MRI of hippocampal volume loss in early Alzheimer's disease in relation to ApoE genotype and biomarkers

By Norbert Schuff, N. Woerner, L. Boreta, T. Kornfield, L. Shaw, John Q. Trojanowski, P. Thompson, Clifford R. Jack Jr., M. Weiner. Brain : a journal of neurology, 2008

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Hippocampal volume change over time, measured with MRI, has huge potential as a marker for Alzheimer's disease. The objectives of this study were: (i) to test if constant and accelerated hippocampal loss can be detected in Alzheimer's disease, mild cognitive impairment and normal ageing over short periods, e.g. 6–12 months, with MRI in the large multicentre setting of the Alzheimer's Disease Neuroimaging Initiative (ADNI); (ii) to determine the extent to which the polymorphism of the apolipoprotein E (ApoE) gene modulates hippocampal change; and (iii) to determine if rates of hippocampal loss correlate with cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease, such as the β-amyloid (Aβ1–42) and tau proteins (tau). The MRI multicentre study included 112 cognitive normal elderly individuals, 226 mild cognitive impairment and 96 Alzheimer's disease patients who all had at least three successive MRI scans, involving 47 different imaging centres. The mild cognitive impairment and Alzheimer's disease groups showed hippocampal volume loss over 6 months and accelerated loss over 1 year. Moreover, increased rates of hippocampal loss were associated with presence of the ApoE allele ɛ4 gene in Alzheimer's disease and lower CSF Aβ1–42 in mild cognitive impairment, irrespective of ApoE genotype, whereas relations with tau were only trends. The power to measure hippocampal change was improved by exploiting correlations statistically between successive MRI observations. The demonstration of considerable hippocampal loss in mild cognitive impairment and Alzheimer's disease patients over only 6 months and accelerated loss over 12 months illustrates the power of MRI to track morphological brain changes over time in a large multisite setting. Furthermore, the relations between faster hippocampal loss in the presence of ApoE allele ɛ4 and decreased CSF Aβ1–42 supports the concept that increased hippocampal loss is an indicator of Alzheimer's disease pathology and a potential marker for the efficacy of therapeutic interventions in Alzheimer's disease.

Subfields: Cognitive Neuroscience, Physiology, Psychiatry and Mental health

View Paper: https://www.semanticscholar.org/paper/22acf1ed45fa7c036ba0d95b7a1a246eec625e41

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Citations in the corpus

Brain imaging in Alzheimer disease. (2012, background): “Even in mildly affected individuals (e.g., mean MMSE of 24/30) entorhinal volumes are already reduced by 20 – 30% and hippocampal volumes by 15–25% (Chan et al. 2001; Dickerson et al. 2001; Schuff et al. 2009).”
What is normal in normal aging? Effects of Aging, Amyloid and Alzheimer’s Disease on the Cerebral Cortex and the Hippocampus (2014, background): “In ADNI, relationships between CSF levels of Ab1–42 and cortical atrophy have been found in MCI patients (Schuff et al., 2009; Fjell et al., 2010b; Jack et al., 2010b; Tosun et al., 2010) and controls (Fjell et al., 2010a; Schott et al., 2010).”
The Alzheimer’s Disease Neuroimaging Initiative: A review of papers published since its inception (2011, methodology): “Schuff et al [121] also found that increased rates of hippocampal atrophy were associated with lower levels of Ab-42 in the MCI, but not AD or control, group.”
One year brain atrophy evident in healthy aging (2009, background): “Further, while atrophy has been demonstrated in mild cognitive impairment over 1 year or less (Schuff et al., 2009), it is not known whether brain changes driven solely by normal aging are large enough to be detectable over such short time intervals.”
Sex Modifies the APOE-Related Risk of Developing Alzheimer's Disease (2014, neutral): “…models have identified potential pathogenic mechanisms related to beta-amyloid (Abeta) clearance, tau hyperphosphorylation, and synaptic function, among others 3 In human studies, some, but not all, imaging biomarker studies have shown early AD-like findings in healthy older APOE4 carriers 4–6 .”
Prediction of MCI to AD conversion, via MRI, CSF biomarkers, pattern classification (2010, neutral): “Studies using CSF biomarkers have also shown the promise of CSF tau and A (cid:1) 42 measures as diagnostic tests for AD as well as potential predictors of risk for developing AD in normal individuals and those with MCI (Hampel et al., 2010a, 2010b; Schuff et al., 2009; Shaw et al., 2009).”
Convolutional Neural Networks for Classification of Alzheimer's Disease: Overview and Reproducible Evaluation (2019, background): “In all the following studies, the ROI chosen was the hippocampus, which is well-known to be affected early in AD (Dickerson et al., 2001; Salvatore et al., 2015; Schuff et al., 2009).”