Association of quantitative histopathology measurements with antemortem medial temporal lobe cortical thickness in the Alzheimer's disease continuum.

The medial temporal lobe (MTL) is a hotspot for neuropathology, and measurements of MTL atrophy are often used as a biomarker for cognitive decline associated with neurodegenerative disease. Due to the aggregation of multiple proteinopathies in this region, the specific relationship of MTL atrophy to distinct neuropathologies is not well understood. Here, we develop two quantitative algorithms using deep learning to measure phosphorylated tau (p-tau) and TDP-43 (pTDP-43) pathology, which are both known to accumulate in the MTL and are associated with MTL neurodegeneration. We focus on these pathologies in the context of Alzheimer's disease (AD) and limbic predominant age-related TDP-43 encephalopathy (LATE) and apply our deep learning algorithms to distinct histology sections, on which MTL subregions were digitally annotated. We demonstrate that both quantitative pathology measures show high agreement with expert visual ratings of pathology and discriminate well between pathology stages. In 140 cases with antemortem MR imaging, we compare the association of semi-quantitative and quantitative postmortem measures of these pathologies in the hippocampus with in vivo structural measures of the MTL and its subregions. We find widespread associations of p-tau pathology with MTL subregional structural measures, whereas pTDP-43 pathology had more limited associations with the hippocampus and entorhinal cortex. Quantitative measurements of p-tau pathology resulted in a significantly better model of antemortem structural measures than semi-quantitative ratings and showed strong associations with cortical thickness and volume. By providing a more granular measure of pathology, the quantitative p-tau measures also showed a significant negative association with structure in a severe AD subgroup where semi-quantitative ratings displayed a ceiling effect. Our findings demonstrate the advantages of using quantitative neuropathology to understand the relationship of pathology to structure, particularly for p-tau, and motivate the use of quantitative pathology measurements in future studies.

Neuroanatomical and cellular degeneration associated with a social disorder characterized by new ritualistic belief systems in a TDP-C patient vs. a Pick patient.

Frontotemporal dementia (FTD) is a spectrum of clinically and pathologically heterogenous neurodegenerative dementias. Clinical and anatomical variants of FTD have been described and associated with underlying frontotemporal lobar degeneration (FTLD) pathology, including tauopathies (FTLD-tau) or TDP-43 proteinopathies (FTLD-TDP). FTD patients with predominant degeneration of anterior temporal cortices often develop a language disorder of semantic knowledge loss and/or a social disorder often characterized by compulsive rituals and belief systems corresponding to predominant left or right hemisphere involvement, respectively. The neural substrates of these complex social disorders remain unclear. Here, we present a comparative imaging and postmortem study of two patients, one with FTLD-TDP (subtype C) and one with FTLD-tau (subtype Pick disease), who both developed new rigid belief systems. The FTLD-TDP patient developed a complex set of values centered on positivity and associated with specific physical and behavioral features of pigs, while the FTLD-tau patient developed compulsive, goal-directed behaviors related to general themes of positivity and spirituality. Neuroimaging showed left-predominant temporal atrophy in the FTLD-TDP patient and right-predominant frontotemporal atrophy in the FTLD-tau patient. Consistent with antemortem cortical atrophy, histopathologic examinations revealed severe loss of neurons and myelin predominantly in the anterior temporal lobes of both patients, but the FTLD-tau patient showed more bilateral, dorsolateral involvement featuring greater pathology and loss of projection neurons and deep white matter. These findings highlight that the regions within and connected to anterior temporal lobes may have differential vulnerability to distinct FTLD proteinopathies and serve important roles in human belief systems.

Ammonia Inhalation Does Not Increase Deadlift 1-Repetition Maximum in College-Aged Male and Female Weight Lifters.

Vigil, JN, Sabatini, PL, Hill, LC, Swain, DP, and Branch, JD. Ammonia inhalation does not increase deadlift 1-repetition maximum in college-aged male and female weight lifters. J Strength Cond Res 32(12): 3392-3397, 2018-Ammonia inhalant use by powerlifters and weight lifters is a prevalent practice with little research support for improved performance. The purpose of this study was to investigate the effects of ammonia as a stimulant on athletic performance during a deadlift 1-repetition maximum (1RM) absolute strength test. Subjects (men: n = 10, mean ± SD age = 21 ± 1 year, mass = 72.5 ± 6.8 kg; and women: n = 10, age = 22 ± 5 years, mass = 66.2 ± 8.1 kg) were required to have at least 2 years of resistance training experience while lacking a history of asthma, lightheadedness, fainting, anaphylaxis, sickle cell traits, and other respiratory disorders. After a baseline 1RM test, subjects were paired by 1RM performance and gender, then randomly assigned in a counterbalanced treatment order to control (water) or ammonia trials after a minimum 72-hour recovery period for another 1RM test involving attempts at 100.0, 102.5, 105.0, and 107.5% of the established 1RM value. Testing was then repeated after the minimum rest period for the remaining trial. Results revealed the expected gender main effect for absolute deadlift 1RM (93.0 ± 29.5 [women]; 152.0 ± 29.5 kg [men]; p < 0.001), but no trial main effect (p = 0.874) or gender by trial interaction effect (baseline = 93.0 ± 15.3, 151.8 ± 42.3 kg; water = 92.0 ± 12.5, 150.9 ± 37.8 kg; ammonia = 92.5 ± 16.4, 153.4 ± 37.9 kg) for women and men, respectively (p = 0.559). Within the limitations of this study, there is no support for the practice of ammonia inhalation to improve deadlift 1RM in training or competition.