Article

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: 8.3). 11/2005; 65(8):1227-31. DOI: 10.1212/01.wnl.0000180958.22678.91
Source: PubMed

ABSTRACT 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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Available from: Maria Shiung, Aug 26, 2015
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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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    • "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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    • "In such situations, the ventricular enlargement that accompanies the brain volume loss is an important candidate surrogate measure, since it can, in principle, be measured from standard two-dimensional (2D) images, thus allowing a more specific assessment of atrophy than whole-brain measures. Ventricular enlargement has proven to be a sensitive indirect measure of ongoing neurodegeneration in MS, AD, and healthy aging (Dalton et al., 2006; Fjell et al., 2006; Jack et al., 2005). "
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