Relative Capability of MR Imaging and FDG PET to Depict Changes Associated with Prodromal and Early Alzheimer Disease

Department of Radiology, University of California, San Diego, La Jolla, CA 92093, USA.
Radiology (Impact Factor: 6.87). 09/2010; 256(3):932-42. DOI: 10.1148/radiol.10091402
Source: PubMed


To quantify the effect sizes of regional metabolic and morphometric measures in patients with preclinical and mild Alzheimer disease (AD) to aid in the identification of noninvasive biomarkers for the early detection of AD.
The study was conducted with institutional review board approval and in compliance with HIPAA regulations. Written informed consent was obtained from each participant or participant's legal guardian. Fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) and magnetic resonance (MR) imaging data were analyzed from 80 healthy control (HC) subjects, 68 individuals with AD, and 156 with amnestic mild cognitive impairment (MCI), 69 of whom had single-domain amnestic MCI. Regions of interest (ROIs) were derived after coregistering FDG PET and MR images by using high-throughput, subject-specific procedures. The Cohen d effect sizes were calculated for 42 predefined ROIs across the brain. Statistical comparison of the largest overall effect sizes for MR imaging and PET was performed. Metabolic effect sizes were determined with and without accounting for regional atrophy. Discriminative accuracy of ROIs showing the largest effect sizes were compared by calculating receiver operating characteristic curves.
For all disease groups, the hippocampus showed the largest morphometric effect size and the entorhinal cortex showed the largest metabolic effect size. In mild AD, the Cohen d effect size for hippocampal volume (1.92) was significantly larger (P < .05) than that for entorhinal metabolism (1.43). Regression of regional atrophy substantially reduced most metabolic effects. For all group comparisons, the areas under the receiver operating characteristic curves were significantly larger for hippocampal volume than for entorhinal metabolism.
The current results show no evidence that FDG PET is more sensitive than MR imaging to the degeneration occurring in preclinical and mild AD, suggesting that an MR imaging finding may be a more practical clinical biomarker for early detection of AD.

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    • "Amnestic MCI (aMCI) is of particular interest since it is considered to be the prodromal phase of Alzheimer's disease (AD)[4]. Relative to cognitively normal (CN) subjects, a pattern of atrophy spreading from mesial temporal lobe to temporo-parietal cortices in aMCI individuals has been well established[1,3,5678. Such pattern is consistent with the current hypothesis of AD pathogenesis[2], thus is implicated in differential diagnosis and/or monitoring of disease progression. "
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    • "While AD dementia is typically associated with declines in cognition and short-term memory resulting from hippocampal atrophy [8], these clinical symptoms only present themselves after significant damage to the brain has already occurred [9]. Thus, neuroimaging studies including individuals in the preclinical (i.e., increased genetic risk) and prodromal (i.e., mild cognitive impairment) stages of AD are essential for the development of early detection strategies . "
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    • "For example, right hippocampus volume in our AD sample reached a Cohen's d of 1.64. Karow et al. reported a d of 1.94 in a sample of mild AD patients [79], and Fennema-Notestine et al. found a value of 1.62 for the right hippocampus and 1.80 for the left one in the ADNI sample [74]. With respect to MCI, Desikan and colleagues reported effect size calculations by splitting their sample on the basis of progression (converters versus non converters) [80]. "
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