Validation of a Bayesian Diagnostic and Inferential Model for Evidence-Based Neuropsychological Practice.

OBJECTIVE: Evidence-based diagnostic methods have clinical and research applications in neuropsychology. A flexible Bayesian model was developed to yield diagnostic posttest probabilities from a single person's neuropsychological score profile by utilizing sample descriptive statistics of the test battery across diagnostic populations of interest. METHODS: Three studies examined the model's performance. One simulation examined estimation accuracy of true z-scores. A diagnostic accuracy simulation utilized descriptive statistics from two popular neuropsychological tests, the Wechsler Adult Intelligence Scale-IV (WAIS-IV) and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The final simulation examined posterior predictive accuracy of scores to those reported in the WAIS manual. RESULTS: The model produced minimally biased z-score estimates (root mean square errors: .02-.18) with appropriate credible intervals (95% credible interval empirical coverage rates: .94-1.00). The model correctly classified 80.87% of simulated normal, mild cognitive impairment, and Alzheimer's disease cases using a four subtest WAIS-IV and the RBANS compared to accuracies of 60.67-65.60% from alternative methods. The posterior predictions of raw scores closely aligned to percentile estimates published in the WAIS-IV manual. CONCLUSION: This model permits estimation of posttest probabilities for various combinations of neuropsychological tests across any number of clinical populations with the principal limitation being the accessibility of applicable reference samples. The model produced minimally biased estimates of true z-scores, high diagnostic classification rates, and accurate predictions of multiple reported percentiles while using only simple descriptive statistics from reference samples. Future nonsimulation research on clinical data is needed to fully explore the utility of such diagnostic prediction models.

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.

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.

Clinical and neuropsychological profile of patients with dementia and chronic traumatic encephalopathy.

OBJECTIVE: To determine whether subjects with chronic traumatic encephalopathy (CTE) and dementia have distinct clinical features compared to subjects with pathologically confirmed Alzheimer's disease (AD). METHODS: Among 339 subjects assessed for CTE in the National Alzheimer's Coordinating Center dataset, 6 subjects with CTE and 25 subjects with AD neuropathologic change matched for age (±5 years) and sex were identified. All subjects had a clinical diagnosis of dementia. Neurological examination, neuropsychological testing and emotional/behavioural data were compared between CTE and AD subjects at the time of dementia diagnosis and last clinical visit near death. RESULTS: A history of traumatic brain injury with loss of consciousness (LOC) was reported in one CTE and one AD subject; information about injuries without LOC or multiple injuries was unavailable. CTE and AD subjects did not differ significantly at the time of diagnosis or last visit on the Unified Parkinson's Disease Rating Scale-Motor Exam, global measures of cognitive functioning (Mini-Mental State Exam and Clinical Dementia Rating Scale), emotional/behaviour symptoms as assessed with the Neuropsychiatric Inventory questionnaire or across neuropsychological measures. All CTE participants had co-occurring neuropathologic processes, including AD and most had TAR DNA-binding protein 43 (TDP-43) neuropathology. CONCLUSIONS: CTE pathology was rare in a large multicentre national dataset, and when present, was accompanied by AD and TDP-43 pathologies. CTE was not associated with a different clinical presentation from AD or with greater cognitive impairment or neurobehavioral symptoms. These findings suggest that CTE may not have a distinct clinical profile when other neuropathologic processes are coexistent with CTE pathology.

Associations of Race-Ethnicity and History of Traumatic Brain Injury With Age at Onset of Alzheimer's Disease.

OBJECTIVE: This study examined whether a history of traumatic brain injury (TBI) is associated with age at onset of Alzheimer's disease (AD) in three racial-ethnic groups. METHODS: Data from 7,577 non-Hispanic Caucasian, 792 African American, and 870 Hispanic participants with clinically diagnosed AD were obtained from the National Alzheimer's Coordinating Center. Participants were categorized by the presence or absence of self-reported remote history of TBI (>1 year before diagnosis of AD) with loss of consciousness (LOC) (TBI+) or no history of TBI with LOC (TBI-). Any group differences in education; sex; APOE ε4 alleles; family history of dementia; or history of depression, stroke, hypertension, hypercholesterolemia, and diabetes were included in analyses of covariance comparing clinician-estimated age at AD symptom onset for the TBI+ and TBI- groups. RESULTS: AD onset occurred 2.3 years earlier for non-Hispanic Caucasians (F=30.49, df=1, 7,572, p<0.001) and 3.4 years earlier for African Americans (F=5.17, df=1, 772, p=0.023) in the TBI+ group. In the Hispanic cohort, females in the TBI+ group had AD onset 5.6 years earlier, compared with females in the TBI- group (F=6.96, df=1, 865, p=0.008); little difference in age at AD onset was observed for Hispanic males with and without a TBI history. CONCLUSIONS: A history of TBI with LOC was associated with AD onset 2-3 years earlier in non-Hispanic Caucasians and African Americans and an onset nearly 6 years earlier in Hispanic females; no association was observed in Hispanic males. Further work in underserved populations is needed to understand possible underlying mechanisms for these differences.

Neuropsychological functioning in ageing retired NFL players: a critical review.

Recent discovery of chronic traumatic encephalopathy in former National Football League (NFL) players has led to a surge of papers investigating cognitive functioning in these former athletes. This critical review of the literature focused on the neuropsychological functioning in these ageing athletes, and included 22 articles published between 2013 and 2019, of which 13 reported on neuroradiological imaging and four focused on dose-response relationships of repetitive head injury on cognitive outcomes. Four studies suggest higher prevalence of MCI and neurodegenerative disease among NFL retirees, although a quantifiable risk and prevalence of cognitive impairment and dementia in these players remains unknown. Decreased verbal memory has been found in some players across multiple studies, though with unknown clinical significance due to small sample sizes, unreported effect sizes, and absence of longitudinal data. Studies investigating a dose-response relationship between cognitive decline and head injury have generated mixed findings utilizing various measures of head injury exposure. Neuroradiological findings are inconsistent, but suggest that some NFL players may be at greater risk for reduced white matter integrity. Future research is needed to understand the relationship between sports-related concussions and the risk of long-term cognitive decline and neurodegenerative disease in ageing NFL players.

Risk factors for earlier dementia onset in autopsy-confirmed Alzheimer's disease, mixed Alzheimer's with Lewy bodies, and pure Lewy body disease.

INTRODUCTION: Clinical Alzheimer's disease (AD) and dementia with Lewy bodies often have mixed AD and Lewy pathology, making it difficult to delineate risk factors. METHODS: Six risk factors for earlier dementia onset due to autopsy-confirmed AD (n = 647), mixed AD and Lewy body disease (AD + LBD; n = 221), and LBD (n = 63) were entered into multiple linear regressions using data from the National Alzheimer's Coordinating Center. RESULTS: In AD and AD + LBD, male sex and apolipoprotein E (APOE) ɛ4 alleles each predicted a 2- to 3-year-earlier onset and depression predicted a 3-year-earlier onset. In LBD, higher education predicted earlier onset and depression predicted a 5.5-year-earlier onset. DISCUSSION: Male sex and APOE ɛ4 alleles increase risk for earlier dementia onset in AD but not LBD. Depression increases risk for earlier dementia onset in AD, LBD, and AD + LBD, but evaluating the course, treatment, and severity is needed in future studies.

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.

A novel speech analysis algorithm to detect cognitive impairment in a Spanish population.

Objective: Early detection of cognitive impairment in the elderly is crucial for diagnosis and appropriate care. Brief, cost-effective cognitive screening instruments are needed to help identify individuals who require further evaluation. This study presents preliminary data on a new screening technology using automated voice recording analysis software in a Spanish population. Method: Data were collected from 174 Spanish-speaking individuals clinically diagnosed as cognitively normal (CN, n = 87) or impaired (mild cognitive impairment [MCI], n = 63; all-cause dementia, n = 24). Participants were recorded performing four common language tasks (Animal fluency, alternating fluency [sports and fruits], phonemic "F" fluency, and Cookie Theft Description). Recordings were processed via text-transcription and digital-signal processing techniques to capture neuropsychological variables and audio characteristics. A training sample of 122 subjects with similar demographics across groups was used to develop an algorithm to detect cognitive impairment. Speech and task features were used to develop five independent machine learning (ML) models to compute scores between 0 and 1, and a final algorithm was constructed using repeated cross-validation. A socio-demographically balanced subset of 52 participants was used to test the algorithm. Analysis of covariance (ANCOVA), covarying for demographic characteristics, was used to predict logistically-transformed algorithm scores. Results: Mean logit algorithm scores were significantly different across groups in the testing sample (p < 0.01). Comparisons of CN with impaired (MCI + dementia) and MCI groups using the final algorithm resulted in an AUC of 0.93/0.90, with overall accuracy of 88.4%/87.5%, sensitivity of 87.5/83.3, and specificity of 89.2/89.2, respectively. Conclusion: Findings provide initial support for the utility of this automated speech analysis algorithm as a screening tool for cognitive impairment in Spanish speakers. Additional study is needed to validate this technology in larger and more diverse clinical populations.

A Critical Review of Neuropsychological Actuarial Criteria for Mild Cognitive Impairment.

BACKGROUND: The concept of mild cognitive impairment (MCI) has evolved since its original conception. So, too, have MCI diagnostic methods, all of which have varying degrees of success in identifying individuals at risk of conversion to dementia. The neuropsychological actuarial method is a straightforward diagnostic approach that has shown promise in large datasets in identifying individuals with MCI who are likely to have progressive courses. This method has been increasingly applied in various iterations and samples, raising questions of how best to apply this method and when caution should be used. OBJECTIVE: Our objective was to review the literature investigating use of the neuropsychological actuarial method to diagnose MCI to identify strengths and weaknesses of this approach, as well as highlight areas for further research. METHODS: Databases PubMed and PsychInfo were systematically searched for studies that compared the neuropsychological actuarial method to some other diagnostic method. RESULTS: We identified 13 articles and extracted relevant study characteristics and findings. Existing literature was reviewed and integrated, with focus on the neuropsychological actuarial method's performance relative to existing diagnostic methods/criteria as well as associations with longitudinal outcomes and biomarkers. Tables with pertinent methodological information and general findings are also provided. CONCLUSION: The neuropsychological actuarial method to diagnose MCI has shown utility some in large-scale homogenous databases compared to research criteria. However, its standing relative to consensus diagnostic methods is unclear, and emerging evidence suggests the neuropsychological actuarial method may be more prone to diagnostic errors in more demographically diverse populations.

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.

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).

Impact of word properties on list learning: An explanatory item analysis.

OBJECTIVE: A variety of factors affect list learning performance and relatively few studies have examined the impact of word selection on these tests. This study examines the effect of both language and memory processing of individual words on list learning. METHOD: Item-response data from 1,219 participants, Mage = 74.41 (SD = 7.13), Medu = 13.30 (SD = 2.72), in the Harmonized Cognitive Assessment Protocol were used. A Bayesian generalized (non)linear multilevel modeling framework was used to specify the measurement and explanatory item-response theory models. Explanatory effects on items due to learning over trials, serial position of words, and six word properties obtained through the English Lexicon Project were modeled. RESULTS: A two parameter logistic (2PL) model with trial-specific learning effects produced the best measurement fit. Evidence of the serial position effect on word learning was observed. Robust positive effects on word learning were observed for body-object integration while robust negative effects were observed for word frequency, concreteness, and semantic diversity. A weak negative effect of average age of acquisition and a weak positive effect for the number of phonemes in the word were also observed. CONCLUSIONS: Results demonstrate that list learning performance depends on factors beyond the repetition of words. Identification of item factors that predict learning could extend to a range of test development problems including translation, form equating, item revision, and item bias. In data harmonization efforts, these methods can also be used to help link tests via shared item features and testing of whether these features are equally explanatory across samples. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The Spectrum of Alzheimer-Type Pathology in Cognitively Normal Individuals.

BACKGROUND: The strongest risk factor for the development of Alzheimer's disease (AD) is age. The progression of Braak stage and Thal phase with age has been demonstrated. However, prior studies did not include cognitive status. OBJECTIVE: We set out to define normative values for Alzheimer-type pathologic changes in individuals without cognitive decline, and then define levels that would qualify them to be resistant to or resilient against these changes. METHODS: Utilizing neuropathology data obtained from the National Alzheimer's Coordinating Center (NACC), we demonstrate the age-related progression of Alzheimer-type pathologic changes in cognitively normal individuals (CDR = 0, n = 542). With plots generated from these data, we establish standard lines that may be utilized to measure the extent to which an individual's Alzheimer-type pathology varies from the estimated normal range of pathology. RESULTS: Although Braak stage and Thal phase progressively increase with age in cognitively normal individuals, the Consortium to Establish a Registry for Alzheimer's Disease neuritic plaque score and Alzheimer's disease neuropathologic change remain at low levels. CONCLUSION: These findings suggest that an increasing burden of neuritic plaques is a strong predictor of cognitive decline, whereas, neurofibrillary degeneration and amyloid-ß (diffuse) plaque deposition, both to some degree, are normal pathologic changes of aging that occur in almost all individuals regardless of cognitive status. Furthermore, we have defined the amount of neuropathologic change in cognitively normal individuals that would qualify them to be "resilient" against the pathology (significantly above the normative values for age, but still cognitively normal) or "resistant" to the development of pathology (significantly below the normative values for age).

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.

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.

Chronic traumatic encephalopathy: understanding the facts and debate.

PURPOSE OF REVIEW: Chronic traumatic encephalopathy (CTE) is hypothesized to be a progressive neurodegenerative disease leading to dementia after repetitive head impacts. This review summarizes the recent evidence on CTE to highlight the facts currently known and the areas that remain poorly understood. RECENT FINDINGS: Increasing evidence suggests that many of the prior assertions about CTE in relation to repetitive head trauma are premature. First, CTE lesions have been observed in individuals with no history of head trauma/impacts. In addition, attempts to characterize possible clinical markers of CTE have had several shortcomings, notably an absence of detailed clinical assessments during life, vague/nonspecific symptom reports, and crude methodology. Moreover, recent studies demonstrate that current CTE pathological criteria have limitations and are in need of refinement/validation. SUMMARY: CTE is still in the early stages of research as a neuropathological condition and no specific clinical criteria exist. Claims about CTE being a progressive disease entity and caused exclusively by head trauma/impacts are not well supported at present. Such assertions may have impeded our understanding of the frequency and significance of this disorder. Refining diagnostic criteria to reduce ambiguity in classifying cases will be essential before risk factors and/or possible clinical markers may be identified.

Traumatic Brain Injury and Age of Onset of Dementia with Lewy Bodies.

BACKGROUND: Traumatic brain injury (TBI) with loss of consciousness (LOC) has been associated with earlier onset of mild cognitive impairment, frontotemporal dementia, Parkinson's disease, and Alzheimer's disease (AD), but has not been examined as a risk factor for earlier onset of dementia with Lewy bodies (DLB). OBJECTIVE: The purpose of this study was to assess the association between a history of TBI and the age of onset of DLB. METHOD: Data from 576 subjects with a clinical diagnosis of DLB were obtained from the National Alzheimer's Coordinating Center (NACC). Analyses of Covariance examined whether self-reported history of remote TBI with LOC (i.e., >1 year prior to the first Alzheimer's Disease Center visit) was associated with earlier DLB symptom onset. RESULTS: Controlling for sex, those with a history of remote TBI had an approximately 1.5-year earlier clinician-estimated age of onset (F = 0.87, p = 0.35) and 0.75-years earlier age of diagnosis (F = 0.14, p = 0.71) of DLB compared to those without a history of TBI, though the differences did not reach statistical significance. Analysis of subjects with autopsy-confirmed diagnoses was underpowered due to the low number of TBI+ subjects. CONCLUSIONS: Remote TBI with LOC was not significantly associated with DLB onset, despite being a significant risk factor for cognitive decline and earlier age of onset in other neurodegenerative conditions. Replication of these results using a larger cohort of DLB subjects with and without a TBI history who have undergone autopsy is indicated, as our TBI+ subjects did show a slightly earlier onset of about 1.5 years. Further investigations into other potential DLB risk factors are also warranted.

Traumatic brain injury history is associated with an earlier age of dementia onset in autopsy-confirmed Alzheimer's disease.

OBJECTIVE: To evaluate whether a history of traumatic brain injury (TBI) with reported loss of consciousness (LOC) is a risk factor for earlier onset of Alzheimer's disease (AD) in an autopsy-confirmed sample. METHOD: Data from 2,133 participants with autopsy-confirmed AD (i.e., at least Braak neurofibrillary tangle stages III to VI and CERAD neuritic plaque score moderate to frequent) were obtained from the National Alzheimer's Coordinating Center (NACC). Participants were categorized by presence/absence of self-reported remote (i.e., >1 year prior to their first Alzheimer's Disease Center visit) history of TBI with LOC (TBI+ vs. TBI-). Analyses of Covariance (ANCOVA) controlling for sex, education, and race compared groups on clinician-estimated age of symptom onset and age of diagnosis. RESULTS: Average age of onset was 2.34 years earlier (p = .01) for the TBI+ group (n = 194) versus the TBI- group (n = 1900). Dementia was diagnosed on average 2.83 years earlier (p = .002) in the TBI+ group (n = 197) versus the TBI- group (n = 1936). Using more stringent neuropathological criteria (i.e., Braak stages V-VI and CERAD frequent), both age of AD onset and diagnosis were 3.6 years earlier in the TBI+ group (both p's < .001). CONCLUSIONS: History of TBI with reported LOC appears to be a risk factor for earlier AD onset. This is the first study to use autopsy-confirmed cases, supporting previous investigations that used clinical criteria for the diagnosis of AD. Further investigation as to possible underlying mechanisms of association is needed. (PsycINFO Database Record