title: Non-linear relationships of cerebrospinal fluid biomarker levels with cognitive function: an observational study.
abstract: BACKGROUND
  Levels of cerebrospinal fluid (CSF) β-amyloid (Aβ) and Tau proteins change in Alzheimer's disease (AD). We tested if the relationships of these biomarkers with cognitive impairment are linear or non-linear.
  
  
  METHODS
  We assessed cognitive function and assayed CSF Aβ and Tau biomarkers in 95 non-demented volunteers and 97 AD patients. We then tested non-linearities in their inter-relations.
  
  
  RESULTS
  CSF biomarkers related to cognitive function in the non-demented range of cognition, but these relations were weak or absent in the patient range; Aβ1-40's relationship was biphasic.
  
  
  CONCLUSIONS
  Major biomarker changes precede clinical AD and index cognitive impairment in AD poorly, if at all.
authors.affiliation: OPTIMA, University of Oxford, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK. drjhw@live.co.uk.
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Williams
authors.forename: Gordon K
authors.initials: GK
authors.lastname: Wilcock
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Seeburger
authors.forename: Aimee
authors.initials: A
authors.lastname: Dallob
authors.forename: Omar
authors.initials: O
authors.lastname: Laterza
authors.forename: William
authors.initials: W
authors.lastname: Potter
authors.forename: A David
authors.initials: AD
authors.lastname: Smith