Subjects with mild cognitive impairment (MCI) and mild Alzheimer disease (AD) can be distinguished from elderly subjects with no cognitive impairment (NCI) by the degree of atrophy in the entorhinal cortex (ERC) and the hippocampus (HPC), quantified by volumetric magnetic resonance image (MRI) studies. Because volumetric MRI requires rigorous standards for image acquisition and analysis and is not suitable for routine clinical use, we have used calibrated visual rating to measure atrophy in the ERC, HPC, and perirhinal cortex (PRC) and evaluated its utility in the diagnosis of very early AD.
Thus far, visual rating methods, which have been found to be reliable and sensitive only for measurement of atrophy of the HPC or for the entire medial temporal region, have been found to be relatively insensitive for discriminating mild AD from elderly NCI subjects. We have developed a computer-based visual rating system (VRS) using reference images for calibration of atrophy ratings in several discrete brain regions, including the ERC, HPC, and PRC. The VRS reference images facilitate training of raters and promote standardization of all atrophy ratings. Interrater and intrarater reliability measurements were assessed; subsequently, the ability of VRS to discriminate the diagnoses among 73 elderly subjects was studied (NCI = 27, MCI = 23, and AD = 23).
Kappa values for interrater reliability of the ERC, HPC, and PRC were between 0.75 and 0.94, and for intrarater reliability, they were between 0.84 and 0.93, indicating that VRS enables highly reliable ratings to be obtained. Atrophy ratings in the ERC, HPC, and PRC distinguished AD from NCI subjects but did not distinguish AD from MCI subjects who tended to have intermediate levels of atrophy. Right and left ERC ratings and the right HPC rating distinguished MCI from NCI subjects.
The visual rating system is the first semiquantitative method that enables reliable measurements of ERC atrophy, and ERC measurement was found to be the best discriminator between MCI and NCI subjects. Visual rating system is a user-friendly tool that can allow a radiologist or a clinician to use structural MRI scans to be used as a biomarker in the diagnosis of prodromal AD.
"Visual rating scales are furthermore insensitive to detect atrophy progression over time (Ridha et al., 2007). A number of studies have examined differences between various techniques to measure atrophy of the MTL, mostly comparing manual with automated hippocampal volumetry (Lehmann et al., 2010; Sanchez-Benavides et al., 2010b; Shen et al., 2010) or volumetric hippocampal measurements to a visual rating scale (Ridha et al., 2007; Scheltens et al., 1992; Urs et al., 2009; Wahlund et al., 2000; Westman et al., 2011). These studies typically evaluate the diagnostic accuracy of different MRI techniques by comparing AD patients with healthy control subjects. "
[Show abstract][Hide abstract] ABSTRACT: Our aim was to compare the predictive accuracy of 4 different medial temporal lobe measurements for Alzheimer's disease (AD) in subjects with mild cognitive impairment (MCI). Manual hippocampal measurement, automated atlas-based hippocampal measurement, a visual rating scale (MTA-score), and lateral ventricle measurement were compared. Predictive accuracy for AD 2 years after baseline was assessed by receiver operating characteristics analyses with area under the curve as outcome. Annual cognitive decline was assessed by slope analyses up to 5 years after baseline. Correlations with biomarkers in cerebrospinal fluid (CSF) were investigated. Subjects with MCI were selected from the Development of Screening Guidelines and Clinical Criteria for Predementia AD (DESCRIPA) multicenter study (n = 156) and the single-center VU medical center (n = 172). At follow-up, area under the curve was highest for automated atlas-based hippocampal measurement (0.71) and manual hippocampal measurement (0.71), and lower for MTA-score (0.65) and lateral ventricle (0.60). Slope analysis yielded similar results. Hippocampal measurements correlated with CSF total tau and phosphorylated tau, not with beta-amyloid 1-42. MTA-score and lateral ventricle volume correlated with CSF beta-amyloid 1-42. We can conclude that volumetric hippocampal measurements are the best predictors of AD conversion in subjects with MCI.
Neurobiology of aging 03/2013; 34(8). DOI:10.1016/j.neurobiolaging.2013.02.002 · 5.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Drug development is a complex and extremely risky process. It involves developing knowledge of the relevant biology at a variety of levels of detail in order to piece together a coherent model of the disease process and the potential point(s) of intervention. Ultimately, this model must be complete enough to support the prediction of effects and the explanation of clinical trial results. Unfortunately, such models of a disease process have been primarily developed and maintained in human minds. Consequently, such models are limited by a human's ability to store all of the needed information, structure it properly, and reason about its consequences involving both complex feedback and time dependencies. The following paper describes a knowledge-centered approach to the development of biological models that support the drug development process. This technique focuses on a multi-level, hierarchical approach that models various levels of the related biology using appropriate representation techniques based on both the type and availability of the knowledge.
[Show abstract][Hide abstract] ABSTRACT: Despite convenience, accessibility, and strong correlation to severity of Alzheimer disease (AD) pathology, medial temporal lobe atrophy (MTA) has not been used as a criterion in the diagnosis of prodromal and probable AD.
Using a newly validated visual rating system, mean MTA scores of three bilateral medial temporal lobe structures were compared for subjects with no cognitive impairment (NCI) (n = 117), nonamnestic mild cognitive impairment (MCI) (n = 46), amnestic MCI (n = 45), and probable AD (n = 53). Correlations between MTA scores and neuropsychological test scores at baseline, and predictors of change in diagnosis at 1-year follow-up were evaluated.
With NCI as the reference group, a mean MTA cut score of 1.33 yielded an optimal sensitivity/specificity of 85%/82% for probable AD subjects and 80%/82% for amnestic MCI subjects. MTA and Clinical Dementia Rating Sum of Boxes scores at baseline were independent and additive predictors of diagnosis at baseline, and of transition from NCI to MCI or from MCI to dementia at 1-year follow-up.
Medial temporal lobe atrophy (MTA) scores 1) distinguish probable Alzheimer disease (AD) and amnestic mild cognitive impairment (MCI) subjects from nonamnestic MCI and no cognitive impairment (NCI) subjects, 2) help predict diagnosis at baseline, and 3) predict transition from NCI to MCI and from MCI to probable AD. MTA scores should be used as a criterion in the clinical diagnosis of AD.
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