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 Carl Petersen, Clifford R Jr. 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

208 Citations (Scopus)

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)
JournalNeurobiology of Aging
Volume33
Issue number7
DOIs
StatePublished - Jul 2012

Fingerprint

Neuropsychological Tests
Alzheimer Disease
Biomarkers
Trail Making Test
Cerebrospinal Fluid
Entorhinal Cortex
Observation
Cognitive Dysfunction

Keywords

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

ASJC Scopus subject areas

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

Cite this

Prediction of conversion from mild cognitive impairment to Alzheimer's disease dementia based upon biomarkers and neuropsychological test performance. / Ewers, Michael; Walsh, Cathal; Trojanowski, John Q.; Shaw, Leslie M.; Petersen, Ronald Carl; Jack, Clifford R Jr.; Feldman, Howard H.; Bokde, Arun L W; Alexander, Gene E.; Scheltens, Philip; Vellas, Bruno; Dubois, Bruno; Weiner, Michael; Hampel, Harald.

In: Neurobiology of Aging, Vol. 33, No. 7, 07.2012.

Research output: Contribution to journalArticle

Ewers, M, Walsh, C, Trojanowski, JQ, Shaw, LM, Petersen, RC, Jack, CRJ, Feldman, HH, Bokde, ALW, Alexander, GE, 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, vol. 33, no. 7. https://doi.org/10.1016/j.neurobiolaging.2010.10.019
Ewers, Michael ; Walsh, Cathal ; Trojanowski, John Q. ; Shaw, Leslie M. ; Petersen, Ronald Carl ; Jack, Clifford R Jr. ; Feldman, Howard H. ; Bokde, Arun L W ; Alexander, Gene E. ; Scheltens, Philip ; Vellas, Bruno ; Dubois, Bruno ; Weiner, Michael ; Hampel, Harald. / Prediction of conversion from mild cognitive impairment to Alzheimer's disease dementia based upon biomarkers and neuropsychological test performance. In: Neurobiology of Aging. 2012 ; Vol. 33, No. 7.
@article{87a59f6bbdad45639dfd8a549f5d64a7,
title = "Prediction of conversion from mild cognitive impairment to Alzheimer's disease dementia based upon biomarkers and neuropsychological test performance",
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.",
keywords = "Aβ, ADNI, Alzheimer's disease, Autopsy-confirmation, Biomarkers, Cerebrospinal fluid, Cerebrospinal fluid (CSF), Dementia, Early detection, Entorhinal cortex, Hippocampus, Mild cognitive impairment, Mild cognitive impairment (MCI), MRI, P-tau, Prodromal, Tau, Volumetry",
author = "Michael Ewers and Cathal Walsh and Trojanowski, {John Q.} and Shaw, {Leslie M.} and Petersen, {Ronald Carl} and Jack, {Clifford R Jr.} and Feldman, {Howard H.} and Bokde, {Arun L W} and Alexander, {Gene E.} and Philip Scheltens and Bruno Vellas and Bruno Dubois and Michael Weiner and Harald Hampel",
year = "2012",
month = "7",
doi = "10.1016/j.neurobiolaging.2010.10.019",
language = "English (US)",
volume = "33",
journal = "Neurobiology of Aging",
issn = "0197-4580",
publisher = "Elsevier Inc.",
number = "7",

}

TY - JOUR

T1 - Prediction of conversion from mild cognitive impairment to Alzheimer's disease dementia based upon biomarkers and neuropsychological test performance

AU - Ewers, Michael

AU - Walsh, Cathal

AU - Trojanowski, John Q.

AU - Shaw, Leslie M.

AU - Petersen, Ronald Carl

AU - Jack, Clifford R Jr.

AU - Feldman, Howard H.

AU - Bokde, Arun L W

AU - Alexander, Gene E.

AU - Scheltens, Philip

AU - Vellas, Bruno

AU - Dubois, Bruno

AU - Weiner, Michael

AU - Hampel, Harald

PY - 2012/7

Y1 - 2012/7

N2 - 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.

AB - 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.

KW - Aβ

KW - ADNI

KW - Alzheimer's disease

KW - Autopsy-confirmation

KW - Biomarkers

KW - Cerebrospinal fluid

KW - Cerebrospinal fluid (CSF)

KW - Dementia

KW - Early detection

KW - Entorhinal cortex

KW - Hippocampus

KW - Mild cognitive impairment

KW - Mild cognitive impairment (MCI)

KW - MRI

KW - P-tau

KW - Prodromal

KW - Tau

KW - Volumetry

UR - http://www.scopus.com/inward/record.url?scp=84861198255&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84861198255&partnerID=8YFLogxK

U2 - 10.1016/j.neurobiolaging.2010.10.019

DO - 10.1016/j.neurobiolaging.2010.10.019

M3 - Article

C2 - 21159408

AN - SCOPUS:84861198255

VL - 33

JO - Neurobiology of Aging

JF - Neurobiology of Aging

SN - 0197-4580

IS - 7

ER -