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Abstract
Worldwide, there are nearly 10 million new cases of dementia annually, of which Alzheimer’s disease (AD) is the most common. New measures are needed to improve the diagnosis of individuals with cognitive impairment due to various etiologies. Here, we report a deep learning framework that accomplishes multiple diagnostic steps in successive fashion to identify persons with normal cognition (NC), mild cognitive impairment (MCI), AD, and non-AD dementias (nADD). We demonstrate a range of models capable of accepting flexible combinations of routinely collected clinical information, including demographics, medical history, neuropsychological testing, neuroimaging, and functional assessments. We then show that these frameworks compare favorably with the diagnostic accuracy of practicing neurologists and neuroradiologists. Lastly, we apply interpretability methods in computer vision to show that disease-specific patterns detected by our models track distinct patterns of degenerative changes throughout the brain and correspond closely with the presence of neuropathological lesions on autopsy. Our work demonstrates methodologies for validating computational predictions with established standards of medical diagnosis.
Here the authors present a deep learning framework for dementia diagnosis, which can identify persons with normal cognition, mild cognitive impairment, Alzheimer’s disease, and dementia due to other etiologies.
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1 Boston University School of Medicine, Department of Medicine, Boston, USA (GRID:grid.189504.1) (ISNI:0000 0004 1936 7558); Boston University, Department of Physics, College of Arts & Sciences, Boston, USA (GRID:grid.189504.1) (ISNI:0000 0004 1936 7558)
2 Boston University School of Medicine, Department of Medicine, Boston, USA (GRID:grid.189504.1) (ISNI:0000 0004 1936 7558)
3 Boston University School of Medicine, Department of Anatomy and Neurobiology, Boston, USA (GRID:grid.189504.1) (ISNI:0000 0004 1936 7558); Boston University School of Dental Medicine, Department of General Dentistry, Boston, USA (GRID:grid.189504.1) (ISNI:0000 0004 1936 7558); Boston University School of Medicine, The Framingham Heart Study, Boston, USA (GRID:grid.189504.1) (ISNI:0000 0004 1936 7558)
4 Boston University School of Medicine, Department of Medicine, Boston, USA (GRID:grid.189504.1) (ISNI:0000 0004 1936 7558); Boston University School of Medicine, Department of Anatomy and Neurobiology, Boston, USA (GRID:grid.189504.1) (ISNI:0000 0004 1936 7558)
5 Tulane University, School of Public Health and Tropical Medicine, New Orleans, USA (GRID:grid.265219.b) (ISNI:0000 0001 2217 8588)
6 Boston University School of Medicine, Department of Anatomy and Neurobiology, Boston, USA (GRID:grid.189504.1) (ISNI:0000 0004 1936 7558)
7 University of Nebraska Medical Center, Department of Radiology, College of Medicine, Omaha, USA (GRID:grid.266813.8) (ISNI:0000 0001 0666 4105)
8 Boston University School of Medicine, Department of Neurology, Boston, USA (GRID:grid.189504.1) (ISNI:0000 0004 1936 7558)
9 Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Department of Neurology, Beijing, China (GRID:grid.413106.1) (ISNI:0000 0000 9889 6335)
10 University of Nebraska Medical Center, Department of Neurological Sciences, College of Medicine, Omaha, USA (GRID:grid.266813.8) (ISNI:0000 0001 0666 4105); Emory University School of Medicine, Department Neurology, Atlanta, USA (GRID:grid.189967.8) (ISNI:0000 0001 0941 6502); Emory University School of Medicine, Department Ophthalmology, Atlanta, USA (GRID:grid.189967.8) (ISNI:0000 0001 0941 6502)
11 Lahey Hospital & Medical Center, Department of Radiology, Burlington, USA (GRID:grid.419182.7)
12 Boston University School of Medicine, Department of Radiology, Boston, USA (GRID:grid.189504.1) (ISNI:0000 0004 1936 7558)
13 University of Nebraska Medical Center, Department of Neurological Sciences, College of Medicine, Omaha, USA (GRID:grid.266813.8) (ISNI:0000 0001 0666 4105)
14 Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Department of Radiology, Beijing, China (GRID:grid.413106.1) (ISNI:0000 0000 9889 6335)
15 Boston University School of Medicine, Department of Neurology, Boston, USA (GRID:grid.189504.1) (ISNI:0000 0004 1936 7558); Boston University Alzheimer’s Disease Research Center, Boston, USA (GRID:grid.189504.1) (ISNI:0000 0004 1936 7558)
16 Boston University School of Medicine, The Framingham Heart Study, Boston, USA (GRID:grid.189504.1) (ISNI:0000 0004 1936 7558); Boston University School of Medicine, Department of Neurology, Boston, USA (GRID:grid.189504.1) (ISNI:0000 0004 1936 7558); Boston University Alzheimer’s Disease Research Center, Boston, USA (GRID:grid.189504.1) (ISNI:0000 0004 1936 7558)
17 Boston University Alzheimer’s Disease Research Center, Boston, USA (GRID:grid.189504.1) (ISNI:0000 0004 1936 7558); Boston University School of Medicine, Department of Pathology and Laboratory Medicine, Boston, USA (GRID:grid.189504.1) (ISNI:0000 0004 1936 7558); Boston VA Healthcare System, Boston, USA (GRID:grid.410370.1) (ISNI:0000 0004 4657 1992); Bedford VA Healthcare System, Bedford, USA (GRID:grid.410370.1)
18 Stanford University, Department of Neurology, Palo Alto, USA (GRID:grid.168010.e) (ISNI:0000000419368956)
19 Boston University School of Medicine, Department of Anatomy and Neurobiology, Boston, USA (GRID:grid.189504.1) (ISNI:0000 0004 1936 7558); Boston University School of Medicine, The Framingham Heart Study, Boston, USA (GRID:grid.189504.1) (ISNI:0000 0004 1936 7558); Boston University School of Medicine, Department of Neurology, Boston, USA (GRID:grid.189504.1) (ISNI:0000 0004 1936 7558); Boston University Alzheimer’s Disease Research Center, Boston, USA (GRID:grid.189504.1) (ISNI:0000 0004 1936 7558); Boston University School of Public Health, Department of Epidemiology, Boston, USA (GRID:grid.189504.1) (ISNI:0000 0004 1936 7558)
20 Boston University School of Medicine, Department of Medicine, Boston, USA (GRID:grid.189504.1) (ISNI:0000 0004 1936 7558); Boston University Alzheimer’s Disease Research Center, Boston, USA (GRID:grid.189504.1) (ISNI:0000 0004 1936 7558); Boston University, Department of Computer Science, Boston, USA (GRID:grid.189504.1) (ISNI:0000 0004 1936 7558); Boston University, Faculty of Computing & Data Sciences, Boston, USA (GRID:grid.189504.1) (ISNI:0000 0004 1936 7558)