title: Dissociable effects of Alzheimer disease and white matter hyperintensities on brain metabolism.
abstract: OBJECTIVE
  Cerebrovascular disease and Alzheimer disease (AD) frequently co-occur and seem to act through different pathways in producing dementia.
  
  
  OBJECTIVE
  To examine cerebrovascular disease and AD markers in relation to brain glucose metabolism in patients with mild cognitive impairment.
  
  
  METHODS
  Cohort study among the Alzheimer Disease Neuroimaging Initiative clinical sites in the United States and Canada.
  
  
  METHODS
  Two hundred three patients having amnestic mild cognitive impairment (74 of whom converted to AD) with serial imaging during a 3-year follow-up period.
  
  
  METHODS
  Quantified white matter hyperintensities (WMHs) represented cerebrovascular disease, and cerebrospinal fluid β-amyloid represented AD pathology. Brain glucose metabolism in temporoparietal and frontal brain regions was measured using positron emission tomography with fluorodeoxyglucose F18.
  
  
  RESULTS
  In converters, greater WMHs were associated with decreased frontal metabolism (-0.048; 95% CI, -0.067 to -0.029) but not temporoparietal metabolism (0.010; 95% CI, -0.010 to 0.030). Greater cerebrospinal fluid β-amyloid (per 10-pg/mL increase) was associated with increased temporoparietal metabolism (0.005; 95% CI, 0.000-0.010) but not frontal metabolism (0.002; 95% CI, -0.004 to 0.007) in the same patients. In nonconverters, similar relationships were observed except for a positive association of greater WMHs with increased temporoparietal metabolism (0.051; 95% CI, 0.027-0.076).
  
  
  CONCLUSIONS
  The dissociation of WMHs and cerebrospinal fluid β-amyloid in relation to regional glucose metabolism suggests that these pathologic conditions operate through different and independent pathways in AD that reflect dysfunction in different brain systems. The positive association of greater WMHs with temporoparietal metabolism suggests that these pathologic processes do not co-occur in nonconverters.
authors.affiliation: Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA 94720-3190, USA. tad@berkeley.edu
authors.forename: Thaddeus J
authors.initials: TJ
authors.lastname: Haight
authors.forename: Susan M
authors.initials: SM
authors.lastname: Landau
authors.forename: Owen
authors.initials: O
authors.lastname: Carmichael
authors.forename: Christopher
authors.initials: C
authors.lastname: Schwarz
authors.forename: Charles
authors.initials: C
authors.lastname: DeCarli
authors.forename: William J
authors.initials: WJ
authors.lastname: Jagust
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid / Q000378:metabolism; D015415:Biomarkers / Q000134:cerebrospinal fluid / Q000378:metabolism; D001930:Brain Injuries / Q000134:cerebrospinal fluid / Q000378:metabolism* / Q000473:pathology*; D002561:Cerebrovascular Disorders / Q000134:cerebrospinal fluid / Q000378:metabolism / Q000473:pathology; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid / Q000378:metabolism / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D056784:Leukoencephalopathies / Q000134:cerebrospinal fluid / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers