Is There Chronic Brain Damage in Retired NFL Players? Neuroradiology, Neuropsychology, and Neurology Examinations of 45 Retired Players

BACKGROUND: Neuropathology and surveys of retired National Football League (NFL) players suggest that chronic brain damage is a frequent result of a career in football. There is limited information on the neurological statuses of living retired players. This study aimed to fill the gap in knowledge by conducting in-depth neurological examinations of 30- to 60-year-old retired NFL players. HYPOTHESIS: In-depth neurological examinations of 30- to 60-year-old retired players are unlikely to detect objective clinical abnormalities in the majority of subjects. STUDY DESIGN: A day-long medical examination was conducted on 45 retired NFL players, including state-of-the-art magnetic resonance imaging (MRI; susceptibility weighted imaging [SWI], diffusion tensor imaging [DTI]), comprehensive neuropsychological and neurological examinations, interviews, blood tests, and APOE (apolipoprotein E) genotyping. LEVEL OF EVIDENCE: Level 3. METHODS: Participants\u27 histories focused on neurological and depression symptoms, exposure to football, and other factors that could affect brain function. The neurological examination included Mini-Mental State Examination (MMSE) evaluation of cognitive function and a comprehensive search for signs of dysarthria, pyramidal system dysfunction, extrapyramidal system dysfunction, and cerebellar dysfunction. The Beck Depression Inventory (BDI) and Patient Health Questionnaire (PHQ) measured depression. Neuropsychological tests included pen-and-paper and ImPACT evaluation of cognitive function. Anatomical examination SWI and DTI MRI searched for brain injuries. The results were statistically analyzed for associations with markers of exposure to football and related factors, such as body mass index (BMI), ethanol use, and APOE4 status. RESULTS: The retired players\u27 ages averaged 45.6 +/- 8.9 years (range, 30-60 years), and they had 6.8 +/- 3.2 years (maximum, 14 years) of NFL play. They reported 6.9 +/- 6.2 concussions (maximum, 25) in the NFL. The majority of retired players had normal clinical mental status and central nervous system (CNS) neurological examinations. Four players (9%) had microbleeds in brain parenchyma identified in SWI, and 3 (7%) had a large cavum septum pellucidum with brain atrophy. The number of concussions/dings was associated with abnormal results in SWI and DTI. Neuropsychological testing revealed isolated impairments in 11 players (24%), but none had dementia. Nine players (20%) endorsed symptoms of moderate or severe depression on the BDI and/or met criteria for depression on PHQ; however, none had dementia, dysarthria, parkinsonism, or cerebellar dysfunction. The number of football-related concussions was associated with isolated abnormalities on the clinical neurological examination, suggesting CNS dysfunction. The APOE4 allele was present in 38% of the players, a larger number than would be expected in the general male population (23%-26%). CONCLUSION: MRI lesions and neuropsychological impairments were found in some players; however, the majority of retired NFL players had no clinical signs of chronic brain damage. CLINICAL RELEVANCE: These results need to be reconciled with the prevailing view that a career in football frequently results in chronic brain damage

Third-Order Incremental Dual-Basis Set Zero-Buffer Approach for Large High-Spin Open-Shell Systems

The third-order incremental dual-basis set zero-buffer approach (inc3-db-B0) is an efficient, accurate, and black-box quantum chemical method for obtaining correlation energies of large systems, and it has been successfully applied to many real chemical problems. In this work, we extend this approach to high-spin open-shell systems. In the open-shell approach, we will first decompose the occupied orbitals of a system into several domains by a K-means clustering algorithm. The essential part is that we preserve the active (singly occupied) orbitals in all the calculations of the domain correlation energies. The duplicated contributions of the active orbitals to the correlation energy are subtracted from the incremental expansion. All techniques of truncating the virtual space such as the B0 approximation can be applied. This open-shell inc3-db-B0 approach is combined with the CCSD and CCSD(T) methods and applied to the computations of a singlet-triplet gap and an electron detachment process. Our approach exhibits an accuracy better than 0.6 kcal/mol or 0.3 eV compared with the standard implementation, while it saves a large amount of the computational time and can be efficiently parallelized