Brain atrophy rates predict subsequent clinical conversion in normal elderly and amnestic MCI

Department of Diagnostic Radiology, Mayo Clinic and Foundation, Rochester, MN 55905, USA.
Neurology (Impact Factor: 8.29). 11/2005; 65(8):1227-31. DOI: 10.1212/01.wnl.0000180958.22678.91
Source: PubMed


To test the hypothesis that the atrophy rate measured from serial MRI studies is associated with time to subsequent clinical conversion to a more impaired state in both cognitively healthy elderly subjects and in subjects with amnestic mild cognitive impairment (MCI).
Ninety-one healthy elderly patients and 72 patients with amnestic MCI who met inclusion criteria were identified from the Mayo Alzheimer's Disease Research Center and Alzheimer's Disease Patient Registry. Atrophy rates of four different brain structures--hippocampus, entorhinal cortex, whole brain, and ventricle--were measured from a pair of MRI studies separated by 1 to 2 years. The time of the second scan marked the beginning of the clinical observation period.
During follow-up, 13 healthy patients converted to MCI or Alzheimer disease (AD), whereas 39 MCI subjects converted to AD. Among those healthy at baseline, only larger ventricular annual percent volume change (APC) was associated with a higher risk of conversion (hazard ratio for a 1-SD increase 1.9, p = 0.03). Among MCI subjects, both greater ventricular volume APC (hazard ratio for a 1-SD increase 1.7, p < 0.001) and greater whole brain APC (hazard ratio for a 1-SD increase 1.4, p = 0.007) increased the risk of conversion to AD. Both ventricular APC (hazard ratio for a 1-SD increase 1.59, p = 0.001) and whole brain APC (hazard ratio for a 1-SD increase 1.32, p = 0.009) provided additional predictive information to covariate-adjusted cross-sectional hippocampal volume at baseline about the risk of converting from MCI to AD.
Higher whole brain and ventricle atrophy rates 1 to 2 years before baseline are associated with an increased hazard of conversion to a more impaired state. Combining a measure of hippocampal volume at baseline with a measure of either whole brain or ventricle atrophy rates from serial MRI scans provides complimentary predictive information about the hazard of subsequent conversion from mild cognitive impairment to Alzheimer disease. However, overlap among those who did vs those who did not convert indicate that these measures are unlikely to provide absolute prognostic information for individual patients.

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    • "Nonetheless, a clinical investigation of inadequate validity has potential for considerable harm, hence formal evaluation may be required. Examples of such formal evaluation in the neuroimaging field include evaluation of hippocampal atrophy as be a biomarker of early Alzheimer's Disease (eg., [Jack et al., 2005]), and lesion load as a surrogate marker of treatment response in multiple sclerosis (eg. [Ciumas et al., 2008]). "
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    ABSTRACT: fMRI is increasingly implemented in the clinic to assess memory function. There are multiple approaches to memory fMRI, but limited data on advantages and reliability of different methods. Here, we compared effect size, activation lateralisation, and between-sessions reliability of seven memory fMRI protocols: Hometown Walking (block design), Scene encoding (block design and event-related design), Picture encoding (block and event-related), and Word encoding (block and event-related). All protocols were performed on three occasions in 16 patients with temporal lobe epilepsy (TLE). Group T-maps showed activity bilaterally in medial temporal lobe for all protocols. Using ANOVA, there was an interaction between hemisphere and seizure-onset lateralisation (P = 0.009) and between hemisphere, protocol and seizure-onset lateralisation (P = 0.002), showing that the distribution of memory-related activity between left and right temporal lobes differed between protocols and between patients with left-onset and right-onset seizures. Using voxelwise intraclass Correlation Coefficient, between-sessions reliability was best for Hometown and Scenes (block and event). The between-sessions spatial overlap of activated voxels was also greatest for Hometown and Scenes. Lateralisation of activity between hemispheres was most reliable for Scenes (block and event) and Words (event). Using receiver operating characteristic analysis to explore the ability of each fMRI protocol to classify patients as left-onset or right-onset TLE, only the Words (event) protocol achieved a significantly above-chance classification of patients at all three sessions. We conclude that Words (event) protocol shows the best combination of between-sessions reliability of the distribution of activity between hemispheres and reliable ability to distinguish between left-onset and right-onset patients. Hum Brain Mapp, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.
    Human Brain Mapping 03/2015; 36(4). DOI:10.1002/hbm.22726 · 5.97 Impact Factor
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    • "The hippocampus is one of the earliest site of pathological changes (Braak and Braak 1991) and atrophy (Jack et al. 1999; Ridha et al. 2006) in Alzheimer's disease (AD). Magnetic resonance imaging (MRI) based measurement of volume and volume change in the hippocampus may be useful markers for AD diagnosis and tracking progression (Dubois et al. 2010; Henneman et al. 2009; Jack et al. 2005, 2008b; Wang et al. 2009). However, the " gold standard " measurement technique of manual segmentation is very labour intensive, taking up to 45 min per side, and is impractical for large studies or clinical trials, making the use of automated segmentation techniques necessary. "
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    ABSTRACT: Hippocampal volumetric measures may be useful for Alzheimer’s disease (AD) diagnosis and disease tracking; however, manual segmentation of the hippocampus is labour-intensive. Therefore, automated techniques are necessary for large studies and to make hippocampal measures feasible for clinical use. As large studies and clinical centres are moving from using 1.5 Tesla (T) scanners to higher field strengths it is important to assess whether specific image processing techniques can be used at these field strengths. This study investigated whether an automated hippocampal segmentation technique (HMAPS: hippocampal multi-atlas propagation and segmentation) and volume change measures (BSI: boundary shift integral) were as accurate at 3T as at 1.5T. Eighteen Alzheimer’s disease patients and 18 controls with 1.5T and 3T scans at baseline and 12-month follow-up were used from the Alzheimer’s Disease Neuroimaging Initiative cohort. Baseline scans were segmented manually and using HMAPS and their similarity was measured by the Jaccard index. BSIs were calculated for serial image pairs. We calculated pair-wise differences between manual and HMAPS rates at 1.5T and 3T and compared the SD of these differences at each field strength. The difference in mean Jaccards (manual and HMAPS) between 1.5T and 3T was small with narrow confidence intervals (CIs) and did not appear to be segmentor dependent. The SDs of the difference between volumes from manual and automated segmentations were similar at 1.5T and 3T, with a relatively narrow CI for their ratios. The SDs of the difference between BSIs from manual and automated segmentations were also similar at 1.5T and 3T but with a wider CI for their ratios. This study supports the use of our automated hippocampal voluming methods, developed using 1.5T images, with 3T images.
    Neuroinformatics 07/2014; 12(3). DOI:10.1007/s12021-013-9217-y · 2.83 Impact Factor
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    • "Finally, to account for global atrophy, measures of intensity and deformation were of high predictive value for memory decline (Duchesne et al., 2010). Similarly, whole brain atrophy measures are predictive for conversion from MCI to Alzheimer's disease (Jack et al., 2005; Spulber et al., 2010). "
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    Frontiers in Systems Neuroscience 04/2014; 8(1):58. DOI:10.3389/fnsys.2014.00058
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