title: Neuropathological basis of magnetic resonance images in aging and dementia.
abstract: OBJECTIVE
  Magnetic resonance (MR) imaging is used widely for assessment of patients with cognitive impairment, but the pathological correlates are unclear, especially when multiple pathologies are present.
  
  
  METHODS
  This report includes 93 subjects from a longitudinally followed cohort recruited for the study of Alzheimer's disease (AD) and subcortical cerebrovascular disease (CVD). MR images were analyzed to quantify cortical gray matter volume, hippocampal volume, white matter hyperintensities, and lacunes. Neuropathological examination quantified CVD parenchymal pathology, AD pathology (defined as Consortium to Establish a Registry for Alzheimer's Disease scores and Braak and Braak stage), and hippocampal sclerosis. Subjects were pathologically classified as 12 healthy control subjects, 46 AD, 14 CVD, 9 mixed AD/CVD, and 12 cognitively impaired patients without significant AD/CVD pathology. Multivariate models tested associations between magnetic resonance and pathological findings across the entire sample.
  
  
  RESULTS
  Pathological correlates of cortical gray matter volume were AD, subcortical vascular pathology, and arteriosclerosis. Hippocampal volume was related to AD pathology and hippocampal sclerosis, and the effects of hippocampal sclerosis were greater for subjects with low levels of AD pathology. White matter hyperintensities were related to age and to white matter pathology. Number of MRI lacunes was related to subcortical vascular pathology.
  
  
  CONCLUSIONS
  In this clinical setting, the presence of lacunes and white matter changes provide a good signal for vascular disease. The neuropathological basis of MR defined cerebral cortical and hippocampal atrophy in aging and dementia is complex, with several pathological processes converging on similar brain structures that mediate cognitive decline.
authors.affiliation: School of Public Health and Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720-3190, USA. jagust@berkeley.edu
authors.forename: William J
authors.initials: WJ
authors.lastname: Jagust
authors.forename: Ling
authors.initials: L
authors.lastname: Zheng
authors.forename: Danielle J
authors.initials: DJ
authors.lastname: Harvey
authors.forename: Wendy J
authors.initials: WJ
authors.lastname: Mack
authors.forename: Harry V
authors.initials: HV
authors.lastname: Vinters
authors.forename: Michael W
authors.initials: MW
authors.lastname: Weiner
authors.forename: William G
authors.initials: WG
authors.lastname: Ellis
authors.forename: Chris
authors.initials: C
authors.lastname: Zarow
authors.forename: Dan
authors.initials: D
authors.lastname: Mungas
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Reed
authors.forename: Joel H
authors.initials: JH
authors.lastname: Kramer
authors.forename: Norbert
authors.initials: N
authors.lastname: Schuff
authors.forename: Charles
authors.initials: C
authors.lastname: DeCarli
authors.forename: Helena C
authors.initials: HC
authors.lastname: Chui
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology*; D000544:Alzheimer Disease / Q000473:pathology* / Q000503:physiopathology; D001161:Arteriosclerosis / Q000473:pathology; D001284:Atrophy / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000098:blood supply / Q000473:pathology* / Q000503:physiopathology; D020520:Brain Infarction / Q000473:pathology / Q000503:physiopathology; D002540:Cerebral Cortex / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D015331:Cohort Studies; D015140:Dementia, Vascular / Q000473:pathology* / Q000503:physiopathology; D003937:Diagnosis, Differential; D005260:Female; D006624:Hippocampus / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000706:statistics & numerical data*; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D011237:Predictive Value of Tests