title: The effect of white matter hyperintensities on neurodegeneration in mild cognitive impairment.
abstract: BACKGROUND
  It is unclear whether white matter hyperintensities (WMHs), magnetic resonance imaging markers of small-vessel cerebrovascular disease, promote neurodegeneration and associated clinical decline in Alzheimer's disease (AD), or simply co-occur with recognized pathogenic processes.
  
  
  METHODS
  In 169 patients with mild cognitive impairment, followed for 3 years, we examined the association of (1) baseline regional WMH and cerebral spinal fluid-derived t-tau (total tau) with entorhinal cortex atrophy rates, as a marker of AD-related neurodegeneration, and conversion to AD; and (2) baseline regional WMH with change in t-tau level.
  
  
  RESULTS
  In participants with low baseline t-tau, higher regional WMH volumes were associated with faster entorhinal cortex atrophy. Higher parietal WMH volume predicted conversion to AD in those with high t-tau. Higher parietal and occipital WMH volumes predicted increasing t-tau.
  
  
  CONCLUSIONS
  WMHs affect AD clinical and pathologic processes both directly and interacting with tau.
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tosto
authors.affiliation: Department of Psychology, Fordham University, Bronx, NY, USA; Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Molly E
authors.initials: ME
authors.lastname: Zimmerman
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
authors.forename: Jamie L
authors.initials: JL
authors.lastname: Hamilton
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, LA, USA.
authors.forename: Owen T
authors.initials: OT
authors.lastname: Carmichael
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA. Electronic address: amb2139@columbia.edu.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Brickman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001284:Atrophy; D060825:Cognitive Dysfunction / Q000473:pathology*; D018450:Disease Progression; D018728:Entorhinal Cortex / Q000473:pathology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D010446:Peptide Fragments / Q000378:metabolism; D066127:White Matter / Q000378:metabolism / Q000473:pathology*; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D016875:tau Proteins
keywords: Alzheimer's disease; CSF tau; Mild cognitive impairment; White matter hyperintensities