title: Relative contributions of biomarkers in Alzheimer's disease.
abstract: OBJECTIVE
  To assess relationships between biomarkers for Alzheimer's disease (AD) and their potential contributions to AD.
  
  
  METHODS
  Biomarkers and cognitive evaluations were assessed longitudinally in 179 patients with mild cognitive impairment, from the Alzheimer's Disease Neuroimaging Initiative from 2003 to 2006, and were used to examine, at any given time, the joint contributions of hippocampal volume, whole brain volume, and brain glucose metabolism on clinical AD progression, using the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog). Marginal structural models were applied, and an inverse-probability of treatment weight estimation was used to account for time-dependent confounding between study variables.
  
  
  RESULTS
  At any given time, population-level differences (e.g., 1-standard deviation [SD] increase) in brain glucose metabolism (-1.036; 95% confidence interval [95% CI], -1.608, -0.464) and hippocampal volume (-1.537; 95% CI, -2.399, -0.674) independently reduced mean (ADAS-Cog), whereas a 1-SD increase in whole brain volume did not (0.372; 95% CI, -0.283, 1.027). The effects of brain glucose metabolism differed in subgroups defined by baseline covariates (e.g., age), but no subgroup effects were observed for hippocampal volume and brain volume.
  
  
  CONCLUSIONS
  Brain glucose metabolism and hippocampal volume represent relevant biological markers in subjects at risk for AD.
authors.affiliation: Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720-3190, USA. tad@berkeley.edu
authors.forename: Thaddeus J
authors.initials: TJ
authors.lastname: Haight
authors.forename: William J
authors.initials: WJ
authors.lastname: Jagust
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002170:Canada; D060825:Cognitive Dysfunction / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D016015:Logistic Models; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D012307:Risk Factors; D012959:Socioeconomic Factors; D014481:United States
chemical_list: D015415:Biomarkers; D001786:Blood Glucose