingulum and fornix tracts. The LLD groups also showed significant disruptions in the uncinate fasciculus and corpus callosal tracts. Higher depressive symptom and lower episodic memory scores were associated with increased diffusivity measures in the fornix and hippocampal cingulum across all subjects.
  
  
  CONCLUSIONS
  Widespread WM microstructural disruptions are present when LLD and aMCI are comorbid -especially in the medial temporal lobe tracts. These WM disruptions may be a marker of disease severity. Also, multiple DTI parameters should be used when evaluating the WM fiber integrity in LLD and aMCI.
authors.affiliation: Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin, Milwaukee, WI, USA. Electronic address: wli@mcw.edu.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, WI, USA. Electronic address: lmuftuler@mcw.edu.
authors.forename: L Tugan
authors.initials: LT
authors.lastname: Muftuler
authors.affiliation: Department of Biophysics, Medical College of Wisconsin, Milwaukee, WI, USA. Electronic address: gachen@mcw.edu.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Biophysics, Medical College of Wisconsin, Milwaukee, WI, USA. Electronic address: ward@mcw.edu.
authors.forename: B Douglas
authors.initials: BD
authors.lastname: Ward
authors.affiliation: Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, WI, USA. Electronic address: mdbudde@mcw.edu.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Budde
authors.affiliation: Department of Neurology, Medical College of Wisconsin, Milwaukee, WI, USA. Electronic address: JlJones@mcw.edu.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Jones
authors.affiliation: Department of Neurology, Medical College of Wisconsin, Milwaukee, WI, USA. Electronic address: MFranczak@mcw.edu.
authors.forename: Malgorzata B
authors.initials: MB
authors.lastname: Franczak
authors.affiliation: Department of Neurology, Medical College of Wisconsin, Milwaukee, WI, USA. Electronic address: PAntuono@mcw.edu.
authors.forename: Piero G
authors.initials: PG
authors.lastname: Antuono
authors.affiliation: Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin, Milwaukee, WI, USA; Department of Biophysics, Medical College of Wisconsin, Milwaukee, WI, USA. Electronic address: sjli@mcw.edu.
authors.forename: Shi-Jiang
authors.initials: SJ
authors.lastname: Li
authors.affiliation: Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin, Milwaukee, WI, USA. Electronic address: jgoveas@mcw.edu.
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Goveas
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D016880:Anisotropy; D001921:Brain / Q000473:pathology; D060825:Cognitive Dysfunction / Q000150:complications / Q000209:etiology / Q000473:pathology; D003863:Depression / Q000150:complications / Q000209:etiology / Q000473:pathology; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D056784:Leukoencephalopathies / Q000150:complications* / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D009483:Neuropsychological Tests; D011569:Psychiatric Status Rating Scales
keywords: Alzheimer's disease; Diffusion tensor imaging; Late-life depression; Mild cognitive impairment; TBSS; White matter