Alzheimer's Disease Neuroimaging Initiative (2009): Automated 3D mapping of hippocampal atrophy and its clinical correlates in 400 subjects with Alzheimer's disease, mild cognitive impairment, and elderly controls

Laboratory of Neuro Imaging, Department of Neurology, UCLA School of Medicine, Los Angeles, California 90095-1769, USA.
Human Brain Mapping (Impact Factor: 6.92). 09/2009; 30(9):2766-88. DOI: 10.1002/hbm.20708
Source: PubMed

ABSTRACT We used a new method we developed for automated hippocampal segmentation, called the auto context model, to analyze brain MRI scans of 400 subjects from the Alzheimer's disease neuroimaging initiative. After training the classifier on 21 hand-labeled expert segmentations, we created binary maps of the hippocampus for three age- and sex-matched groups: 100 subjects with Alzheimer's disease (AD), 200 with mild cognitive impairment (MCI) and 100 elderly controls (mean age: 75.84; SD: 6.64). Hippocampal traces were converted to parametric surface meshes and a radial atrophy mapping technique was used to compute average surface models and local statistics of atrophy. Surface-based statistical maps visualized links between regional atrophy and diagnosis (MCI versus controls: P = 0.008; MCI versus AD: P = 0.001), mini-mental state exam (MMSE) scores, and global and sum-of-boxes clinical dementia rating scores (CDR; all P < 0.0001, corrected). Right but not left hippocampal atrophy was associated with geriatric depression scores (P = 0.004, corrected); hippocampal atrophy was not associated with subsequent decline in MMSE and CDR scores, educational level, ApoE genotype, systolic or diastolic blood pressure measures, or homocysteine. We gradually reduced sample sizes and used false discovery rate curves to examine the method's power to detect associations with diagnosis and cognition in smaller samples. Forty subjects were sufficient to discriminate AD from normal and correlate atrophy with CDR scores; 104, 200, and 304 subjects, respectively, were required to correlate MMSE with atrophy, to distinguish MCI from normal, and MCI from AD.

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Available from: Paul Thompson, Aug 29, 2015
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    • "The hippocampus plays a central role in early memory loss in AD patients [5]. The earliest neuropathological changes in AD are consistently observed in the medial temporal lobe (entorhinal cortex and hippocampus) [6], and hippocampal volume loss is the best established diagnostic marker for AD and highly predictive of disease progression [7]. Early deficits in hippocampal memory performance and synaptic plasticity have been established in various animal models of AD, before neuropathological changes are observed and in the absence of neurodegeneration [8,9]. "
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    06/2014; 2(1):76. DOI:10.1186/PREACCEPT-1259006781131998
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    • "The most pronounced atrophy in AD has been found in the anterior hippocampus (as well as posterior parahippocampal gyrus and the precuneus) compared to age-matched controls (Raji et al., 2009). Moreover, hippocampal head (anterior) atrophy has been reported as a predictive marker of conversion to AD (Csernansky et al., 2005; Apostolova et al., 2006; Morra et al., 2009a; Costafreda et al., 2011). Costafreda et al. identified more pronounced changes in the right lateral and medial aspects of hippocampal head in individuals that later converted to AD and his results correspond with previous reports of anterior CA1 (Csernansky et al., 2005; Apostolova et al., 2006; Costafreda et al., 2011). "
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    • "For example, obvious pathological changes within the hippocampal formation occur in Alzheimer's disease and related dementias, associated with the memory impairments observed in these disorders (Hodges, 2012). Some level of hippocampal pathology is thought to contribute to major depression that occurs late in life, which also may relate to mild cognitive impairment (MCI; Morra et al., 2009). Additionally, a very complex interplay exists between TBV, aging and hippocampal volume and the transitions from healthy aging to MCI, and from MCI to frank dementia (Apostolova et al., 2012). "
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