The latent dementia phenotype δ is associated with cerebrospinal fluid biomarkers of Alzheimer's disease and predicts conversion to dementia in subjects with mild cognitive impairment

Alexander Koppara, Steffen Wolfsgruber, Luca Kleineidam, Klaus Schmidtke, Lutz Frölich, Alexander Kurz, Stefanie Schulz, Harald Hampel, Isabella Heuser, Oliver Peters, Friedel M. Reischies, Holger Jahn, Christian Luckhaus, Michael Hüll, Hermann Josef Gertz, Johannes Schröder, Johannes Pantel, Otto Rienhoff, Eckart Rüther, Fritz HennJens Wiltfang, Wolfgang Maier, Frank Jessen, Johannes Kornhuber, Michael Wagner

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Background: The recently proposed latent variable δ is a new tool for dementia case finding. It is built in a structural equation modeling framework of cognitive and functional data and constitutes a novel endophenotype for Alzheimer's disease (AD) research and clinical trials. Objective: To investigate the association of δ with AD biomarkers and to compare the prediction of δ with established scales for conversion to dementia in patients with mild cognitive impairment (MCI). Methods: Using data from a multicenter memory clinic study, we examined the external associations of the latent variable δ and compared δ with well-established cognitive and functional scales and cognitive-functional composite scores. For that purpose, logistic regressions with cerebrospinal fluid (CSF) biomarkers and conversion to dementia as dependent variables were performed with the investigated scores. The models were tested for significant differences. Results: In patients with MCI, δ based on a broad range of cognitive scales (including theADAS-cog, theMMSE,and theCERAD neuropsychological battery) predicted an abnormal CSF Aβ42/tau ratio indicative of AD (n = 340, AUC= 0.78, p < 0.001), and predicted incident dementia within 1-3 years of follow-up (n = 525, AUC= 0.84, p < 0.001). These associations were generally stronger than for any other scale or cognitive-functional composite examined. Homologs of δ based on reduced test batteries yielded somewhat lower effects. Conclusion: These findings support the interpretation of δ as a construct capturing the disease-related "essence" of cognitive and functional impairments in patients with MCI and dementia, and suggest that δ might become an analytical tool for dementia research.

Original languageEnglish
Pages (from-to)547-560
Number of pages14
JournalJournal of Alzheimer's Disease
Volume49
Issue number2
DOIs
StatePublished - 9 Oct 2015

Keywords

  • CSF AD biomarker signature
  • delta model
  • incident dementia
  • mild cognitive impairment

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