title: Effects of Hormone Therapy on Brain Volumes Changes of Postmenopausal Women Revealed by Optimally-Discriminative Voxel-Based Morphometry.
abstract: BACKGROUND
  The Women's Health Initiative Memory Study Magnetic Resonance Imaging (WHIMS-MRI) provides an opportunity to evaluate how menopausal hormone therapy (HT) affects the structure of older women's brains. Our earlier work based on region of interest (ROI) analysis demonstrated potential structural changes underlying adverse effects of HT on cognition. However, the ROI-based analysis is limited in statistical power and precision, and cannot provide fine-grained mapping of whole-brain changes.
  
  
  METHODS
  We aimed to identify local structural differences between HT and placebo groups from WHIMS-MRI in a whole-brain refined level, by using a novel method, named Optimally-Discriminative Voxel-Based Analysis (ODVBA). ODVBA is a recently proposed imaging pattern analysis approach for group comparisons utilizing a spatially adaptive analysis scheme to accurately locate areas of group differences, thereby providing superior sensitivity and specificity to detect the structural brain changes over conventional methods.
  
  
  RESULTS
  Women assigned to HT treatments had significant Gray Matter (GM) losses compared to the placebo groups in the anterior cingulate and the adjacent medial frontal gyrus, and the orbitofrontal cortex, which persisted after multiple comparison corrections. There were no regions where HT was significantly associated with larger volumes compared to placebo, although a trend of marginal significance was found in the posterior cingulate cortical area. The CEE-Alone and CEE+MPA groups, although compared with different placebo controls, demonstrated similar effects according to the spatial patterns of structural changes.
  
  
  CONCLUSIONS
  HT had adverse effects on GM volumes and risk for cognitive impairment and dementia in older women. These findings advanced our understanding of the neurobiological underpinnings of HT effects.
authors.affiliation: Center for Biomedical Image Computing and Analytics, Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Tianhao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America.
authors.forename: Ramon
authors.initials: R
authors.lastname: Casanova
authors.affiliation: Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, Maryland, United States of America.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Resnick
authors.affiliation: Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.|Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: JoAnn E
authors.initials: JE
authors.lastname: Manson
authors.affiliation: Department of Internal Medicine and Epidemiology, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America.
authors.forename: Laura D
authors.initials: LD
authors.lastname: Baker
authors.affiliation: Sierra Pacific Mental Illness Research, Education and Clinical Center, VA Palo Alto Health Care System, Palo Alto, California, United States of America.|Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California, United States of America.
authors.forename: Claudia B
authors.initials: CB
authors.lastname: Padual
authors.affiliation: Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Lewis H
authors.initials: LH
authors.lastname: Kuller
authors.affiliation: Center for Biomedical Image Computing and Analytics, Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: R Nick
authors.initials: RN
authors.lastname: Bryan
authors.affiliation: Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Espeland
authors.affiliation: Center for Biomedical Image Computing and Analytics, Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Christos
authors.initials: C
authors.lastname: Davatzikos
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D004966:Estrogens, Conjugated (USP) / Q000627:therapeutic use*; D005260:Female; D066128:Gray Matter / Q000000981:diagnostic imaging*; D006179:Gyrus Cinguli / Q000000981:diagnostic imaging*; D020249:Hormone Replacement Therapy; D006801:Humans; D009929:Organ Size / Q000187:drug effects; D017698:Postmenopause; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging*; D011859:Radiography
chemical_list: D004966:Estrogens, Conjugated (USP)