skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Diagnosis and prognosis of Alzheimer's disease using brain morphometry and white matter connectomes

Journal Article · · NeuroImage: Clinical
ORCiD logo [1];  [2];  [2];  [3];  [4];  [5];  [6];  [7]; ORCiD logo [8]
  1. Columbia Univ., New York, NY (United States). Medical Center. Dept. of Psychiatry
  2. Stony Brook Univ., NY (United States). Dept. of Applied Mathematics
  3. Columbia Univ., New York, NY (United States). Medical Center. Dept. of Biostatistics. School of Public Health
  4. Columbia Univ., New York, NY (United States). Medical Center. Dept. of Neurology
  5. Brookhaven National Lab. (BNL), Upton, NY (United States). Computational Science Initiative
  6. National Health Insurance Service Ilsan Hospital, Goyang (Korea, Republic of). Dept. of Neurology
  7. National Health Insurance Service Ilsan Hospital, Goyang (Korea, Republic of). Dept. of Physical Medicine and Rehabilitation
  8. Columbia Univ., New York, NY (United States). Medical Center. Dept. of Psychiatry. Data Science Inst.

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.

Research Organization:
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 Organization:
USDOE; National Inst. of Health (NIH) (United States); National Health Insurance Ilsan Hospital Research Fund (Korea, Republic of)
Grant/Contract Number:
SC0012704; K01 MH109836
OSTI ID:
1514489
Report Number(s):
BNL-211602-2019-JAAM
Journal Information:
NeuroImage: Clinical, Vol. 23; ISSN 2213-1582
Publisher:
ElsevierCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 15 works
Citation information provided by
Web of Science

References (51)

Histological Validation of DW-MRI Tractography in Human Postmortem Tissue journal February 2012
CSF biomarker changes precede symptom onset of mild cognitive impairment journal October 2013
Integrated multimodal imaging in neurodegenerative disease journal October 2015
Just pretty pictures? What diffusion tractography can add in clinical neuroscience journal August 2006
The basis of anisotropic water diffusion in the nervous system - a technical review journal January 2002
The Neonatal Connectome During Preterm Brain Development journal May 2014
Machine learning for neuroimaging with scikit-learn journal January 2014
DTI measures in crossing-fibre areas: Increased diffusion anisotropy reveals early white matter alteration in MCI and mild Alzheimer's disease journal April 2011
Seoul Neuropsychological Screening Battery-Dementia Version (SNSB-D): A Useful Tool for Assessing and Monitoring Cognitive Impairments in Dementia Patients journal January 2010
Neural Correlates of Aggression in Medication-Naive Children with ADHD: Multivariate Analysis of Morphometry and Tractography journal February 2015
Can lumbar puncture help to identify patients with incipient Alzheimer's disease? journal October 2006
Diffusion Tensor Tractography Reveals Abnormal Topological Organization in Structural Cortical Networks in Alzheimer's Disease journal December 2010
Denoising of diffusion MRI using random matrix theory journal November 2016
Disrupted structural and functional brain connectomes in mild cognitive impairment and Alzheimer’s disease journal April 2014
Direct estimation of the fiber orientation density function from diffusion-weighted MRI data using spherical deconvolution journal November 2004
White matter damage in frontotemporal dementia and Alzheimer's disease measured by diffusion MRI journal May 2009
Multimodal classification of Alzheimer's disease and mild cognitive impairment journal April 2011
A Direct Demonstration of Functional Differences between Subdivisions of Human V5/MT+ journal November 2016
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
Inter-site and inter-scanner diffusion MRI data harmonization journal July 2016
Diffusion-based tractography in neurological disorders: concepts, applications, and future developments journal August 2008
Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade journal January 2010
N4ITK: Improved N3 Bias Correction journal June 2010
Mild cognitive impairment as a diagnostic entity journal September 2004
Clinical validity of CSF biomarkers for Alzheimer's disease: necessary indeed, but sufficient? journal June 2016
FreeSurfer journal August 2012
The Human Connectome: a Complex Network journal April 2012
An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest journal July 2006
A Validation Study of Multicenter Diffusion Tensor Imaging: Reliability of Fractional Anisotropy and Diffusivity Values journal December 2011
The organisation of the elderly connectome journal July 2015
Absolute diffusivities define the landscape of white matter degeneration in Alzheimer's disease journal November 2009
An integrated approach to correction for off-resonance effects and subject movement in diffusion MR imaging journal January 2016
Validation of High-Resolution Tractography AgainstIn VivoTracing in the Macaque Visual Cortex journal March 2015
Abnormal reward circuitry in anorexia nervosa: A longitudinal, multimodal MRI study journal October 2016
Automatic parcellation of human cortical gyri and sulci using standard anatomical nomenclature journal October 2010
Measuring the thickness of the human cerebral cortex from magnetic resonance images journal September 2000
Cortical Surface-Based Analysis journal February 1999
Harmonization of multi-site diffusion tensor imaging data journal November 2017
Association between CSF biomarkers and incipient Alzheimer's disease in patients with mild cognitive impairment: a follow-up study journal March 2006
Alzheimer's Disease: The Challenge of the Second Century journal April 2011
Extracting and summarizing white matter hyperintensities using supervised segmentation methods in Alzheimer's disease risk and aging studies journal February 2014
APP binds DR6 to trigger axon pruning and neuron death via distinct caspases journal February 2009
CSF and blood biomarkers for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis journal June 2016
Machine learning of neuroimaging for assisted diagnosis of cognitive impairment and dementia: A systematic review journal January 2018
Connectome imaging for mapping human brain pathways journal May 2017
The human connectome: a complex network journal January 2011
Multimodal imaging in Alzheimer's disease: validity and usefulness for early detection journal October 2015
Comparison of diffusion tractography and tract-tracing measures of connectivity strength in rhesus macaque connectome journal June 2015
Assessing and tuning brain decoders: Cross-validation, caveats, and guidelines journal January 2017
Identification of MCI individuals using structural and functional connectivity networks journal February 2012
Connectome-scale assessments of structural and functional connectivity in MCI journal September 2013

Figures / Tables (5)