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Article ; Online: Author response.

Montenigro, Philip H / Stern, Robert A

2014 Volume 83, Issue 21, Page(s) 1992–1993

MeSH term(s)	Behavioral Symptoms/etiology ; Brain Injury, Chronic ; Cognition Disorders/etiology ; Humans ; Male
Language	English
Publishing date	2014-11-18
Publishing country	United States
Document type	Comment ; Letter
ZDB-ID	207147-2
ISSN	1526-632X ; 0028-3878
ISSN (online)	1526-632X
ISSN	0028-3878
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Article ; Online: Clinical features of repetitive traumatic brain injury and chronic traumatic encephalopathy.

Montenigro, Philip H / Bernick, Charles / Cantu, Robert C

Brain pathology (Zurich, Switzerland)

2015 Volume 25, Issue 3, Page(s) 304–317

Abstract: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease characterized by a distinct pattern of hyperphosphorylated tau (p-tau). Thought to be caused by repetitive concussive and subconcussive injuries, CTE is considered largely preventable. ...

Abstract	Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease characterized by a distinct pattern of hyperphosphorylated tau (p-tau). Thought to be caused by repetitive concussive and subconcussive injuries, CTE is considered largely preventable. The majority of neuropathologically confirmed cases have occurred in professional contact sport athletes (eg, boxing, football). A recent post-mortem case series has magnified concerns for the public's health following its identification in six high school level athletes. CTE is diagnosed with certainty only following a post-mortem autopsy. Efforts to define the etiology and clinical progression during life are ongoing. The goal of this article is to characterize the clinical concepts associated with short- and long-term effects of repetitive traumatic brain injury, with a special emphasis on new clinical diagnostic criteria for CTE. Utilizing these new diagnostic criteria, two cases of neuropathologically confirmed CTE, one in a professional football player and one in a professional boxer, are reported. Differences in cerebellar pathology in CTE confirmed cases in boxing and football are discussed.
MeSH term(s)	Athletic Injuries/complications ; Biomechanical Phenomena ; Brain Injuries/complications ; Brain Injuries/etiology ; Chronic Disease ; Disease Progression ; Humans ; Male ; Middle Aged ; Neurodegenerative Diseases/etiology ; Risk Factors
Language	English
Publishing date	2015-04-23
Publishing country	Switzerland
Document type	Case Reports ; Journal Article ; Review
ZDB-ID	1051484-3
ISSN	1750-3639 ; 1015-6305
ISSN (online)	1750-3639
ISSN	1015-6305
DOI	10.1111/bpa.12250
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Article ; Online: Chronic traumatic encephalopathy: a neurodegenerative consequence of repetitive traumatic brain injury.

Kiernan, Patrick T / Montenigro, Philip H / Solomon, Todd M / McKee, Ann C

Seminars in neurology

2015 Volume 35, Issue 1, Page(s) 20–28

Abstract: Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease that develops as a result of repetitive mild traumatic brain injury. Chronic traumatic encephalopathy is characterized by a unique pattern of accumulation of ... ...

Abstract	Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease that develops as a result of repetitive mild traumatic brain injury. Chronic traumatic encephalopathy is characterized by a unique pattern of accumulation of hyperphosphorylated tau in neurons and astrocytes. The tau abnormalities begin focally and perivascularly at the depths of the cerebral sulci, spread to the superficial layers of the adjacent cortex, and eventually become widespread throughout the medial temporal lobes, diencephalon, and brainstem. Abnormalities in 43 kDa TAR DNA-binding protein are also found in most cases of CTE. To date, CTE can only be diagnosed by postmortem neuropathological examination, although there are many ongoing research studies examining imaging techniques and biomarkers that might prove to have diagnostic utility. Currently, the incidence and prevalence of CTE are unknown, although great strides are being made to better understand the clinical symptoms and signs of CTE. Further research is critically needed to better identify the genetic and environmental risk factors for CTE as well as potential rehabilitation and therapeutic strategies.
MeSH term(s)	Animals ; Brain Injuries/complications ; Brain Injuries/etiology ; Chronic Disease ; DNA-Binding Proteins/metabolism ; Disease Progression ; Humans ; Neurodegenerative Diseases/etiology ; Neurodegenerative Diseases/metabolism
Chemical Substances	DNA-Binding Proteins
Language	English
Publishing date	2015-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	603165-1
ISSN	1098-9021 ; 0271-8235
ISSN (online)	1098-9021
ISSN	0271-8235
DOI	10.1055/s-0035-1545080
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Article ; Online: Chronic traumatic encephalopathy: historical origins and current perspective.

Montenigro, Philip H / Corp, Daniel T / Stein, Thor D / Cantu, Robert C / Stern, Robert A

Annual review of clinical psychology

2015 Volume 11, Page(s) 309–330

Abstract: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that is most often identified in postmortem autopsies of individuals exposed to repetitive head impacts, such as boxers and football players. The neuropathology of CTE is characterized ...

Abstract	Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that is most often identified in postmortem autopsies of individuals exposed to repetitive head impacts, such as boxers and football players. The neuropathology of CTE is characterized by the accumulation of hyperphosphorylated tau protein in a pattern that is unique from that of other neurodegenerative diseases, including Alzheimer's disease. The clinical features of CTE are often progressive, leading to dramatic changes in mood, behavior, and cognition, frequently resulting in debilitating dementia. In some cases, motor features, including parkinsonism, can also be present. In this review, the historical origins of CTE are revealed and an overview of the current state of knowledge of CTE is provided, including the neuropathology, clinical features, proposed clinical and pathological diagnostic criteria, potential in vivo biomarkers, known risk factors, and treatment options.
MeSH term(s)	Biomarkers ; Boxing/history ; Boxing/injuries ; Brain/pathology ; Brain Injury, Chronic/diagnosis ; Brain Injury, Chronic/etiology ; Brain Injury, Chronic/history ; Brain Injury, Chronic/pathology ; Brain Injury, Chronic/psychology ; Football/injuries ; History, 20th Century ; History, 21st Century ; Humans ; Neuroimaging ; Risk Factors
Chemical Substances	Biomarkers
Language	English
Publishing date	2015
Publishing country	United States
Document type	Historical Article ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	2194815-X
ISSN	1548-5951 ; 1548-5943
ISSN (online)	1548-5951
ISSN	1548-5943
DOI	10.1146/annurev-clinpsy-032814-112814
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Article ; Online: Frequency of head-impact-related outcomes by position in NCAA division I collegiate football players.

Baugh, Christine M / Kiernan, Patrick T / Kroshus, Emily / Daneshvar, Daniel H / Montenigro, Philip H / McKee, Ann C / Stern, Robert A

Journal of neurotrauma

2014 Volume 32, Issue 5, Page(s) 314–326

Abstract: Concussions and subconcussive impacts sustained in American football have been associated with short- and long-term neurological impairment, but differences in head impact outcomes across playing positions are not well understood. The American Medical ... ...

Abstract	Concussions and subconcussive impacts sustained in American football have been associated with short- and long-term neurological impairment, but differences in head impact outcomes across playing positions are not well understood. The American Medical Society for Sports Medicine has identified playing position as a key risk factor for concussion in football and one for which additional research is needed. This study examined variation in head impact outcomes across primary football playing positions in a group of 730 National Collegiate Athletic Association Division I Football Championship Series athletes, using a self-report questionnaire. Although there were no significant differences between position groups in the number of diagnosed concussions during the 2012 football season, there were significant differences between groups in undiagnosed concussions (p=0.008) and "dings" (p<0.001); offensive linemen reported significantly higher numbers than most other positions. Significant differences were found between position groups in the frequencies of several postimpact symptoms, including dizziness (p<0.001), headache (p<0.001), and seeing stars (p<0.001) during the 2012 football season, with offensive linemen reporting significantly more symptoms compared to most other groups. There were also positional differences in frequency of returning to play while symptomatic (p<0.001) and frequency of participating in full-contact practice (p<0.001). Offensive linemen reported having returned to play while experiencing symptoms more frequently and participating in more full-contact practices than other groups. These findings suggest that offensive linemen, a position group that experiences frequent, but low-magnitude, head impacts, develop more postimpact symptoms than other playing positions, but do not report these symptoms as a concussion.
MeSH term(s)	Adult ; Athletes/statistics & numerical data ; Football/injuries ; Head Injuries, Closed/epidemiology ; Humans ; Male ; Sports Medicine/statistics & numerical data ; Surveys and Questionnaires ; Young Adult
Language	English
Publishing date	2014-12-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	645092-1
ISSN	1557-9042 ; 0897-7151
ISSN (online)	1557-9042
ISSN	0897-7151
DOI	10.1089/neu.2014.3582
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Article: Chronic Traumatic Encephalopathy: A Neurodegenerative Consequence of Repetitive Traumatic Brain Injury

Kiernan, Patrick T. / Montenigro, Philip H. / Solomon, Todd M. / McKee, Ann C.

Seminars in Neurology

(Traumatic Brain Injury)

2015 Volume 35, Issue 01, Page(s) 20–28

Series title	Traumatic Brain Injury
Abstract	Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease that develops as a result of repetitive mild traumatic brain injury. Chronic traumatic encephalopathy is characterized by a unique pattern of accumulation of hyperphosphorylated tau in neurons and astrocytes. The tau abnormalities begin focally and perivascularly at the depths of the cerebral sulci, spread to the superficial layers of the adjacent cortex, and eventually become widespread throughout the medial temporal lobes, diencephalon, and brainstem. Abnormalities in 43 kDa TAR DNA-binding protein are also found in most cases of CTE. To date, CTE can only be diagnosed by postmortem neuropathological examination, although there are many ongoing research studies examining imaging techniques and biomarkers that might prove to have diagnostic utility. Currently, the incidence and prevalence of CTE are unknown, although great strides are being made to better understand the clinical symptoms and signs of CTE. Further research is critically needed to better identify the genetic and environmental risk factors for CTE as well as potential rehabilitation and therapeutic strategies.
Keywords	chronic traumatic encephalopathy ; traumatic brain injury ; tauopathy ; TDP-43 ; Alzheimer disease
Language	English
Publishing date	2015-02-01
Publisher	Thieme Medical Publishers
Publishing place	Stuttgart ; New York
Document type	Article
ZDB-ID	603165-1
ISSN	1098-9021 ; 0271-8235
ISSN (online)	1098-9021
ISSN	0271-8235
DOI	10.1055/s-0035-1545080
Database	Thieme publisher's database

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Article ; Online: Validity of the 2014 traumatic encephalopathy syndrome criteria for CTE pathology.

Mez, Jesse / Alosco, Michael L / Daneshvar, Daniel H / Saltiel, Nicole / Baucom, Zachary / Abdolmohammadi, Bobak / Uretsky, Madeline / Nicks, Raymond / Martin, Brett M / Palmisano, Joseph N / Nowinski, Christopher J / Montenigro, Philip / Solomon, Todd M / Mahar, Ian / Cherry, Jonathan D / Alvarez, Victor E / Dwyer, Brigid / Goldstein, Lee E / Katz, Douglas I /

Cantu, Robert C / Kowall, Neil W / Tripodis, Yorghos / Huber, Bertrand R / Stein, Thor D / Stern, Robert A / McKee, Ann C

Alzheimer's & dementia : the journal of the Alzheimer's Association

2021 Volume 17, Issue 10, Page(s) 1709–1724

Abstract: Introduction: Validity of the 2014 traumatic encephalopathy syndrome (TES) criteria, proposed to diagnose chronic traumatic encephalopathy (CTE) in life, has not been assessed.: Methods: A total of 336 consecutive brain donors exposed to repetitive ... ...

Abstract	Introduction: Validity of the 2014 traumatic encephalopathy syndrome (TES) criteria, proposed to diagnose chronic traumatic encephalopathy (CTE) in life, has not been assessed. Methods: A total of 336 consecutive brain donors exposed to repetitive head impacts from contact sports, military service, and/or physical violence were included. Blinded to clinical information, neuropathologists applied National Institute on Neurological Disorders and Stroke/National Institute of Biomedical Imaging and Bioengineering CTE criteria. Blinded to neuropathological information, clinicians interviewed informants and reviewed medical records. An expert panel adjudicated TES diagnoses. Results: A total of 309 donors were diagnosed with TES; 244 donors had CTE pathology. TES criteria demonstrated sensitivity and specificity of 0.97 and 0.21, respectively. Cognitive (odds ratio [OR] = 3.6; 95% confidence interval [CI]: 1.2-5.1), but not mood/behavior or motor symptoms, were significantly associated with CTE pathology. Having Alzheimer's disease (AD) pathology was significantly associated with reduced TES accuracy (OR = 0.27; 95% CI: 0.12-0.59). Discussion: TES criteria provided good evidence to rule out, but limited evidence to rule in, CTE pathology. Requiring cognitive symptoms in revised criteria and using AD biomarkers may improve CTE pathology prediction.
MeSH term(s)	Alzheimer Disease/pathology ; Autopsy ; Brain/pathology ; Brain Injuries, Traumatic/pathology ; Chronic Traumatic Encephalopathy/diagnosis ; Chronic Traumatic Encephalopathy/pathology ; Female ; Humans ; Male ; Middle Aged
Language	English
Publishing date	2021-04-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Validation Study
ZDB-ID	2211627-8
ISSN	1552-5279 ; 1552-5260
ISSN (online)	1552-5279
ISSN	1552-5260
DOI	10.1002/alz.12338
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Zs.A 6316: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MO 540: Show issues

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Article ; Online: Microglial neuroinflammation contributes to tau accumulation in chronic traumatic encephalopathy.

Cherry, Jonathan D / Tripodis, Yorghos / Alvarez, Victor E / Huber, Bertrand / Kiernan, Patrick T / Daneshvar, Daniel H / Mez, Jesse / Montenigro, Philip H / Solomon, Todd M / Alosco, Michael L / Stern, Robert A / McKee, Ann C / Stein, Thor D

Acta neuropathologica communications

2016 Volume 4, Issue 1, Page(s) 112

Abstract: The chronic effects of repetitive head impacts (RHI) on the development of neuroinflammation and its relationship to chronic traumatic encephalopathy (CTE) are unknown. Here we set out to determine the relationship between RHI exposure, neuroinflammation, ...

Abstract	The chronic effects of repetitive head impacts (RHI) on the development of neuroinflammation and its relationship to chronic traumatic encephalopathy (CTE) are unknown. Here we set out to determine the relationship between RHI exposure, neuroinflammation, and the development of hyperphosphorylated tau (ptau) pathology and dementia risk in CTE. We studied a cohort of 66 deceased American football athletes from the Boston University-Veteran's Affairs-Concussion Legacy Foundation Brain Bank as well as 16 non-athlete controls. Subjects with a neurodegenerative disease other than CTE were excluded. Counts of total and activated microglia, astrocytes, and ptau pathology were performed in the dorsolateral frontal cortex (DLF). Binary logistic and simultaneous equation regression models were used to test associations between RHI exposure, microglia, ptau pathology, and dementia. Duration of RHI exposure and the development and severity of CTE were associated with reactive microglial morphology and increased numbers of CD68 immunoreactive microglia in the DLF. A simultaneous equation regression model demonstrated that RHI exposure had a significant direct effect on CD68 cell density (p < 0.0001) and ptau pathology (p < 0.0001) independent of age at death. The effect of RHI on ptau pathology was partially mediated through increased CD68 positive cell density. A binary logistic regression demonstrated that a diagnosis of dementia was significantly predicted by CD68 cell density (OR = 1.010, p = 0.011) independent of age (OR = 1.055, p = 0.007), but this effect disappeared when ptau pathology was included in the model. In conclusion, RHI is associated with chronic activation of microglia, which may partially mediate the effect of RHI on the development of ptau pathology and dementia in CTE. Inflammatory molecules may be important diagnostic or predictive biomarkers as well as promising therapeutic targets in CTE.
MeSH term(s)	Adult ; Age Factors ; Aged ; Antigens, CD/metabolism ; Antigens, Differentiation, Myelomonocytic/metabolism ; Athletes ; Athletic Injuries/complications ; Athletic Injuries/immunology ; Athletic Injuries/pathology ; Cell Count ; Chronic Traumatic Encephalopathy/etiology ; Chronic Traumatic Encephalopathy/immunology ; Chronic Traumatic Encephalopathy/pathology ; Cohort Studies ; Encephalitis/etiology ; Encephalitis/immunology ; Encephalitis/pathology ; Football/injuries ; Frontal Lobe/immunology ; Frontal Lobe/pathology ; Humans ; Male ; Microglia/immunology ; Microglia/pathology ; Regression Analysis ; Severity of Illness Index ; tau Proteins/metabolism
Chemical Substances	Antigens, CD ; Antigens, Differentiation, Myelomonocytic ; CD68 antigen, human ; MAPT protein, human ; tau Proteins
Language	English
Publishing date	2016-10-28
Publishing country	England
Document type	Journal Article
ZDB-ID	2715589-4
ISSN	2051-5960 ; 2051-5960
ISSN (online)	2051-5960
ISSN	2051-5960
DOI	10.1186/s40478-016-0382-8
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Article ; Online: Cumulative Head Impact Exposure Predicts Later-Life Depression, Apathy, Executive Dysfunction, and Cognitive Impairment in Former High School and College Football Players.

Montenigro, Philip H / Alosco, Michael L / Martin, Brett M / Daneshvar, Daniel H / Mez, Jesse / Chaisson, Christine E / Nowinski, Christopher J / Au, Rhoda / McKee, Ann C / Cantu, Robert C / McClean, Michael D / Stern, Robert A / Tripodis, Yorghos

Journal of neurotrauma

2016 Volume 34, Issue 2, Page(s) 328–340

Abstract: The term "repetitive head impacts" (RHI) refers to the cumulative exposure to concussive and subconcussive events. Although RHI are believed to increase risk for later-life neurological consequences (including chronic traumatic encephalopathy), ... ...

Abstract	The term "repetitive head impacts" (RHI) refers to the cumulative exposure to concussive and subconcussive events. Although RHI are believed to increase risk for later-life neurological consequences (including chronic traumatic encephalopathy), quantitative analysis of this relationship has not yet been examined because of the lack of validated tools to quantify lifetime RHI exposure. The objectives of this study were: 1) to develop a metric to quantify cumulative RHI exposure from football, which we term the "cumulative head impact index" (CHII); 2) to use the CHII to examine the association between RHI exposure and long-term clinical outcomes; and 3) to evaluate its predictive properties relative to other exposure metrics (i.e., duration of play, age of first exposure, concussion history). Participants included 93 former high school and collegiate football players who completed objective cognitive and self-reported behavioral/mood tests as part of a larger ongoing longitudinal study. Using established cutoff scores, we transformed continuous outcomes into dichotomous variables (normal vs. impaired). The CHII was computed for each participant and derived from a combination of self-reported athletic history (i.e., number of seasons, position[s], levels played), and impact frequencies reported in helmet accelerometer studies. A bivariate probit, instrumental variable model revealed a threshold dose-response relationship between the CHII and risk for later-life cognitive impairment (p < 0.0001), self-reported executive dysfunction (p < 0.0001), depression (p < 0.0001), apathy (p = 0.0161), and behavioral dysregulation (p < 0.0001). Ultimately, the CHII demonstrated greater predictive validity than other individual exposure metrics.
MeSH term(s)	Adult ; Apathy/physiology ; Brain Concussion/complications ; Brain Concussion/diagnosis ; Brain Concussion/psychology ; Cognitive Dysfunction/diagnosis ; Cognitive Dysfunction/etiology ; Cognitive Dysfunction/psychology ; Depression/diagnosis ; Depression/etiology ; Depression/psychology ; Executive Function/physiology ; Football/injuries ; Football/psychology ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; Neuropsychological Tests ; Predictive Value of Tests ; Recurrence ; Retrospective Studies ; Schools/trends ; Self Report ; Students/psychology ; Universities/trends
Language	English
Publishing date	2016-06-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	645092-1
ISSN	1557-9042 ; 0897-7151
ISSN (online)	1557-9042
ISSN	0897-7151
DOI	10.1089/neu.2016.4413
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Article ; Online: Cognitive Reserve as a Modifier of Clinical Expression in Chronic Traumatic Encephalopathy: A Preliminary Examination.

Alosco, Michael L / Mez, Jesse / Kowall, Neil W / Stein, Thor D / Goldstein, Lee E / Cantu, Robert C / Katz, Douglas I / Solomon, Todd M / Kiernan, Patrick T / Murphy, Lauren / Abdolmohammadi, Bobak / Daneshvar, Daniel / Montenigro, Philip H / Nowinski, Christopher J / Stern, Robert A / McKee, Ann C

The Journal of neuropsychiatry and clinical neurosciences

2016 Volume 29, Issue 1, Page(s) 6–12

Abstract: This study conducted a preliminary examination on cognitive reserve (CR) as a modifier of symptom expression in subjects with autopsy-confirmed chronic traumatic encephalopathy (CTE). The sample included 25 former professional football players ... ...

Abstract	This study conducted a preliminary examination on cognitive reserve (CR) as a modifier of symptom expression in subjects with autopsy-confirmed chronic traumatic encephalopathy (CTE). The sample included 25 former professional football players neuropathologically diagnosed with CTE stage III or IV. Next of kin interviews ascertained age at cognitive and behavioral/mood symptom onset and demographic/athletic characteristics. Years of education and occupational attainment defined CR. High occupational achievement predicted later age at cognitive (p=0.02) and behavioral/mood (p=0.02) onset. Education was not an individual predictor. These preliminary findings suggest that CR may forestall the clinical manifestation of CTE.
MeSH term(s)	Age of Onset ; Aged ; Athletes ; Athletic Injuries/complications ; Athletic Injuries/diagnosis ; Athletic Injuries/psychology ; Behavioral Symptoms ; Chronic Traumatic Encephalopathy/diagnosis ; Chronic Traumatic Encephalopathy/etiology ; Chronic Traumatic Encephalopathy/psychology ; Cognitive Dysfunction/diagnosis ; Cognitive Dysfunction/etiology ; Cognitive Dysfunction/psychology ; Cognitive Reserve ; Educational Status ; Family ; Football ; Humans ; Interviews as Topic ; Linear Models ; Male ; Occupations ; Retrospective Studies
Language	English
Publishing date	2016-08-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	1036340-3
ISSN	1545-7222 ; 0895-0172
ISSN (online)	1545-7222
ISSN	0895-0172
DOI	10.1176/appi.neuropsych.16030043
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