title: Injury markers predict time to dementia in subjects with MCI and amyloid pathology.
abstract: OBJECTIVE
  Alzheimer disease (AD) can now be diagnosed in subjects with mild cognitive impairment (MCI) using biomarkers. However, little is known about the rate of decline in those subjects. In this cohort study, we aimed to assess the conversion rate to dementia and identify prognostic markers in subjects with MCI and evidence of amyloid pathology.
  
  
  METHODS
  We pooled subjects from the VU University Medical Center Alzheimer Center and the Development of Screening Guidelines and Criteria for Predementia Alzheimer's Disease (DESCRIPA) study. We included subjects with MCI, an abnormal level of β-amyloid(1-42) (Aβ(1-42)) in the CSF, and at least one diagnostic follow-up visit. We assessed the effect of APOE genotype, CSF total tau (t-tau) and tau phosphorylated at threonine 181 (p-tau) and hippocampal volume on time to AD-type dementia using Cox proportional hazards models and on decline on the Mini-Mental State Examination (MMSE) using linear mixed models.
  
  
  RESULTS
  We included 110 subjects with MCI with abnormal CSF Aβ(1-42) and a mean MMSE score of 26.3 ± 2.8. During a mean follow-up of 2.2 ± 1.0 (range 0.4-5.0) years, 63 subjects (57%) progressed to AD-type dementia. Abnormal CSF t-tau (hazard ratio [HR] 2.3, 95% confidence interval [CI] 1.1-4.6, p = 0.03) and CSF p-tau (HR 3.5, 95% CI 1.3-9.2, p = 0.01) concentration and hippocampal atrophy (HR 2.5, 95% CI 1.1-5.6, p = 0.02) predicted time to dementia. For subjects with both abnormal t-tau concentration and hippocampal atrophy, HR was 7.3 (95% CI 1.0-55.9, p = 0.06). Furthermore, abnormal CSF t-tau and p-tau concentrations and hippocampal atrophy predicted decline in MMSE score.
  
  
  CONCLUSIONS
  In subjects with MCI and evidence of amyloid pathology, the injury markers CSF t-tau and p-tau and hippocampal atrophy can predict further cognitive decline.
authors.affiliation: Department of Neurology, Alzheimer Center, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Ineke A
authors.initials: IA
authors.lastname: van Rossum
authors.forename: Stephanie J B
authors.initials: SJ
authors.lastname: Vos
authors.forename: Leah
authors.initials: L
authors.lastname: Burns
authors.forename: Dirk L
authors.initials: DL
authors.lastname: Knol
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
authors.forename: Hilkka
authors.initials: H
authors.lastname: Soininen
authors.forename: Lars-Olof
authors.initials: LO
authors.lastname: Wahlund
authors.forename: Harald
authors.initials: H
authors.lastname: Hampel
authors.forename: Magda
authors.initials: M
authors.lastname: Tsolaki
authors.forename: Lennart
authors.initials: L
authors.lastname: Minthon
authors.forename: Gilbert
authors.initials: G
authors.lastname: L'italien
authors.forename: Wiesje M
authors.initials: WM
authors.lastname: van der Flier
authors.forename: Charlotte E
authors.initials: CE
authors.lastname: Teunissen
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.forename: Daniel
authors.initials: D
authors.lastname: Rueckert
authors.forename: Robin
authors.initials: R
authors.lastname: Wolz
authors.forename: Frans
authors.initials: F
authors.lastname: Verhey
authors.forename: Pieter Jelle
authors.initials: PJ
authors.lastname: Visser
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000235:genetics / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001057:Apolipoproteins E / Q000235:genetics*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000473:pathology*; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D008297:Male; D015337:Multicenter Studies as Topic; D009483:Neuropsychological Tests; D011237:Predictive Value of Tests; D011569:Psychiatric Status Rating Scales; D013997:Time Factors; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D015415:Biomarkers; D016875:tau Proteins