title: Correlating Cognitive Decline with White Matter Lesion and Brain Atrophy Magnetic Resonance Imaging Measurements in Alzheimer's Disease.
abstract: BACKGROUND
  Vascular risk factors are increasingly recognized as risks factors for Alzheimer's disease (AD) and early conversion from mild cognitive impairment (MCI) to dementia. While neuroimaging research in AD has focused on brain atrophy, metabolic function, or amyloid deposition, little attention has been paid to the effect of cerebrovascular disease to cognitive decline.
  
  
  OBJECTIVE
  To investigate the correlation of brain atrophy and white matter lesions with cognitive decline in AD, MCI, and control subjects.
  
  
  METHODS
  Patients with AD and MCI, and healthy subjects were included in this study. Subjects had a baseline MRI scan, and baseline and follow-up neuropsychological battery (CERAD). Regional volumes were measured, and white matter lesion segmentation was performed. Correlations between rate of CERAD score decline and white matter lesion load and brain structure volume were evaluated. In addition, voxel-based correlations between baseline CERAD scores and atrophy and white matter lesion measures were computed.
  
  
  RESULTS
  CERAD rate of decline was most significantly associated with lesion loads located in the fornices. Several temporal lobe ROI volumes were significantly associated with CERAD decline. Voxel-based analysis demonstrated strong correlation between baseline CERAD scores and atrophy measures in the anterior temporal lobes. Correlation of baseline CERAD scores with white matter lesion volumes achieved significance in multilobar subcortical white matter.
  
  
  CONCLUSIONS
  Both baseline and declines in CERAD scores correlate with white matter lesion load and gray matter atrophy. Results of this study highlight the dominant effect of volume loss, and underscore the importance of small vessel disease as a contributor to cognitive decline in the elderly.
authors.affiliation: Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Michel
authors.initials: M
authors.lastname: Bilello
authors.affiliation: Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Jimit
authors.initials: J
authors.lastname: Doshi
authors.affiliation: Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: S Ali
authors.initials: SA
authors.lastname: Nabavizadeh
authors.affiliation: Department of Pathology & Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Jon B
authors.initials: JB
authors.lastname: Toledo
authors.affiliation: Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Guray
authors.initials: G
authors.lastname: Erus
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Sharon X
authors.initials: SX
authors.lastname: Xie
authors.affiliation: Department of Pathology & Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Han
authors.affiliation: Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Christos
authors.initials: C
authors.lastname: Davatzikos
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000473:pathology* / Q000523:psychology*; D001284:Atrophy; D001921:Brain / Q000473:pathology*; D003071:Cognition; D060825:Cognitive Dysfunction / Q000473:pathology / Q000523:psychology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D009929:Organ Size; D060388:Support Vector Machine; D066127:White Matter / Q000473:pathology*
keywords: Alzheimer’s disease; atrophy; cognitive decline; mild cognitive impairment; vascular disease; white matter lesions