Article

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

ABSTRACT

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.

Download full-text

Full-text

Available from: Carl Hoh
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Underpinnings of mild cognitive impairment (MCI) change with increasing age. We hypothesize that MRI signatures of mild cognitive impairment (MCI) would be different at a higher age compared to younger elders. Methods - 244 participants (71-103 years) from the Sydney Memory and Ageing Study and the Sydney Centenarian Study were categorized as amnestic MCI (aMCI), non-amnestic MCI (naMCI) or cognitively normal (CN). Brain "atrophy" and white matter hyper-intensities (WMHs) associated with MCI subtypes and age effects were examined by general linear models, controlling for confounding factors. Reduced logistic regressions were performed to determine structures that best discriminated aMCI from CN in individuals <85 and those ≥85 years. Results - aMCI was associated with smaller volumes of overall cortex, medial temporal structures, anterior corpus callosum, and select frontal and parietal regions compared to CN; such associations did not significantly change with age. Structures that best discriminated aMCI from CN differed however in the <85 and ≥85 age groups: cortex, putamen, parahippocampal, precuneus and superior frontal cortex in <85 years, and the hippocampus, pars triangularis and temporal pole in ≥85 years. Differences between naMCI and CN were small and non-significant in the sample. WMHs were not significantly associated with MCI subtypes. Conclusions - Structural MRI distinguishes aMCI, but not naMCI, from CN in elderly individuals. The structures that best distinguish aMCI from CN differ in those <85 from those ≥85, suggesting different neuropathological underpinnings of cognitive impairment in the very old.
    No preview · Article · Dec 2015 · Current Alzheimer research
    • "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 . "
    [Show abstract] [Hide abstract]
    ABSTRACT: Alzheimer's disease (AD) is typically associated with impairments in memory and other aspects of cognition, while deficits in complex movements are commonly observed later in the course of the disease. Recent studies, however, have indicated that subtle deteriorations in visuomotor control under cognitively demanding conditions may in fact be an early identifying feature of AD. Our previous work has shown that the ability to perform visuomotor tasks that rely on visual-spatial and rule-based transformations is disrupted in prodromal and preclinical AD. Here, in a sample of 30 female participants (10 young: mean age = 26.6 ± 2.7, 10 low AD risk: mean age = 58.7 ± 5.6, and 10 high AD risk: mean age = 58.5 ± 6.9), we test the hypothesis that these cognitive-motor impairments are associated with early AD-related brain alterations. Using diffusion-weighted magnetic resonance imaging, we examined changes in white matter (WM) integrity associated with normal aging and increased AD risk, and assessed the relationship between these underlying WM alterations and cognitive-motor performance. Our whole-brain analysis revealed significant age-related declines in WM integrity, which were more widespread in high relative to low AD risk participants. Furthermore, analysis of mean diffusivity measures within isolated WM clusters revealed a stepwise decline in WM integrity across young, low AD risk, and high AD risk groups. In support of our hypothesis, we also observed that lower WM integrity was associated with poorer cognitive-motor performance. These results are the first to demonstrate a relationship between AD-related WM alterations and impaired cognitive-motor control. The application of these findings may provide a novel clinical strategy for the early detection of individuals at increased AD risk.
    No preview · Article · Nov 2014 · Journal of Alzheimer's disease: JAD
  • Source
    • "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]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to characterize the neuropsychological and neuroimaging profiles of mild cognitive impairment (MCI) and Alzheimer's disease (AD) patients, and to study the magnitude of the differences by comparing both outcomes with healthy subjects in a cross-sectional manner. Five hundred and thirty-five subjects (356 cognitively normal adults (CONT), 79 MCI, and 100 AD) were assessed with the NEURONORMA neuropsychological battery. Thirty CONT, 23 MCI, and 23 AD subjects from this sample were included in the neuroimaging substudy. Patients' raw cognitive scores were converted to age and education-adjusted scaled ones (range 2-18) using co-normed reference values. Medians were plotted to examine the cognitive profile. MRIs were processed by means of FreeSurfer. Effect size indices (Cohen's d) were calculated in order to compare the standardized differences between patients and healthy subjects. Graphically, the observed cognitive profiles for MCI and AD groups produced near to parallel lines. Verbal and visual memories were the most impaired domains in both groups, followed by executive functions and linguistic/semantic ones. The largest effect size between AD and cognitively normal subjects was found for the FCSRT (d = 4.05, AD versus CONT), which doubled the value obtained by the best MRI measure, the right hippocampus (d = 1.65, AD versus CONT). Our results support the notion of a continuum in cognitive profile between MCI and AD. Neuropsychological outcomes, in particular the FCSRT, are better than neuroimaging ones at detecting differences among subjects.
    Full-text · Article · Apr 2014 · Journal of Alzheimer's disease: JAD
Show more