title: Vascular burden and Alzheimer disease pathologic progression.
abstract: OBJECTIVE
  To investigate the vascular contribution to longitudinal changes in Alzheimer disease (AD) biomarkers.
  
  
  METHODS
  The Alzheimer's Disease Neuroimaging Initiative is a clinic based, longitudinal study with CSF, PET, and MRI biomarkers repeatedly measured in participants with normal cognition (NC), mild cognitive impairment (MCI), and mild AD. Participants with severe cerebrovascular risks were excluded. Cardiovascular risk scores and MRI white matter hyperintensities (WMHs) were treated as surrogate markers for vascular burden. Generalized estimating equations were applied, and both vascular burden and its interaction with time (vascular burden × time) or time-varying WMHs were entered into regression models to assess whether biomarker rates of change were modified by vascular burden.
  
  
  RESULTS
  Cardiovascular risk profiles were not predictive of progression in CSF β₄₂-amyloid, [¹⁸F]fluorodeoxyglucose (FDG) PET uptake, and MRI hippocampal atrophy. Greater baseline cardiovascular risks or WMHs were generally associated with cognitive impairment, particularly poor executive function. WMHs increased over time with a faster rate in MCI and AD than in NC. Increased time-varying WMH was associated with faster decline in executive function and lower FDG uptake in NC. Otherwise, WMH was not associated with CSF and MRI biomarkers in the 3 groups. These findings remained unchanged after accounting for APOE4.
  
  
  CONCLUSIONS
  Increased WMHs are associated with aging, decreased glucose metabolism, and decline in executive function but do not affect AD-specific pathologic progression, suggesting that the vascular contribution to dementia is probably additive although not necessarily independent of the amyloid pathway.
authors.affiliation: Division of Epidemiology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA. rayyenyu@hotmail.com
authors.forename: Raymond Y
authors.initials: RY
authors.lastname: Lo
authors.forename: William J
authors.initials: WJ
authors.lastname: Jagust
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000473:pathology* / Q000503:physiopathology*; D001284:Atrophy; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid / Q000473:pathology / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006801:Humans; D056784:Leukoencephalopathies / Q000473:pathology* / Q000503:physiopathology; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods*