Prediction of conversion from mild cognitive impairment to Alzheimer's disease dementia based upon biomarkers and neuropsychological test performance

Michael Ewers, Cathal Walsh, John Q. Trojanowski, Leslie M. Shaw, Ronald C. Petersen, Clifford R. Jack, Howard H. Feldman, Arun L.W. Bokde, Gene E. Alexander, Philip Scheltens, Bruno Vellas, Bruno Dubois, Michael Weiner, Harald Hampel

Research output: Contribution to journalArticle

219 Scopus citations

Abstract

The current study tested the accuracy of primary MRI and cerebrospinal fluid (CSF) biomarker candidates and neuropsychological tests for predicting the conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD) dementia. In a cross-validation paradigm, predictor models were estimated in the training set of AD (N = 81) and elderly control subjects (N = 101). A combination of CSF t-tau/Aβ1-4 ratio and MRI biomarkers or neuropsychological tests (free recall and trail making test B (TMT-B)) showed the best statistical fit in the AD vs. HC comparison, reaching a classification accuracy of up to 64% when applied to the prediction of MCI conversion (3.3-year observation interval, mean = 2.3 years). However, several single-predictor models showed a predictive accuracy of MCI conversion comparable to that of any multipredictor model. The best single predictors were right entorhinal cortex (prediction accuracy = 68.5% (95% CI (59.5, 77.4))) and TMT-B test (prediction accuracy 64.6% (95% CI (55.5, 73.4%))). In conclusion, short-term conversion to AD is predicted by single marker models to a comparable degree as by multimarker models in amnestic MCI subjects.

Original languageEnglish (US)
Pages (from-to)1203-1214.e2
JournalNeurobiology of aging
Volume33
Issue number7
DOIs
StatePublished - Jul 2012

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Keywords

  • ADNI
  • Alzheimer's disease
  • Autopsy-confirmation
  • Biomarkers
  • Cerebrospinal fluid
  • Cerebrospinal fluid (CSF)
  • Dementia
  • Early detection
  • Entorhinal cortex
  • Hippocampus
  • MRI
  • Mild cognitive impairment
  • Mild cognitive impairment (MCI)
  • P-tau
  • Prodromal
  • Tau
  • Volumetry

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

Ewers, M., Walsh, C., Trojanowski, J. Q., Shaw, L. M., Petersen, R. C., Jack, C. R., Feldman, H. H., Bokde, A. L. W., Alexander, G. E., Scheltens, P., Vellas, B., Dubois, B., Weiner, M., & Hampel, H. (2012). Prediction of conversion from mild cognitive impairment to Alzheimer's disease dementia based upon biomarkers and neuropsychological test performance. Neurobiology of aging, 33(7), 1203-1214.e2. https://doi.org/10.1016/j.neurobiolaging.2010.10.019