Journal of Alzheimer's Disease
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Home > 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.

TitlePrediction 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.
Publication TypeJournal Article
Year of Publication2018
AuthorsLange, C, Suppa, P, Pietrzyk, U, Makowski, MR, Spies, L, Peters, O, Buchert, R
Corporate AuthorsAlzheimer’s Disease Neuroimaging Initiative
JournalJ Alzheimers Dis
Volume61
Issue1
Pagination373-388
Date Published2018
ISSN1875-8908
KeywordsAged, Aged, 80 and over, Alzheimer Disease, Amyloidosis, Brain, Cognitive Dysfunction, Female, Fluorodeoxyglucose F18, Humans, Imaging, Three-Dimensional, Longitudinal Studies, Magnetic Resonance Imaging, Male, Middle Aged, Neuropsychological Tests, Positron-Emission Tomography, Survival Analysis, tau Proteins
Abstract

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.

DOI10.3233/JAD-170705
Alternate JournalJ. Alzheimers Dis.
PubMed ID29154285
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Source URL: https://www.j-alz.com/content/prediction-alzheimers-dementia-patients-amnestic-mild-cognitive-impairment-clinical-routine