Diagnosis and prognosis of Alzheimer's disease using brain morphometry and white matter connectomes
Abstract
Accurate, reliable prediction of risk for Alzheimer's disease (AD) is essential for early, disease-modifying therapeutics. Multimodal MRI, such as structural and diffusion MRI, is likely to contain complementary information of neurodegenerative processes in AD. Here we tested the utility of the multimodal MRI (T1-weighted structure and diffusion MRI), combined with high-throughput brain phenotyping—morphometry and structural connectomics—and machine learning, as a diagnostic tool for AD. We used, firstly, a clinical cohort at a dementia clinic (National Health Insurance Service-Ilsan Hospital [NHIS-IH]; N = 211; 110 AD, 64 mild cognitive impairment [MCI], and 37 cognitively normal with subjective memory complaints [SMC]) to test the diagnostic models; and, secondly, Alzheimer's Disease Neuroimaging Initiative (ADNI)-2 to test the generalizability. Our machine learning models trained on the morphometric and connectome estimates (number of features = 34,646) showed optimal classification accuracy (AD/SMC: 97% accuracy, MCI/SMC: 83% accuracy; AD/MCI: 97% accuracy) in NHIS-IH cohort, outperforming a benchmark model (FLAIR-based white matter hyperintensity volumes). In ADNI-2 data, the combined connectome and morphometry model showed similar or superior accuracies (AD/HC: 96%; MCI/HC: 70%; AD/MCI: 75% accuracy) compared with the CSF biomarker model (t-tau, p-tau, and Amyloid β, and ratios). In predicting MCI to AD progression in a smaller cohortmore »
- Authors:
-
- Columbia Univ., New York, NY (United States). Medical Center. Dept. of Psychiatry
- Stony Brook Univ., NY (United States). Dept. of Applied Mathematics
- Columbia Univ., New York, NY (United States). Medical Center. Dept. of Biostatistics. School of Public Health
- Columbia Univ., New York, NY (United States). Medical Center. Dept. of Neurology
- Brookhaven National Lab. (BNL), Upton, NY (United States). Computational Science Initiative
- National Health Insurance Service Ilsan Hospital, Goyang (Korea, Republic of). Dept. of Neurology
- National Health Insurance Service Ilsan Hospital, Goyang (Korea, Republic of). Dept. of Physical Medicine and Rehabilitation
- Columbia Univ., New York, NY (United States). Medical Center. Dept. of Psychiatry. Data Science Inst.
- Publication Date:
- Research Org.:
- Brookhaven National Laboratory (BNL), Upton, NY (United States); Columbia Univ., New York, NY (United States); National Health Insurance Service Ilsan Hospital, Goyang (Korea, Republic of)
- Sponsoring Org.:
- USDOE; National Inst. of Health (NIH) (United States); National Health Insurance Ilsan Hospital Research Fund (Korea, Republic of)
- OSTI Identifier:
- 1514489
- Report Number(s):
- BNL-211602-2019-JAAM
Journal ID: ISSN 2213-1582
- Grant/Contract Number:
- SC0012704; K01 MH109836
- Resource Type:
- Accepted Manuscript
- Journal Name:
- NeuroImage: Clinical
- Additional Journal Information:
- Journal Volume: 23; Journal ID: ISSN 2213-1582
- Publisher:
- Elsevier
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES; Alzheimer's disease; multimodal MRI; DWI; machine learning
Citation Formats
Wang, Yun, Xu, Chenxiao, Park, Ji-Hwan, Lee, Seonjoo, Stern, Yaakov, Yoo, Shinjae, Kim, Jong Hun, Kim, Hyoung Seop, and Cha, Jiook. Diagnosis and prognosis of Alzheimer's disease using brain morphometry and white matter connectomes. United States: N. p., 2019.
Web. doi:10.1016/j.nicl.2019.101859.
Wang, Yun, Xu, Chenxiao, Park, Ji-Hwan, Lee, Seonjoo, Stern, Yaakov, Yoo, Shinjae, Kim, Jong Hun, Kim, Hyoung Seop, & Cha, Jiook. Diagnosis and prognosis of Alzheimer's disease using brain morphometry and white matter connectomes. United States. https://doi.org/10.1016/j.nicl.2019.101859
Wang, Yun, Xu, Chenxiao, Park, Ji-Hwan, Lee, Seonjoo, Stern, Yaakov, Yoo, Shinjae, Kim, Jong Hun, Kim, Hyoung Seop, and Cha, Jiook. Mon .
"Diagnosis and prognosis of Alzheimer's disease using brain morphometry and white matter connectomes". United States. https://doi.org/10.1016/j.nicl.2019.101859. https://www.osti.gov/servlets/purl/1514489.
@article{osti_1514489,
title = {Diagnosis and prognosis of Alzheimer's disease using brain morphometry and white matter connectomes},
author = {Wang, Yun and Xu, Chenxiao and Park, Ji-Hwan and Lee, Seonjoo and Stern, Yaakov and Yoo, Shinjae and Kim, Jong Hun and Kim, Hyoung Seop and Cha, Jiook},
abstractNote = {Accurate, reliable prediction of risk for Alzheimer's disease (AD) is essential for early, disease-modifying therapeutics. Multimodal MRI, such as structural and diffusion MRI, is likely to contain complementary information of neurodegenerative processes in AD. Here we tested the utility of the multimodal MRI (T1-weighted structure and diffusion MRI), combined with high-throughput brain phenotyping—morphometry and structural connectomics—and machine learning, as a diagnostic tool for AD. We used, firstly, a clinical cohort at a dementia clinic (National Health Insurance Service-Ilsan Hospital [NHIS-IH]; N = 211; 110 AD, 64 mild cognitive impairment [MCI], and 37 cognitively normal with subjective memory complaints [SMC]) to test the diagnostic models; and, secondly, Alzheimer's Disease Neuroimaging Initiative (ADNI)-2 to test the generalizability. Our machine learning models trained on the morphometric and connectome estimates (number of features = 34,646) showed optimal classification accuracy (AD/SMC: 97% accuracy, MCI/SMC: 83% accuracy; AD/MCI: 97% accuracy) in NHIS-IH cohort, outperforming a benchmark model (FLAIR-based white matter hyperintensity volumes). In ADNI-2 data, the combined connectome and morphometry model showed similar or superior accuracies (AD/HC: 96%; MCI/HC: 70%; AD/MCI: 75% accuracy) compared with the CSF biomarker model (t-tau, p-tau, and Amyloid β, and ratios). In predicting MCI to AD progression in a smaller cohort of ADNI-2 (n = 60), the morphometry model showed similar performance with 69% accuracy compared with CSF biomarker model with 70% accuracy. Our comparisons of the classifiers trained on structural MRI, diffusion MRI, FLAIR, and CSF biomarkers showed the promising utility of the white matter structural connectomes in classifying AD and MCI in addition to the widely used structural MRI-based morphometry, when combined with machine learning.},
doi = {10.1016/j.nicl.2019.101859},
journal = {NeuroImage: Clinical},
number = ,
volume = 23,
place = {United States},
year = {Mon May 13 00:00:00 EDT 2019},
month = {Mon May 13 00:00:00 EDT 2019}
}
Web of Science
Figures / Tables:
Works referenced in this record:
Histological Validation of DW-MRI Tractography in Human Postmortem Tissue
journal, February 2012
- Seehaus, A. K.; Roebroeck, A.; Chiry, O.
- Cerebral Cortex, Vol. 23, Issue 2
CSF biomarker changes precede symptom onset of mild cognitive impairment
journal, October 2013
- Moghekar, A.; Li, S.; Lu, Y.
- Neurology, Vol. 81, Issue 20
Integrated multimodal imaging in neurodegenerative disease
journal, October 2015
- Grossman, Murray
- The Lancet Neurology, Vol. 14, Issue 10
Just pretty pictures? What diffusion tractography can add in clinical neuroscience
journal, August 2006
- Johansen-Berg, Heidi; Behrens, Timothy EJ
- Current Opinion in Neurology, Vol. 19, Issue 4
The basis of anisotropic water diffusion in the nervous system - a technical review
journal, January 2002
- Beaulieu, Christian
- NMR in Biomedicine, Vol. 15, Issue 7-8
The Neonatal Connectome During Preterm Brain Development
journal, May 2014
- van den Heuvel, Martijn P.; Kersbergen, Karina J.; de Reus, Marcel A.
- Cerebral Cortex, Vol. 25, Issue 9
Machine learning for neuroimaging with scikit-learn
journal, January 2014
- Abraham, Alexandre; Pedregosa, Fabian; Eickenberg, Michael
- Frontiers in Neuroinformatics, Vol. 8
DTI measures in crossing-fibre areas: Increased diffusion anisotropy reveals early white matter alteration in MCI and mild Alzheimer's disease
journal, April 2011
- Douaud, Gwenaëlle; Jbabdi, Saâd; Behrens, Timothy E. J.
- NeuroImage, Vol. 55, Issue 3
Seoul Neuropsychological Screening Battery-Dementia Version (SNSB-D): A Useful Tool for Assessing and Monitoring Cognitive Impairments in Dementia Patients
journal, January 2010
- Ahn, Hyun-Jung; Chin, Juhee; Park, Aram
- Journal of Korean Medical Science, Vol. 25, Issue 7
Neural Correlates of Aggression in Medication-Naive Children with ADHD: Multivariate Analysis of Morphometry and Tractography
journal, February 2015
- Cha, Jiook; Fekete, Tomer; Siciliano, Francesco
- Neuropsychopharmacology, Vol. 40, Issue 7
Can lumbar puncture help to identify patients with incipient Alzheimer's disease?
journal, October 2006
- Bouwman, Femke H.; van der Flier, Wiesje M.; Scheltens, Philip
- Nature Clinical Practice Neurology, Vol. 2, Issue 10
Diffusion Tensor Tractography Reveals Abnormal Topological Organization in Structural Cortical Networks in Alzheimer's Disease
journal, December 2010
- Lo, Chun-Yi; Wang, Pei-Ning; Chou, Kun-Hsien
- The Journal of Neuroscience, Vol. 30, Issue 50
Denoising of diffusion MRI using random matrix theory
journal, November 2016
- Veraart, Jelle; Novikov, Dmitry S.; Christiaens, Daan
- NeuroImage, Vol. 142
Disrupted structural and functional brain connectomes in mild cognitive impairment and Alzheimer’s disease
journal, April 2014
- Dai, Zhengjia; He, Yong
- Neuroscience Bulletin, Vol. 30, Issue 2
Direct estimation of the fiber orientation density function from diffusion-weighted MRI data using spherical deconvolution
journal, November 2004
- Tournier, J. -Donald; Calamante, Fernando; Gadian, David G.
- NeuroImage, Vol. 23, Issue 3
White matter damage in frontotemporal dementia and Alzheimer's disease measured by diffusion MRI
journal, May 2009
- Zhang, Y.; Schuff, N.; Du, A. -T.
- Brain, Vol. 132, Issue 9
Multimodal classification of Alzheimer's disease and mild cognitive impairment
journal, April 2011
- Zhang, Daoqiang; Wang, Yaping; Zhou, Luping
- NeuroImage, Vol. 55, Issue 3
A Direct Demonstration of Functional Differences between Subdivisions of Human V5/MT+
journal, November 2016
- Strong, Samantha L.; Silson, Edward H.; Gouws, André D.
- Cerebral Cortex, Vol. 27, Issue 1
Random forest feature selection, fusion and ensemble strategy: Combining multiple morphological MRI measures to discriminate among healhy elderly, MCI, cMCI and alzheimer’s disease patients: From the alzheimer’s disease neuroimaging initiative (ADNI) database
journal, May 2018
- Dimitriadis, S. I.; Liparas, Dimitris; Tsolaki, Magda N.
- Journal of Neuroscience Methods, Vol. 302
Inter-site and inter-scanner diffusion MRI data harmonization
journal, July 2016
- Mirzaalian, H.; Ning, L.; Savadjiev, P.
- NeuroImage, Vol. 135
Diffusion-based tractography in neurological disorders: concepts, applications, and future developments
journal, August 2008
- Ciccarelli, Olga; Catani, Marco; Johansen-Berg, Heidi
- The Lancet Neurology, Vol. 7, Issue 8
Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade
journal, January 2010
- Jack, Clifford R.; Knopman, David S.; Jagust, William J.
- The Lancet Neurology, Vol. 9, Issue 1
N4ITK: Improved N3 Bias Correction
journal, June 2010
- Tustison, Nicholas J.; Avants, Brian B.; Cook, Philip A.
- IEEE Transactions on Medical Imaging, Vol. 29, Issue 6
Mild cognitive impairment as a diagnostic entity
journal, September 2004
- Petersen, R. C.
- Journal of Internal Medicine, Vol. 256, Issue 3
Clinical validity of CSF biomarkers for Alzheimer's disease: necessary indeed, but sufficient?
journal, June 2016
- Frisoni, Giovanni B.; Hansson, Oskar
- The Lancet Neurology, Vol. 15, Issue 7
The Human Connectome: a Complex Network
journal, April 2012
- Sporns, Olaf
- Schizophrenia Research, Vol. 136
An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest
journal, July 2006
- Desikan, Rahul S.; Ségonne, Florent; Fischl, Bruce
- NeuroImage, Vol. 31, Issue 3
A Validation Study of Multicenter Diffusion Tensor Imaging: Reliability of Fractional Anisotropy and Diffusivity Values
journal, December 2011
- Fox, R. J.; Sakaie, K.; Lee, J. -C.
- American Journal of Neuroradiology, Vol. 33, Issue 4
The organisation of the elderly connectome
journal, July 2015
- Perry, Alistair; Wen, Wei; Lord, Anton
- NeuroImage, Vol. 114
Machine learning for neuroimaging with scikit-learn
journal, January 2014
- Abraham, Alexandre; Pedregosa, Fabian; Eickenberg, Michael
- Frontiers in Neuroinformatics, Vol. 8
Absolute diffusivities define the landscape of white matter degeneration in Alzheimer's disease
journal, November 2009
- Acosta-Cabronero, Julio; Williams, Guy B.; Pengas, George
- Brain, Vol. 133, Issue 2
Seoul Neuropsychological Screening Battery-Dementia Version (SNSB-D): A Useful Tool for Assessing and Monitoring Cognitive Impairments in Dementia Patients
journal, January 2010
- Ahn, Hyun-Jung; Chin, Juhee; Park, Aram
- Journal of Korean Medical Science, Vol. 25, Issue 7
An integrated approach to correction for off-resonance effects and subject movement in diffusion MR imaging
journal, January 2016
- Andersson, Jesper L. R.; Sotiropoulos, Stamatios N.
- NeuroImage, Vol. 125
Validation of High-Resolution Tractography AgainstIn VivoTracing in the Macaque Visual Cortex
journal, March 2015
- Azadbakht, Hojjatollah; Parkes, Laura M.; Haroon, Hamied A.
- Cerebral Cortex, Vol. 25, Issue 11
The basis of anisotropic water diffusion in the nervous system - a technical review
journal, January 2002
- Beaulieu, Christian
- NMR in Biomedicine, Vol. 15, Issue 7-8
Neural Correlates of Aggression in Medication-Naive Children with ADHD: Multivariate Analysis of Morphometry and Tractography
journal, February 2015
- Cha, Jiook; Fekete, Tomer; Siciliano, Francesco
- Neuropsychopharmacology, Vol. 40, Issue 7
Abnormal reward circuitry in anorexia nervosa: A longitudinal, multimodal MRI study
journal, October 2016
- Cha, Jiook; Ide, Jaime S.; Bowman, F. Dubois
- Human Brain Mapping, Vol. 37, Issue 11
Disrupted structural and functional brain connectomes in mild cognitive impairment and Alzheimer’s disease
journal, April 2014
- Dai, Zhengjia; He, Yong
- Neuroscience Bulletin, Vol. 30, Issue 2
An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest
journal, July 2006
- Desikan, Rahul S.; Ségonne, Florent; Fischl, Bruce
- NeuroImage, Vol. 31, Issue 3
Automatic parcellation of human cortical gyri and sulci using standard anatomical nomenclature
journal, October 2010
- Destrieux, Christophe; Fischl, Bruce; Dale, Anders
- NeuroImage, Vol. 53, Issue 1
Random forest feature selection, fusion and ensemble strategy: Combining multiple morphological MRI measures to discriminate among healhy elderly, MCI, cMCI and alzheimer’s disease patients: From the alzheimer’s disease neuroimaging initiative (ADNI) database
journal, May 2018
- Dimitriadis, S. I.; Liparas, Dimitris; Tsolaki, Magda N.
- Journal of Neuroscience Methods, Vol. 302
DTI measures in crossing-fibre areas: Increased diffusion anisotropy reveals early white matter alteration in MCI and mild Alzheimer's disease
journal, April 2011
- Douaud, Gwenaëlle; Jbabdi, Saâd; Behrens, Timothy E. J.
- NeuroImage, Vol. 55, Issue 3
Measuring the thickness of the human cerebral cortex from magnetic resonance images
journal, September 2000
- Fischl, B.; Dale, A. M.
- Proceedings of the National Academy of Sciences, Vol. 97, Issue 20
Cortical Surface-Based Analysis
journal, February 1999
- Fischl, Bruce; Sereno, Martin I.; Dale, Anders M.
- NeuroImage, Vol. 9, Issue 2
Harmonization of multi-site diffusion tensor imaging data
journal, November 2017
- Fortin, Jean-Philippe; Parker, Drew; Tunç, Birkan
- NeuroImage, Vol. 161
Association between CSF biomarkers and incipient Alzheimer's disease in patients with mild cognitive impairment: a follow-up study
journal, March 2006
- Hansson, Oskar; Zetterberg, Henrik; Buchhave, Peder
- The Lancet Neurology, Vol. 5, Issue 3
Alzheimer's Disease: The Challenge of the Second Century
journal, April 2011
- Holtzman, D. M.; Morris, J. C.; Goate, A. M.
- Science Translational Medicine, Vol. 3, Issue 77
Extracting and summarizing white matter hyperintensities using supervised segmentation methods in Alzheimer's disease risk and aging studies
journal, February 2014
- Ithapu, Vamsi; Singh, Vikas; Lindner, Christopher
- Human Brain Mapping, Vol. 35, Issue 8
Just pretty pictures? What diffusion tractography can add in clinical neuroscience
journal, August 2006
- Johansen-Berg, Heidi; Behrens, Timothy EJ
- Current Opinion in Neurology, Vol. 19, Issue 4
Inter-site and inter-scanner diffusion MRI data harmonization
journal, July 2016
- Mirzaalian, H.; Ning, L.; Savadjiev, P.
- NeuroImage, Vol. 135
CSF biomarker changes precede symptom onset of mild cognitive impairment
journal, October 2013
- Moghekar, A.; Li, S.; Lu, Y.
- Neurology, Vol. 81, Issue 20
APP binds DR6 to trigger axon pruning and neuron death via distinct caspases
journal, February 2009
- Nikolaev, Anatoly; McLaughlin, Todd; O’Leary, Dennis D. M.
- Nature, Vol. 457, Issue 7232
CSF and blood biomarkers for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis
journal, June 2016
- Olsson, Bob; Lautner, Ronald; Andreasson, Ulf
- The Lancet Neurology, Vol. 15, Issue 7
Machine learning of neuroimaging for assisted diagnosis of cognitive impairment and dementia: A systematic review
journal, January 2018
- Pellegrini, Enrico; Ballerini, Lucia; Hernandez, Maria del C. Valdes
- Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, Vol. 10, Issue 1
The organisation of the elderly connectome
journal, July 2015
- Perry, Alistair; Wen, Wei; Lord, Anton
- NeuroImage, Vol. 114
Mild cognitive impairment as a diagnostic entity
journal, September 2004
- Petersen, R. C.
- Journal of Internal Medicine, Vol. 256, Issue 3
Histological Validation of DW-MRI Tractography in Human Postmortem Tissue
journal, February 2012
- Seehaus, A. K.; Roebroeck, A.; Chiry, O.
- Cerebral Cortex, Vol. 23, Issue 2
Connectome imaging for mapping human brain pathways
journal, May 2017
- Shi, Y.; Toga, A. W.
- Molecular Psychiatry, Vol. 22, Issue 9
The human connectome: a complex network
journal, January 2011
- Sporns, Olaf
- Annals of the New York Academy of Sciences, Vol. 1224, Issue 1
Multimodal imaging in Alzheimer's disease: validity and usefulness for early detection
journal, October 2015
- Teipel, Stefan; Drzezga, Alexander; Grothe, Michel J.
- The Lancet Neurology, Vol. 14, Issue 10
Direct estimation of the fiber orientation density function from diffusion-weighted MRI data using spherical deconvolution
journal, November 2004
- Tournier, J. -Donald; Calamante, Fernando; Gadian, David G.
- NeuroImage, Vol. 23, Issue 3
Comparison of diffusion tractography and tract-tracing measures of connectivity strength in rhesus macaque connectome
journal, June 2015
- van den Heuvel, Martijn P.; de Reus, Marcel A.; Feldman Barrett, Lisa
- Human Brain Mapping, Vol. 36, Issue 8
The Neonatal Connectome During Preterm Brain Development
journal, May 2014
- van den Heuvel, Martijn P.; Kersbergen, Karina J.; de Reus, Marcel A.
- Cerebral Cortex, Vol. 25, Issue 9
Assessing and tuning brain decoders: Cross-validation, caveats, and guidelines
journal, January 2017
- Varoquaux, Gaël; Raamana, Pradeep Reddy; Engemann, Denis A.
- NeuroImage, Vol. 145
Denoising of diffusion MRI using random matrix theory
journal, November 2016
- Veraart, Jelle; Novikov, Dmitry S.; Christiaens, Daan
- NeuroImage, Vol. 142
Identification of MCI individuals using structural and functional connectivity networks
journal, February 2012
- Wee, Chong-Yaw; Yap, Pew-Thian; Zhang, Daoqiang
- NeuroImage, Vol. 59, Issue 3
White matter damage in frontotemporal dementia and Alzheimer's disease measured by diffusion MRI
journal, May 2009
- Zhang, Y.; Schuff, N.; Du, A. -T.
- Brain, Vol. 132, Issue 9
Multimodal classification of Alzheimer's disease and mild cognitive impairment
journal, April 2011
- Zhang, Daoqiang; Wang, Yaping; Zhou, Luping
- NeuroImage, Vol. 55, Issue 3
Connectome-scale assessments of structural and functional connectivity in MCI
journal, September 2013
- Zhu, Dajiang; Li, Kaiming; Terry, Douglas P.
- Human Brain Mapping, Vol. 35, Issue 7
Figures / Tables found in this record: