IC‐P‐084: Use of an fdg‐pet‐derived hypometabolic convergence index enrichment strategy to reduce sample sizes in alzheimer's disease clinical trials: Findings from the Alzheimer's Disease Neuroimaging Initiative (ADNI)
Year: 2011
Type: article
Abstract: While the Alzheimer's disease Assessment Scale-Cognitive Subscale (ADAS-Cog) is commonly used to measure cognitive decline in probable Alzheimer's disease (pAD) and mild cognitive impairment (MCI) patients, rates of decline vary. We previously introduced a single index, Hypometabolic Convergence Index (HCI), to characterize the extent to which the pattern and magnitude of cerebral hypometabolism in a person's fluorodeoxyglucose-positron emission tomography (FDG-PET) image corresponds to that in pAD patients. Here, we used data from ADNI to examine the extent to which 1) a person's baseline HCI predicts cognitive decline using the ADAS-Cog, Mini-Mental State Exam (MMSE), Clinical Dementia Rating-sum of boxes (CDR-SB) and Auditory-Verbal Learning Test (AVLT-Total), and 2) the HCI could be used to enrich clinical trials for clinical decline and reduce the number of patients needed to detect a treatment's clinical effects. Baseline HCIs were computed for 120 MCI and 54 mild AD patients who had up to 24-month data. We first characterized the extent to which HCIs correlated with 12-month and 24-month clinical declines. We then estimated the sample sizes needed to detect an AD-slowing treatment's effects on ADAS-Cog before/after enrichment for those patients with HCIs greater than the predetermined threshold of 13.82 for pAD and 8.19 for MCI (Chen et al., 2011, Neuroimage) with 80% power, 0.05 type-I error and a 25% treatment effect. In pAD, HCIs correlated (p < = 0.05) with subsequent ADAS-Cog, MMSE, CDR-SB and AVLT-Total 12-month (24-month) decline (r = 0.42(0.47), -0.35(-0.55), 0.28(0.29), -0.40(-0.43), respectively). In MCI, HCI also correlated with subsequent decline at 12-month (24-month) (r = 0.33(0.32), -0.43(-0.50), 0.29(0.37), -0.17(-0.32), respectively). HCI enrichment is estimated to reduce the number of pAD patients needed per treatment arm to detect an AD-slowing treatment's effect on ADAS-Cog from 406 to 243 in a 12-month trial and from 168 to 137 in a 24-month trial. Similarly, it is estimated to reduce the number of MCI patients from 1,718 to 749 in a 12-month trial and from 926 to 374 in a 24-month trial. Baseline HCIs could be used to predict subsequent clinical declines in pAD and MCI patients and to reduce the number of patients needed to detect an AD-slowing treatment's effects in randomized clinical trials.
Source: Alzheimer s & Dementia
Authors: Napatkamon Ayutyanont, Kewei Chen, Auttawut Roontiva, Adam Fleisher, Jessica Langbaum, Cole Reschke, Wendy Lee, Xiaofen Liu, Dan Bandy, Gene Alexander, Norman Foster, Danielle Harvey, Michael Weiner, Robert Koeppe, William Jagust, Eric Reiman, The Alzheimer's Disease Neuroimaging Initiative
Institutions: Banner - University Medical Center Phoenix, Banner Alzheimer’s Institute, Arizona Alzheimer’s Consortium, Arizona State University, University of Arizona, University of Utah, University of California, Davis, University of California, San Francisco, Translational Genomics Research Institute, University of Michigan, University of California, Berkeley, Alzheimer’s Disease Neuroimaging Initiative
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2022176186