Non-linear relationships of cerebrospinal fluid biomarker levels with cognitive function: an observational study

INTRODUCTION: 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.