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Article ; Online: ADSS: A Composite Score to Detect Disease Progression in Alzheimer's Disease.

Shan, Guogen / Lu, Xinlin / Li, Zhigang / Caldwell, Jessica Z K / Bernick, Charles / Cummings, Jeffrey

Journal of Alzheimer's disease reports

2024 Volume 8, Issue 1, Page(s) 307–316

Abstract: Background: Composite scores have been increasingly used in trials for Alzheimer's disease (AD) to detect disease progression, such as the AD Composite Score (ADCOMS) in the lecanemab trial.: Objective: To develop a new composite score to improve the ...

Abstract	Background: Composite scores have been increasingly used in trials for Alzheimer's disease (AD) to detect disease progression, such as the AD Composite Score (ADCOMS) in the lecanemab trial. Objective: To develop a new composite score to improve the prediction of outcome change. Methods: We proposed to develop a new composite score based on the statistical model in the ADCOMS, by removing duplicated sub-scales and adding the model selection in the partial least squares (PLS) regression. Results: The new Conclusions: ADSS can be utilized in AD trials to improve the success rate of drug development with a high sensitivity to detect disease progression in early stages.
Language	English
Publishing date	2024-02-20
Publishing country	Netherlands
Document type	Journal Article
ISSN	2542-4823
ISSN (online)	2542-4823
DOI	10.3233/ADR-230043
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Effects of dose change on the success of clinical trials.

Shan, Guogen / Ritter, Aaron / Miller, Justin / Bernick, Charles

Contemporary clinical trials communications

2022 Volume 30, Page(s) 100988

Abstract: The search for disease modifying therapies in Alzheimers disease (AD) has recently led to promising results but also revealed design issues in clinical trials themselves. Of particular importance is the potential statistical challenges that can arise ... ...

Abstract	The search for disease modifying therapies in Alzheimers disease (AD) has recently led to promising results but also revealed design issues in clinical trials themselves. Of particular importance is the potential statistical challenges that can arise when dosages change after an interim analysis, which is not uncommon in contemporary AD trials. Following the recent Aducanumab trials, we sought to study the implications of dose changes on the statistical power of an AD trial. We conducted extensive simulations to calculate statistical power when the relationship between treatment effect size and time is linear or non-linear, and the investigated drug has delayed treatment effect or not. Statistical power depends on many design factors including the dose change time, correlation, population homogeneity, and treatment effect time. We recommend that researchers conduct simulation studies at the interim analysis to justify the modified sample size and/or follow-up time modification meanwhile the type I and II error rates are controlled.
Language	English
Publishing date	2022-09-05
Publishing country	Netherlands
Document type	Journal Article
ISSN	2451-8654
ISSN (online)	2451-8654
DOI	10.1016/j.conctc.2022.100988
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Article ; Online: History of Chronic Traumatic Encephalopathy.

Cantu, Robert C / Bernick, Charles

Seminars in neurology

2020 Volume 40, Issue 4, Page(s) 353–358

Abstract: The long-term effects of repetitive head impacts have been recognized for close to a century. What is now referred to as chronic traumatic encephalopathy (CTE) was first described by Martland in 1928 in a series of boxers. Over the years, several ... ...

Abstract	The long-term effects of repetitive head impacts have been recognized for close to a century. What is now referred to as chronic traumatic encephalopathy (CTE) was first described by Martland in 1928 in a series of boxers. Over the years, several important articles were published, including Critchley's 1957 report where he introduced the term "chronic traumatic encephalopathy," Robert's study in 1969 which provided evidence of the prevalence of neurological impairment in retired fighters, and Corsellis' initial description of the pathology of CTE. However, what brought public attention to the issue of CTE in sports were the postmortem findings of CTE pathology in professional American football players, initially reported by Omalu and subsequently in a large series by McKee. There is now standardization of pathological criteria for CTE and recognition that it can be seen across all activities that involve repetitive head impacts.
MeSH term(s)	Athletic Injuries/history ; Chronic Traumatic Encephalopathy/history ; History, 20th Century ; History, 21st Century ; Humans
Language	English
Publishing date	2020-08-10
Publishing country	United States
Document type	Historical Article ; Journal Article ; Review
ZDB-ID	603165-1
ISSN	1098-9021 ; 0271-8235
ISSN (online)	1098-9021
ISSN	0271-8235
DOI	10.1055/s-0040-1713622
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Article ; Online: Cocaine history and impulsiveness in professional boxers and mixed martial arts fighters.

Young, Lisa / Esagoff, Aaron I / Reisch, Anne / Bernick, Charles B / Peters, Matthew E / Narapareddy, Bharat R

The American journal on addictions

2023 Volume 33, Issue 1, Page(s) 92–95

Abstract: Background/objectives: Impulsiveness is linked to cocaine history (CH) in the general population and greater fight exposure in professional fighters. Among fighters, no previous studies have quantified CH or investigated its relationship with ... ...

Abstract	Background/objectives: Impulsiveness is linked to cocaine history (CH) in the general population and greater fight exposure in professional fighters. Among fighters, no previous studies have quantified CH or investigated its relationship with impulsiveness. Methods: Adjusted multivariable regressions were utilized to examine the relationship between CH and impulsiveness in 335 fighters from the Professional Fighters Brain Health Study. Results: Twenty percent of fighters reported CH. CH was significantly associated with impulsiveness overall and on three subscales. Discussion/conclusion: Cocaine's prevalence and significant association with impulsiveness in fighters merit further study. Scientific significance: We quantify CH and demonstrate its significant association with impulsiveness in professional fighters for the first time.
MeSH term(s)	Humans ; Brain ; Martial Arts
Language	English
Publishing date	2023-09-05
Publishing country	England
Document type	Journal Article
ZDB-ID	1141440-6
ISSN	1521-0391 ; 1055-0496
ISSN (online)	1521-0391
ISSN	1055-0496
DOI	10.1111/ajad.13479
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Article ; Online: Repetitive head impacts among professional fighters: a pilot study evaluating Traumatic Encephalopathy Syndrome and postural balance.

Conway Kleven, Brooke / Chien, Lung-Chang / Young, Daniel L / Cross, Chad L / Labus, Brian / Bernick, Charles

The Physician and sportsmedicine

2024 , Page(s) 1–7

Abstract: Objectives: Clinical criteria for Traumatic Encephalopathy Syndrome (ccTES) were developed for research purposes to reflect the clinical symptoms of Chronic Traumatic Encephalopathy (CTE). The aims of this study were to 1) determine whether there was an ...

Abstract	Objectives: Clinical criteria for Traumatic Encephalopathy Syndrome (ccTES) were developed for research purposes to reflect the clinical symptoms of Chronic Traumatic Encephalopathy (CTE). The aims of this study were to 1) determine whether there was an association between the research diagnosis of TES and impaired postural balance among retired professional fighters, and 2) determine repetitive head impacts (RHI) exposure thresholds among both TES positive and TES negative groups in retired professional fighters when evaluating for balance impairment. Methods: This was a pilot study evaluating postural balance among participants of the Professional Athletes Brain Health Study (PABHS). Among the cohort, 57 retired professional fighters met the criteria for inclusion in this study. A generalized linear model with generalized estimating equations was used to compare various balance measures longitudinally between fighters with and without TES. Results: A significant association was observed between a TES diagnosis and worsening performance on double-leg balance assessments when stratifying by RHI exposure thresholds. Additionally, elevated exposure to RHI was significantly associated with increased odds of developing TES; The odds for TES diagnosis were 563% (95% CI = 113, 1963; p-value = 0.0011) greater among athletes with 32 or more professional fights compared to athletes with less than 32 fights when stratifying by balance measures. Likewise, the odds for TES diagnosis were 43% (95% CI = 10, 102; p-value = 0.0439) greater with worsening double leg stance balance in athletes exposed to 32 or more fights. Conclusion: This pilot study provides preliminary evidence of a relationship between declining postural balance and a TES diagnosis among retired professional fighters with elevated RHI exposure. Further research exploring more complex assessments such as the Functional Gait Assessment may be of benefit to improve clinical understanding of the relationship between TES, RHI, and balance.
Language	English
Publishing date	2024-03-06
Publishing country	England
Document type	Journal Article
ZDB-ID	753046-8
ISSN	2326-3660 ; 0091-3847
ISSN (online)	2326-3660
ISSN	0091-3847
DOI	10.1080/00913847.2024.2325331
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Article ; Online: Traumatic encephalopathy syndrome: application of new criteria to a cohort exposed to repetitive head impacts.

Ritter, Aaron / Shan, Guogen / Montes, Arturo / Randall, Rebekah / Bernick, Charles

British journal of sports medicine

2022 Volume 57, Issue 7, Page(s) 389–394

Abstract: Objective: To examine the characteristics of those who fulfil the recent National Institute of Neurological Disease and Stroke (NINDS) Consensus Diagnostic Criteria for Traumatic Encephalopathy Syndrome (TES) and test whether they show differences in ... ...

Abstract	Objective: To examine the characteristics of those who fulfil the recent National Institute of Neurological Disease and Stroke (NINDS) Consensus Diagnostic Criteria for Traumatic Encephalopathy Syndrome (TES) and test whether they show differences in MRI-based regional brain volumes, cognitive domains, and certain plasma biomarkers. Methods: Professional fighters 35 years of age or older and/or retired were included. Participants were categorised as either having TES (TES+) or not (non-TES). TES+ participants were further subtyped by their cognitive profile. Multiple linear regression models were used to compare MRI-based regional brain volumes, cognitive performance, plasma tau and neurofilament light levels between TES- and TES+ groups. Results: 176 participants (110 boxers and 66 MMA) were included in the analysis. 72 (41%)/176 were categorised as having TES, the likelihood of TES increasing with age. TES+ participants tended to be boxers, started fighting at a younger age, had more professional fights and knocked out more frequently. The TES+ group had lower regional brain volumes including both grey and white matter structures. TES+ also had lower scores on simple and choice reaction time, psychomotor speed and Trails A . Conclusion: The new TES criteria does distinguish a group of fighters with differences in regional brain volumes and reduced cognitive function. Our findings support the use of the NINDS criteria for TES in further research of the long-term effects of repetitive head impacts.
MeSH term(s)	Humans ; Brain Injuries, Traumatic ; Cognition ; Neuroimaging ; White Matter/diagnostic imaging ; Magnetic Resonance Imaging ; Boxing
Language	English
Publishing date	2022-12-14
Publishing country	England
Document type	Journal Article
ZDB-ID	600592-5
ISSN	1473-0480 ; 0306-3674
ISSN (online)	1473-0480
ISSN	0306-3674
DOI	10.1136/bjsports-2022-105819
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Article: Assessing Clinical Change in Individuals Exposed to Repetitive Head Impacts: The Repetitive Head Impact Composite Index.

Bernick, Charles / Shan, Guogen / Bennett, Lauren / Alberts, Jay / Cummings, Jeffrey

Frontiers in neurology

2021 Volume 12, Page(s) 605318

Abstract: Background: ...

Abstract	Background:
Language	English
Publishing date	2021-07-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564214-5
ISSN	1664-2295
ISSN	1664-2295
DOI	10.3389/fneur.2021.605318
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Article ; Online: 7T MRI Versus 3T MRI of the Brain in Professional Fighters and Patients With Head Trauma.

Lee, Jonathan K / Bernick, Charles / Stephen, Steve / Ritter, Aaron / Bullen, Jennifer / Mangat, Arvindpaul / Joyce, Jennifer / Jones, Stephen E

Neurotrauma reports

2023 Volume 4, Issue 1, Page(s) 342–349

Abstract: Many studies have investigated the imaging sequelae of repetitive head trauma with mixed results, particularly with regard to the detection of intracranial white matter changes (WMCs) and cerebral microhemorrhages (CMHs) on ≤3 Tesla (T) field magnetic ... ...

Abstract	Many studies have investigated the imaging sequelae of repetitive head trauma with mixed results, particularly with regard to the detection of intracranial white matter changes (WMCs) and cerebral microhemorrhages (CMHs) on ≤3 Tesla (T) field magnetic resonance imaging (MRI). 7T MRI, which has recently been approved for clinical use, is more sensitive at detecting lesions associated with multiple neurological diagnoses. In this study, we sought to determine whether 7T MRI would detect more WMCs and CMHs than 3T MRI in 19 professional fighters, 16 patients with single TBI, versus 82 normal healthy controls (NHCs). Fighters and patients with TBI underwent both 3T and 7T MRI; NHCs underwent either 3T (
Language	English
Publishing date	2023-05-18
Publishing country	United States
Document type	Journal Article
ISSN	2689-288X
ISSN (online)	2689-288X
DOI	10.1089/neur.2023.0001
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Article: History of Chronic Traumatic Encephalopathy

Cantu, Robert C. / Bernick, Charles

Seminars in Neurology

(Chronic Traumatic Encephalopathy)

2020 Volume 40, Issue 04, Page(s) 353–358

Series title	Chronic Traumatic Encephalopathy
Abstract	The long-term effects of repetitive head impacts have been recognized for close to a century. What is now referred to as chronic traumatic encephalopathy (CTE) was first described by Martland in 1928 in a series of boxers. Over the years, several important articles were published, including Critchley's 1957 report where he introduced the term “chronic traumatic encephalopathy,” Robert's study in 1969 which provided evidence of the prevalence of neurological impairment in retired fighters, and Corsellis' initial description of the pathology of CTE. However, what brought public attention to the issue of CTE in sports were the postmortem findings of CTE pathology in professional American football players, initially reported by Omalu and subsequently in a large series by McKee. There is now standardization of pathological criteria for CTE and recognition that it can be seen across all activities that involve repetitive head impacts.
Keywords	chronic traumatic encephalopathy ; brain damage ; natural history
Language	English
Publishing date	2020-08-01
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-0040-1713622
Database	Thieme publisher's database

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Article ; Online: Machine learning methods to predict amyloid positivity using domain scores from cognitive tests.

Shan, Guogen / Bernick, Charles / Caldwell, Jessica Z K / Ritter, Aaron

Scientific reports

2021 Volume 11, Issue 1, Page(s) 4822

Abstract: Amyloid-[Formula: see text] (A[Formula: see text]) is the target in many clinical trials for Alzheimer's disease (AD). Preclinical AD patients are heterogeneous with regards to different backgrounds and diagnosis. Accurately predicting A[Formula: see ... ...

Abstract	Amyloid-[Formula: see text] (A[Formula: see text]) is the target in many clinical trials for Alzheimer's disease (AD). Preclinical AD patients are heterogeneous with regards to different backgrounds and diagnosis. Accurately predicting A[Formula: see text] status of participants by using machine learning (ML) models based on easily accessible data, could improve the effectiveness of AD clinical trials. We will develop optimal ML models for each subpopulation stratified by sex and disease stages using sub scores from screening neurological tests. Data from the AD Neuroimaging Initiative (ADNI) were used to build the ML models, for three groups: individuals with significant memory concern, early mild cognitive impairment (MCI), and late MCI. Data were further separated into 6 groups by disease stage (3 levels) and sex (2 categories). The outcome was defined as the A[Formula: see text] status confirmed by the PET imaging, and the features include demographic data, newly identified risk factors, screening tests, and the domain scores from screening tests. Monte Carlo simulation studies were used together with k-fold cross-validation technique to compute model performance metric. We also develop a new feature selection method based on the stochastic ordering to avoiding searching all possible combinations of features. Accuracy of the identified optimal model for SMC male was over 90% by using domain scores, and accuracy for LMCI female was above 86%. Domain scores can improve the ML model prediction as compared to the total scores. Accurate ML prediction models can identify the proper population for AD clinical trials.
MeSH term(s)	Aged ; Aged, 80 and over ; Alzheimer Disease/diagnostic imaging ; Alzheimer Disease/metabolism ; Alzheimer Disease/physiopathology ; Amyloid beta-Peptides/metabolism ; Brain/diagnostic imaging ; Brain/metabolism ; Cognitive Dysfunction/diagnostic imaging ; Cognitive Dysfunction/metabolism ; Cognitive Dysfunction/physiopathology ; Female ; Humans ; Male ; Middle Aged ; Models, Neurological ; Neuroimaging ; Neuropsychological Tests ; Predictive Value of Tests
Chemical Substances	Amyloid beta-Peptides
Language	English
Publishing date	2021-03-01
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-83911-9
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