Premium
O4‐01‐05: Use of biomarkers as endpoint in trials with subjects with preclinical and prodromal Alzheimer's disease: An ADNI study
Author(s) -
Bertens Daniela,
Scheltens Philip,
Visser Pieter Jelle
Publication year - 2012
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2012.05.1638
Subject(s) - cognitive decline , biomarker , medicine , oncology , neuropsychology , population , alzheimer's disease , cognition , alzheimer's disease neuroimaging initiative , neuroimaging , prodromal stage , disease , dementia , psychiatry , biochemistry , chemistry , environmental health
Alzheimer’s disease progression scale (ADPS) against which each biomarker is visualized. Nine biomarkers from the ADNI dataset are chosen by experts for their importance in AD: MRI hippocampal volume divided by the intra-cranial volume (Hippo), thickness of the entorhinal cortex (EC), ADAS, MMSE, CSF protein concentration of tau and Aß42, CDRSB, RAVLT 30 minutes and the mean FDG PET uptake value of Left Angular, Right Angular, Left Temporal, Right Temporal and Bilateral Posterior Results: The estimated sigmoid curves for each biomarker are standardized and plotted against the ADPS in Figure 1. RAVLT-30min is the earliest biomarker to become dynamic, as measured by the location of the inflexion point on the ADPS. A group of four biomarkers follows including Hippo, Aß42, tau, EC, followed by the FDG PET measurement. The cognitive biomarkers, including MMSE, SDR-SD, and ADAS, are maximally dynamic during the latter part of the disease. 75% confidence intervals for the ADPS value at which each biomarker is the most dynamic (inflexion point) are also provided below the sigmoid curves. Conclusions: This method demonstrates a multiple biomarker, data-driven approach to assess and hypothesize time-dependent changes of biomarkers in AD and to localize subjects on a scale of disease progression over the entire range of progression represented in the ADNI cohort.