title: Disease progression model in subjects with mild cognitive impairment from the Alzheimer's disease neuroimaging initiative: CSF biomarkers predict population subtypes.
abstract: OBJECTIVE
  The objective is to develop a semi-mechanistic disease progression model for mild cognitive impairment (MCI) subjects. The model aims to describe the longitudinal progression of ADAS-cog scores from the Alzheimer's disease neuroimaging initiative trial that had data from 198 MCI subjects with cerebrospinal fluid (CSF) information who were followed for 3 years.
  
  
  METHODS
  Various covariates were tested on disease progression parameters and these variables fell into six categories: imaging volumetrics, biochemical, genetic, demographic, cognitive tests and CSF biomarkers.
  
  
  RESULTS
  CSF biomarkers were associated with both baseline disease score and disease progression rate in subjects with MCI. Baseline disease score was also correlated with atrophy measured using hippocampal volume. Progression rate was also predicted by executive functioning as measured by the Trail B-test.
  
  
  CONCLUSIONS
  CSF biomarkers have the ability to discriminate MCI subjects into sub-populations that exhibit markedly different rates of disease progression on the ADAS-cog scale. These biomarkers can therefore be utilized for designing clinical trials enriched with subjects that carry the underlying disease pathology.
authors.affiliation: Johnson & Johnson Pharmaceutical Research & Development, Clinical Pharmacology Department, Raritan, New Jersey 08869, USA. msamtani@its.jnj.com
authors.forename: Mahesh N
authors.initials: MN
authors.lastname: Samtani
authors.forename: Nandini
authors.initials: N
authors.lastname: Raghavan
authors.forename: Yingqi
authors.initials: Y
authors.lastname: Shi
authors.forename: Gerald
authors.initials: G
authors.lastname: Novak
authors.forename: Michael
authors.initials: M
authors.lastname: Farnum
authors.forename: Victor
authors.initials: V
authors.lastname: Lobanov
authors.forename: Tim
authors.initials: T
authors.lastname: Schultz
authors.forename: Eric
authors.initials: E
authors.lastname: Yang
authors.forename: Allitia
authors.initials: A
authors.lastname: DiBernardo
authors.forename: Vaibhav A
authors.initials: VA
authors.lastname: Narayan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid; D001057:Apolipoproteins E / Q000235:genetics; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D002784:Cholesterol / Q000097:blood; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D059906:Neuroimaging
chemical_list: D001057:Apolipoproteins E; D015415:Biomarkers; D002784:Cholesterol