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Abstract Background Traumatic brain injury (TBI) and repetitive head impacts (RHI) have been linked to increased risk for multiple types of neurodegenerative disease, higher dementia risk, and earlier age of dementia symptom onset, suggesting transdiagnostic implications for later-life brain health. Frontotemporal dementia (FTD) and primary progressive aphasia (PPA) represent a spectrum of clinical phenotypes that are neuropathologically diverse. FTD/PPA diagnoses bring unique challenges due to complex cognitive and behavioral symptoms that disproportionately present as an early-onset dementia (before age 65). We performed a detailed characterization of lifetime head trauma exposure in individuals with FTD and PPA compared to healthy controls to examine frequency of lifetime TBI and RHI and associated clinical implications. Methods We studied 132 FTD/PPA (age 68.9 ± 8.1, 65% male) and 132 sex-matched healthy controls (HC; age 73.4 ± 7.6). We compared rates of prior TBI and RHI (contact/collision sports) between FTD/PPA and HC (chi-square, logistic regression, analysis of variance). Within FTD/PPA, we evaluated associations with age of symptom onset (analysis of variance). Within behavioral variant FTD, we evaluated associations with cognitive function and neuropsychiatric symptoms (linear regression controlling for age, sex, and years of education). Results Years of participation were greater in FTD/PPA than HC for any contact/collision sport (8.5 ± 6.7yrs vs. 5.3 ± 4.5yrs, p = .008) and for American football (6.2yrs ± 4.3yrs vs. 3.1 ± 2.4yrs; p = .003). Within FTD/PPA, there were dose-dependent associations with earlier age of symptom onset for TBI (0 TBI: 62.1 ± 8.1, 1 TBI: 59.9 ± 6.9, 2 + TBI: 57.3 ± 8.4; p = .03) and years of American football (0yrs: 62.2 ± 8.7, 1-4yrs: 59.7 ± 7.0, 5 + yrs: 55.9 ± 6.3; p = .009). Within bvFTD, those who played American football had worse memory (z-score: -2.4 ± 1.2 vs. -1.4 ± 1.6, p = .02, d = 1.1). Conclusions Lifetime head trauma may represent a preventable environmental risk factor for FTD/PPA. Dose-dependent exposure to TBI or RHI influences FTD/PPA symptom onset and memory function in bvFTD. Clinico-pathological studies are needed to better understand the neuropathological correlates linking RHI or TBI to FTD/PPA onset and symptoms.

Abstract Background Plasma phosphorylated tau (p-tau) has emerged as a promising biomarker for Alzheimer’s disease (AD). Studies have reported strong associations between p-tau and tau-PET that are mainly driven by differences between amyloid-positive and amyloid-negative patients. However, the relationship between p-tau and tau-PET is less characterized within cognitively impaired patients with a biomarker-supported diagnosis of AD. We conducted a head-to-head comparison between plasma p-tau217 and tau-PET in patients at the clinical stage of AD and further assessed their relationships with demographic, clinical, and biomarker variables. Methods We retrospectively included 87 amyloid-positive patients diagnosed with MCI or dementia due to AD who underwent structural MRI, amyloid-PET (11C-PIB), tau-PET (18F-flortaucipir, FTP), and blood draw assessments within 1 year (age = 66 ± 10, 48% female). Amyloid-PET was quantified in Centiloids (CL) while cortical tau-PET binding was measured using standardized uptake value ratios (SUVRs) referenced against inferior cerebellar cortex. Plasma p-tau217 concentrations were measured using an electrochemiluminescence-based assay on the Meso Scale Discovery platform. MRI-derived cortical volume was quantified with FreeSurfer. Mini-Mental State Examination (MMSE) scores were available at baseline (n = 85) and follow-up visits (n = 28; 1.5 ± 0.7 years). Results Plasma p-tau217 and cortical FTP-SUVR were correlated (r = 0.61, p

This study examined the mental health of NCAA collegiate golf coaches. Utilizing the person-environment fit theory and previous literature on coaches' well-being, this study examined four outcomes among 48 participants, namely: depressive and anxiety symptoms, burnout, and job turnover intentions. Results suggested that coaching stressors (e.g., administrative tasks, practice plans, pressure to win) only associate with greater burnout. More consistent evidence showed that workplace stress (e.g., lack of control and autonomy, poor work-family balance) associated with higher levels of all outcomes. Finally, greater perceived organizational support had a beneficial association with each outcome. The findings of the current study suggest golf coaches are at risk of mental health problems because of the stressors of this job. Taken as a whole, athletic departments, coaches, and student-athletes must reconsider norms that overemphasize performance and underemphasize self-care and work-life balance.

Coach education is a learner-centred process, which often fails to consider the preferences of the consumer. Historically, research into performers’ experiences of coaching have been influenced by the social constructivism of learning: in short, an expressed preference for what the performer has experienced as determined by their coach, rather than their own personal preferences. Therefore, this research used skateboarding as a natural laboratory in order to explore the current practices and preferences of performers in a coach-free environment. Ninety-one skateboarders from parks in the United Kingdom and New Zealand offered information relating to their current learning practices, how they learnt about learning, and how the top-level performers in their environment were differentiated. Findings suggest that a number of learning tools are used by performers, which are closely aligned with a more traditional, cognitive view of coaching (e.g., demonstration, drills, and error usage). Results also suggest that performers deployed a number of cognitive skills (e.g., imagery, analogy, and understanding) to enhance storage of a movement as an internal representation. Finally, in the absence of formal coaching, performers use their knowledge of learning to appoint informal leaders. Implications for practice are discussed.

BackgroundTraumatic brain injury (TBI) and repetitive head impacts (RHI) have been linked to increased risk for multiple types of neurodegenerative disease, higher dementia risk, and earlier age of dementia symptom onset, suggesting transdiagnostic implications for later-life brain health. Frontotemporal dementia (FTD) and primary progressive aphasia (PPA) represent a spectrum of clinical phenotypes that are neuropathologically diverse. FTD/PPA diagnoses bring unique challenges due to complex cognitive and behavioral symptoms that disproportionately present as an early-onset dementia (before age 65). We performed a detailed characterization of lifetime head trauma exposure in individuals with FTD and PPA compared to healthy controls to examine frequency of lifetime TBI and RHI and associated clinical implications.MethodsWe studied 132 FTD/PPA (age 68.9 ± 8.1, 65% male) and 132 sex-matched healthy controls (HC; age 73.4 ± 7.6). We compared rates of prior TBI and RHI (contact/collision sports) between FTD/PPA and HC (chi-square, logistic regression, analysis of variance). Within FTD/PPA, we evaluated associations with age of symptom onset (analysis of variance). Within behavioral variant FTD, we evaluated associations with cognitive function and neuropsychiatric symptoms (linear regression controlling for age, sex, and years of education).ResultsYears of participation were greater in FTD/PPA than HC for any contact/collision sport (8.5 ± 6.7yrs vs. 5.3 ± 4.5yrs, p = .008) and for American football (6.2yrs ± 4.3yrs vs. 3.1 ± 2.4yrs; p = .003). Within FTD/PPA, there were dose-dependent associations with earlier age of symptom onset for TBI (0 TBI: 62.1 ± 8.1, 1 TBI: 59.9 ± 6.9, 2 + TBI: 57.3 ± 8.4; p = .03) and years of American football (0yrs: 62.2 ± 8.7, 1-4yrs: 59.7 ± 7.0, 5 + yrs: 55.9 ± 6.3; p = .009). Within bvFTD, those who played American football had worse memory (z-score: -2.4 ± 1.2 vs. -1.4 ± 1.6, p = .02, d = 1.1).ConclusionsLifetime head trauma may represent a preventable environmental risk factor for FTD/PPA. Dose-dependent exposure to TBI or RHI influences FTD/PPA symptom onset and memory function in bvFTD. Clinico-pathological studies are needed to better understand the neuropathological correlates linking RHI or TBI to FTD/PPA onset and symptoms.

Developing talent requires consideration of social networks that can facilitate or inhibit progression. Of fundamental influence in this regard is the family, with recent investigation extending its focus from parents to the role of siblings. As such, the purpose of this Conceptual Analysis article is to, firstly, review the characteristics of the sibling relationship that may support or inhibit talent development. Secondly, the analysis then provides empirically derived practical examples to emphasize the holistic and complex role that siblings can play in talent development. Thirdly, strategies are proposed to support practitioners identify specific sibling characteristics, alongside recommendations for how the relationship can be utilized within both the formal and informal environments by coaches and psychologists. Finally, and crucially, important implications of these characteristics are considered to support effective coach and sport psychologist decision making.

This study examined the validity of an inertial measurement unit system for measuring lower-limb joint kinematics during linear decelerations. A male team athlete (age 36 years, stature 1.75 m, mass 80.0 kg) performed multiple linear decelerations, following 20 m runs at 50%, 75% and 100% self-perceived effort. Inertial measurement unit sensors were strapped to lower-limb segments and retroreflective markers were adhered to the lower-limbs for 3D optical motion analysis. Ground contact time, foot to centre of mass displacement (foot-COM), peak and minimum angle, mean angular velocity and range of motion at the ankle, knee and hip during the contact phases of each deceleration were determined. Measures were valid if a very large correlation (r ≥ 0.7) and small bias (effect size < 0.6) were evident. Following 50% effort, ground contact time, foot-COM and most hip and knee kinematics were valid. Ground contact time, foot-COM and knee flexion velocity and range of motion were valid following 75% efforts. Ground contact time and knee flexion velocity were valid following 100% effort. Therefore, the inertial measurement unit system tested can be used to assess temporal-spatial parameters during a deceleration regardless of the preceding effort, and hip and knee kinematics following low intensity running.

Abstract Introduction Apolipoprotein E (APOE) ε4, the strongest non‐Mendelian genetic risk factor for Alzheimer's disease (AD), has been shown to affect brain capillaries in mice, with potential implications for AD‐related neurodegenerative disease. However, human brain capillaries cannot be directly visualized in vivo. We therefore used retinal imaging to test APOE ε4 effects on human central nervous system capillaries. Methods We collected retinal optical coherence tomography angiography, cognitive testing, and brain imaging in research participants and built statistical models to test genotype–phenotype associations. Results Our analyses demonstrate lower retinal capillary densities in early disease, in cognitively normal APOE ε4 gene carriers. Furthermore, through regression modeling with a measure of brain perfusion (arterial spin labeling), we provide support for the relevance of these findings to cerebral vasculature. Discussion These results suggest that APOE ε4 affects capillary health in humans and that retinal capillary measures could serve as surrogates for brain capillaries, providing an opportunity to study microangiopathic contributions to neurodegenerative disorders directly in humans.

Background: Increasing evidence shows that the semantic variant of primary progressive aphasia (svPPA) is characterized by hippocampal atrophy. However, less is known about disease-related morphological hippocampal changes. The goal of the present study is to conduct a detailed characterization of the impact of svPPA on global hippocampus volume and morphology compared with control subjects and patients with Alzheimer’s disease (AD). Methods: We measured hippocampal volume and deformation-based shape differences in 22 patients with svPPA compared with 99 patients with AD and 92 controls. Multiple Automatically Generated Templates Brain Segmentation Algorithm (MAGeT-Brain) was used on MRI images obtained at the diagnostic visit. Results: Comparable left and right hippocampal atrophy were observed in svPPA and AD. Deformation-based shape analysis showed a common pattern of morphological deformation in svPPA and AD compared with controls. More specifically, both svPPA and AD showed inward deformations in the dorsal surface of the hippocampus, from head to tail on the left side, and more limited to the anterior portion of the body in the right hemisphere. These results also pointed out that both diseases are characterized by a lateral displacement of the central part (body) of the hippocampus. Discussion: Our study provides critical new evidence of hippocampal morphological changes in svPPA, similar to those found in AD. These findings highlight the importance of considering morphological hippocampal changes as part of the anatomical profile of patients with svPPA.

Learning theories provide philosophically informed, basic principles for understanding the mechanisms through which people learn based on a combination of field or laboratory studies. Unfortunately, however, there are several clear conflicts between theoretical approaches and common methods in teaching. Consequently, key challenges among teachers relate to knowing which theoretical approach to adopt and, therefore, methods to apply. This contradiction is even more confusing since some arguments from each approach are coherent with current practice, whilst others are either inconsistent, unclear or even counter to established teaching views. In short, the implications for teachers are, at best, suboptimal. Accordingly, this paper aims to explore the differences in theoretical perspectives and thence, to propose that there is a need for multiple approaches, possibly used in combination. We hope to offer clearer guidance for practitioners and provide some direction to promote better application from researchers.

Over the past 35 years, the dance domain has adopted sports medicine as a key driver of professional practice. However, similar to limitations identified within sport, research is yet to achieve its full translational potential within applied settings. This "Viewpoints" paper begins to identify and unpick key philosophical and methodological aspects, with the view to stimulate discussion in this rapidly growing and developing domain. First, we outline a pragmatic philosophy that underpins expert professional practice as a basis to evaluate research. Second, we critically appraise study design characteristics to exemplify a gap between accepted scientific research protocols and professional needs within applied settings. Third, we comment on recommendations/insights made within the literature against the requirements and practices of professionals. Finally, based on this appraisal we suggest an exemplar new line of research that draws upon a pragmatic philosophy; namely, motor skill refinement. In enacting these 'new moves', we look forward to increased collaboration between practitioners and academics to fully realise a strong applied evidence-base. This task will not be easy, as with any interdisciplinary research, and should draw upon interdisciplinary expertise to do so. Hopefully our brief comments will provide a stimulus for further discussion, planning and future action.

Tau PET has enabled the visualization of paired helical filaments of 3 or 4 C-terminal repeat tau in Alzheimer disease (AD), but its ability to detect aggregated tau in frontotemporal lobar degeneration (FTLD) spectrum disorders is uncertain. We investigated 2-(2-([18F]fluoro)pyridin-4-yl)-9H-pyrrolo[2,3-b:4,5c']dipyridine ([18F]PI-2620), a newer tracer with ex vivo evidence for binding to FTLD tau, in a convenience sample of patients with suspected FTLD and AD using a static acquisition protocol and parametric SUV ratio (SUVr) images. Methods: We analyzed [18F]PI-2620 PET data from 65 patients with clinical diagnoses associated with AD or FTLD neuropathology; most (60/65) also had amyloid-β (Aβ) PET. Scans were acquired 30-60 min after injection; SUVr maps (reference, inferior cerebellar cortex) were created for the full acquisition and for 10-min truncated sliding windows (30-40, 35-45,…50-60 min). Age- and sex-adjusted z score maps were computed for each patient, relative to 23 Aβ-negative cognitively healthy controls (HC). Mean SUVr in the globus pallidus, substantia nigra, subthalamic nuclei, dentate nuclei, white matter, and temporal gray matter was extracted for the full and truncated windows. Results: Patients with suspected AD neuropathology (Aβ-positive patients with mild cognitive impairment or AD dementia) showed high-intensity temporoparietal cortex-predominant [18F]PI-2620 binding. At the group level, patients with clinical diagnoses associated with FTLD (progressive supranuclear palsy with Richardson syndrome [PSP Richardson syndrome], corticobasal syndrome, and nonfluent-variant primary progressive aphasia) exhibited higher globus pallidus SUVr than did HCs; pallidal retention was highest in the PSP Richardson syndrome group, in whom SUVr was correlated with symptom severity (ρ = 0.53, P = 0.05). At the individual level, only half of PSP Richardson syndrome, corticobasal syndrome, and nonfluent-variant primary progressive aphasia patients had a pallidal SUVr above that of HCs. Temporal SUVr discriminated AD patients from HCs with high accuracy (area under the receiver operating characteristic curve, 0.94 [95% CI, 0.83-1.00]) for all time windows, whereas discrimination between patients with PSP Richardson syndrome and HCs using pallidal SUVr was fair regardless of time window (area under the receiver operating characteristic curve, 0.77 [95% CI, 0.61-0.92] at 30-40 min vs. 0.81 [95% CI, 0.66-0.96] at 50-60 min; P = 0.67). Conclusion: [18F]PI-2620 SUVr shows an intense and consistent signal in AD but lower-intensity, heterogeneous, and rapidly decreasing binding in patients with suspected FTLD. Further work is needed to delineate the substrate of [18F]PI-2620 binding and the usefulness of [18F]PI2620 SUVr quantification outside the AD continuum.

This study addressed several inconsistencies and omissions in golf putting research by testing the performance impact of target focused aiming. Participants were 22 high-level and experienced golfers, currently using ball focused aiming. Participants were allocated in a quasi-random fashion to ball or target focused aiming conditions and each performed 32 putts under competitive conditions on a natural putting green from a distance of 8 ft. Data were recorded as putts holed or missed and further categorised into putts missed long, short, left, right, short left, short right, long left and long right. There was no significant difference between conditions (p > 0.05) for any of the categories tested, despite participants’ prior extreme familiarity and expressed preference for the ball focused technique. These results notwithstanding, we discuss possible explanations for target focused benefits, including the role of vision during putting, the impact of intention during execution and possible expectancy effects. While these findings hold potential implications for golf coaching, more research is clearly required to further understand causative mechanisms and to clarify the existence and nature of advantage for one technique over the other. Based on this study, we recommend that high-level and experienced golfers might try target focused aiming as a ‘cost-free’ experiment.

ImportancePlasma phosphorylated tau217 (p-tau217), a biomarker of Alzheimer disease (AD), is of special interest in corticobasal syndrome (CBS) because autopsy studies have revealed AD is the driving neuropathology in up to 40% of cases. This differentiates CBS from other 4-repeat tauopathy (4RT)-associated syndromes, such as progressive supranuclear palsy Richardson syndrome (PSP-RS) and nonfluent primary progressive aphasia (nfvPPA), where underlying frontotemporal lobar degeneration (FTLD) is typically the primary neuropathology.ObjectiveTo validate plasma p-tau217 against positron emission tomography (PET) in 4RT-associated syndromes, especially CBS.Design, setting, and participantsThis multicohort study with 6, 12, and 24-month follow-up recruited adult participants between January 2011 and September 2020 from 8 tertiary care centers in the 4RT Neuroimaging Initiative (4RTNI). All participants with CBS (n = 113), PSP-RS (n = 121), and nfvPPA (n = 39) were included; other diagnoses were excluded due to rarity (n = 29). Individuals with PET-confirmed AD (n = 54) and PET-negative cognitively normal control individuals (n = 59) were evaluated at University of California San Francisco. Operators were blinded to the cohort.Main outcome and measuresPlasma p-tau217, measured by Meso Scale Discovery electrochemiluminescence, was validated against amyloid-β (Aβ) and flortaucipir (FTP) PET. Imaging analyses used voxel-based morphometry and bayesian linear mixed-effects modeling. Clinical biomarker associations were evaluated using longitudinal mixed-effect modeling.ResultsOf 386 participants, 199 (52%) were female, and the mean (SD) age was 68 (8) years. Plasma p-tau217 was elevated in patients with CBS with positive Aβ PET results (mean [SD], 0.57 [0.43] pg/mL) or FTP PET (mean [SD], 0.75 [0.30] pg/mL) to concentrations comparable to control individuals with AD (mean [SD], 0.72 [0.37]), whereas PSP-RS and nfvPPA showed no increase relative to control. Within CBS, p-tau217 had excellent diagnostic performance with area under the receiver operating characteristic curve (AUC) for Aβ PET of 0.87 (95% CI, 0.76-0.98; P

Comprehensive understanding and application of decision making is important for the professional practice and status of sports coaches. Accordingly, building on a strong work base exploring the use of professional judgement and decision making in sport, we report a preliminary investigation into uses of intuition by high-level coaches. Two contrasting groups of high-level coaches from adventure sports (n = 10) and rugby union (n = 8), were interviewed on their experiences of using intuitive and deliberative decision making styles, the source of these skills, and the interaction between the two. Participants reported similarly high levels of usage to other professions. Interaction between the two styles was apparent to varying degrees, while the role of experience was seen as an important precursor to greater intuitive practice and employment. Initially intuitive then deliberate decision making was a particular feature, offering participants an immediate check on the accuracy and validity of the decision. Integration of these data with the extant literature and implications for practice are discussed.

BackgroundPlasma phosphorylated tau (p-tau) has emerged as a promising biomarker for Alzheimer's disease (AD). Studies have reported strong associations between p-tau and tau-PET that are mainly driven by differences between amyloid-positive and amyloid-negative patients. However, the relationship between p-tau and tau-PET is less characterized within cognitively impaired patients with a biomarker-supported diagnosis of AD. We conducted a head-to-head comparison between plasma p-tau217 and tau-PET in patients at the clinical stage of AD and further assessed their relationships with demographic, clinical, and biomarker variables.MethodsWe retrospectively included 87 amyloid-positive patients diagnosed with MCI or dementia due to AD who underwent structural MRI, amyloid-PET (11C-PIB), tau-PET (18F-flortaucipir, FTP), and blood draw assessments within 1 year (age = 66 ± 10, 48% female). Amyloid-PET was quantified in Centiloids (CL) while cortical tau-PET binding was measured using standardized uptake value ratios (SUVRs) referenced against inferior cerebellar cortex. Plasma p-tau217 concentrations were measured using an electrochemiluminescence-based assay on the Meso Scale Discovery platform. MRI-derived cortical volume was quantified with FreeSurfer. Mini-Mental State Examination (MMSE) scores were available at baseline (n = 85) and follow-up visits (n = 28; 1.5 ± 0.7 years).ResultsPlasma p-tau217 and cortical FTP-SUVR were correlated (r = 0.61, p

In contrast to the abundance of motor skill acquisition and performance research, there is a paucity of work which addresses how athletes with an already learnt and well-established skill may go about making a subtle change, or refinement, to that skill. Accordingly, the purpose of this review paper is to provide a comprehensive overview of current understanding pertaining to such practice. Specifically, this review addresses deliberately initiated refinements to closed and self-paced skills (e.g., javelin throwing, golf swing and horizontal jumps). In doing so, focus is directed to three fundamental considerations within applied coaching practice and future research endeavours; the intended outcomes, process and evaluative measures of skill refinement. Conclusions suggest that skill refinement is not the same as skill acquisition or performing already learnt skills with high-levels of automaticity. Due to the complexity of challenge faced, refinements are best addressed as an interdisciplinary solution, with objective measures informing coach decision making.

ObjectiveThere are minimal data directly comparing plasma neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) in aging and neurodegenerative disease research. We evaluated associations of plasma NfL and plasma GFAP with brain volume and cognition in two independent cohorts of older adults diagnosed as clinically normal (CN), mild cognitive impairment (MCI), or Alzheimer's dementia.MethodsWe studied 121 total participants (Cohort 1: n = 50, age 71.6 ± 6.9 years, 78% CN, 22% MCI; Cohort 2: n = 71, age 72.2 ± 9.2 years, 45% CN, 25% MCI, 30% dementia). Gray and white matter volumes were obtained for total brain and broad subregions of interest (ROIs). Neuropsychological testing evaluated memory, executive functioning, language, and visuospatial abilities. Plasma samples were analyzed in duplicate for NfL and GFAP using single molecule array assays (Quanterix Simoa). Linear regression models with structural MRI and cognitive outcomes included plasma NfL and GFAP simultaneously along with relevant covariates.ResultsHigher plasma GFAP was associated with lower white matter volume in both cohorts for temporal (Cohort 1: β = -0.33, p = .002; Cohort 2: β = -0.36, p = .03) and parietal ROIs (Cohort 1: β = -0.31, p = .01; Cohort 2: β = -0.35, p = .04). No consistent findings emerged for gray matter volumes. Higher plasma GFAP was associated with lower executive function scores (Cohort 1: β = -0.38, p = .01; Cohort 2: β = -0.36, p = .007). Plasma NfL was not associated with gray or white matter volumes, or cognition after adjusting for plasma GFAP.ConclusionsPlasma GFAP may be more sensitive to white matter and cognitive changes than plasma NfL. Biomarkers reflecting astroglial pathophysiology may capture complex dynamics of aging and neurodegenerative disease.

Learning theories provide philosophically informed, basic principles for understanding the mechanisms through which people learn based on a combination of field or laboratory studies. Unfortunately, however, there are several clear conflicts between theoretical approaches and common methods in teaching. Consequently, key challenges among teachers relate to knowing which theoretical approach to adopt and, therefore, methods to apply. This contradiction is even more confusing since some arguments from each approach are coherent with current practice, whilst others are either inconsistent, unclear or even counter to established teaching views. In short, the implications for teachers are, at best, suboptimal. Accordingly, this paper aims to explore the differences in theoretical perspectives and thence, to propose that there is a need for multiple approaches, possibly used in combination. We hope to offer clearer guidance for practitioners and provide some direction to promote better application from researchers. [ABSTRACT FROM AUTHOR]

BackgroundWe evaluated the role of cortical amyloid deposition as a factor contributing to memory dysfunction and increased risk of dementia associated with late-life depression (LLD).MethodsA total of 119 older adult participants with a current diagnosis of major depression (LLD) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) Depression Project study and 119 nondepressed (ND) cognitively unimpaired participants matched on age, sex, and APOE genotype were obtained from the ADNI database.ResultsThirty-three percent of LLD participants met ADNI criteria for mild cognitive impairment. Compared with ND individuals, the LLD group exhibited less global amyloid beta (Aβ) accumulation (p = .05). The proportion of amyloid positivity in the LLD group was 19.3% compared with 31.1% for the ND participants (p = .02). Among LLD participants, global Aβ was not associated with lifetime number of depressive episodes, lifetime length of depression, length of lifetime selective serotonin reuptake inhibitor use, or lifetime length of untreated depression (p > .21 for all). Global Aβ was associated with worse memory performance (p = .05). Similar results were found in secondary analyses restricting comparisons to the cognitively unimpaired LLD participants as well as when comparing the LLD group with an ND group that included participants with mild cognitive impairment.ConclusionsContrary to expectation, the LLD group showed less Aβ deposition than the ND group and Aβ deposition was not associated with depression history characteristics. Aβ was associated with memory, but this relationship did not differ between LLD and ND. Our results suggest that memory deficits and accelerated cognitive decline reported in previous studies of LLD are not due to greater cortical Aβ accumulation.

Recent expansion of the sporting domain has meant sports have lacked distinct definitions. These definitions have pertained to specific activities and/or a general perception of an assumed experience, which arguably misunderstands these modern sports. While growth in this domain is encouraging, a clear understanding of modern sports remains a requirement for optimal research, coaching practice and participation. Therefore, we critically consider the difference between these types of sport. In an attempt to address this, the article revisits current definitions of these modern, non-competitive, sports. Specifically, we exemplify issues of conflation within research as justification for our desired clarity. Secondly, we propose a two-dimensional conceptual framework to meaningfully differentiate between these sporting domains and finally, propose several implications for future research, education and applied practice. We hope this article brings clarity within research and the potential positive flow to enhancing education to achieve appropriate outcomes for various participants.

BackgroundCognitive impairment (CI) is a key feature of late life depression (LLD), but the contribution of underlying neurodegenerative pathology remains unclear.ObjectiveTo evaluate cognitive dysfunction in LLD relative to a sample of nondepressed (ND) older adults with matched levels of memory impairment and amyloid-β (Aβ) burden.MethodsParticipants included 120 LLD and 240 ND older adults matched on age, education, sex, Mini-Mental State Exam, mild cognitive impairment diagnosis, and PET Aβ burden.ResultsLLD showed higher rates of impairment relative to ND with 54.6% of the LLD sample demonstrating impairment in at least one cognitive domain compared to 42.9% of controls (H = 7.13, p = 0.008). LLD had poorer performance and higher rates of impairment on Rey Auditory Verbal Learning Test learning and memory compared to controls. In the overall sample, Aβ positivity was associated with worse performance on Logical Memory I (p = 0.044), Logical Memory II (p = 0.011), and Trail Making Test -B (p = 0.032), and APOEɛ4 genotype was associated with worse performance on Logical Memory I (p = 0.022); these relationships did not differ between LLD and ND.ConclusionLLD showed higher rates of CI driven by focal deficits in verbal learning and memory. Alzheimer's disease (AD) biomarkers were associated with worse performance on timed set-shifting and story learning and memory, and these relationships were not impacted by depression status. These findings suggest that AD may account for a portion of previously reported multi-domain CI in LLD and highlight the potential for AD to confound studies of cognition in LLD.

IntroductionApolipoprotein E (APOE) ε4, the strongest non-Mendelian genetic risk factor for Alzheimer's disease (AD), has been shown to affect brain capillaries in mice, with potential implications for AD-related neurodegenerative disease. However, human brain capillaries cannot be directly visualized in vivo. We therefore used retinal imaging to test APOE ε4 effects on human central nervous system capillaries.MethodsWe collected retinal optical coherence tomography angiography, cognitive testing, and brain imaging in research participants and built statistical models to test genotype-phenotype associations.ResultsOur analyses demonstrate lower retinal capillary densities in early disease, in cognitively normal APOE ε4 gene carriers. Furthermore, through regression modeling with a measure of brain perfusion (arterial spin labeling), we provide support for the relevance of these findings to cerebral vasculature.DiscussionThese results suggest that APOE ε4 affects capillary health in humans and that retinal capillary measures could serve as surrogates for brain capillaries, providing an opportunity to study microangiopathic contributions to neurodegenerative disorders directly in humans.

Diffusion imaging is very useful for the diagnosis of sporadic Creutzfeldt-Jakob disease, but it has limitations in tracking disease progression as mean diffusivity changes non-linearly across the disease course. We previously showed that mean diffusivity changes across the disease course follow a quasi J-shaped curve, characterized by decreased values in earlier phases and increasing values later in the disease course. Understanding how MRI metrics change over-time, as well as their correlations with clinical deficits are crucial steps in developing radiological biomarkers for trials. Specifically, as mean diffusivity does not change linearly and atrophy mainly occurs in later stages, neither alone is likely to be a sufficient biomarker throughout the disease course. We therefore developed a model combining mean diffusivity and Volume loss (MRI Disease-Staging) to take into account mean diffusivity's non-linearity. We then assessed the associations between clinical outcomes and mean diffusivity alone, Volume alone and finally MRI Disease-Staging. In 37 sporadic Creutzfeldt-Jakob disease subjects and 30 age- and sex-matched healthy controls, high angular resolution diffusion and high-resolution T1 imaging was performed cross-sectionally to compute z-scores for mean diffusivity (MD) and Volume. Average MD and Volume were extracted from 41 GM volume of interest (VOI) per hemisphere, within the images registered to the Montreal Neurological Institute (MNI) space. Each subject's volume of interest was classified as either "involved" or "not involved" using a statistical threshold of ± 2 standard deviation (SD) for mean diffusivity changes and/or -2 SD for Volume. Volumes of interest were MRI Disease-Staged as: 0 = no abnormalities; 1 = decreased mean diffusivity only; 2 = decreased mean diffusivity and Volume; 3 = normal ("pseudo-normalized") mean diffusivity, reduced Volume; 4 = increased mean diffusivity, reduced Volume. We correlated Volume, MD and MRI Disease-Staging with several clinical outcomes (scales, score and symptoms) using 4 major regions of interest (Total, Cortical, Subcortical and Cerebellar gray matter) or smaller regions pre-specified based on known neuroanatomical correlates. Volume and MD z-scores correlated inversely with each other in all four major ROIs (cortical, subcortical, cerebellar and total) highlighting that ROIs with lower Volumes had higher MD and vice-versa. Regarding correlations with symptoms and scores, higher MD correlated with worse Mini-Mental State Examination and Barthel scores in cortical and cerebellar gray matter, but subjects with cortical sensory deficits showed lower MD in the primary sensory cortex. Volume loss correlated with lower Mini-Mental State Examination, Barthel scores and pyramidal signs. Interestingly, for both Volume and MD, changes within the cerebellar ROI showed strong correlations with both MMSE and Barthel. Supporting using a combination of MD and Volume to track sCJD progression, MRI Disease-Staging showed correlations with more clinical outcomes than Volume or MD alone, specifically with Mini-Mental State Examination, Barthel score, pyramidal signs, higher cortical sensory deficits, as well as executive and visual-spatial deficits. Additionally, when subjects in the cohort were subdivided into tertiles based on their Barthel scores and their percentile of disease duration/course ("Time-Ratio"), subjects in the lowest (most impaired) Barthel tertile showed a much greater proportion of more advanced MRI Disease-Stages than the those in the highest tertile. Similarly, subjects in the last Time-Ratio tertile (last tertile of disease) showed a much greater proportion of more advanced MRI Disease-Stages than the earliest tertile. Therefore, in later disease stages, as measured by time or Barthel, there is overall more Volume loss and increasing MD. A combined multiparametric quantitative MRI Disease-Staging is a useful tool to track sporadic Creutzfeldt-Jakob- disease progression radiologically.

BackgroundIncreasing evidence shows that the semantic variant of primary progressive aphasia (svPPA) is characterized by hippocampal atrophy. However, less is known about disease-related morphological hippocampal changes. The goal of the present study is to conduct a detailed characterization of the impact of svPPA on global hippocampus volume and morphology compared with control subjects and patients with Alzheimer's disease (AD).MethodsWe measured hippocampal volume and deformation-based shape differences in 22 patients with svPPA compared with 99 patients with AD and 92 controls. Multiple Automatically Generated Templates Brain Segmentation Algorithm (MAGeT-Brain) was used on MRI images obtained at the diagnostic visit.ResultsComparable left and right hippocampal atrophy were observed in svPPA and AD. Deformation-based shape analysis showed a common pattern of morphological deformation in svPPA and AD compared with controls. More specifically, both svPPA and AD showed inward deformations in the dorsal surface of the hippocampus, from head to tail on the left side, and more limited to the anterior portion of the body in the right hemisphere. These results also pointed out that both diseases are characterized by a lateral displacement of the central part (body) of the hippocampus.DiscussionOur study provides critical new evidence of hippocampal morphological changes in svPPA, similar to those found in AD. These findings highlight the importance of considering morphological hippocampal changes as part of the anatomical profile of patients with svPPA.

Growth in the adventure sector has increased the demands on adventure sport professionals. Satisfying a diverse range of participatory motivations, however, requires an adaptable and flexible workforce. In this discursive paper, we suggested that a narrowing of service skills caused by commodification and sportification are compounded by general (mis)perceptions of "who" best suits the adventure sector. Accordingly, this paper discussed two important implications for outdoor professionals to improve inclusivity standards. Specifically, using mountain leadership as an exemplar, we firstly, presented themes in connection with motivations and social dynamics. Secondly, we contextualised these themes against pertinent environmental challenges. Finally, we presented a decision making approach and its requisite planning and reflective skill-sets, designed to assist mountaineering professionals to negotiate the complexity presented by individualised service provision. We concluded that there are no simple solutions to these complex and multiple issues. Services require better alignment between epistemology and delivery via an epistemological chain.

Neurodegenerative dementia syndromes are characterized by spreading of pathological protein deposition along syndrome-specific neural networks. Structural and functional MRI measures can assess the integrity of these networks and have been proposed as biomarkers of disease progression for clinical trials. The relationship between in vivo imaging measures and pathological features, at the single subject level, remains largely unknown. Patient-specific maps of atrophy and seed-based intrinsic connectivity disruption, as compared to normal controls, were obtained for 27 patients subsequently diagnosed with progressive supranuclear palsy (n = 16, seven males, age at death 68.9 ± 6.0 years, imaging-to-pathology interval = 670.2 ± 425.1 days) or corticobasal degeneration (n = 11, two males, age at death 66.7 ± 5.4 years, imaging-to-pathology interval = 696.2 ± 482.2 days). A linear mixed effect model with crossed random effects was used to test regional and single-subject level associations between post-mortem regional measures of neurodegeneration and tau inclusion burden, on the one hand, and regional volume loss and seed-based intrinsic connectivity reduction, on the other. A significant association was found between tau inclusion burden and in vivo volume loss, at the regional level and independent of neurodegeneration severity, in both progressive supranuclear palsy [n = 340 regions; beta 0.036; 95% confidence interval (CI): 0.001, 0.072; P = 0.046] and corticobasal degeneration (n = 215 regions; beta 0.044; 95% CI: 0.009, 0.079; P = 0.013). We also found a significant association between post-mortem neurodegeneration and in vivo volume loss in both progressive supranuclear palsy (n = 340 regions; beta 0.155; 95% CI: 0.061, 0.248; P = 0.001) and corticobasal degeneration (n = 215 regions; beta 0.277; 95% CI: 0.104, 0.450; P = 0.002). We found a significant association between regional neurodegeneration and intrinsic connectivity dysfunction in corticobasal degeneration (n = 215 regions; beta 0.074; 95% CI: 0.005, 0.143; P = 0.035), but no other associations between post-mortem measures of tauopathy and intrinsic connectivity dysfunction reached statistical significance. Our data suggest that in vivo structural imaging measures reflect independent contributions from neurodegeneration and tau burden in progressive supranuclear palsy and corticobasal degeneration. Seed-based measures of intrinsic connectivity dysfunction showed less reliable predictive value when used as in vivo biomarkers of tauopathy. The findings provide important guidance for the use of imaging biomarkers as indirect in vivo assays of microscopic pathology.

The default mode network (DMN) supports memory functioning and may be sensitive to preclinical Alzheimer's pathology. Little is known, however, about the longitudinal trajectory of this network's intrinsic functional connectivity (FC). In this study, we evaluated longitudinal FC in 111 cognitively normal older human adults (ages 49-87, 46 women/65 men), 92 of whom had at least three task-free fMRI scans (n = 353 total scans). Whole-brain FC and three DMN subnetworks were assessed: (1) within-DMN, (2) between anterior and posterior DMN, and (3) between medial temporal lobe network and posterior DMN. Linear mixed-effects models demonstrated significant baseline age × time interactions, indicating a nonlinear trajectory. There was a trend toward increasing FC between ages 50-66 and significantly accelerating declines after age 74. A similar interaction was observed for whole-brain FC. APOE status did not predict baseline connectivity or change in connectivity. After adjusting for network volume, changes in within-DMN connectivity were specifically associated with changes in episodic memory and processing speed but not working memory or executive functions. The relationship with processing speed was attenuated after covarying for white matter hyperintensities (WMH) and whole-brain FC, whereas within-DMN connectivity remained associated with memory above and beyond WMH and whole-brain FC. Whole-brain and DMN FC exhibit a nonlinear trajectory, with more rapid declines in older age and possibly increases in connectivity early in the aging process. Within-DMN connectivity is a marker of episodic memory performance even among cognitively healthy older adults.SIGNIFICANCE STATEMENT Default mode network and whole-brain connectivity, measured using task-free fMRI, changed nonlinearly as a function of age, with some suggestion of early increases in connectivity. For the first time, longitudinal changes in DMN connectivity were shown to correlate with changes in episodic memory, whereas volume changes in relevant brain regions did not. This relationship was not accounted for by white matter hyperintensities or mean whole-brain connectivity. Functional connectivity may be an early biomarker of changes in aging but should be used with caution given its nonmonotonic nature, which could complicate interpretation. Future studies investigating longitudinal network changes should consider whole-brain changes in connectivity.

Over the past 35 years, the dance domain has adopted sports medicine as a key driver of professional practice. However, similar to limitations identified within sport, research is yet to achieve its full translational potential within applied settings. This Viewpoints paper begins to identify and unpick key philosophical and methodological aspects, with the view to stimulate discussion in this rapidly growing and developing domain. First, we outline a pragmatic philosophy that underpins expert professional practice as a basis to evaluate research. Second, we critically appraise study design characteristics to exemplify a gap between accepted scientific research protocols and professional needs within applied settings. Third, we comment on recommendations/insights made within the literature against the requirements and practices of professionals. Finally, based on this appraisal we suggest an exemplar new line of research that draws upon a pragmatic philosophy; namely, motor skill refinement. In enacting these 'new moves', we look forward to increased collaboration between practitioners and academics to fully realise a strong applied evidence-base. This task will not be easy, as with any interdisciplinary research, and should draw upon interdisciplinary expertise to do so. Hopefully our brief comments will provide a stimulus for further discussion, planning and future action. [ABSTRACT FROM AUTHOR]

Pompa, D, Carson, HJ, Beato, M, di Fronso, S, and Bertollo, M. Attentional focus effects on lower-limb muscular strength in athletes: A systematic review. J Strength Cond Res 38(2): 419-434, 2024--Evidence links an athlete's focus of attention to enhancing strength performance. However, additional research is needed to investigate the applicability of studies beyond the tasks and population currently examined. Therefore, we aimed to systematically review studies concerning attentional focus effects on strength characteristics on lower-limb tasks in athletes. Scopus, Web of Science, and EBSCO databases were searched using PRISMA PERSIST guidelines and keywords related to the focus of attention, force production processes, and athletes. Subjects were categorized: world class (tier 5); elite (tier 4); highly trained (tier 3); trained/developmental (tier 2); nonathletes (tiers 1-0); and mixed (different levels). Fifteen of 296 studies met the inclusion criteria. Included studies investigated the focus of attention effects on performance (n56), between skill levels (n52), and for learning (n55), with respect to subject preference (n51); one study did not state the aim. Studies achieved an average risk of bias score of "excellent"; however, findings suffered in the assessment of certainty. Only 2 studies reported an advantage for one type of attentional focus (external focus) across conditions (g 5 0.13-0.42) with tier 2 and mixed tier athletes. Research does not address the needs of elite athletes, and there is limited evidence on each type of strength characteristics and muscle action. There is also a need to incorporate methodological steps to promote task-relevant instructions. Research should focus on contextualized information within professional practice to offer stronger translational implications for athletes and coaches. [ABSTRACT FROM AUTHOR]