Participation and engagement in online cognitive testing.

Web-based testing of cognitive abilities allows for large-scale assessments without geographical constraints. Yet, the extent to which it can reach populations beyond the typical demographic groups recruited for cognitive studies is unclear. This study focused on comparing the characteristics of individuals from a general population study (HUNT4) who chose to participate in a cognitive study (HUNT4-Hjernetrim) with those who did not. Additionally, we investigated participants' engagement and user experience. We obtained data on socio-demographics, health conditions (both physical and mental), self-reported cognitive or learning difficulties, and lifestyle factors of Hjernetrim participants and non-participants from the HUNT4 database. Hjernetrim involved 13 cognitive tests, administered through the online platform Memoro. We used logistic regressions to assess participation biases and linear regressions to assess participants' engagement and user experience. Of 65,851 HUNT4 participants invited via regular mail to Hjernetrim, 5634 (9.4%, aged 13-97, 54% women) participated. The best represented in the sample were 50-79-year-olds, women, tertiary educated, living alone, from urban areas, not occupationally active, and reporting memory complaints. Individuals who were aged 80+, had motor or vision impairments, and teenagers with learning disabilities, were underrepresented. Participants were more likely to have mental health problems, have or survived cancer and less likely to have cardiovascular disease. Participants logged on mainly during weekdays, the preferred time of day varied by age. On average, participants used 42 min and completed 78% of the tasks. Using PCs provided the most complete data. In terms of user experiences, 65% were positive while 14% were negative or reported technical difficulties. Overall, the study demonstrated that web-based methodology allowed for a relatively well-represented sample that included groups typically difficult to reach. The presence of somatic and mental diseases had a variable influence on participation. Participants finished most tests and reported positive experiences overall.

Chronic immunosuppression across 12 months and high ability of acute and subacute CNS-injury biomarker concentrations to identify individuals with complicated mTBI on acute CT and MRI.

BACKGROUND: Identifying individuals with intracranial injuries following mild traumatic brain injury (mTBI), i.e. complicated mTBI cases, is important for follow-up and prognostication. The main aims of our study were (1) to assess the temporal evolution of blood biomarkers of CNS injury and inflammation in individuals with complicated mTBI determined on computer tomography (CT) and magnetic resonance imaging (MRI); (2) to assess the corresponding discriminability of both single- and multi-biomarker panels, from acute to chronic phases after injury. METHODS: Patients with mTBI (n = 207), defined as Glasgow Coma Scale score between 13 and 15, loss of consciousness < 30 min and post-traumatic amnesia < 24 h, were included. Complicated mTBI - i.e., presence of any traumatic intracranial injury on neuroimaging - was present in 8% (n = 16) on CT (CT+) and 12% (n = 25) on MRI (MRI+). Blood biomarkers were sampled at four timepoints following injury: admission (within 72 h), 2 weeks (± 3 days), 3 months (± 2 weeks) and 12 months (± 1 month). CNS biomarkers included were glial fibrillary acidic protein (GFAP), neurofilament light (NFL) and tau, along with 12 inflammation markers. RESULTS: The most discriminative single biomarkers of traumatic intracranial injury were GFAP at admission (CT+: AUC = 0.78; MRI+: AUC = 0.82), and NFL at 2 weeks (CT+: AUC = 0.81; MRI+: AUC = 0.89) and 3 months (MRI+: AUC = 0.86). MIP-1ß and IP-10 concentrations were significantly lower across follow-up period in individuals who were CT+ and MRI+. Eotaxin and IL-9 were significantly lower in individuals who were MRI+ only. FGF-basic concentrations increased over time in MRI- individuals and were significantly higher than MRI+ individuals at 3 and 12 months. Multi-biomarker panels improved discriminability over single biomarkers at all timepoints (AUCs > 0.85 for admission and 2-week models classifying CT+ and AUC ≈ 0.90 for admission, 2-week and 3-month models classifying MRI+). CONCLUSIONS: The CNS biomarkers GFAP and NFL were useful single diagnostic biomarkers of complicated mTBI, especially in acute and subacute phases after mTBI. Several inflammation markers were suppressed in patients with complicated versus uncomplicated mTBI and remained so even after 12 months. Multi-biomarker panels improved diagnostic accuracy at all timepoints, though at acute and 2-week timepoints, the single biomarkers GFAP and NFL, respectively, displayed similar accuracy compared to multi-biomarker panels.

Longitudinal Associations Between Persistent Post-Concussion Symptoms and Blood Biomarkers of Inflammation and CNS-Injury After Mild Traumatic Brain Injury.

The aim of our study was to investigate the biological underpinnings of persistent post-concussion symptoms (PPCS) at 3 months following mild traumatic brain injury (mTBI). Patients (n = 192, age 16-60 years) with mTBI, defined as Glasgow Coma Scale (GCS) score between 13 and 15, loss of consciousness (LOC) <30 min, and post-traumatic amnesia (PTA) <24 h were included. Blood samples were collected at admission (within 72 h), 2 weeks, and 3 months. Concentrations of blood biomarkers associated with central nervous system (CNS) damage (glial fibrillary acidic protein [GFAP], neurofilament light [NFL], and tau) and inflammation (interferon gamma [IFNγ], interleukin [IL]-8, eotaxin, macrophage inflammatory protein-1-beta [MIP]-1ß, monocyte chemoattractant protein [MCP]-1, interferon-gamma-inducible protein [IP]-10, IL-17A, IL-9, tumor necrosis factor [TNF], basic fibroblast growth factor [FGF]-basic platelet-derived growth factor [PDGF], and IL-1 receptor antagonist [IL-1ra]) were obtained. Demographic and injury-related factors investigated were age, sex, GCS score, LOC, PTA duration, traumatic intracranial finding on magnetic resonance imaging (MRI; within 72 h), and extracranial injuries. Delta values, that is, time-point differences in biomarker concentrations between 2 weeks minus admission and 3 months minus admission, were also calculated. PPCS was assessed with the British Columbia Post-Concussion Symptom Inventory (BC-PSI). In single variable analyses, longer PTA duration and a higher proportion of intracranial findings on MRI were found in the PPCS group, but no single biomarker differentiated those with PPCS from those without. In multi-variable models, female sex, longer PTA duration, MRI findings, and lower GCS scores were associated with increased risk of PPCS. Inflammation markers, but not GFAP, NFL, or tau, were associated with PPCS. At admission, higher concentrations of IL-8 and IL-9 and lower concentrations of TNF, IL-17a, and MCP-1 were associated with greater likelihood of PPCS; at 2 weeks, higher IL-8 and lower IFNγ were associated with PPCS; at 3 months, higher PDGF was associated with PPCS. Higher delta values of PDGF, IL-17A, and FGF-basic at 2 weeks compared with admission, MCP-1 at 3 months compared with admission, and TNF at 2 weeks and 3 months compared with admission were associated with greater likelihood of PPCS. Higher IL-9 delta values at both time-point comparisons were negatively associated with PPCS. Discriminability of individual CNS-injury and inflammation biomarkers for PPCS was around chance level, whereas the optimal combination of biomarkers yielded areas under the curve (AUCs) between 0.62 and 0.73. We demonstrate a role of biological factors on PPCS, including both positive and negative effects of inflammation biomarkers that differed based on sampling time-point after mTBI. PPCS was associated more with acute inflammatory processes, rather than ongoing inflammation or CNS-injury biomarkers. However, the modest discriminative ability of the models suggests other factors are more important in the development of PPCS.

Trajectories of occupational physical activity and risk of later-life mild cognitive impairment and dementia: the HUNT4 70+ study.

Background: High levels of occupational physical activity (PA) have been linked to an increased risk of dementia. We assessed the association of trajectories of occupational PA at ages 33-65 with risk of dementia and mild cognitive impairment (MCI) at ages 70+. Methods: We included 7005 participants (49.8% were women, 3488/7005) from the HUNT4 70+ Study. Group-based trajectory modelling was used to identify four trajectories of occupational PA based on national registry data from 1960 to 2014: stable low (30.9%, 2162/7005), increasing then decreasing (8.9%, 625/7005), stable intermediate (25.1%, 1755/7005), and stable high (35.2%, 2463/7005). Dementia and MCI were clinically assessed in 2017-2019. We performed adjusted multinomial regression to estimate relative risk ratios (RRR) with 95% confidence intervals (CI) for dementia and MCI. Findings: 902 participants were diagnosed with dementia and 2407 were diagnosed with MCI. Absolute unadjusted risks for dementia and MCI were 8.8% (95% CI: 7.6-10.0) and 27.4% (25.5-29.3), respectively, for those with a stable low PA trajectory, 8.2% (6.0-10.4) and 33.3% (29.6-37.0) for those with increasing, then decreasing PA; while they were 16.0% (14.3-17.7) and 35% (32.8-37.2) for those with stable intermediate, and 15.4% (14.0-16.8) and 40.2% (38.3-42.1) for those with stable high PA trajectories. In the adjusted model, participants with a stable high trajectory had a higher risk of dementia (RRR 1.34, 1.04-1.73) and MCI (1.80, 1.54-2.11), whereas participants with a stable intermediate trajectory had a higher risk of MCI (1.36, 1.15-1.61) compared to the stable low trajectory. While not statistically significant, participants with increasing then decreasing occupational PA had a 24% lower risk of dementia and 18% higher risk of MCI than the stable low PA group. Interpretation: Consistently working in an occupation with intermediate or high occupational PA was linked to an increased risk of cognitive impairment, indicating the importance of developing strategies for individuals in physically demanding occupations to prevent cognitive impairment. Funding: This work was supported by the National Institutes of Health (R01AG069109-01) and the Research Council of Norway (296297, 262700, 288083).

Retirement age and disability status as pathways to later-life cognitive impairment: Evidence from the Norwegian HUNT Study linked with Norwegian population registers.

BACKGROUND: Research shows that retirement age is associated with later-life cognition but has not sufficiently distinguished between retirement pathways. We examined how retirement age was associated with later-life dementia and mild cognitive impairment (MCI) for people who retired via the disability pathway (received a disability pension prior to old-age pension eligibility) and those who retired via the standard pathway. METHODS: The study sample comprised 7210 participants from the Norwegian Trøndelag Health Study (HUNT4 70+, 2017-2019) who had worked for at least one year in 1967-2019, worked until age 55+, and retired before HUNT4. Dementia and MCI were clinically assessed in HUNT4 70+ when participants were aged 69-85 years. Historical data on participants' retirement age and pathway were retrieved from population registers. We used multinomial regression to assess the dementia/MCI risk for women and men retiring via the disability pathway, or early (<67 years), on-time (age 67, old-age pension eligibility) or late (age 68+) via the standard pathway. RESULTS: In our study sample, 9.5% had dementia, 35.3% had MCI, and 28.1% retired via the disability pathway. The disability retirement group had an elevated risk of dementia compared to the on-time standard retirement group (relative risk ratio [RRR]: 1.64, 95% CI 1.14-2.37 for women, 1.70, 95% CI 1.17-2.48 for men). MCI risk was lower among men who retired late versus on-time (RRR, 0.76, 95% CI 0.61-0.95). CONCLUSION: Disability retirees should be monitored more closely, and preventive policies should be considered to minimize the dementia risk observed among this group of retirees.

Poorer sleep health is associated with altered brain activation during cognitive control processing in healthy adults.

This study investigated how proactive and reactive cognitive control processing in the brain was associated with habitual sleep health. BOLD fMRI data were acquired from 81 healthy adults with normal sleep (41 females, age 20.96-39.58 years) during a test of cognitive control (Not-X-CPT). Sleep health was assessed in the week before MRI scanning, using both objective (actigraphy) and self-report measures. Multiple measures indicating poorer sleep health-including later/more variable sleep timing, later chronotype preference, more insomnia symptoms, and lower sleep efficiency-were associated with stronger and more widespread BOLD activations in fronto-parietal and subcortical brain regions during cognitive control processing (adjusted for age, sex, education, and fMRI task performance). Most associations were found for reactive cognitive control activation, indicating that poorer sleep health is linked to a "hyper-reactive" brain state. Analysis of time-on-task effects showed that, with longer time on task, poorer sleep health was predominantly associated with increased proactive cognitive control activation, indicating recruitment of additional neural resources over time. Finally, shorter objective sleep duration was associated with lower BOLD activation with time on task and poorer task performance. In conclusion, even in "normal sleepers," relatively poorer sleep health is associated with altered cognitive control processing, possibly reflecting compensatory mechanisms and/or inefficient neural processing.

Hippocampal neurochemicals are associated with exercise group and intensity, psychological health, and general cognition in older adults.

Based on the premise that physical activity/exercise impacts hippocampal structure and function, we investigated if hippocampal metabolites for neuronal viability and cell membrane density (i.e., N-acetyl aspartate (NAA), choline (Cho), creatine (Cr)) were higher in older adults performing supervised exercise compared to following national physical activity guidelines. Sixty-three participants (75.3 ± 1.9 years after 3 years of intervention) recruited from the Generation 100 study (NCT01666340_date:08.16.2012) were randomized into a supervised exercise group (SEG) performing twice weekly moderate- to high-intensity training, and a control group (CG) following national physical activity guidelines of ≥ 30-min moderate physical activity ≥ 5 days/week. Hippocampal body and head volumes and NAA, Cho, and Cr levels were acquired at 3T with magnetic resonance imaging and spectroscopic imaging. Sociodemographic data, peak oxygen uptake (VO2peak), exercise characteristics, psychological health, and cognition were recorded. General linear models were used to assess group differences and associations corrected for age, sex, education, and hippocampal volume. Both groups adhered to their training, where SEG trained at higher intensity. SEG had significantly lower NAA/Cr in hippocampal body than CG (p = 0.04). Across participants, higher training intensity was associated with lower Cho/Cr in hippocampal body (p < 0.001). Change in VO2peak, increasing VO2peak from baseline to 3 years, or VO2peak at 3 years were not associated with hippocampal neurochemicals. Lower NAA/Cr in hippocampal body was associated with poorer psychological health and slightly higher cognitive scores. Thus, following the national physical activity guidelines and not training at the highest intensity level were associated with the best neurochemical profile in the hippocampus at 3 years.

Effects of a 5-Year Exercise Intervention on White Matter Microstructural Organization in Older Adults. A Generation 100 Substudy.

Aerobic fitness and exercise could preserve white matter (WM) integrity in older adults. This study investigated the effect on WM microstructural organization of 5 years of exercise intervention with either supervised moderate-intensity continuous training (MICT), high-intensity interval training (HIIT), or following the national physical activity guidelines. A total of 105 participants (70-77 years at baseline), participating in the randomized controlled trial Generation 100 Study, volunteered to take part in this longitudinal 3T magnetic resonance imaging (MRI) study. The HIIT group (n = 33) exercised for four intervals of 4 min at 90% of peak heart rate two times a week, the MICT group (n = 24) exercised continuously for 50 min at 70% peak heart rate two times a week, and the control group (n = 48) followed the national guidelines of ≥30 min of physical activity almost every day. At baseline and at 1-, 3-, and 5-year follow-ups, diffusion tensor imaging (DTI) scans were performed, cardiorespiratory fitness (CRF) was measured as peak oxygen uptake (VO2peak) with ergospirometry, and information on exercise habits was collected. There was no group*time or group effect on any of the DTI indices at any time point during the intervention. Across all groups, CRF was positively associated with fractional anisotropy (FA) and axial diffusivity (AxD) at the follow-ups, and the effect became smaller with time. Exercise intensity was associated with mean diffusivity (MD)/FA, with the greatest effect at 1-year and no effect at 5-year follow-up. There was an association between exercise duration and FA and radial diffusivity (RD) only after 1 year. Despite the lack of group*time interaction or group effect, both higher CRF and exercise intensity was associated with better WM microstructural organization throughout the intervention, but the effect became attenuated over time. Different aspects of exercising affected the WM metrics and WM tracts differently with the greatest and most overlapping effects in the corpus callosum. The current study indicates not only that high CRF and exercise intensity are associated with WM microstructural organization in aging but also that exercise's positive effects on WM may decline with increasing age.

Longitudinal study of the effect of a 5-year exercise intervention on structural brain complexity in older adults. A Generation 100 substudy.

Physical inactivity has been identified as an important risk factor for dementia. High levels of cardiorespiratory fitness (CRF) have been shown to reduce the risk of dementia. However, the mechanism by which exercise affects brain health is still debated. Fractal dimension (FD) is an index that quantifies the structural complexity of the brain. The purpose of this study was to investigate the effects of a 5-year exercise intervention on the structural complexity of the brain, measured through the FD, in a subset of 105 healthy older adults participating in the randomized controlled trial Generation 100 Study. The subjects were randomized into control, moderate intensity continuous training, and high intensity interval training groups. Both brain MRI and CRF were acquired at baseline and at 1-, 3- and 5-years follow-ups. Cortical thickness and volume data were extracted with FreeSurfer, and FD of the cortical lobes, cerebral and cerebellar gray and white matter were computed. CRF was measured as peak oxygen uptake (VO2peak) using ergospirometry during graded maximal exercise testing. Linear mixed models were used to investigate exercise group differences and possible CRF effects on the brain's structural complexity. Associations between change over time in CRF and FD were performed if there was a significant association between CRF and FD. There were no effects of group membership on the structural complexity. However, we found a positive association between CRF and the cerebral gray matter FD (p < 0.001) and the temporal lobe gray matter FD (p < 0.001). This effect was not present for cortical thickness, suggesting that FD is a more sensitive index of structural changes. The change over time in CRF was associated with the change in temporal lobe gray matter FD from baseline to 5-year follow-up (p < 0.05). No association of the change was found between CRF and cerebral gray matter FD. These results demonstrated that entering old age with high and preserved CRF levels protected against loss of structural complexity in areas sensitive to aging and age-related pathology.

Effects of 5 Years Aerobic Exercise on Cognition in Older Adults: The Generation 100 Study: A Randomized Controlled Trial.

OBJECTIVE: The objective of this study was to investigate whether a 5-year exercise intervention and change in peak oxygen uptake ([Formula: see text]) is associated with cognitive function in older adults. METHODS: Nine hundred and forty-five participants (48% women, mean age at study end 78.2 ± 2.02 years) from the Generation 100 Study were randomized 2:1:1 to a control group, moderate-intensity continuous training or high-intensity interval training twice weekly for 5 years. Peak oxygen uptake was measured using ergospirometry at baseline and after 5 years. Global cognition and mild cognitive impairment (MCI) were assessed with the Montreal Cognitive Assessment scale (MoCA) after 5 years. RESULTS: Compared to the control group, the combined moderate-intensity continuous training plus high-intensity interval training (ExComb) group did not have significantly different cognitive scores (beta value 0.26, 95% confidence interval [CI] - 0.17, 0.69) or odds of MCI (odds ratio 0.86, 95% CI 0.66, 1.13). Men in the ExComb group had 0.80 points higher MoCA (95% CI 0.21, 1.40) and 32% lower odds of MCI compared with male controls (95% CI 0.47, 0.99), with no such findings in women. In the total sample, each 1 metabolic equivalent of task increase in [Formula: see text] corresponded to 0.46 points higher MoCA (95% CI 0.25, 0.67) and 27% lower odds of MCI (95% CI 0.63, 0.85). Compared to [Formula: see text] stable, participants whose [Formula: see text] increased did not have significantly different cognitive scores (beta value 0.24, CI - 0.68, 1.15) or odds of MCI (odds ratio 0.70, 95% CI 0.36, 1.34), whereas participants whose [Formula: see text] decreased had 0.64 points lower MoCA (95% CI - 1.15, - 0.14) and 35% higher odds of MCI (95% CI 0.98, 1.87). CONCLUSIONS: Overall, exercise was not significantly associated with cognition among older adults. However, maintaining or increasing [Formula: see text] appeared to benefit cognition. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01666340.

One-Year Prospective Study of Plasma Biomarkers From CNS in Patients With Mild Traumatic Brain Injury.

Objective: To investigate the longitudinal evolution of three blood biomarkers: neurofilament light (NFL), glial fibrillary acidic protein (GFAP) and tau, in out-patients and hospitalized patients with mild traumatic brain injury (mTBI) compared to controls, along with their associations-in patients-with clinical injury characteristics and demographic variables, and ability to discriminate patients with mTBI from controls. Methods: A longitudinal observation study including 207 patients with mTBI, 84 age and sex-matched community controls (CCs) and 52 trauma controls (TCs). Blood samples were collected at 5 timepoints: acute (<24 h), 72 h (24-72 h post-injury), 2 weeks, 3 and 12 months. Injury-related, clinical and demographic variables were obtained at inclusion and brain MRI within 72 h. Results: Plasma GFAP and tau were most elevated acutely and NFL at 2 weeks and 3 months. The group of patients with mTBI and concurrent other somatic injuries (mTBI+) had the highest elevation in all biomarkers across time points, and were more likely to be victims of traffic accidents and violence. All biomarkers were positively associated with traumatic intracranial findings on MRI obtained within 72 h. Glial fibrillary acidic protein and NFL levels were associated with Glasgow Coma Scale (GCS) score and presence of other somatic injuries. Acute GFAP concentrations showed the highest discriminability between patients and controls with an Area Under the Curve (AUC) of 0.92. Acute tau and 2-week NFL concentrations showed moderate discriminability (AUC = 0.70 and AUC = 0.75, respectively). Tau showed high discriminability between mTBI+ and TCs (AUC = 0.80). Conclusions: The association of plasma NFL with traumatic intracranial MRI findings, together with its later peak, could reflect ongoing secondary injury or repair mechanisms, allowing for a protracted diagnostic time window. Patients experiencing both mTBI and other injuries appear to be a subgroup with greater neural injury, differing from both the mTBI without other injuries and from both control groups. Acute GFAP concentrations showed the highest discriminability between patients and controls, were highly associated with intracranial traumatic injury, and showed the largest elevations compared to controls at the acute timepoint, suggesting it to be the most clinically useful plasma biomarker of primary CNS injury in mTBI.

Normative data for pituitary size and volume in the general population between 50 and 66 years.

PURPOSE: The main aim of this study was to provide normative data for pituitary height and volume in persons between 50 and 66 years in the general population. The secondary aim was to establish a convenient surrogate marker of pituitary size for use in routine radiological practice. METHODS: From a geographically defined prospective healthy study, 1006 participants between 50 and 66 years had a brain MRI, of which 988 (519 women) were included in this study. We measured the mid-sagittal height, max-sagittal height and total volume of the anterior pituitary lobe based on T1-weighted 3D MRI images. RESULTS: Both the mean mid-sagittal and max-sagittal pituitary height were significantly larger in women compared to men, with 4.9 ± 1.7 mm versus 4.4 ± 1.4 mm (p < .001) for the mean mid-sagittal height and 6.8 ± 1.2 mm versus 6.1 ± 1.1 mm (p < 0.001) for the mean max-sagittal height. The mean anterior pituitary lobe volume was also significantly larger in women than in men (494 ± 138 mm3 vs. 405 ± 118 mm3) (p < 0.001). There were no significant differences in these pituitary sagittal heights nor volume in either sex between the age groups 50-54, 55-59 and 60-66 years. The 95th percentile for mid-sagittal height, max-sagittal height and pituitary volume was 7.7 mm, 8.6 mm and 851 mm3 for women and 6.6 mm, 7.8 mm and 610 mm3 for men. CONCLUSION: This study show that women have a larger pituitary gland than men in the age group between 50 and 66 years and provides normative data for pituitary size estimates which can be used for clinical diagnostic purposes as well as future research.

Examining the Subacute Effects of Mild Traumatic Brain Injury Using a Traditional and Computerized Neuropsychological Test Battery.

This study investigates subacute cognitive effects of mild traumatic brain injury (MTBI) in the Trondheim Mild TBI Study, as measured, in part, by the neuropsychological test battery of the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) program, including computerized tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) and traditional paper-and-pencil tests. We investigated whether cognitive function was associated with injury severity: intracranial traumatic lesions on neuroimaging, witnessed loss of consciousness (LOC), or post-traumatic amnesia (PTA) >1 h. Further, we explored which of the tests in the CENTER-TBI battery might be associated with the largest subacute effects of MTBI (i.e., at 2 weeks post-injury). We recruited 177 patients with MTBI (16-59 years of age) from a regional trauma center and an outpatient clinic,79 trauma control participants, and 81 community control participants. The MTBI group differed from community controls only on one traditional test of processing speed (coding; p = 0.009, Cliff's delta [Δ] = 0.20). Patients with intracranial abnormalities performed worse than those without on a traditional test (phonemic verbal fluency; p = 0.043, Δ = 0.27), and patients with LOC performed differently on the Attention Switching Task from the CANTAB (p = 0.020, Δ = -0.20). Patients with PTA >1 h performed worse than those with <1 h on 10 measures, from traditional tests and the CANTAB (Δ = 0.33-0.20), likely attributable, at least in part, to pre-existing differences in intellectual functioning between groups. In general, those with MTBI had good neuropsychological outcome 2 weeks after injury and no particular CENTER-TBI computerized or traditional tests seemed to be more sensitive to subtle cognitive deficits.

Traumatic axonal injury on clinical MRI: association with the Glasgow Coma Scale score at scene of injury or at admission and prolonged posttraumatic amnesia.

OBJECTIVE: The aim in this study was to investigate if MRI findings of traumatic axonal injury (TAI) after traumatic brain injury (TBI) are related to the admission Glasgow Coma Scale (GCS) score and prolonged duration of posttraumatic amnesia (PTA). METHODS: A total of 490 patients with mild to severe TBI underwent brain MRI within 6 weeks of injury (mild TBI: median 2 days; moderate to severe TBI: median 8 days). The location of TAI lesions and measures of total TAI lesion burden (number and volume of lesions on FLAIR and diffusion-weighted imaging and number of lesions on T2*-weighted gradient echo or susceptibility-weighted imaging) were quantified in a blinded manner for clinical information. The volume of contusions on FLAIR was likewise recorded. Associations between GCS score and the location and burden of TAI lesions were examined with multiple linear regression, adjusted for age, Marshall CT score (which includes compression of basal cisterns, midline shift, and mass lesions), and alcohol intoxication. The predictive value of TAI lesion location and burden for duration of PTA > 28 days was analyzed with multiple logistic regression, adjusted for age and Marshall CT score. Complete-case analyses of patients with TAI were used for the regression analyses of GCS scores (n = 268) and PTA (n = 252). RESULTS: TAI lesions were observed in 58% of patients: in 7% of mild, 69% of moderate, and 93% of severe TBI cases. The TAI lesion location associated with the lowest GCS scores were bilateral lesions in the brainstem (mean difference in GCS score -2.5), followed by lesions bilaterally in the thalamus, unilaterally in the brainstem, and lesions in the splenium. The volume of TAI on FLAIR was the measure of total lesion burden most strongly associated with the GCS score. Bilateral TAI lesions in the thalamus had the largest predictive value for PTA > 28 days (OR 16.2, 95% CI 3.9-87.4). Of the measures of total TAI lesion burden, the FLAIR volume of TAI predicted PTA > 28 days the best. CONCLUSIONS: Bilateral TAI lesions in the brainstem and thalamus, as well as the total volume of TAI lesions on FLAIR, had the strongest association with the GCS score and prolonged PTA. The current study proposes a first step toward a modified classification of TAI, with grades ranked according to their relation to these two measures of clinical TBI severity.

The Prevalence and Stability of Sleep-Wake Disturbance and Fatigue throughout the First Year after Mild Traumatic Brain Injury.

In this prospective, longitudinal study, we aimed to determine the prevalence and stability of sleep-wake disturbance (SWD) and fatigue in a large representative sample of patients (Trondheim mild traumatic brain injury [mTBI] follow-up study). We included 378 patients with mTBI (age 16-60), 82 matched trauma controls with orthopedic injuries, and 83 matched community controls. Increased sleep need, poor sleep quality, excessive daytime sleepiness, and fatigue were assessed at 2 weeks, 3 months, and 12 months after injury. Mixed logistic regression models were used to evaluate clinically relevant group differences longitudinally. Prevalence of increased sleep need, poor sleep quality, and fatigue was significantly higher in patients with mTBI than in both trauma controls and community controls at all time points. More patients with mTBI reported problems with excessive daytime sleepiness compared to trauma controls, but not community controls, at all time points. Patients with complicated mTBI (intracranial findings on computed tomography or magnetic resonance imaging) had more fatigue problems compared to those with uncomplicated mTBI, at all three time points. In patients with mTBI who experienced SWDs and fatigue 2 weeks after injury, around half still had problems at 3 months and approximately one third at 12 months. Interestingly, we observed limited overlap between the different symptom measures; a large number of patients reported one specific problem with SWD or fatigue rather than several problems. In conclusion, our results provide strong evidence that mTBI contributes significantly to the development and maintenance of SWDs and fatigue.

Therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy in India (THIN study): a randomised controlled trial.

OBJECTIVE: To evaluate the neuroprotective effect of therapeutic hypothermia (TH) induced by phase changing material (PCM) on MRI biomarkers in infants with hypoxic-ischaemic encephalopathy (HIE) in a low-resource setting. DESIGN: Open-label randomised controlled trial. SETTING: One neonatal intensive care unit in a tertiary care centre in India. PATIENTS: 50 term/near-term infants admitted within 5 hours after birth with predefined physiological criteria and signs of moderate/severe HIE. INTERVENTIONS: Standard care (n=25) or standard care plus 72 hours of hypothermia (33.5°C±0.5°C, n=25) induced by PCM. MAIN OUTCOME MEASURES: Primary outcome was fractional anisotropy (FA) in the posterior limb of the internal capsule (PLIC) on neonatal diffusion tensor imaging analysed according to intention to treat. RESULTS: Primary outcome was available for 22 infants (44%, 11 in each group). Diffusion tensor imaging showed significantly higher FA in the cooled than the non-cooled infants in left PLIC and several white matter tracts. After adjusting for sex, birth weight and gestational age, the mean difference in PLIC FA between groups was 0.026 (95% CI 0.004 to 0.048, p=0.023). Conventional MRI was available for 46 infants and demonstrated significantly less moderate/severe abnormalities in the cooled (n=2, 9%) than in the non-cooled (n=10, 43%) infants. There was no difference in adverse events between groups. CONCLUSIONS: This study confirmed that TH induced by PCM reduced brain injury detected on MRI in infants with moderate HIE in a neonatal intensive care unit in India. Future research should focus on optimal supportive treatment during hypothermia rather than looking at efficacy of TH in low-resource settings. TRIAL REGISTRATION NUMBER: CTRI/2013/05/003693.

Association of cause of injury and traumatic axonal injury: a clinical MRI study of moderate and severe traumatic brain injury.

OBJECTIVE: The authors investigated the association between the cause of injury and the occurrence and grade of traumatic axonal injury (TAI) on clinical MRI in patients with moderate or severe traumatic brain injury (TBI). METHODS: Data for a total of 396 consecutive patients, aged 7-70 years, with moderate or severe TBI admitted to a level 1 trauma center were prospectively registered. Data were included for analysis from the 219 patients who had MRI performed within 35 days (median 8, IQR 4-17 days) and for whom cause of injury was known. Cause of injury was registered as road traffic accident (RTA) or fall (both with respective subcategories), alpine skiing or snowboarding accident, or violence. The MRI protocol consisted of T2*-weighted gradient echo, FLAIR, and diffusion-weighted imaging scans. TAI lesions were evaluated in a blinded manner and categorized into 3 grades, hemispheric/cerebellar white matter (grade 1), corpus callosum (grade 2), and brainstem (grade 3). The absence of TAI was analyzed as grade 0. Contusions and mass lesions on CT were also registered. RESULTS: Cause of injury did not differ between included and nonincluded patients. TAI was found in 83% of patients in the included group after RTAs and 62% after falls (p < 0.001). Observed TAI grades differed between the subcategories of both RTAs (p = 0.004) and falls (p = 0.006). Pedestrians in RTAs, car drivers/passengers in RTAs, and alpine skiers had the highest prevalence of TAI (89%-100%) and the highest TAI grades (70%-82% TAI grades 2-3). TAI was found in 76% of patients after falls from > own height (45% TAI grade 2-3), 63% after falls down the stairs (26% TAI grade 2-3), and 31% after falls from ≤ own height (12% TAI grade 2-3). Moreover, 53% of patients with TAI after RTAs and 68% with TAI after falls had cortical contusions or mass lesions on CT. CONCLUSIONS: This prospective study of moderate and severe TBI is to the authors' knowledge the first clinical MRI study to demonstrate both the high prevalence and grade of TAI after most of the different types of RTAs, alpine skiing accidents, and falls from a height. Importantly, TAI was also common following more low-energy trauma such as falls down the stairs or from own height. Physicians managing TBI patients in the acute phase should be aware of the possibility of TAI no matter the cause of injury and also when the CT scan shows cortical contusions or mass lesions.

Incidence of Mild Traumatic Brain Injury: A Prospective Hospital, Emergency Room and General Practitioner-Based Study.

Background: There are no recent estimates of incidence rates of mild traumatic brain injury (MTBI) from Norway. Moreover, reported incidence rates rarely comprise cases of MTBI evaluated in the primary care setting. In this study, we utilized existing data collected as part of the recruitment to a large, follow-up study of patients with MTBI. We estimated the incidence rate of MTBI, including patients who visited outpatient clinics, in the age group 16-59 years in a Norwegian region. Methods: During 81 weeks in 2014 and 2015, all persons aged 16-59 years, presenting with possible MTBI to the emergency department (ED) at St. Olavs Hospital, Trondheim University Hospital or to the general practitioner (GP)-run Trondheim municipal outpatient ED, were evaluated for a diagnosis of MTBI. Patients were identified by computerized tomography (CT) referrals and patient lists. Patients referred to acute CT from their primary GP with suspicion of MTBI were also recorded. This approach identified 732 patients with MTBI. Age- and sex-specific incidence rates of MTBI were calculated using population figures from the regional catchment area. Results: Overall incidence of MTBI in people between 16 and 59 years was 302 per 100,000 person-years (95% confidence interval 281-324). The incidence rate was highest in the age group 16-20 years, where rates were 835 per 100,000 person-years in males and 726 in females. Conclusion: The overall incidence rate of MTBI was lower than expected from existing estimates. Like other reports, the incidence was highest in the late teens.

Patients with Mild Traumatic Brain Injury Recruited from Both Hospital and Primary Care Settings: A Controlled Longitudinal Magnetic Resonance Imaging Study.

With an emphasis on traumatic axonal injury (TAI), frequency and evolution of traumatic intracranial lesions on 3T clinical magnetic resonance imaging (MRI) were assessed in a combined hospital and community-based study of patients with mild traumatic brain injury (mTBI). The findings were related to post-concussion symptoms (PCS) at 3 and 12 months. Prospectively, 194 patients (16-60 years of age) were recruited from the emergency departments at a level 1 trauma center and a municipal outpatient clinic into the Trondheim mTBI follow-up study. MRI was acquired within 72 h (n = 194) and at 3 (n = 165) and 12 months (n = 152) in patients and community controls (n = 78). The protocol included T2, diffusion weighted imaging, fluid attenuated inversion recovery (FLAIR), and susceptibility weighted imaging (SWI). PCS was assessed with British Columbia Post Concussion Symptom Inventory in patients and controls. Traumatic lesions were present in 12% on very early MRI, and in 5% when computed tomography (CT) was negative. TAI was found in 6% and persisted for 12 months on SWI, whereas TAI lesions on FLAIR disappeared or became less conspicuous on follow-up. PCS occurred in 33% of patients with lesions on MRI and in 19% in patients without lesions at 3 months (p = 0.12) and in 21% with lesions and 14% without lesions at 12 months (p = 0.49). Very early MRI depicted cases of TAI in patients with mTBI with microbleeds persisting for 12 months. Patients with traumatic lesions may have a more protracted recovery, but the study was underpowered to detect significant differences for PCS because of the low frequency of trauma-related MRI lesions.