title: Amyloid imaging and CSF biomarkers in predicting cognitive impairment up to 7.5 years later.
abstract: OBJECTIVE
  We compared the ability of molecular biomarkers for Alzheimer disease (AD), including amyloid imaging and CSF biomarkers (Aβ42, tau, ptau181, tau/Aβ42, ptau181/Aβ42), to predict time to incident cognitive impairment among cognitively normal adults aged 45 to 88 years and followed for up to 7.5 years.
  
  
  METHODS
  Longitudinal data from Knight Alzheimer's Disease Research Center participants (N = 201) followed for a mean of 3.70 years (SD = 1.46 years) were used. Participants with amyloid imaging and CSF collection within 1 year of a clinical assessment indicating normal cognition were eligible. Cox proportional hazards models tested whether the individual biomarkers were related to time to incident cognitive impairment. "Expanded" models were developed using the biomarkers and participant demographic variables. The predictive values of the models were compared.
  
  
  RESULTS
  Abnormal levels of all biomarkers were associated with faster time to cognitive impairment, and some participants with abnormal biomarker levels remained cognitively normal for up to 6.6 years. No differences in predictive value were found between the individual biomarkers (p > 0.074), nor did we find differences between the expanded biomarker models (p > 0.312). Each expanded model better predicted incident cognitive impairment than the model containing the biomarker alone (p < 0.005).
  
  
  CONCLUSIONS
  Our results indicate that all AD biomarkers studied here predicted incident cognitive impairment, and support the hypothesis that biomarkers signal underlying AD pathology at least several years before the appearance of dementia symptoms.
authors.affiliation: Knight Alzheimer's Disease Research Center, Washington University School of Medicine, 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: Jason
authors.initials: J
authors.lastname: Hassenstab
authors.forename: Krista L
authors.initials: KL
authors.lastname: Moulder
authors.forename: Denise
authors.initials: D
authors.lastname: Maue Dreyfus
authors.forename: Courtney L
authors.initials: CL
authors.lastname: Sutphen
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; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D003072:Cognition Disorders / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D003704:Dementia / Q000134:cerebrospinal fluid / Q000175:diagnosis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D059906:Neuroimaging / Q000379:methods / Q000639:trends; D011237:Predictive Value of Tests; D011446:Prospective Studies; D013997:Time Factors; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D016875:tau Proteins