Cerebrospinal fluid biomarkers, education, brain volume, and future cognition

Arch Neurol. 2011 Sep;68(9):1145-51. doi: 10.1001/archneurol.2011.192.

Abstract

Background: Cross-sectional studies suggest that the cognitive impact of Alzheimer disease pathology varies depending on education and brain size.

Objective: To evaluate the combination of cerebrospinal fluid biomarkers of β-amyloid(42) (Aβ(42)), tau, and phosphorylated tau (ptau(181)) with education and normalized whole-brain volume (nWBV) to predict incident cognitive impairment.

Design: Longitudinal cohort study.

Setting: Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University, St Louis, Missouri.

Participants: A convenience sample of 197 individuals 50 years and older with normal cognition (Clinical Dementia Rating of 0) at baseline observed for a mean of 3.3 years.

Main outcome measure: Time to Clinical Dementia Rating ≥ 0.5.

Results: Three-factor interactions among the baseline biomarker values, education, and nWBV were found for Cox proportional hazards regression models testing tau (P = .02) and ptau (P = .008). In those with lower tau values, nWBV (hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.31-0.91; P = .02), but not education, was related to time to cognitive impairment. For participants with higher tau values, education interacted with nWBV to predict incident impairment (P = .01). For individuals with lower ptau values, there was no effect of education or nWBV. Education interacted with nWBV to predict incident cognitive impairment in those with higher ptau values (P = .02).

Conclusion: In individuals with normal cognition and higher levels of cerebrospinal fluid tau and ptau at baseline, time to incident cognitive impairment is moderated by education and brain volume as predicted by the cognitive/brain reserve hypothesis.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / pathology
  • Alzheimer Disease / prevention & control
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Biomarkers / cerebrospinal fluid
  • Brain / anatomy & histology*
  • Brain / metabolism*
  • Brain / pathology
  • Cognition / physiology*
  • Cognition Disorders / cerebrospinal fluid*
  • Cognition Disorders / pathology
  • Cognition Disorders / prevention & control
  • Cognitive Reserve / physiology
  • Cohort Studies
  • Educational Status
  • Female
  • Follow-Up Studies
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Organ Size
  • Peptide Fragments / cerebrospinal fluid*
  • Phosphorylation / physiology
  • Predictive Value of Tests
  • Prospective Studies
  • tau Proteins / cerebrospinal fluid*

Substances

  • Amyloid beta-Peptides
  • Biomarkers
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • tau Proteins