title: Cerebrospinal fluid profiles and prospective course and outcome in patients with amnestic mild cognitive impairment.
abstract: OBJECTIVE
  To examine the effect of specific cerebrospinal fluid (CSF) profiles on the rate of cognitive decline, disease progression, and risk of conversion to Alzheimer disease (AD) dementia in patients with amnestic mild cognitive impairment (MCI).
  
  
  METHODS
  Total tau (T-tau), tau phosphorylated at threonine 181, and β-amyloid 1-42 peptide (Aβ42) were immunoassayed in CSF samples obtained from patients with MCI enrolled in the Alzheimer's Disease Neuroimaging Initiative. Patients were then stratified by CSF profiles: (1) normal T-tau and normal Aβ42 (ie, normal-T-tauAβ42), (2) normal T-tau but abnormal Aβ42 (ie, abnormal-Aβ42), (3) abnormal T-tau but normal Aβ42 (ie, abnormal-T-tau), and (4) abnormal T-tau and abnormal Aβ42 (ie, abnormal-T-tauAβ42).
  
  
  METHODS
  Fifty-eight sites in the United States and Canada.
  
  
  METHODS
  One hundred ninety-five patients with MCI.
  
  
  METHODS
  A composite cognitive measure, the Clinical Dementia Rating Scale-sum of boxes subscale, and conversion to AD dementia.
  
  
  RESULTS
  Patients with MCI with a CSF profile of abnormal-Aβ42 or abnormal-T-tauAβ42 experienced a faster rate of decline on the composite cognitive measure and the Clinical Dementia Rating Scale-sum of boxes subscale compared with those with normal-T-tauAβ42. They also had a greater risk of converting to AD dementia relative to the normal-T-tauAβ42 group. In contrast, those with a CSF profile of abnormal-T-tau did not differ from the normal-T-tauAβ42 group on any outcome. These findings were generally replicated when the sample was reclassified by patterns of tau phosphorylated at threonine 181 and Aβ42 abnormalities.
  
  
  CONCLUSIONS
  β-Amyloid abnormalities but not tau alterations are associated with cognitive deterioration, disease progression, and increased risk of conversion to AD dementia in patients with MCI. Patients with abnormal Aβ42 may be prime candidates for drug treatment and clinical trials in MCI.
authors.affiliation: Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. ozioma@jhmi.edu
authors.forename: Ozioma C
authors.initials: OC
authors.lastname: Okonkwo
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Mielke
authors.forename: H Randall
authors.initials: HR
authors.lastname: Griffith
authors.forename: Abhay R
authors.initials: AR
authors.lastname: Moghekar
authors.forename: Richard J
authors.initials: RJ
authors.lastname: O'Brien
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Shaw
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
authors.forename: Marilyn S
authors.initials: MS
authors.lastname: Albert
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000523:psychology; D000647:Amnesia / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000523:psychology*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D003072:Cognition Disorders / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000523:psychology*; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D011446:Prospective Studies; D016896:Treatment Outcome; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins