Correlation of CSF- and MRI-Biomarkers and Progression of Cognitive Decline in an Open Label MCI Trial

  • L. K. Joachim
  • L. Frölich
  • E. Rüther
  • J. Wiltfang
  • W. Maier
  • J. Kornhuber
  • C. Bauer
  • I. Heuser
  • Oliver Peters
Open Access
Original Research


BACKGROUND: In several randomized controlled trials (RCT) acetylcholinesterase-inhibitors (AChE-I) were tested in patients with mild cognitive impairment (MCI) but were ineffective in delaying disease progression as determined by neuropsychological testing only. Here we present data from an open label observational extension of a multicenter RCT in order to assess if biomarkers are providing useful additional information about a drug’s efficacy. We followed 83 amnestic MCI patients and performed correlational analyses of Aβ 1–42 and total-Tau in the cerebrospinal fluid (CSF), hippocampal and amygdala volume at baseline, the total duration of blinded and open label AChE-I treatment and the outcome 24 months after inclusion into the RCT. Twelve out of 83 amnestic MCI (14%) had progressed to Alzheimer’s disease (AD). Overall, worsening and disease progression as measured by the Alzheimer’s Disease Assessment Scale - cognitive subscale (ADAS-cog), Alzheimer’s Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) and Clinical Dementia Rating (CDR) did not correlate with the duration of AChE-I treatment. However, a specific multidimensional biomarker profile at baseline indicated more reliably than cognitive testing alone progression to AD. We conclude that pharmacological RCTs testing symptomatic treatment effects in MCI should include biomarker assessment.

Key words

Cerebrospinal fluid Alzheimer’s disease amyloid β1-42 total-Tau hippocampal atrophy galantamine AChE-I 

Supplementary material

42414_2018_35_MOESM1_ESM.pdf (109 kb)
Supplementary material, approximately 109 KB.


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© The Author(s) 2018

Open Access: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits use, duplication, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license and indicate if changes were made.

Authors and Affiliations

  • L. K. Joachim
    • 1
  • L. Frölich
    • 2
  • E. Rüther
    • 3
  • J. Wiltfang
    • 3
    • 7
  • W. Maier
    • 4
    • 8
  • J. Kornhuber
    • 5
  • C. Bauer
    • 6
  • I. Heuser
    • 1
  • Oliver Peters
    • 1
    • 9
    • 10
  1. 1.Department of PsychiatryCharité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Campus Benjamin FranklinBerlinGermany
  2. 2.Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty MannheimUniversity of HeidelbergMannheimGermany
  3. 3.Department of Psychiatry and PsychotherapyUniversity Medical Center GöttingenGöttingenGermany
  4. 4.Department of PsychiatryUniversity BonnBonnGermany
  5. 5.Department of PsychiatryFriedrich-Alexander-University of Erlangen-NurembergErlangenGermany
  6. 6.MicroDiscovery GmbHBerlinGermany
  7. 7.German Center for Neurodegenerative Diseases (DZNE) GöttingenGöttingenGermany
  8. 8.German Center for Neurodegenerative Diseases (DZNE) BonnBonnGermany
  9. 9.German Center for Neurodegenerative Diseases (DZNE) BerlinBerlinGermany
  10. 10.Department of Psychiatry and PsychotherapyCharité – Universitätsmedizin Berlin, Campus Benjamin FranklinBerlinGermany

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