Early-Onset Dementia in War Veterans: Brain Polypathology and Clinicopathologic Complexity
Abstract
The neuropathology associated with cognitive decline in military personnel exposed to traumatic brain injury (TBI) and chronic stress is incompletely understood. Few studies have examined clinicopathologic correlations between phosphorylated-tau neurofibrillary tangles, β-amyloid neuritic plaques, neuroinflammation, or white matter (WM) lesions, and neuropsychiatric disorders in veterans. We describe clinicopathologic findings in 4 military veterans with early-onset dementia (EOD) who had varying histories of blunt- and blast-TBI, cognitive decline, behavioral abnormalities, post-traumatic stress disorder, suicidal ideation, and suicide. We found that pathologic lesions in these military-EOD cases could not be categorized as classic Alzheimer’s disease (AD), chronic traumatic encephalopathy, traumatic axonal injury, or other well-characterized clinicopathologic entities. Rather, we observed a mixture of polypathology with unusual patterns compared with pathologies found in AD or other dementias. Also, ultrahigh resolution ex vivo MRI in 2 of these 4 brains revealed unusual patterns of periventricular WM injury. These findings suggest that military-EOD cases are associated with atypical combinations of brain lesions and distribution rarely seen in nonmilitary populations. Future prospective studies that acquire neuropsychiatric data before and after deployments, as well as genetic and environmental exposure data, are needed to further elucidate clinicopathologic correlations in military-EOD.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Dec 18, 2019
- Source ID
- 10.1093/jnen/nlz122
Entities
People
- Brian L. Edlow
- Bruce Fischl
- Daniel P. Perl
- David Cifu
- Diego Iacono
- Henry L. Lew
- John Lichtenberger
- Kimbra Kenney
- Kristen Dams-o’connor
- Nichelle Gray
- Patricia Lee
- Peter Liacouras
- Scott Lozanoff
- Sidney R. Hinds
Organizations
- Blueprint for Neuroscience Research
- Center for Neuroscience and Regenerative Medicine
- Chronic Effects of Neurotrauma Consortium
- F. Edward Hébert School of Medicine
- Harvard Medical School
- Henry M. Jackson Foundation for the Advancement of Military Medicine
- Icahn School of Medicine at Mount Sinai
- James S. McDonnell Foundation
- Massachusetts Institute of Technology
- National Institute of Biomedical Imaging and Bioengineering
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Institute of Neurological Disorders and Stroke
- National Institute on Aging
- National Institutes of Health
- Uniformed Services University of the Health Sciences
- United States Department of Veterans Affairs
- University of Hawaiʻi System
- University of Hawaiʻi at Mānoa