title: Cerebrospinal fluid biomarkers, education, brain volume, and future cognition.
abstract: BACKGROUND
  Cross-sectional studies suggest that the cognitive impact of Alzheimer disease pathology varies depending on education and brain size.
  
  
  OBJECTIVE
  To evaluate the combination of cerebrospinal fluid biomarkers of β-amyloid(42) (Aβ(42)), tau, and phosphorylated tau (ptau(181)) with education and normalized whole-brain volume (nWBV) to predict incident cognitive impairment.
  
  
  METHODS
  Longitudinal cohort study.
  
  
  METHODS
  Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University, St Louis, Missouri.
  
  
  METHODS
  A convenience sample of 197 individuals 50 years and older with normal cognition (Clinical Dementia Rating of 0) at baseline observed for a mean of 3.3 years.
  
  
  METHODS
  Time to Clinical Dementia Rating ≥ 0.5.
  
  
  RESULTS
  Three-factor interactions among the baseline biomarker values, education, and nWBV were found for Cox proportional hazards regression models testing tau (P = .02) and ptau (P = .008). In those with lower tau values, nWBV (hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.31-0.91; P = .02), but not education, was related to time to cognitive impairment. For participants with higher tau values, education interacted with nWBV to predict incident impairment (P = .01). For individuals with lower ptau values, there was no effect of education or nWBV. Education interacted with nWBV to predict incident cognitive impairment in those with higher ptau values (P = .02).
  
  
  CONCLUSIONS
  In individuals with normal cognition and higher levels of cerebrospinal fluid tau and ptau at baseline, time to incident cognitive impairment is moderated by education and brain volume as predicted by the cognitive/brain reserve hypothesis.
authors.affiliation: Knight Alzheimer’s Disease Research Center, St Louis, MO, USA. cathyr@wustl.edu
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Roe
authors.forename: Anne M
authors.initials: AM
authors.lastname: Fagan
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Grant
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Marcus
authors.forename: Tammie L S
authors.initials: TL
authors.lastname: Benzinger
authors.forename: Mark A
authors.initials: MA
authors.lastname: Mintun
authors.forename: David M
authors.initials: DM
authors.lastname: Holtzman
authors.forename: John C
authors.initials: JC
authors.lastname: Morris
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000473:pathology / Q000517:prevention & control; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000033:anatomy & histology* / Q000378:metabolism* / Q000473:pathology; D003071:Cognition / Q000502:physiology*; D003072:Cognition Disorders / Q000134:cerebrospinal fluid* / Q000473:pathology / Q000517:prevention & control; D058245:Cognitive Reserve / Q000502:physiology; D015331:Cohort Studies; D004522:Educational Status; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009929:Organ Size; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D010766:Phosphorylation / Q000502:physiology; D011237:Predictive Value of Tests; D011446:Prospective Studies; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins