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Few studies have examined clinicopathologic correlations between phosphorylated-tau neurofibrillary tangles, \u03b2-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\u2019s 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.<\/jats:p>","DOI":"10.1093\/jnen\/nlz122","type":"journal-article","created":{"date-parts":[[2019,12,18]],"date-time":"2019-12-18T14:57:54Z","timestamp":1576681074000},"page":"144-162","source":"Crossref","is-referenced-by-count":30,"title":["Early-Onset Dementia in War Veterans: Brain Polypathology and Clinicopathologic Complexity"],"prefix":"10.1093","volume":"79","author":[{"given":"Diego","family":"Iacono","sequence":"first","affiliation":[{"name":"Brain Tissue Repository & Neuropathology Core, Center for Neuroscience and Regenerative Medicine (CNRM), Uniformed Services University (USU) , Bethesda, Maryland"},{"name":"Department of Neurology, F. Edward H\u00e9bert School of Medicine, Uniformed Services University (USU) , Bethesda, Maryland"},{"name":"Department of Pathology, F. Edward H\u00e9bert School of Medicine, Uniformed Services University (USU) , Bethesda, Maryland"},{"name":"The Henry M. Jackson Foundation for the Advancement of Military Medicine (HJF) , Bethesda, Maryland"},{"name":"Neurodegenerative Clinics, National Institute of Neurological Disorders and Stroke (NINDS) , NIH, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Lee","sequence":"additional","affiliation":[{"name":"Brain Tissue Repository & Neuropathology Core, Center for Neuroscience and Regenerative Medicine (CNRM), Uniformed Services University (USU) , Bethesda, Maryland"},{"name":"The Henry M. Jackson Foundation for the Advancement of Military Medicine (HJF) , Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian L","family":"Edlow","sequence":"additional","affiliation":[{"name":"Brain Tissue Repository & Neuropathology Core, Center for Neuroscience and Regenerative Medicine (CNRM), Uniformed Services University (USU) , Bethesda, Maryland"},{"name":"Department of Neurology, Center for Neurotechnology and Neurorecovery (BLE) and Department of Radiology , Athinoula A. Martinos Center for Biomedical Imaging"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nichelle","family":"Gray","sequence":"additional","affiliation":[{"name":"Brain Tissue Repository & Neuropathology Core, Center for Neuroscience and Regenerative Medicine (CNRM), Uniformed Services University (USU) , Bethesda, Maryland"},{"name":"The Henry M. Jackson Foundation for the Advancement of Military Medicine (HJF) , Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce","family":"Fischl","sequence":"additional","affiliation":[{"name":"Brain Tissue Repository & Neuropathology Core, Center for Neuroscience and Regenerative Medicine (CNRM), Uniformed Services University (USU) , Bethesda, Maryland"},{"name":"Department of Neurology, Center for Neurotechnology and Neurorecovery (BLE) and Department of Radiology , Athinoula A. Martinos Center for Biomedical Imaging"},{"name":"Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Department of Radiology, Harvard Medical School , Boston, Massachusetts"},{"name":"Harvard-MIT Program in Health Sciences and Technology (HST)\/Computer Science & Artificial Intelligence Lab (CSAIL) , MIT, Cambridge, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimbra","family":"Kenney","sequence":"additional","affiliation":[{"name":"Brain Tissue Repository & Neuropathology Core, Center for Neuroscience and Regenerative Medicine (CNRM), Uniformed Services University (USU) , Bethesda, Maryland"},{"name":"Department of Neurology, F. 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School of Medicine, University of Hawaii , Honolulu, Hawaii"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Liacouras","sequence":"additional","affiliation":[{"name":"Brain Tissue Repository & Neuropathology Core, Center for Neuroscience and Regenerative Medicine (CNRM), Uniformed Services University (USU) , Bethesda, Maryland"},{"name":"Department of Radiology and Radiological Sciences, F. Edward H\u00e9bert School of Medicine, Uniformed Services University (USU) , Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Lichtenberger","sequence":"additional","affiliation":[{"name":"Brain Tissue Repository & Neuropathology Core, Center for Neuroscience and Regenerative Medicine (CNRM), Uniformed Services University (USU) , Bethesda, Maryland"},{"name":"Department of Rehabilitation Medicine (KD-O) and Department of Neurology (KD-O), Icahn School of Medicine at Mount Sinai, New York City, New York; Department of Physical Medicine and Rehabilitation, Virginia Commonwealth University , Richmond, Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen","family":"Dams-O\u2019Connor","sequence":"additional","affiliation":[{"name":"Brain Tissue Repository & Neuropathology Core, Center for Neuroscience and Regenerative Medicine (CNRM), Uniformed Services University (USU) , Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Cifu","sequence":"additional","affiliation":[{"name":"Brain Tissue Repository & Neuropathology Core, Center for Neuroscience and Regenerative Medicine (CNRM), Uniformed Services University (USU) , Bethesda, Maryland"},{"name":"Department of Veterans Affairs, Chronic Effects of NeuroTrauma Consortium (CENC) , Richmond, Virginia"},{"name":"DoD Brain Health Research Program, Blast Injury Research Program Coordinating Office, Research and Technology United States Army Medical Research and Materiel Command , Fort Detrick, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sidney R","family":"Hinds","sequence":"additional","affiliation":[{"name":"Brain Tissue Repository & Neuropathology Core, Center for Neuroscience and Regenerative Medicine (CNRM), Uniformed Services University (USU) , Bethesda, Maryland"},{"name":"Chronic Effects of NeuroTrauma Consortium (CENC) , Fort Detrick, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel P","family":"Perl","sequence":"additional","affiliation":[{"name":"Brain Tissue Repository & Neuropathology Core, Center for Neuroscience and Regenerative Medicine (CNRM), Uniformed Services University (USU) , Bethesda, Maryland"},{"name":"Department of Pathology, F. 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