{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:01:31Z","timestamp":1787022091654,"version":"build-2736575974"},"reference-count":55,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2021,11,17]],"date-time":"2021-11-17T00:00:00Z","timestamp":1637107200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JES Edwards Foundation","award":["RP2007"],"award-info":[{"award-number":["RP2007"]}]},{"DOI":"10.13039\/100002995","name":"Graham and Carolyn Holloway Family Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002995","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Center for Alzheimer\u2019s and Neurodegenerative Disease Research","award":["RI10024"],"award-info":[{"award-number":["RI10024"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>Epidemiologists report a 56% increased risk of veterans with (+) mild traumatic brain injury (mTBI) developing Parkinson\u2019s disease (PD) within 12-years post-injury. The most relevant contributors to this high risk of PD in veterans (+) mTBI is unknown. As cognitive problems often precede PD diagnosis, identifying specific domains most involved with mTBI-related PD onset is critical.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To discern which cognitive domains underlie the mTBI-PD risk relationship proposed in epidemiology studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Design and setting<\/jats:title>\n                    <jats:p>This exploratory match-controlled, cross-sectional study was conducted in a medical school laboratory from 2017\u20132020.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Participants<\/jats:title>\n                    <jats:p>Age- and IQ-matched veterans with (+) and without mTBI, non-veteran healthy controls, and IQ-matched non-demented early-stage PD were compared. Chronic neurological, unremitted\/debilitating diseases, disorders, dementia, and substance use among others were excluded.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec005\">\n                    <jats:title>Exposure<\/jats:title>\n                    <jats:p>Veterans were or were not exposed to non-penetrating combat-related mTBI occurring within the past 7-years. No other groups had recent military service or mTBI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec006\">\n                    <jats:title>Main outcomes \/ measures<\/jats:title>\n                    <jats:p>Cognitive flexibility, attention, memory, visuospatial ability, and verbal fluency were examined with well-known standardized neuropsychological assessments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec007\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Out of 200 volunteers, 114 provided evaluable data. Groups significantly differed on cognitive tests [\n                      <jats:italic>F<\/jats:italic>\n                      (21,299) = 3.09,\n                      <jats:italic>p<\/jats:italic>\n                      &lt;0.0001]. Post hoc tests showed veterans (+) mTBI performed significantly worse than matched-control groups on four out of eight cognitive tests (range:\n                      <jats:italic>p<\/jats:italic>\n                      = .009 to .049), and more often than not performed comparably to early-stage PD (range:\n                      <jats:italic>p<\/jats:italic>\n                      = .749 to .140).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec008\">\n                    <jats:title>Conclusions and relevance<\/jats:title>\n                    <jats:p>We found subtle, premature cognitive decline occurring in very specific cognitive domains in veterans (+) mTBI that would typically be overlooked in a clinic setting, This result potentially puts them at-risk for continual cognitive decline that may portend to the eventual onset of PD or some other neurodegenerative disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0258851","type":"journal-article","created":{"date-parts":[[2021,11,17]],"date-time":"2021-11-17T13:23:39Z","timestamp":1637155419000},"page":"e0258851","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":23,"title":["Premature cognitive decline in specific domains found in young veterans with mTBI coincide with elder normative scores and advanced-age subjects with early-stage Parkinson\u2019s disease"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6935-1739","authenticated-orcid":true,"given":"Vicki A.","family":"Nejtek","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachael N.","family":"James","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael F.","family":"Salvatore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helene M.","family":"Alphonso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary W.","family":"Boehm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,11,17]]},"reference":[{"issue":"20","key":"pone.0258851.ref001","doi-asserted-by":"crossref","first-page":"e1771","DOI":"10.1212\/WNL.0000000000005522","article-title":"Mild TBI and risk of Parkinson disease: A Chronic Effects of Neurotrauma Consortium Study","volume":"90","author":"RC Gardner","year":"2018","journal-title":"Neurology"},{"key":"pone.0258851.ref002","unstructured":"DoD Numbers for Traumatic Brain Injury Worldwide Totals. Defense Medical Surveillance System (DMSS) and Theater Medical Data Store (TMDS) provided by the Armed Forces Health Surveillance Branch (AFHSB). 2000\u20132018 Q1. Prepared by the Defense and Veterans Brain Injury Center (DVBIC), 2019."},{"key":"pone.0258851.ref003","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1056\/NEJMoa072972","article-title":"Mild Traumatic Brain Injury in U.S. Soldiers Returning from Iraq","volume":"358","author":"CW Hoge","year":"2008","journal-title":"N Engl J Med"},{"issue":"8","key":"pone.0258851.ref004","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1212\/WNL.55.8.1158","article-title":"Documented head injury in early adulthood and risk of Alzheimer\u2019s disease and other dementias","volume":"55","author":"BL Plassman","year":"2000","journal-title":"Neurology"},{"key":"pone.0258851.ref005","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1017\/S1355617705050289","article-title":"Long-term neuropsychological outcomes following mild traumatic brain injury","volume":"11","author":"RD Vanderploeg","year":"2005","journal-title":"J Int Neuropsychol Soc"},{"key":"pone.0258851.ref006","first-page":"221","article-title":"Disability caused by minor head injury","volume":"9","author":"R.W. Rimel","year":"1981","journal-title":"Neurosurgery"},{"key":"pone.0258851.ref007","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.psc.2013.11.004","article-title":"Cognitive Sequelae of Traumatic Brain Injury","volume":"37","author":"AR Rabinowitz","year":"2014","journal-title":"Psychiatr Clin N Am"},{"issue":"6","key":"pone.0258851.ref008","doi-asserted-by":"crossref","first-page":"e0218423","DOI":"10.1371\/journal.pone.0218423","article-title":"Correction: Mild Traumatic Brain Injury (mTBI) and chronic cognitive impairment: A scoping review","volume":"14","author":"K McInnes","year":"2019","journal-title":"PLoS ONE"},{"issue":"5Supp. 2","key":"pone.0258851.ref009","first-page":"A235","article-title":"The Brief Traumatic Brain Injury Screen (BTBIS): Investigating the validity of a self-report instrument for detecting traumatic brain injury (TBI) in troops returning from deployment in Afghanistan and Iraq","volume":"66","author":"K A Schwab","year":"2006","journal-title":"Neurology"},{"issue":"2","key":"pone.0258851.ref010","first-page":"177","article-title":"Mild Traumatic Brain Injury in 2019\u20132020","volume":"323","author":"ND Silverberg","year":"2020","journal-title":"JAMA"},{"issue":"9","key":"pone.0258851.ref011","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1001\/jamaneurol.2019.1313","article-title":"Recovery After Mild Traumatic Brain Injury in Patients Presenting to US Level I Trauma Centers: A Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Study","volume":"76","author":"LD Nelson","year":"2019","journal-title":"JAMA Neurol"},{"issue":"7","key":"pone.0258851.ref012","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1080\/1380339049091290","article-title":"Interpreting the trail making test following traumatic brain injury: comparison of traditional time scores and derived indices","volume":"27","author":"RT Lange","year":"2005","journal-title":"J Clin Exp Neuropsychol"},{"issue":"12","key":"pone.0258851.ref013","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1002\/mds.27135","article-title":"Cognitive changes in prodromal Parkinson\u2019s disease: A review","volume":"32","author":"S Fengler","year":"2017","journal-title":"Mov Disord"},{"key":"pone.0258851.ref014","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1111\/ene.13919","article-title":"Prevalence and duration of non-motor symptoms in prodromal Parkinson\u2019s disease","volume":"26","author":"R Durcan","year":"2019","journal-title":"Eur J Neurol"},{"issue":"12","key":"pone.0258851.ref015","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1001\/jamaneurol.2017.2248","article-title":"Association Between Poor Cognitive Functioning and Risk of Incident Parkinsonism: The Rotterdam Study","volume":"74","author":"SK Darweesh","year":"2017","journal-title":"JAMA Neurol"},{"issue":"Part B","key":"pone.0258851.ref016","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.mcn.2015.03.001","article-title":"Epidemiology of mild traumatic brain injury and neurodegenerative disease","volume":"66","author":"RC Gardner","year":"2015","journal-title":"Mol Cell Neurosci"},{"issue":"30","key":"pone.0258851.ref017","first-page":"S242","article-title":"Military-related traumatic brain injury and neurodegeneration","volume":"10","author":"AC McKee","year":"2014","journal-title":"Alzheimers Dement"},{"issue":"9","key":"pone.0258851.ref018","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1002\/mds.25458","article-title":"Head injury and risk of Parkinson Disease: A systematic review and meta-analysis","volume":"28","author":"S Jafari","year":"2013","journal-title":"Mov Disord"},{"issue":"3 Suppl 2","key":"pone.0258851.ref019","first-page":"S238","volume":"95","author":"C Marras","year":"2018","journal-title":"Arch. Phys. Med. Rehabil"},{"key":"pone.0258851.ref020","doi-asserted-by":"crossref","first-page":"S19","DOI":"10.3233\/JPD-181457","article-title":"From Prodromal to Overt Parkinson\u2019s Disease: Towards a New Definition in the Year 2040","volume":"8","author":"D Berg","year":"2018","journal-title":"J Parkinsons Dis"},{"issue":"6","key":"pone.0258851.ref021","first-page":"933","article-title":"Development and validation of a model for estimating premorbid verbal intelligence in the elderly","volume":"13","author":"E Grober","year":"1991","journal-title":"J Clin Exp Neurol"},{"key":"pone.0258851.ref022","first-page":"189","article-title":"\"Mini-mental state\": A practical method for grading the cognitive state of patients for the clinician","volume":"12","author":"MF Folstein","year":"1975","journal-title":"J Psychiatr Res"},{"issue":"18","key":"pone.0258851.ref023","doi-asserted-by":"crossref","first-page":"2386","DOI":"10.1001\/jama.1993.03500180078038","article-title":"Population-based norms for the mini-mental state examination by age and educational level","volume":"269","author":"RM Crum","year":"1993","journal-title":"JAMA"},{"issue":"Suppl 20","key":"pone.0258851.ref024","first-page":"22","article-title":"The Mini-International Neuropsychiatric Interview (M.I.N.I): The development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10","volume":"59","author":"D V Sheehan","year":"1998","journal-title":"J Clin Psychiatry"},{"key":"pone.0258851.ref025","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1212\/WNL.17.5.427","article-title":"Parkinsonism: onset, progression, and mortality","volume":"17","author":"MM Hoehn","year":"1967","journal-title":"Neurology"},{"key":"pone.0258851.ref026","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1002\/mds.20213","article-title":"Movement disorder society task force report on the Hoehn and Yahr staging scale: status and recommendations","volume":"19","author":"CG Goetz","year":"2004","journal-title":"Mov Disord"},{"issue":"7","key":"pone.0258851.ref027","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1002\/mds.10473","article-title":"The Unified Parkinson\u2019s Disease Rating Scale (UPDRS): status and recommendations","volume":"18","author":"Movement Disorder Society Task Force on Rating Scales for Parkinson\u2019s Disease (2003)","year":"2003","journal-title":"Mov Disord"},{"issue":"1","key":"pone.0258851.ref028","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1001\/archneurol.2009.295","article-title":"The clinically important difference on the Unified Parkinson\u2019s Disease Rating Scale","volume":"67","author":"LM Shulman","year":"2010","journal-title":"Arch Neurol"},{"issue":"6","key":"pone.0258851.ref029","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1097\/01.HTR.0000300227.67748.77","article-title":"Initial reliability and validity of the OSU TBI Identification Method","volume":"22","author":"JD Corrigan","year":"2007","journal-title":"J Head Trauma Rehabil"},{"issue":"1","key":"pone.0258851.ref030","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1097\/HTR.0b013e3182865859","article-title":"The Boston Assessment of Traumatic brain injury-Lifetime (BAT-L)","volume":"29","author":"CB Fortier","year":"2014","journal-title":"J Head Trauma Rehabil"},{"key":"pone.0258851.ref031","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1080\/13854046.2017.1378371","article-title":"Consistency of traumatic brain injury reporting in older adults with and without cognitive impairment","volume":"32","author":"K Wilmoth","year":"2018","journal-title":"Clin Neuropsychol"},{"key":"pone.0258851.ref032","unstructured":"Weathers F, Litz B, Herman D, Huska J, Keane T. The PTSD Checklist (PCL): Reliability, validity, and diagnostic utility. Paper presented at the Annual Convention of the International Society for Traumatic Stress Studies, San Antonio, TX, 1993."},{"key":"pone.0258851.ref033","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/0022-3956(82)90033-4","article-title":"Development and validation of a geriatric depression screening scale: a preliminary report","volume":"17","author":"JA Yesavage","year":"1983","journal-title":"J Psychiatr Res"},{"key":"pone.0258851.ref034","volume-title":"WMS-III Wechsler Memory Scale","author":"D Wechsler","year":"1997","edition":"3"},{"issue":"5","key":"pone.0258851.ref035","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1136\/jnnp.64.5.588","article-title":"CLOX: An executive clock drawing task","volume":"64","author":"DR Royall","year":"1998","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"pone.0258851.ref036","volume-title":"A Compendium of Neuropsychological Tests: Administration, Norms, and Commentary","author":"E Strauss","year":"2006","edition":"3"},{"issue":"2","key":"pone.0258851.ref037","first-page":"167","article-title":"Normative Data Stratified by Age and Education for Two Measures of Verbal Fluency: FAS and Animal Naming","volume":"14","author":"TN Tombaugh","year":"1999","journal-title":"Arch Clin Neuropsychol"},{"issue":"2","key":"pone.0258851.ref038","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S0887-6177(03)00039-8","article-title":"Trail Making Test A and B: Normative data stratified by age and education","volume":"19","author":"TN Tombaugh","year":"2004","journal-title":"Arch Clin Neuropsychol"},{"key":"pone.0258851.ref039","volume-title":"Loring DW et al. Neuropsychological assessment","author":"MD Lezak","year":"2004","edition":"4"},{"issue":"5","key":"pone.0258851.ref040","doi-asserted-by":"crossref","first-page":"2277","DOI":"10.1038\/nprot.2006.390","article-title":"Administration and interpretation of the Trail Making Test","volume":"1","author":"CR Bowie","year":"2006","journal-title":"Nat Protoc"},{"issue":"2","key":"pone.0258851.ref041","first-page":"129","article-title":"Trail Making Test errors in normal aging, mild cognitive impairment, and dementia","volume":"23","author":"L Ashendorf","journal-title":"Arch Clin Neuropsychol 2008"},{"key":"pone.0258851.ref042","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1093\/arclin\/acq047","article-title":"Normative Performance on an Executive Clock Drawing Task (CLOX) in a Community-Dwelling Sample of Older Adults","volume":"25","author":"M Crowe","year":"2010","journal-title":"Arch Clin Neuropsychol"},{"issue":"2","key":"pone.0258851.ref043","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1080\/13825589708256642","article-title":"Effect of age on forward and backward spans","volume":"4","author":"J Gregoire","year":"1997","journal-title":"Aging Neuropsychology and Cognition"},{"issue":"1","key":"pone.0258851.ref044","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing","volume":"57","author":"Y Benjamini","year":"1995","journal-title":"Journal of the Royal Statistical Society Series B (Methodological)"},{"key":"pone.0258851.ref045","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1016\/j.jclinepi.2014.03.012","article-title":"False discovery rate control is a recommended alternative to Bonferroni-type adjustments in health studies","volume":"67","author":"ME Glickman","year":"2014","journal-title":"J Clin Epidemiol"},{"key":"pone.0258851.ref046","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1002\/ana.25239","article-title":"How does dementia with Lewy bodies start? Prodromal cognitive changes in REM sleep behavior disorder","volume":"83","author":"DG Marchand","year":"2018","journal-title":"Ann Neurol"},{"key":"pone.0258851.ref047","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.3233\/JPD-191857","article-title":"Detecting the cognitive prodrome of dementia in Parkinson\u2019s disease","volume":"10","author":"J DeRoy","year":"2020","journal-title":"J Parkinsons Dis"},{"issue":"Issue 3","key":"pone.0258851.ref048","article-title":"Mini-Mental State Examination (MMSE) for the detection of Alzheimer\u2019s disease and other dementias in people with mild cognitive impairment (MCI)","author":"I Arevalo-Rodriguez","year":"2015","journal-title":"Cochrane Database Syst Rev"},{"key":"pone.0258851.ref049","doi-asserted-by":"crossref","first-page":"S107","DOI":"10.3233\/JPD-181473","article-title":"Cognitive interventions in Parkinson\u2019s Disease: Where we want to go within 20 years","volume":"8","author":"E Kalbe","year":"2018","journal-title":"J Parkinsons Dis"},{"key":"pone.0258851.ref050","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bandc.2018.01.002","article-title":"Aerobic exercise is more effective than goal-based exercise for the treatment of cognition in Parkinson\u2019s disease","volume":"122","author":"CRA Silveira","year":"2018","journal-title":"Brain and Cognition"},{"issue":"2","key":"pone.0258851.ref051","doi-asserted-by":"crossref","first-page":"35","DOI":"10.3390\/healthcare6020035","article-title":"A Rationale for Music Training to Enhance Executive Functions in Parkinson\u2019s Disease: An Overview of the Problem","volume":"6","author":"T Lesiuk","year":"2018","journal-title":"Healthcare"},{"key":"pone.0258851.ref052","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/s41531-018-0055-3","article-title":"Cognitive impairment in Parkinson\u2019s disease: a report from a multidisciplinary symposium on unmet needs and future directions to maintain cognitive health","volume":"4","author":"J.G. Goldman","year":"2018","journal-title":"npj Parkinson\u2019s Disease"},{"issue":"9","key":"pone.0258851.ref053","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1682\/JRRD.2009.10.0162","article-title":"Executive clock drawing correlates with performance-based functional status in people with combat-related mild traumatic brain injury and comorbid posttraumatic stress disorder","volume":"47","author":"BW Writer","year":"2010","journal-title":"J Rehabil Res Dev"},{"key":"pone.0258851.ref054","article-title":"Is there a neurobiological rationale for the utility of the Iowa Gambling Task in Parkinson\u2019s disease?","author":"MF Salvatore","year":"2020","journal-title":"J Parkinsons Dis"},{"issue":"5","key":"pone.0258851.ref055","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1111\/ane.12189","article-title":"Cognitive impairment in early-stage non-demented Parkinson\u2019s disease patients","volume":"129","author":"HC Pfeiffer","year":"2014","journal-title":"Acta Neurol Scand"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0258851","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,17]],"date-time":"2021-11-17T13:24:42Z","timestamp":1637155482000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0258851"}},"subtitle":[],"editor":[{"given":"Firas H","family":"Kobeissy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,11,17]]},"references-count":55,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,11,17]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0258851","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,17]]}}}