Todd M. Solomon

Clinicopathological evaluation of chronic traumatic encephalopathy in players of American football

Importance Players of American football may be at increased risk of long-term neurological conditions, particularly chronic traumatic encephalopathy (CTE). Objective To determine the neuropathological and clinical features of deceased football players with CTE. Design, Setting, and Participants Case series of 202 football players whose brains were donated for research. Neuropathological evaluations and retrospective telephone clinical assessments (including head trauma history) with informants were performed blinded. Online questionnaires ascertained athletic and military history. Exposures Participation in American football at any level of play. Main Outcomes and Measures Neuropathological diagnoses of neurodegenerative diseases, including CTE, based on defined diagnostic criteria; CTE neuropathological severity (stages I to IV or dichotomized into mild [stages I and II] and severe [stages III and IV]); informant-reported athletic history and, for players who died in 2014 or later, clinical presentation, including behavior, mood, and cognitive symptoms and dementia. Results Among 202 deceased former football players (median age at death, 66 years [interquartile range, 47-76 years]), CTE was neuropathologically diagnosed in 177 players (87%; median age at death, 67 years [interquartile range, 52-77 years]; mean years of football participation, 15.1 [SD, 5.2]), including 0 of 2 pre–high school, 3 of 14 high school (21%), 48 of 53 college (91%), 9 of 14 semiprofessional (64%), 7 of 8 Canadian Football League (88%), and 110 of 111 National Football League (99%) players. Neuropathological severity of CTE was distributed across the highest level of play, with all 3 former high school players having mild pathology and the majority of former college (27 [56%]), semiprofessional (5 [56%]), and professional (101 [86%]) players having severe pathology. Among 27 participants with mild CTE pathology, 26 (96%) had behavioral or mood symptoms or both, 23 (85%) had cognitive symptoms, and 9 (33%) had signs of dementia. Among 84 participants with severe CTE pathology, 75 (89%) had behavioral or mood symptoms or both, 80 (95%) had cognitive symptoms, and 71 (85%) had signs of dementia. Conclusions and Relevance In a convenience sample of deceased football players who donated their brains for research, a high proportion had neuropathological evidence of CTE, suggesting that CTE may be related to prior participation in football.

Overdependence on Degraded Gist Memory in Alzheimer's Disease

Alzheimers disease (AD) reduces associative effects on false recognition in the Deese-Roediger-McDermott task, either due to impaired memory for gist or impaired use of gist in memory decisions. Gist processes were manipulated by blocking or mixing studied words according to their associations and by varying the associative strength between studied and nonstudied words at test. Both associative blocking and associative strength had smaller effects on false recognition in AD patients than in control participants, consistent with gist memory impairments. However, unlike the case with control participants, blocking influenced true and false recognition equally in AD patients, demonstrating an overdependence on gist when making memory decisions. AD also impaired item-specific recollections, relative to control participants, as true recognition of studied words was reduced even when the two groups were equated on gist-based false recognition. We propose that the overdependence on degraded gist memory in AD is caused by even larger impairments in item-specific recollections.

Microglial neuroinflammation contributes to tau accumulation in chronic traumatic encephalopathy

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.

Substance Use in the MSM Population of New York City during the Era of HIV/AIDS

This literature review considers the historical significance, emergence of, and interplay between the HIV and illicit drug use epidemics among gay, bisexual, and other men who have sex with men (MSM) in New York City (NYC). The continual rise in HIV infections in recent years among MSM, particularly among young MSM (YMSM), commands a need for the examination of the effectiveness of current HIV prevention strategies and a more comprehensive understanding of the complex biopsychosocial influences that place YMSM at risk. A chronological perspective of both the HIV and illicit drug use epidemics affecting NYC MSM is presented, followed by a review of the existing research on the synergistic relation between the two. Special consideration is given to the patterns and interconnectivity between HIV, substance use, and housing instability specific to YMSM, as they represent the demographic currently at greatest risk for HIV transmission in NYC. Thereafter, an overview of treatment research is provided. We conclude by offering recommendations for future research and best practices as we move forward in an attempt to reduce the incidence of HIV transmission.

Pathologically Confirmed Chronic Traumatic Encephalopathy in a 25-Year-Old Former College Football Player

Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy associated with repetitive head impacts.1 Presently, CTE only can be diagnosed pathologically; however, research efforts, such as the ongoing Understanding Neurological Injury and Traumatic Encephalopathy (UNITE) Study,2 are investigating ways to diagnose CTE during life. As part of the UNITE Study, a panel of clinicians, blinded to neuropathology, make retrospective clinical consensus diagnoses using published criteria, including proposed clinical research criteria for CTE.3 Here, we present an informative case from the UNITE Study.

Alcohol Use Among Young Men Who Have Sex With Men

This study reveals associations between alcohol use and demographic variables, as well as the relation between alcohol use and sexual activity, using episodic data. Data were obtained during summer and fall from a sample of 558 gay, bisexual, and other young men who have sex with men (YMSM), ages of 13–29 years in New York City. Recruitment strategies targeted potential participants at gay-related venues and public spaces often frequented by YMSM. Alcohol use varied by race/ethnicity, with White YMSM consuming significantly more alcohol than other races/ethnicities. Participants over the age of 21 drank significantly more alcohol than participants ages 13–20. Alcohol use was not found to be associated with sexual risk-taking activity. Our findings are enriched by a large, diverse sample of urban YMSM. Study limitations are noted.

Methamphetamine Use among Gay, Bisexual and Non-identified Men-Who-Have-Sex-with-Men An Analysis of Daily Patterns

This study sought to understand the patterns, methods of administration and contexts for methamphetamine use (MA) in a sample of racially diverse men who have sex with men (MSM). Inclusion into the study required participants to be classified as clinically dependent on MA, but indicate no other illicit substance use. Use was assessed using Timeline Followback for a period of 30 days. Of the 900 assessed days, MA use was reported on 217. Participants reported an average of seven days of use, with the majority of use occurring on the weekend. The weekend usage pattern suggests an incorporation of drugs into the lives of gay men as a means of socialization and recreation.

Cognitive Executive Functioning in Relation to HIV Medication Adherence Among Gay, Bisexual, and other Men who have Sex with Men

A longitudinal study of 300 HIV-positive gay, bisexual or non-gay-identified men-who-have-sex-with-men was undertaken to consider patterns relating to HIV medication adherence. The purpose of our analyses was to consider the rate of adherence in relation to both age and executive functioning as assessed by the Trail Making Test A and B. Executive functioning was assessed at baseline and month 10. Our analytic sample consisted of 213 men who remained on the same protease inhibitor throughout the assessment timeframe. Adherence rates were relatively high with more than 50% of the sample maintaining a 95%+ adherence rate at both baseline and month 10. Analyses at baseline indicated executive functioning and age were related to rate of adherence. Analyses at month 10 indicated no significant relations. Findings support previous research and suggest that the status of executive functioning as well as age be given consideration when working with HIV-positive individuals.

Chronic traumatic encephalopathy: a neurodegenerative consequence of repetitive traumatic brain injury

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.

Temporal relations between methamphetamine use and HIV seroconversion in gay, bisexual, and other men who have sex with men

Data from a cross-sectional study of gay, bisexual, and other men who have sex with men who were active methamphetamine users were analyzed to assess temporal relations between HIV seroconversion and initiation of methamphetamine use. Of the 100 men, 58 reported being HIV-positive. Most HIV-positive participants (65%) initiated methamphetamine use after seroconverting. Among those who initiated use before seroconversion, 8 years elapsed between onset of use and time of infection. Findings suggest the need to develop nuanced and targeted interventions aimed at disentangling the “meth-sex” link in this population. Findings also suggest use of the drug as a coping mechanism for those living with HIV.