TY  - JOUR
AU  - Lange, Catharina
AU  - Suppa, Per
AU  - Pietrzyk, Uwe
AU  - Makowski, Marcus R.
AU  - Spies, Lothar
AU  - Peters, Oliver
AU  - Buchert, Ralph
TI  - Prediction of Alzheimer’s Dementia in Patients with Amnestic Mild Cognitive Impairment in Clinical Routine: Incremental Value of Biomarkers of Neurodegeneration and Brain Amyloidosis Added Stepwise to Cognitive Status
JO  - Journal of Alzheimer's disease
VL  - 61
IS  - 1
SN  - 1875-8908
CY  - Amsterdam
PB  - IOS Press
M1  - FZJ-2018-01316
SP  - 373 - 388
PY  - 2018
AB  - The aim of this study was to evaluate the incremental benefit of biomarkers for prediction of Alzheimer’s disease dementia (ADD) in patients with mild cognitive impairment (MCI) when added stepwise in the order of their collection in clinical routine. The model started with cognitive status characterized by the ADAS-13 score. Hippocampus volume (HV), cerebrospinal fluid (CSF) phospho-tau (pTau), and the FDG t-sum score in an AD meta-region-of-interest were compared as neurodegeneration markers. CSF-Aβ1-42 was used as amyloidosis marker. The incremental prognostic benefit from these markers was assessed by stepwise Kaplan-Meier survival analysis in 402 ADNI MCI subjects. Predefined cutoffs were used to dichotomize patients as ‘negative’ or ‘positive’ for AD characteristic alteration with respect to each marker. Among the neurodegeneration markers, CSF-pTau provided the best incremental risk stratification when added to ADAS-13. FDG PET outperformed HV only in MCI subjects with relatively preserved cognition. Adding CSF-Aβ provided further risk stratification in pTau-positive subjects, independent of their cognitive status. Stepwise integration of biomarkers allows stepwise refinement of risk estimates for MCI-to-ADD progression. Incremental benefit strongly depends on the patient’s status according to the preceding diagnostic steps. The stepwise Kaplan-Meier curves might be useful to optimize diagnostic workflow in individual patients.
LB  - PUB:(DE-HGF)16
UR  - <Go to ISI:>//WOS:000416369700032
DO  - DOI:10.3233/JAD-170705
UR  - https://juser.fz-juelich.de/record/843773
ER  -