TY - JOUR
T1 - Twelve-month metabolic declines in probable Alzheimer's disease and amnestic mild cognitive impairment assessed using an empirically pre-defined statistical region-of-interest
T2 - Findings from the Alzheimer's Disease Neuroimaging Initiative
AU - Chen, Kewei
AU - Langbaum, Jessica B.S.
AU - Fleisher, Adam S.
AU - Ayutyanont, Napatkamon
AU - Reschke, Cole
AU - Lee, Wendy
AU - Liu, Xiaofen
AU - Bandy, Dan
AU - Alexander, Gene E.
AU - Thompson, Paul M.
AU - Foster, Norman L.
AU - Harvey, Danielle J.
AU - de Leon, Mony J.
AU - Koeppe, Robert A.
AU - Jagust, William J.
AU - Weiner, Michael W.
AU - Reiman, Eric M.
N1 - Funding Information:
Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI; Principal Investigator: Michael Weiner; NIH grant U01 AG024904 ). ADNI is funded by the National Institute on Aging , the National Institute of Biomedical Imaging and Bioengineering (NIBIB) , and through generous contributions from the following: Pfizer Inc. , Wyeth Research , Bristol-Myers Squibb , Eli Lilly and Company , GlaxoSmithKline, Merck & Co. Inc. , AstraZeneca AB , Novartis Pharmaceuticals Corporation , Alzheimer's Association , Eisai Global Clinical Development , Elan Corporation plc , Forest Laboratories , and the Institute for the Study of Aging , with participation from the U.S. Food and Drug Administration . Industry partnerships are coordinated through the Foundation for the National Institutes of Health. The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory of Neuro Imaging at the University of California, Los Angeles.
Funding Information:
This work was also partly supported by grants from the National Institute on Aging (R01AG031581 [EMR], P30AG19610 [EMR], R01AG025526 [GEA]), the National Institute of Mental Health (R01MH057899 [EMR]), the Evelyn G. McKnight Brain Institute (GEA), the state of Arizona (EMR, RJC, GEA, KC), and contributions from the Banner Alzheimer's Foundation and Mayo Clinic Foundation.
PY - 2010/6
Y1 - 2010/6
N2 - Alzheimer's disease (AD) is characterized by specific and progressive reductions in fluorodeoxyglucose positron emission tomography (FDG PET) measurements of the cerebral metabolic rate for glucose (CMRgl), some of which may precede the onset of symptoms. In this report, we describe twelve-month CMRgl declines in 69 probable AD patients, 154 amnestic mild cognitive impairment (MCI) patients, and 79 cognitively normal controls (NCs) from the AD Neuroimaging Initiative (ADNI) using statistical parametric mapping (SPM). We introduce the use of an empirically pre-defined statistical region-of-interest (sROI) to characterize CMRgl declines with optimal power and freedom from multiple comparisons, and we estimate the number of patients needed to characterize AD-slowing treatment effects in multi-center randomized clinical trials (RCTs). The AD and MCI groups each had significant twelve-month CMRgl declines bilaterally in posterior cingulate, medial and lateral parietal, medial and lateral temporal, frontal and occipital cortex, which were significantly greater than those in the NC group and correlated with measures of clinical decline. Using sROIs defined based on training sets of baseline and follow-up images to assess CMRgl declines in independent test sets from each patient group, we estimate the need for 66 AD patients or 217 MCI patients per treatment group to detect a 25% AD-slowing treatment effect in a twelve-month, multi-center RCT with 80% power and two-tailed alpha=0.05, roughly one-tenth the number of the patients needed to study MCI patients using clinical endpoints. Our findings support the use of FDG PET, brain-mapping algorithms and empirically pre-defined sROIs in RCTs of AD-slowing treatments.
AB - Alzheimer's disease (AD) is characterized by specific and progressive reductions in fluorodeoxyglucose positron emission tomography (FDG PET) measurements of the cerebral metabolic rate for glucose (CMRgl), some of which may precede the onset of symptoms. In this report, we describe twelve-month CMRgl declines in 69 probable AD patients, 154 amnestic mild cognitive impairment (MCI) patients, and 79 cognitively normal controls (NCs) from the AD Neuroimaging Initiative (ADNI) using statistical parametric mapping (SPM). We introduce the use of an empirically pre-defined statistical region-of-interest (sROI) to characterize CMRgl declines with optimal power and freedom from multiple comparisons, and we estimate the number of patients needed to characterize AD-slowing treatment effects in multi-center randomized clinical trials (RCTs). The AD and MCI groups each had significant twelve-month CMRgl declines bilaterally in posterior cingulate, medial and lateral parietal, medial and lateral temporal, frontal and occipital cortex, which were significantly greater than those in the NC group and correlated with measures of clinical decline. Using sROIs defined based on training sets of baseline and follow-up images to assess CMRgl declines in independent test sets from each patient group, we estimate the need for 66 AD patients or 217 MCI patients per treatment group to detect a 25% AD-slowing treatment effect in a twelve-month, multi-center RCT with 80% power and two-tailed alpha=0.05, roughly one-tenth the number of the patients needed to study MCI patients using clinical endpoints. Our findings support the use of FDG PET, brain-mapping algorithms and empirically pre-defined sROIs in RCTs of AD-slowing treatments.
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U2 - 10.1016/j.neuroimage.2010.02.064
DO - 10.1016/j.neuroimage.2010.02.064
M3 - Article
C2 - 20202480
AN - SCOPUS:77951965415
SN - 1053-8119
VL - 51
SP - 654
EP - 664
JO - NeuroImage
JF - NeuroImage
IS - 2
ER -