MRI of hippocampal volume loss in early Alzheimer's disease in relation to ApoE genotype and biomarkers
Open accessAbstract
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 beta-amyloid (Abeta(1-42)) 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 epsilon4 gene in Alzheimer's disease and lower CSF Abeta(1-42) 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 epsilon4 and decreased CSF Abeta(1-42) 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.
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A number of studies have suggested that CSF markers in combination with neuroimaging and neuropsychological tools add to the accuracy of AD diagnosis.
“A number of studies have suggested that CSF markers in combination with neuroimaging and neuropsychological tools add to the accuracy of AD diagnosis (Richard et al., 2013; Schuff et al., 2009; Vemuri et al., 2010).”
From T1rho MRI and CSF biomarkers in diagnosis of Alzheimer's disease (2015) · cites this paper as Schuff et al., 2009
The Introduction and Discussion describe using CSF markers with MRI and say the two measures provide complementary information about Alzheimer’s disease pathology. But the Discussion explicitly says their diagnostic value together remains unclear, and the paper does not show that adding neuropsychological tools improves diagnostic accuracy. Page numbers are unavailable in our copy. (LLM, conf=0.86)
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- Authors
- Schuff, N., Woerner, N., Boreta, L., Kornfield, T., Shaw, L. M., Trojanowski, J. Q., Thompson, P. M., Jack, C. R., Weiner, M. W., & Initiative, T. A. D. N.
- Affiliations
- San Francisco VA Medical Center (US)
- University of Pennsylvania (US)
- University of California, Los Angeles (US)
- Mayo Clinic (US)
- Corresponding author
- Schuff, N.
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-05-21
- Volume
- 132
- Issue
- 4
- Pages
- 1067-1077
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- 0006-8950 (ISSN-L)
- 1460-2156
- PMC
- PMC2668943
- OpenAlex
- W2104048700
- Cited by
- 679
- References
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- Bristol-Myers Squibb
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- GlaxoSmithKline
- Alzheimer's Disease Neuroimaging Initiative
- National Institutes of Health (5u01ag024904-10)
- University of California, Davis
- University of California, San Diego
- University of California, San Francisco
- National Institute on Aging (U01-AG-024904, U19AG010483)
- National Institute of Biomedical Imaging and Bioengineering
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
- Keywords
- hippocampal atrophy, Alzheimer's disease, mild cognitive impairment, apolipoprotein E, APOE ε4, cerebrospinal fluid biomarkers, amyloid-beta, tau protein, longitudinal MRI, normal aging, Alzheimer's Disease Neuroimaging Initiative
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Apolipoproteins E, Cognition Disorders, Female, Genotype, Hippocampus, Humans, Magnetic Resonance Imaging, Male, Peptide Fragments, Polymorphism, Genetic, Psychiatric Status Rating Scales, Biomarkers, Amyloid beta-Peptides, Sample Size, Disease Progression, Genetic Predisposition to Disease
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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