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Antemortem MRI based STructural Abnormality iNDex (STAND)-scores correlate with postmortem Braak neurofibrillary tangle stage
Open accessAbstract
The clinical diagnosis of Alzheimer's disease (AD) does not exactly match the pathological findings at autopsy in every subject. Therefore, in-vivo imaging measures, such as Magnetic Resonance Imaging (MRI) that reflect underlying pathology, would be clinically useful independent supplementary measures of disease stage. We have developed an algorithm that extracts atrophy information from individual patient's 3D MRI scans and assigns a STructural Abnormality iNDex (STAND)-score to the scan based on the degree of atrophy in comparison to patterns extracted from a large library of clinically well characterized AD and CN (cognitively normal) subject's MRI scans. STAND-scores can be adjusted for demographics to give adjusted-STAND (aSTAND)-scores which are >0 for subjects with brains identified as abnormal by the algorithm. Since histopathological findings are considered to represent the "ground truth", our objective was to assess the sensitivity of aSTAND-scores to pathological AD staging. This was done by comparing antemortem MRI based aSTAND-scores with postmortem grading of disease severity in 101 subjects who had both antemortem MRI and postmortem Braak neurofibrillary tangle (NFT) staging. We found a rank correlation of 0.62 (p<0.0001) between Braak NFT stage and aSTAND-scores. The results show that optimally extracted information from MRI scans such as STAND-scores accurately capture the severity of neuronal pathology and can be used as an independent approximate surrogate marker for in-vivo pathological staging as well as for early identification of AD in individual subjects.
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“As well as revealing signs of atrophy, which can inform differential diagnosis of the disease, antemortem MRI has previously been found to correlate well with measures of cognitive deterioration and post-mortem Braak staging of the disease (Csernansky et al., 2004, Jack et al., 2002, Vemuri et al., 2008, Whitwell et al., 2008).”
From In vivo imaging of tau pathology using multi-parametric quantitative MRI (2015) · cites this paper as Vemuri et al., 2008
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Cites
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Jack, C. R., Knopman, D. S., Jagust, W. J., Petersen, R. C., Weiner, M. W., Aisen, P. S., Shaw, L. M., Vemuri, P., Wiste, H. J., Weigand, S. D., et al. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(12)70291-0 · Cited by 4,396
Self-citationThe clinical use of structural MRI in Alzheimer disease
Frisoni, G. B., Fox, N. C., Jack, C. R., Scheltens, P., & Thompson, P. M. (2010) · Nature Reviews Neurology · doi:10.1038/nrneurol.2009.215 · Cited by 2,113
Self-citationRevising the definition of Alzheimer's disease: a new lexicon
Dubois, B., Feldman, H. H., Jacova, C., Cummings, J. L., DeKosky, S. T., Barberger-Gateau, P., Delacourte, A., Frisoni, G., Fox, N. C., Galasko, D., et al. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70223-4 · Cited by 1,869
Jack, C. R., Lowe, V. J., Weigand, S. D., Wiste, H. J., Senjem, M. L., Knopman, D. S., Shiung, M. M., Gunter, J. L., Boeve, B. F., Kemp, B. J., et al. (2009) · Brain · doi:10.1093/brain/awp062 · Cited by 1,099
Self-citationBiomarker Modeling of Alzheimer’s Disease
Jack, C. R., & Holtzman, D. M. (2013) · Neuron · doi:10.1016/j.neuron.2013.12.003 · Cited by 1,002
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Metadata
- Authors
- Vemuri, P., Whitwell, J. L., Kantarci, K., Josephs, K. A., Parisi, J. E., Shiung, M. S., Knopman, D. S., Boeve, B. F., Petersen, R. C., Dickson, D. W., & Jack, C. R.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Jack, Clifford R.
- ORCID
- Venue
- NeuroImage
- Publisher
- Elsevier BV
- Published
- 2008-08
- Volume
- 42
- Issue
- 2
- Pages
- 559-567
- ISSN
- 1053-8119 (ISSN-L)
- PMC
- PMC3097053
- OpenAlex
- W1990502495
- Cited by
- 172
- References
- 60
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 4 · 2023: 3 · 2022: 6 · 2021: 11 · 2020: 9 · 2019: 7 · 2018: 8 · 2017: 9 · 2016: 14 · 2015: 11 · 2014: 16 · 2013: 15 · 2012: 13
- FWCI
- 9.14
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- NeuroImage (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R01AG11378, K23AG030935, P50‐AG16574, R01 AG06786, U01AG006786, R01AG011378, P50AG016574)
- National Center for Research Resources (KL2RR024151, K12RR24151, C06RR018898)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Keywords
- Alzheimer's disease, neurofibrillary tangles, Braak staging, brain atrophy, postmortem neuropathology, disease staging, early detection of Alzheimer's disease
- MeSH terms
- Alzheimer Disease, Brain, Diagnosis, Female, Humans, Magnetic Resonance Imaging, Male, Sensitivity and Specificity, Severity of Illness Index, Statistics as Topic, Reproducibility of Results, Neurofibrillary Tangles, Imaging, Three-Dimensional
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