A Critical Review of Noninvasive Brain Stimulation Technologies in Alzheimer's Dementia and Primary Progressive Aphasia.

Multiple pharmacologic agents now have been approved in the United States and other countries as treatment to slow disease and clinical progression for Alzheimer's disease. Given these treatments have not been proven to lessen the cognitive deficits already manifested in the Alzheimer's Clinical Syndrome (ACS), and none are aimed for another debilitating dementia syndrome identified as primary progressive aphasia (PPA), there is an urgent need for new, safe, tolerable, and efficacious treatments to mitigate the cognitive deficits experienced in ACS and PPA. Noninvasive brain stimulation has shown promise for enhancing cognitive functioning, and there has been interest in its potential therapeutic value in ACS and PPA. This review critically examines the evidence of five technologies in ACS and PPA: transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), transcranial random noise stimulation (tRNS), repetitive transcranial magnetic stimulation (rTMS), and noninvasive vagus nerve stimulation (nVNS). Many randomized controlled trials of tDCS and rTMS report positive treatment effects on cognition in ACS and PPA that persist out to at least 8 weeks, whereas there are few trials for tACS and none for tRNS and nVNS. However, most positive trials did not identify clinically meaningful changes, underscoring that clinical efficacy has yet to be established in ACS and PPA. Much is still to be learned about noninvasive brain stimulation in ACS and PPA, and shifting the focus to prioritize clinical significance in addition to statistical significance in trials could yield greater success in understanding its potential cognitive effects and optimal parameters.

Verbal retrieval deficits due to traumatic brain injury are associated with changes in event related potentials during a Go-NoGo task.

OBJECTIVE: Verbal retrieval (VR) deficits often occur after traumatic brain injury (TBI), but the mechanisms remain unclear. We examined how event-related potentials (ERPs) during a Go-NoGo task were associated with VR deficits. METHODS: Sixty veterans with a history of TBI underwent a neuropsychological battery and a Go-NoGo task with concurrent EEG recording. We compared task performance and ERP measures (N2, P3) between those with and those without persistent injury-related VR deficits. We then used generalized linear modeling to examine the relationship between ERP measures and scores on measures of executive function and processing speed. RESULTS: Go-NoGo task performance was comparable between the groups. Those with VR deficits had larger N2 amplitude in NoGo than in Go conditions. In participants with VR deficits, larger NoGo N2/P3 amplitude predicted faster processing speed. Furthermore, larger P3 amplitude and shorter P3 latency of the difference wave (NoGo - Go) predicted faster processing speed in those with VR deficits. CONCLUSIONS: Despite no difference in Go-NoGo task performance, ERP amplitude and latency measures associated with cognitive control during Go-NoGo distinguished TBI individuals with VR deficits from those without. SIGNIFICANCE: This study furthers our understanding of VR deficits in TBI and implicates potential application of ERP measures in monitoring and treating such deficits.

Traumatic Brain Injury Characteristics Are Not Related to Neurocognitive Decline in Older Adults: A Nationwide Longitudinal Cohort Study.

OBJECTIVE: Evaluate whether traumatic brain injury (TBI) characteristics, age of injury, or recency of injury predicts the course of neurocognitive decline and/or increases conversion rates to mild cognitive impairment (MCI) or dementia. METHODS: Data were obtained from the National Alzheimer's Coordinating Center for participants 50-85 years old with 3-5 visits from 2015 to 2022, with or without TBI history (TBI+ = 508; TBI- = 2,382). Groups were stratified by self-reported TBI history (i.e., single TBI without loss of consciousness [LOC], single TBI with LOC, multiple TBI without LOC, and multiple TBI with LOC), age of most recent TBI, and recency of TBI. Mixed linear models compared neuropsychological composite trajectories (executive functioning/attention/speed, language, memory, and global), co-varying for age, gender, education, apolipoprotein E4 status, race/ethnicity, and baseline diagnosis (normal aging n = 1,720, MCI n = 749, or dementia n = 417). Logistic binary regression examined MCI/dementia conversion rates. RESULTS: There was a slightly higher frequency of MCI/dementia in those with multiple TBIs (50% to 60% with and without LOC, compared to 39% with no TBI) at baseline, but longitudinal trajectories were similar. TBI history, age of injury, or recency of injury did not impact neurocognitive trajectories or conversion rates to MCI/dementia (all p's > .01). CONCLUSIONS: TBI history, regardless of injury characteristics, age of injury, or recency of injury, did not worsen neurocognitive decline or MCI/dementia conversion. Additional longitudinal research in more diverse cohorts with a wider range of TBI severity is needed to evaluate the specific factors and possible mechanisms in which TBI may increase dementia risk.

Blood Markers in Relation to a History of Traumatic Brain Injury Across Stages of Cognitive Impairment in a Diverse Cohort.

BACKGROUND: Traumatic brain injury (TBI) has been linked to multiple pathophysiological processes that could increase risk for Alzheimer's disease and related dementias (ADRD). However, the impact of prior TBI on blood biomarkers for ADRD remains unknown. OBJECTIVE: Using cross-sectional data, we assessed whether a history of TBI influences serum biomarkers in a diverse cohort (approximately 50% Hispanic) with normal cognition, mild cognitive impairment, or dementia. METHODS: Levels of glial fibrillary acidic protein (GFAP), neurofilament light (NFL), total tau (T-tau), and ubiquitin carboxy-terminal hydrolase-L1 (UCHL1) were measured for participants across the cognitive spectrum. Participants were categorized based on presence and absence of a history of TBI with loss of consciousness, and study samples were derived through case-control matching. Multivariable general linear models compared concentrations of biomarkers in relation to a history of TBI and smoothing splines modelled biomarkers non-linearly in the cognitively impaired groups as a function of time since symptom onset. RESULTS: Each biomarker was higher across stages of cognitive impairment, characterized by clinical diagnosis and Mini-Mental State Examination performance, but these associations were not influenced by a history of TBI. However, modelling biomarkers in relation to duration of cognitive symptoms for ADRD showed differences by history of TBI, with only GFAP and UCHL1 being elevated. CONCLUSIONS: Serum GFAP, NFL, T-tau, and UCHL1 were higher across stages of cognitive impairment in this diverse clinical cohort, regardless of TBI history, though longitudinal investigation of the timing, order, and trajectory of the biomarkers in relation to prior TBI is warranted.

Identification of Factors in Moderate-Severe TBI Related to a Functional Decline in Cognition Decades After Injury.

OBJECTIVE: To investigate whether a functional decline in cognitive activities decades after moderate-to-severe traumatic brain injury (m-sTBI) might relate to injury features and/or lifetime health factors, some of which may emerge as consequences of the injury. DESIGN: Secondary analysis of the TBI Model Systems National Database, a prospective, multi-center, longitudinal study of patients with m-sTBI. SETTING: TBI Model Systems Centers. PARTICIPANTS: Included were 732 participants rated on the cognitive subscale of the Functional Independence Measure (FIM Cognitive), a metric for everyday cognitive skills, across 3 time points out to 20 years (visits at 2-, 10-, and 20-year follow-ups; N=732). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE(S): FIM Cognitive Scale. Injury characteristics such as timing and features pertaining to severity and health-related factors (eg, alcohol use, socioeconomic status) were examined to discriminate stable from declining participants on the FIM Cognitive Scale using logistic regression. RESULTS: At 20 years post-injury, there was a low base rate of FIM Cognitive decline (11%, n=78), with most being stable or having meaningful improvement (89%, n=654). Older age at injury, longer duration of post-traumatic amnesia, and presence of repetitive seizures were significant predictors of FIM Cognitive decline in the final model (area under the curve=0.75), while multiple health-related factors that can represent independent co-morbidities or possible consequences of injury were not. CONCLUSION(S): The strongest contributors to reported functional decline in cognitive activities later-in-life were related to acute characteristics of m-sTBI and experiencing post-traumatic seizures. Future studies are needed integrating functional with performance-based cognitive assessments to affirm conclusions and identify the timeline and trajectory of cognitive decline.

History of traumatic brain injury does not alter course of neurocognitive decline in older adults with and without cognitive impairment.

OBJECTIVE: Traumatic brain injury (TBI) history is associated with dementia risk, but it is unclear whether TBI history significantly hastens neurocognitive decline in older adults. METHOD: Data were derived from the National Alzheimer's Coordinating Center (NACC) data set. Participants with a history of TBI (TBI +; n = 1,467) were matched to individuals without a history of TBI (TBI-; n = 1,467) based on age (50-97, M = 71.61, SD = 8.40), sex, education, race, ethnicity, cognitive diagnosis, functional decline, number of Apolipoprotein ε4 (APOE ε4) alleles, and number of annual visits (3-6). Mixed linear models were used to assess longitudinal neuropsychological test composite scores of executive functioning/attention/speed, language, and memory in TBI + and TBI- participants. Interactions between TBI and demographics, APOE ε4 status, and cognitive diagnosis were also examined. RESULTS: Longitudinal neuropsychological functioning did not differ between TBI groups (p's > .001). There was a significant three-way interaction (age, TBI history, time) in language (F[20, 5750.1] = 3.133, p < .001) and memory performance (F[20, 6580.8] = 3.386, p < .001), but post hoc analyses revealed TBI history was not driving this relationship (all p's > .096). No significant interactions were observed between TBI history and sex, education, race/ethnicity, number of APOE ε4 alleles, or cognitive diagnosis (p's > .001). CONCLUSIONS: Findings suggest TBI history, regardless of demographic factors, APOE ε4 status, or cognitive diagnosis, does not alter the course of neurocognitive functioning later-in-life in older adults with or without cognitive impairment. Future clinicopathological longitudinal studies that well-characterize head injuries and the associated clinical course are needed to help clarify the mechanism in which TBI may increase dementia risk. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

No association between age beginning tackle football, or years played and neurocognitive performance later-in-life among older National Football League retirees.

OBJECTIVE: In a retrospective cohort, we evaluated whether age beginning tackle football (ABTF) and more total years of playing football (TYPF) were associated with worse later-in-life neuropsychological change among older retired National Football League (NFL) players. METHOD: Participants were 19 older NFL retirees aged 54-79, including 12 who returned for follow-up evaluation 15-51 months later. Mixed-linear models evaluated the association between ABTF/TYFP and baseline neuropsychological composite scores (executive functioning/attention/speed, language, memory), and neuropsychological composites over time. RESULTS: ABTF and TYPF were not significantly associated with neuropsychological composites at baseline or over time (all p's > .05). There were no significant differences in neuropsychological performance between those ABTF <12 and ≥ 12 years old (all p's ≥ .475) or between those with TYPF <19 or ≥ 19 years played (median split; all p's ≥ .208). CONCLUSIONS: Preliminary findings suggest that ABTF and TYPF does not worsen neurocognitive decline later-in-life among older NFL retirees.

Early vs. delayed evaluation and persisting concussion symptoms during recovery in adults.

Objective: Persisting concussion symptoms may adversely affect return to work and functioning in daily activities. This study compared adults who were initially evaluated < 30 days versus those evaluated ≥ 30 days following a concussion at a specialty concussion clinic to determine if delayed initial evaluation is associated with persisting symptoms during recovery. Method: Participants (N = 205) 18 years of age and older who sustained a concussion and presented to a North Texas Concussion Registry (ConTex) clinic were evaluated at two time points: initial clinical visit and three-month follow-up. Participants provided medical history, injury related information, and completed the Sport Concussion Assessment Tool-5 Symptom Evaluation, Generalized Anxiety Disorder 7-item scale (GAD-7), and Patient Health Questionnaire (PHQ-8). Participants were divided into two groups: early and delayed evaluation (±30 days post injury). Results: Number and severity of concussion symptoms were similar between both groups at their initial clinical visit. However, linear regression models showed that a delayed clinical evaluation was associated with a greater number and severity of concussion symptoms along with greater aggravation of symptoms from physical and cognitive activity at three-month follow-up. Conclusions: Individuals who sought care at specialty concussion clinics regardless of previous care 30 or more days following their injury reported more serious persisting concussion symptoms at three month follow-up than those who sought care sooner. Education to improve adults' recognition of concussions when they occur and obtaining earlier clinical evaluation may represent important opportunities in promoting better recovery and reducing persisting concussion symptoms.

Effect of traumatic brain injury on mild behavioral impairment domains prior to all-cause dementia diagnosis and throughout disease progression.

Introduction: Traumatic brain injury (TBI) may alter dementia progression, although co-occurring neuropsychiatric symptoms (NPS) have received less attention. Originally designed to evaluate behavioral disruption prior to dementia diagnosis, the mild behavioral impairment (MBI) construct relates NPS to underlying neural circuit disruptions, with probable relevance across the progression of neurodegenerative disease. Therefore, the MBI construct may represent a valuable tool to identify and evaluate related NPS both preceding diagnosis of all-cause dementia throughout the progression of disease, representing an important area of inquiry regarding TBI and dementia. This investigation sought to evaluate the effect of TBI on NPS related by the MBI construct in participants progressing from normal cognitive status to all-cause dementia. Methods: Using National Alzheimer's Coordinating Center data, individuals progressing from normal cognition to all-cause dementia (clinician diagnosed) over 7.6 ± 3.0 years were studied to estimate prevalence of MBI domains in 124 participants with prior TBI history (57 with loss of consciousness [LOC] <5 minutes, 22 with LOC >5 min, 45 unknown severity) compared to 822 without. MBI domain prevalence was evaluated (1) prior to dementia onset (including only time points preceding time at dementia diagnosis, as per MBI's original definition) and (2) throughout dementia progression (evaluating all available time points, including both before and after dementia diagnosis). Results: More severe TBI (LOC >5 minutes) was associated with the social inappropriateness MBI domain (adjusted odds ratio = 4.034; P = 0.024) prior to dementia onset, and the abnormal perception/thought content domain looking across dementia progression (adjusted hazard ratio [HRadj] = 3.703; P = 0.005). TBI (all severities) was associated with the decreased motivation domain looking throughout dementia progression (HRadj. = 1.546; P = 0.014). Discussion: TBI history is associated with particular MBI profiles prior to onset and throughout progression of dementia. Understanding TBI's impact on inter-related NPS may help elucidate underlying neuropathology with implications for surveillance, detection, and treatment of behavioral concerns in aging TBI survivors. Highlights: The mild behavioral impairment (MBI) construct links related neuropsychiatric symptoms (NPS) by probable underlying neural network dysfunction.Traumatic brain injury (TBI) with loss of consciousness (LOC) > 5 minutes was associated with pre-dementia social inappropriateness.TBI was associated with decreased motivation looking across dementia progression.TBI with LOC > 5 minutes was associated with abnormal perception/thought content.The MBI construct may be useful for examining related NPS across dementia progression.

Neurocognitive outcomes of older National Football League retirees.

OBJECTIVE: Determine if head-injury exposure relates to later-in-life cognitive decline in older National Football League (NFL) retirees. METHOD: NFL retirees (aged 50+) with or without cognitive impairment underwent baseline (n = 53) and follow-up (n = 29; 13-59 months later) neuropsychological evaluations. Cognitively normal (CN) retirees (n = 26) were age- and education-matched to healthy controls (n = 26). Cognitively impaired (CI) retirees with mild cognitive impairment or dementia (n = 27) were matched to a clinical sample (CS) by age, sex, education, and diagnosis (n = 83). ANOVAs compared neuropsychological composites at baseline and over time between retirees and their matched groups. Regression models evaluated whether concussions, concussions with loss of consciousness (LOC), or games played predicted neuropsychological functioning. RESULTS: At baseline, CN retirees had slightly worse memory than controls (MCN retirees = 50.69, SECN retirees = 1.320; MHealthy controls = 57.08, SEHealthy controls = 1.345; p = 0.005). No other group diferences were observed, and head-injury exposure did not predict neurocognitive performance at baseline or over time. CONCLUSIONS: Head-injury exposure was not associated with later-in-life cognition, regardless of cognitive diagnosis. Some retirees may exhibit lower memory scores compared to age-matched peers, though this is of unclear clinical significance.

Using RBANS to characterize cognitive treatment response in autoimmune encephalopathy.

INTRODUCTION: Autoimmune encephalopathy (AE) is an increasingly recognized cause of cognitive impairment. This study investigates the use of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to characterize treatment response of AE cognitive symptoms in ambulatory clinical practice. METHODS: Retrospective evaluation of 29 consecutive patients treated for AE at the University of Cincinnati Memory Disorders Clinic. All patients underwent RBANS before treatment and 4-5 weeks after treatment. The Reliable Change index and clinically meaningful improvement method were used to determine if changes in RBANS performance were clinically significant. RESULTS: Clinically meaningful improvement was seen in 20 out of 29 (69 %) subjects on one or more RBANS domains and in 13 patients (45 %) for the global RBANS index. Measured improvement on one or more cognitive domain scores showed excellent agreement with clinical impression of change. CONCLUSION: The RBANS provided an efficient and effective means to document cognitive outcomes and treatment response in AE. The brief administration time, availability of normative data, and alternate versions make the RBANS useful in clinical practice and in clinical research related to AE.

Mild Traumatic Brain Injury Is Related to Elevated Cerebrospinal Fluid Tau in Alzheimer's Disease Dementia.

Few studies have examined an association between mild traumatic brain injury (mTBI) and Alzheimer's disease (AD). For this reason, we compared an AD dementia group with an mTBI history (n = 10) to a matched AD control group (n = 20) on measures of cognitive function, cerebral glucose metabolism, and markers of amyloid and tau deposition. Only a trend and medium-to-large effect size for higher phosphorylated and total tau was identified for the mTBI group. A history of mTBI may be associated with greater tau in AD, indicating a potential pathway for increasing risk for AD, though further evaluation with larger samples is needed.

Predictors of Life Expectancy in Autopsy-Confirmed Alzheimer's Disease.

BACKGROUND: Life expectancy (LE) following Alzheimer's disease (AD) is highly variable. The literature to date is limited by smaller sample sizes and clinical diagnoses. OBJECTIVE: No study to date has evaluated predictors of AD LE in a retrospective large autopsy-confirmed sample, which was the primary objective of this study. METHODS: Participants (≥50 years old) clinically and neuropathologically diagnosed with AD were evaluated using National Alzheimer's Coordinating Center (N = 1,401) data. Analyses focused on 21 demographic, medical, neuropsychiatric, neurological, functional, and global cognitive predictors of LE at AD dementia diagnosis. These 21 predictors were evaluated in univariate analyses. Variables found to be significant were then entered into a forward multiple regression. LE was defined as months between AD diagnosis and death. RESULTS: Fourteen predictors were significant in univariate analyses and entered into the regression. Seven predictors explained 27% of LE variance in 764 total participants. Mini-Mental State Examination (MMSE) score was the strongest predictor of LE, followed by sex, age, race/ethnicity, neuropsychiatric symptoms, abnormal neurological exam results, and functional impairment ratings. Post-hoc analyses revealed correlations of LE were strongest with MMSE ≤12. CONCLUSION: Global cognitive functioning was the strongest predictor of LE following diagnosis, and AD patients with severe impairment had the shortest LE. AD patients who are older, male, white, and have more motor symptoms, functional impairment, and neuropsychiatric symptoms were also more likely have shorter LE. While this model cannot provide individual prognoses, additional studies may focus on these variables to enhance predictions of LE in patients with AD.

Sex differences in reporting of concussion symptoms in adults.

Objective: To examine differences in concussion symptom reporting between female and male adults considering current psychological symptoms such as anxiety and depression and pre-injury factors in order to identify sex differences which may guide treatment efforts. Method: This prospective study is part of the North Texas Concussion Registry (ConTex). Subjects (N = 132) age 19 to 78 years had sustained a concussion within 30 days of clinic visit. The independent variable was sex and covariates included age, ethnicity, current anxiety and depression ratings, history of attention deficit disorder, history of headache/migraine, and time to clinic. The dependent variables were 22 post-concussion symptoms as measured by the Sport Concussion Assessment Tool-5 Post-Concussion Symptom Scale. Results: Analysis of covariance and ordinal logistic regression results both revealed that females had a greater likelihood of reporting increased symptom severity for 15/22 concussion symptoms. The largest risk ratios (effect size) in symptom reporting between sexes (higher symptoms in females) included: feeling more emotional 4.05 (0.72), fatigue or low energy 4.05 (0.72), sensitivity to light 3.74 (0.69), headache 3.65 (0.57), balance problems 3.31 (0.53), pressure in head 3.06 (0.51), and neck pain 2.97 (0.60). Conclusions: Adult females in our sample reported higher levels of many concussion symptoms than males and showed an increased risk of developing these same symptoms following concussion. Examination of the magnitude of sex difference in concussion symptom reporting will better inform medical staff to anticipate and address symptoms that may present greater challenges for adult females.

Southwestern Assessment of Processing Speed (SWAPS): A new brief test with demographically-corrected norms in an ethnically and educationally diverse population.

Objective. Neuropsychological measures of processing speed have long been used as sensitive indices of cognitive functioning. Most of these commonly used tests are proprietary, and there is a need for brief, freely available tools that can be used in diverse clinical and research settings. The Southwestern Assessment of Processing Speed (SWAPS) is a 60-second digit-symbol transcription task developed as a brief alternative to commercially available coding tests. Demographically-corrected normative data are presented along with reliability and sensitivity/specificity values in older adults with and without cognitive impairment.Method. SWAPS data from 915 healthy aging individuals (NC) and 858 subjects with clinical diagnoses of mild cognitive impairment (MCI; n = 430) and Alzheimer's disease clinical syndrome (ADCS; n = 428) were obtained from the Texas Alzheimer's Research and Care Consortium (TARCC). TARCC participants represent ethnically and educationally diverse community-dwelling individuals age 50+.Results. SWAPS scores showed the expected associations with age, sex, and education, and the interaction between age and education were significant predictors of SWAPS scores. Test-retest reliability in NC was good, and the SWAPS distinguished impaired and non-impaired groups with adequate to excellent sensitivity and specificity for the primary analyses, with optimal cut-off points provided. Raw score- to uncorrected normalized T-scores and demographically-corrected SWAPS T-scores using regression-based norms are presented along with scoring programs for the calculation of each.Conclusions. The SWAPS is a brief, free, easily administered test with demographically-corrected regression-based norms and promising utility for detection of cognitive impairment and efficient assessment of processing speed.

Resilience and recovery from sports related concussion in adolescents and young adults.

INTRODUCTION: Recovery and return to play are important milestones for athletes who sustain sport-related concussions (SRC). Several factors have been shown to influence resolution of post-concussion related symptoms (PCS), but resilience, a trait that reflects the ability to overcome adversity, is another factor that may influence recovery. The aim of this study was to determine the relationship of resilience with resolution of symptoms during recovery in adolescents and young adults following SRC. METHOD: This prospective study is part of the North Texas Concussion Registry (ConTex). Subjects (N = 332) aged 13 to 25 years who sustained a SRC within 10 days of presenting to clinic were evaluated at two time points: initial clinical visit and three-month follow-up. Resilience was measured by the self-report Brief Resilience Survey (BRS) and PCS by the Sport Concussion Assessment Tool-5 Symptom Evaluation Post-Concussion Symptom Scale (PCSS). Recovery was determined by self-reported return to sports/physical activity and percent back to normal. RESULTS: Repeated measures ANCOVA and linear regression models showed that lower resilience ratings at initial visit were associated with a greater number and severity of PCSS symptoms along with higher levels of anxiety and depression symptoms during recovery from SRC. At three months, subjects with lower initial resilience ratings were less likely to report feeling back to normal and had greater aggravation of symptoms from physical and cognitive activity even when they had returned to sports/physical activity. CONCLUSIONS: Lower resilience was associated with greater symptoms and delayed recovery from SRC. Results suggest that resilience may be another important factor to address in recovery from SRC. Future research is needed to examine the extent to which resilience measured after SRC reflects pre-injury characteristics and to better inform the development of interventions to promote resilience during recovery.

Correction: A Quantitative Analysis of Social Media to Determine Trends in Brain Tumor Care and Treatment.

[This corrects the article DOI: 10.7759/cureus.11530.].

Frequency and Predictors of Traumatic Encephalopathy Syndrome in a Prospective Cohort of Retired Professional Athletes.

Traumatic encephalopathy syndrome (TES) is proposed to represent the long-term impact of repetitive head-injury exposure and the clinical manifestation of chronic traumatic encephalopathy (CTE). This study aimed to evaluate the frequency of TES in a cohort of retired professional contact sport athletes, compare the frequency of TES to clinical consensus diagnoses, and identify predictors that increase the likelihood of TES diagnosis. Participants were 85 retired professional contact sport athletes from a prospective cohort at the University of Texas Southwestern Medical Center and the University of Texas at Dallas. Participants ranged in age from 23 to 79 (M = 55.95, SD = 13.82) and obtained 7 to 19 years of education (M = 16.08, SD = 1.03). Retirees were either non-Hispanic white (n = 62) or African-American (n = 23). Retired athletes underwent a standard clinical evaluation, which included a clinical interview, neurological exam, neuroimaging, neuropsychological testing, and consensus diagnosis of normal, mild cognitive impairment, or dementia. TES criteria were applied to all 85 athletes, and frequencies of diagnoses were compared. Fourteen predictors of TES diagnosis were evaluated using binary logistic regressions, and included demographic, neuropsychological, depression symptoms, and head-injury exposure variables. A high frequency (56%) of TES was observed among this cohort of retired athletes, but 54% of those meeting criteria for TES were diagnosed as cognitively normal via consensus diagnosis. Games played in the National Football League (OR = 0.993, p = 0.087), number of concussions (OR = 1.020, p = 0.532), number of concussions with loss of consciousness (OR = 1.141 p = 0.188), and years playing professionally (OR = 0.976, p = 0.627) were not associated with TES diagnosis. Degree of depressive symptomatology, as measured by the total score on the Beck Depression Inventory-II, was the only predictor of TES diagnosis (OR = 1.297, p < 0.001). Our results add to previous findings underscoring the risk for false positive diagnosis, highlight the limitations of the TES criteria in clinical and research settings, and question the relationship between TES and head-injury exposure. Future research is needed to examine depression in retired professional athletes.