Search

Study Objectives: Obstructive sleep apnea (OSA) may increase risk of dementia. A potential pathway for this risk is through cerebral small vessel disease (CSVD). In the context of an existing randomized trial of aspirin for primary prevention, we aimed to investigate OSA's impact on CSVD imaging measures and explore whether aspirin effects these measures over 3 years that differ in the presence or absence of OSA., Methods: A sub-study of the ASPirin in Reducing Events in the Elderly randomized placebo-controlled trial of low-dose aspirin. Community-dwelling participants aged 70 years and above, without cognitive impairment, cardiovascular disease or known OSA completed an unattended limited-channel sleep study that calculated the oxygen desaturation index and apnea-hypopnea index. At baseline and 3 years later, volumes of white matter hyperintensities (WMH) and silent brain infarctions (SBI) were measured on 1.5 Tesla brain magnetic resonance imaging, and retinal vessel calibers were calculated from retinal vascular imaging., Results: Mild and moderate/severe OSA was detected in 48.9% and 29.9%, respectively, of the 311 participants, who had a mean age of 73.7 years (SD 3.4 years), 38.6% female. OSA of any severity did not associate with WMH volumes, SBI, nor with retinal vessel calibers at baseline, nor with change in these measures in the 277 participants with repeated measures acquired after 3 years. OSA of any severity did not interact with aspirin on change in these measures over 3 years., Conclusion: In healthy older adults undiagnosed OSA was not associated with retinal vascular calibers and neuroimaging measures of CSVD., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society.)

Up to half of all people with multiple sclerosis experience communication difficulties due to dysarthria, a disorder that impacts the motor aspects of speech production. Dysarthria in multiple sclerosis is linked to cerebellar dysfunction, disease severity and lesion load, but the neuroanatomical substrates of these symptoms remain unclear. In this study, 52 participants with multiple sclerosis and 14 age- and sex-matched healthy controls underwent structural and diffusion MRI, clinical assessment of disease severity and cerebellar dysfunction and a battery of motor speech tasks. Assessments of regional brain volume and white matter integrity, and their relationships with clinical and speech measures, were undertaken. White matter tracts of interest included the interhemispheric sensorimotor tract, cerebello-thalamo-cortical tract and arcuate fasciculus, based on their roles in motor and speech behaviours. Volumetric analyses were targeted to Broca's area, Wernicke's area, the corpus callosum, thalamus and cerebellum. Our results indicated that multiple sclerosis participants scored worse on all motor speech tasks. Fixel-based diffusion MRI analyses showed significant evidence of white matter tract atrophy in each tract of interest. Correlational analyses further indicated that higher speech naturalness-a perceptual measure of dysarthria-and lower reading rate were associated with axonal damage in the interhemispheric sensorimotor tract and left arcuate fasciculus in people with multiple sclerosis. Axonal damage in all tracts of interest also correlated with clinical scales sensitive to cerebellar dysfunction. Participants with multiple sclerosis had lower volumes of the thalamus and corpus callosum compared with controls, although no brain volumetrics correlated with measures of dysarthria. These findings indicate that axonal damage, particularly when measured using diffusion metrics, underpin dysarthria in multiple sclerosis., Competing Interests: K.H.K., F.M.C.B., M.S. and A.M. have nothing to disclose. A.v.d.W. served on advisory boards and receives unrestricted research grants from Novartis, Biogen, Merck and Roche; has received speaker’s honoraria and travel support from Novartis, Roche and Merck; and receives grant support from the National Health and Medical Research Council of Australia and MS Research Australia. A.P.V. is the chief science officer of Redenlab Inc. G.N. works in the scientific development for Redenlab Inc. S.K. received unrestricted research grants from Biogen and grant support from MS Research Australia. I.H.H receives grants from the National Health and Medical Research Council and honoraria from Steminent Biotherapeutics and PTC therapeutics., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Identifying when recovery from a sports-related concussion (SRC) has occurred remains a challenge in clinical practice. This study investigated the utility of ocular motor (OM) assessment to monitor recovery post-SRC between sexes and compared to common clinical measures. From 139 preseason baseline assessments (i.e. before they sustained an SRC), 18 (12 males, 6 females) consequent SRCs were sustained and the longitudinal follow-ups were collected at 2, 6, and 13 days post-SRC. Participants completed visually guided, antisaccade (AS), and memory-guided saccade tasks requiring a saccade toward, away from, and to a remembered target, respectively. Changes in latency (processing speed), visual-spatial accuracy, and errors were measured. Clinical measures included The Sports Concussion Assessment Tool, King-Devick test, Stroop task, and Digit span. AS latency was significantly longer at 2 days and returned to baseline by 13-days post-SRC in females only (P < 0.001). Symptom numbers recovered from 2 to 6 days and 13 days (P < 0.05). Persistently poorer AS visual-spatial accuracy was identified at 2, 6 and 13 days post-SRC (P < 0.05) in both males and females but with differing trajectories. Clinical measures demonstrated consistent improvement reminiscent of practice effects. OM saccade assessment may have improved utility in tracking recovery compared to conventional measures and between sexes., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Preclinical studies of remote degeneration have largely focused on brain changes over the first few days or weeks after stroke. Accumulating evidence suggests that neurodegeneration occurs in other brain regions remote to the site of infarction for months and even years following ischaemic stroke. Brain atrophy appears to be driven by both axonal degeneration and widespread brain inflammation. The evolution and duration of these changes are increasingly being described in human studies, using advanced brain imaging techniques. Here, we sought to investigate long-term structural brain changes in a model of mild focal ischaemic stroke following injection of endothlin-1 in adult Long-Evans rats ( n  = 14) compared with sham animals ( n  = 10), over a clinically relevant time-frame of 48 weeks. Serial structural and diffusion-weighted MRI data were used to assess dynamic volume and white matter trajectories. We observed dynamic regional brain volume changes over the 48 weeks, reflecting both normal changes with age in sham animals and neurodegeneration in regions connected to the infarct following ischaemia. Ipsilesional cortical volume loss peaked at 24 weeks but was less prominent at 36 and 48 weeks. We found significantly reduced fractional anisotropy in both ipsi- and contralesional motor cortex and cingulum bundle regions of infarcted rats ( P  < 0.05) from 4 to 36 weeks, suggesting ongoing white matter degeneration in tracts connected to but distant from the stroke. We conclude that there is evidence of significant cortical atrophy and white matter degeneration up to 48 weeks following infarct, consistent with enduring, pervasive stroke-related degeneration., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Sports-related concussion (SRC) is a form of mild traumatic brain injury that has been linked to long-term neurological abnormalities. Australian rules football is a collision sport with wide national participation and is growing in popularity worldwide. However, the chronic neurological consequences of SRC in Australian footballers remain poorly understood. This study investigated the presence of brain abnormalities in Australian footballers with a history of sports-related concussion (HoC) using multimodal MRI. Male Australian footballers with HoC (n = 26), as well as noncollision sport athletes with no HoC (n = 27), were recruited to the study. None of the footballers had sustained a concussion in the preceding 6 months, and all players were asymptomatic. Data were acquired using a 3T MRI scanner. White matter integrity was assessed using diffusion tensor imaging. Cortical thickness, subcortical volumes, and cavum septum pellucidum (CSP) were analyzed using structural MRI. Australian footballers had evidence of widespread microstructural white matter damage and cortical thinning. No significant differences were found regarding subcortical volumes or CSP. These novel findings provide evidence of persisting white and gray matter abnormalities in Australian footballers with HoC, and raise concerns related to the long-term neurological health of these athletes., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

HIF1A is a transcription factor that plays a central role for the adaptation to tissue hypoxia and for the inflammatory response of myeloid cells, including DCs. HIF1A is stabilized by hypoxia but also by TLR ligands under normoxic conditions. The underlying signaling events leading to the accumulation of HIF1A in the presence of oxygen are still poorly understood. Here, we show that in contrast to hypoxic stabilization of HIF1A, normoxic, TLR-mediated HIF1A accumulation in DCs follows a different pathway that predominantly requires MYD88-dependent NF-κB activity. The TLR-induced HIF1A controls a subset of proinflammatory genes that are insufficiently induced following hypoxia-mediated HIF1A induction. Thus, TLR activation and hypoxia stabilize HIF1A via distinct signaling pathways, resulting in differential HIF1A-dependent gene expression.