Temporal evolution of biomarkers and cognitive markers in the asymptomatic, MCI, and dementia stage of Alzheimer's disease

Alzheimers Dement. 2015 May;11(5):511-22. doi: 10.1016/j.jalz.2014.05.1754. Epub 2014 Aug 20.

Abstract

Background: We investigated the pattern of disease progression in the asymptomatic, mild cognitive impairment (MCI), and dementia stage of Alzheimer's disease (AD).

Methods: We selected 284 subjects with AD pathology, defined as abnormal levels of amyloid beta 1-42 (Aβ1-42) in cerebrospinal fluid (CSF). Disease outcome measures included six biomarkers and five cognitive markers. We compared differences in baseline measures and decline over 4 years between the AD stages and tested whether these changes differed from subjects, without AD pathology (N = 132).

Results: CSF Aβ1-42 reached the maximum abnormality level in the asymptomatic stage and tau in the MCI stage. The imaging and cognitive markers started to decline in the asymptomatic stage, and decline accelerated with advancing clinical stage.

Conclusion: This study provides further evidence for a temporal evolution of AD biomarkers. Our findings may be helpful to determine stage specific outcome measures for clinical trials.

Keywords: Alzheimer's disease; Asymptomatic; Biomarkers; Cognitive markers; Dementia; Longitudinal; MCI; Observational.

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / pathology*
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Cognitive Dysfunction / cerebrospinal fluid*
  • Cognitive Dysfunction / diagnostic imaging
  • Cognitive Dysfunction / pathology*
  • Disease Progression
  • Female
  • Fluorodeoxyglucose F18 / metabolism
  • Humans
  • Image Processing, Computer-Assisted
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Peptide Fragments / cerebrospinal fluid*
  • Positron-Emission Tomography
  • tau Proteins / cerebrospinal fluid*

Substances

  • Amyloid beta-Peptides
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • tau Proteins
  • Fluorodeoxyglucose F18