Cerebrospinal Fluid Biomarkers and Clinical Progression in Patients with Subjective Cognitive Decline and Mild Cognitive Impairment

J Alzheimers Dis. 2017;58(3):939-950. doi: 10.3233/JAD-161252.


Background: There is very limited data on the prevalence of abnormal cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) and their predictive value for clinical progression in memory clinic patients with subjective cognitive decline (SCD).

Objective: To assess the frequency of abnormal CSF biomarkers of AD and their predictive value for clinical progression in memory clinic patients with SCD in comparison to patients with mild cognitive impairment (MCI) from the same cohort.

Methods: We analyzed prospective data from memory clinic patients of the German Competence Network Dementia cohort with a baseline diagnosis of SCD (n = 82) or MCI (n = 134), distinguished by actuarial neuropsychological MCI criteria ("Jak-Bondi criteria"). Risk of clinical progression during 3-year follow-up was evaluated with Cox-Proportional-Hazard models.

Results: Prevalence of abnormal values in CSF markers of tau-mediated neurodegeneration (67.8% versus 46.3%) but not of amyloid deposition (40.3% versus 35.4%) was significantly higher in MCI compared to SCD. The rate of incident AD dementia (26.1% versus 12.2%) was also significantly higher in MCI. In SCD, additional 22% progressed to MCI during follow-up. Combined amyloid/tau abnormality was the strongest predictor of clinical progression in both groups.

Conclusion: High prevalence of biomarker abnormality and clinical progression, together with the predictive value of CSF biomarkers, in memory clinic patients with SCD support the validity and usefulness of this condition as a "pre-MCI" at risk stage of AD.

Keywords: Alzheimer’s disease; cerebrospinal fluid; mild cognitive impairment; subjective cognitive decline.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Biomarkers / cerebrospinal fluid
  • Cognitive Dysfunction / cerebrospinal fluid*
  • Cognitive Dysfunction / classification
  • Diagnostic Self Evaluation
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Humans
  • Incidence
  • Kaplan-Meier Estimate
  • Longitudinal Studies
  • Male
  • Neuropsychological Tests
  • Peptide Fragments / cerebrospinal fluid*
  • Phosphorylation
  • Prevalence
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Factors
  • tau Proteins / cerebrospinal fluid*


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