Serie, Amanda M.

AbstractChronic traumatic encephalopathy is a debilitating neurodegenerative disorder associated with repetitive traumatic brain injuries often sustained through prior contact sport participation. The frequency of this disorder in a diverse population, including amateur athletes, is unknown. Primary historical obituary and yearbook records were queried for 2566 autopsy cases in the Mayo Clinic Tissue Registry resulting in identification of 300 former athletes and 450 non‐athletes. In these cases, neocortical tissue was screened for tau pathology with immunohistochemistry, including pathology consistent with chronic traumatic encephalopathy, blinded to exposure or demographic information. Using research infrastructure of the Rochester Epidemiology Project, a comprehensive and established medical records‐linkage system of care providers in southern Minnesota and western Wisconsin, medical diagnostic billing codes pertaining to head trauma, dementia, movement disorders, substance abuse disorders and psychiatric disorders were recorded for cases and controls in a blinded manner. A total of 42 individuals had pathology consistent with, or features of, chronic traumatic encephalopathy. It was more frequent in athletes compared to non‐athletes (27 cases versus 15 cases) and was largely observed in men (except for one woman). For contact sports, American football had the highest frequency of chronic traumatic encephalopathy pathology (15% of cases) and an odds ratio of 2.62 (P‐value = 0.005). Cases with chronic traumatic encephalopathy pathology had higher frequencies of antemortem clinical features of dementia, psychosis, movement disorders and alcohol abuse compared to cases without chronic traumatic encephalopathy pathology. Understanding the frequency of chronic traumatic encephalopathy pathology in a large autopsy cohort with diverse exposure backgrounds provides a baseline for future prospective studies assessing the epidemiology and public health impact of chronic traumatic encephalopathy and sports‐related repetitive head trauma.

Background: TDP-43 has been shown to be strongly associated with memory loss, smaller hippocampal volumes, and faster rates of hippocampal atrophy in Alzheimer’s disease (AD) patients with an amnestic presentation. Whether TDP-43 has any clinical or anatomical associations in AD patients with non-amnestic phenotype is unknown. Objective: To determine whether TDP-43 plays a significant role in the clinic-anatomic features of non-amnestic AD. Methods: All cases with pathologically confirmed intermediate-high probability AD from 1996–2012 were identified and retrospectively sub-classified into amnestic versus non-amnestic dementia at the time of presentation. Neurofibrillary tangle counts were performed in those with a non-amnestic presentation using thioflavin-S microscopy in the hippocampus and three neocortical regions, and all cases were subtyped into hippocampal-sparing, limbic-predominant, and typical AD pathology. TDP-43 immunoreactivity was used to assess for the presence of TDP-43. Statistical analyses helped determine whether pathologic subtype or TDP-43 was more strongly associated with clinico-imaging features. Results: Out of 172 pathologically confirmed AD cases, 36 (19%) were classified as non-amnestic. Twenty-five of these 36 (69%) had typical pathology, 0 limbic-predominant pathology, and 11 (31%) hippocampal-sparing pathology. Eleven (44%) of the 25 cases with typical pathology were TDP-43+. Of the 11 cases with hippocampal-sparing pathology, 4 (36%) were TDP-43+. There were no differences in demographic, clinical, or neuroimaging features in those with TDP-43 versus those without except for older age at onset ( p = 0.02) and age at death ( p = 0.02) in those with TDP-43. AD pathological subtype accounted for slightly more of the variances in the neocortex than TDP-43. Conclusion: In non-amnestic AD, we find little evidence that clinical or anatomical features of the disease are related to TDP-43.