Head trauma in sports - clinical characteristics, epidemiology and biomarkers.

Traumatic brain injury (TBI) is clinically divided into a spectrum of severities, with mild TBI being the least severe form and a frequent occurrence in contact sports, such as ice hockey, American football, rugby, horse riding and boxing. Mild TBI is caused by blunt nonpenetrating head trauma that causes movement of the brain and stretching and tearing of axons, with diffuse axonal injury being a central pathogenic mechanism. Mild TBI is in principle synonymous with concussion; both have similar criteria in which the most important elements are acute alteration or loss of consciousness and/or post-traumatic amnesia following head trauma and no apparent brain changes on standard neuroimaging. Symptoms in mild TBI are highly variable and there are no validated imaging or fluid biomarkers to determine whether or not a patient with a normal computerized tomography scan of the brain has neuronal damage. Mild TBI typically resolves within a few weeks but 10-15% of concussion patients develop postconcussive syndrome. Repetitive mild TBI, which is frequent in contact sports, is a risk factor for a complicated recovery process. This overview paper discusses the relationships between repetitive head impacts in contact sports, mild TBI and chronic neurological symptoms. What are these conditions, how common are they, how are they linked and can they be objectified using imaging or fluid-based biomarkers? It gives an update on the current state of research on these questions with a specific focus on clinical characteristics, epidemiology and biomarkers.

Longitudinal relationships among depressive symptoms, cortisol, and brain atrophy in the neocortex and the hippocampus.

OBJECTIVE: Depression is associated with accelerated aging and age-related diseases. However, mechanisms underlying this relationship remain unclear. The aim of this study was to longitudinally assess the link between depressive symptoms, brain atrophy, and cortisol levels. METHOD: Participants from the Betula prospective cohort study (mean age = 59 years, SD = 13.4 years) underwent clinical, neuropsychological and brain 3T MRI assessments at baseline and a 4-year follow-up. Cortisol levels were measured at baseline in four saliva samples. Cortical and hippocampal atrophy rates were estimated and compared between participants with and without depressive symptoms (n = 81) and correlated with cortisol levels (n = 49). RESULTS: Atrophy in the left superior frontal gyrus and right lingual gyrus developed in parallel with depressive symptoms, and in the left temporal pole, superior temporal cortex, and supramarginal cortex after the onset of depressive symptom. Depression-related atrophy was significantly associated with elevated cortisol levels. Elevated cortisol levels were also associated with widespread prefrontal, parietal, lateral, and medial temporal atrophy. CONCLUSION: Depressive symptoms and elevated cortisol levels are associated with atrophy of the prefrontal and limbic areas of the brain.

Healthy minds from 0-100 years: Optimising the use of European brain imaging cohorts ("Lifebrain").

The main objective of "Lifebrain" is to identify the determinants of brain, cognitive and mental (BCM) health at different stages of life. By integrating, harmonising and enriching major European neuroimaging studies across the life span, we will merge fine-grained BCM health measures of more than 5,000 individuals. Longitudinal brain imaging, genetic and health data are available for a major part, as well as cognitive and mental health measures for the broader cohorts, exceeding 27,000 examinations in total. By linking these data to other databases and biobanks, including birth registries, national and regional archives, and by enriching them with a new online data collection and novel measures, we will address the risk factors and protective factors of BCM health. We will identify pathways through which risk and protective factors work and their moderators. Exploiting existing European infrastructures and initiatives, we hope to make major conceptual, methodological and analytical contributions towards large integrative cohorts and their efficient exploitation. We will thus provide novel information on BCM health maintenance, as well as the onset and course of BCM disorders. This will lay a foundation for earlier diagnosis of brain disorders, aberrant development and decline of BCM health, and translate into future preventive and therapeutic strategies. Aiming to improve clinical practice and public health we will work with stakeholders and health authorities, and thus provide the evidence base for prevention and intervention.

Effects of a self-guided, web-based activity programme for patients with persistent musculoskeletal pain in primary healthcare: A randomized controlled trial.

BACKGROUND: Web-based interventions for pain management are increasingly used with possible benefits, but never used in addition to multimodal rehabilitation (MMR). MMR is recommended treatment for persistent pain in Sweden. The aim was to evaluate the effects of a self-guided, web-based programme added to MMR for work ability, pain, disability and health-related quality of life. METHODS: We included 99 participants with persistent musculoskeletal pain in a randomized study with two intervention arms: (1) MMR and web-based intervention, and (2) MMR. Data was collected at baseline, 4 and 12 months. Outcome measures were work ability, working percentage, average pain intensity, pain-related disability, and health-related quality of life. RESULTS: There were no significant effects of adding the web-based intervention to MMR regarding any of the outcome variables. CONCLUSIONS: This trial provides no support for adding a self-guided, web-based activity programme to MMR for patients with persistent musculoskeletal pain. SIGNIFICANCE: The comprehensive self-guided, web-based programme for activity, Web-BCPA, added to multimodal treatment in primary health care had no effect on work ability, pain, disability or health-related quality of life. Future web-based interventions should be tailored to patients' individual needs and expectations.

Short telomere length is associated with impaired cognitive performance in European ancestry cohorts.

The association between telomere length (TL) dynamics on cognitive performance over the life-course is not well understood. This study meta-analyses observational and causal associations between TL and six cognitive traits, with stratifications on APOE genotype, in a Mendelian Randomization (MR) framework. Twelve European cohorts (N=17 052; mean age=59.2±8.8 years) provided results for associations between qPCR-measured TL (T/S-ratio scale) and general cognitive function, mini-mental state exam (MMSE), processing speed by digit symbol substitution test (DSST), visuospatial functioning, memory and executive functioning (STROOP). In addition, a genetic risk score (GRS) for TL including seven known genetic variants for TL was calculated, and used in associations with cognitive traits as outcomes in all cohorts. Observational analyses showed that longer telomeres were associated with better scores on DSST (ß=0.051 per s.d.-increase of TL; 95% confidence interval (CI): 0.024, 0.077; P=0.0002), and MMSE (ß=0.025; 95% CI: 0.002, 0.047; P=0.03), and faster STROOP (ß=-0.053; 95% CI: -0.087, -0.018; P=0.003). Effects for DSST were stronger in APOE ɛ4 non-carriers (ß=0.081; 95% CI: 0.045, 0.117; P=1.0 × 10-5), whereas carriers performed better in STROOP (ß=-0.074; 95% CI: -0.140, -0.009; P=0.03). Causal associations were found for STROOP only (ß=-0.598 per s.d.-increase of TL; 95% CI: -1.125, -0.072; P=0.026), with a larger effect in ɛ4-carriers (ß=-0.699; 95% CI: -1.330, -0.069; P=0.03). Two-sample replication analyses using CHARGE summary statistics showed causal effects between TL and general cognitive function and DSST, but not with STROOP. In conclusion, we suggest causal effects from longer TL on better cognitive performance, where APOE ɛ4-carriers might be at differential risk.

Functional brain imaging of episodic memory decline in ageing.

The episodic long-term memory system supports remembering of events. It is considered to be the most age-sensitive system, with an average onset of decline around 60 years of age. However, there is marked interindividual variability, such that some individuals show faster than average change and others show no or very little change. This variability may be related to the risk of developing dementia, with elevated risk for individuals with accelerated episodic memory decline. Brain imaging with functional magnetic resonance imaging (MRI) of blood oxygen level-dependent (BOLD) signalling or positron emission tomography (PET) has been used to reveal the brain bases of declining episodic memory in ageing. Several studies have demonstrated a link between age-related episodic memory decline and the hippocampus during active mnemonic processing, which is further supported by studies of hippocampal functional connectivity in the resting state. The hippocampus interacts with anterior and posterior neocortical regions to support episodic memory, and alterations in hippocampus-neocortex connectivity have been shown to contribute to impaired episodic memory. Multimodal MRI studies and more recently hybrid MRI/PET studies allow consideration of various factors that can influence the association between the hippocampal BOLD signal and memory performance. These include neurovascular factors, grey and white matter structural alterations, dopaminergic neurotransmission, amyloid-Β and glucose metabolism. Knowledge about the brain bases of episodic memory decline can guide interventions to strengthen memory in older adults, particularly in those with an elevated risk of developing dementia, with promising results for combinations of cognitive and physical stimulation.

Fractional anisotropy in the substantia nigra in Parkinson's disease: a complex picture.

BACKGROUND AND PURPOSE: This study employs magnetic resonance imaging (MRI) diffusion tensor imaging to compare diffusion measures in the brains of patients with Parkinson's disease (PD) with healthy controls using longitudinal data. METHODS: One-hundred and twenty-two patients and 34 controls were included at baseline. The MRI investigations were repeated after 1, 3 and 5 years. The diffusion measures were quantified using fractional anisotropy and mean, radial and axial diffusion (FA, MD, RD, AD). Regions of interest included the anterior, middle and posterior substantia nigra (SN), but also other areas. Linear models were used to test for the effect of disease and hemispheric lateralization. The P value was set at 0.05 (Bonferroni corrected). RESULTS: Fractional anisotropy and AD were increased in the three nigral subareas in PD (P < 0.01), but MD and RD were unaltered. The right SN had higher FA than the left in all subareas (P < 0.01). MD and AD were increased in the right anterior part (P < 0.04), whereas MD and RD were decreased in the right middle and posterior parts (P < 0.001). The left middle cerebellar peduncle had increased FA and AD (P < 0.001) and decreased MD and RD (P < 0.01) compared to the right. Diffusion measures did not progress over time and side differences were not related to disease or lateralization of symptoms. CONCLUSIONS: Increased FA in the SN in PD indicates gliosis and inflammation in the nuclei, but possibly also intrusion of surrounding fibres into the shrinking structure. The hemispheric side differences of diffusion might reflect natural lateralization of connectivity, but their relation to PD must be studied further.

Fast size-determination of intact bacterial plasmids using nanofluidic channels.

We demonstrate how nanofluidic channels can be used as a tool to rapidly determine the number and sizes of plasmids in bacterial isolates. Each step can be automated at low cost, opening up opportunities for general use in microbiology labs.

Extension of nanoconfined DNA: Quantitative comparison between experiment and theory.

The extension of DNA confined to nanochannels has been studied intensively and in detail. However, quantitative comparisons between experiments and model calculations are difficult because most theoretical predictions involve undetermined prefactors, and because the model parameters (contour length, Kuhn length, effective width) are difficult to compute reliably, leading to substantial uncertainties. Here we use a recent asymptotically exact theory for the DNA extension in the "extended de Gennes regime" that allows us to compare experimental results with theory. For this purpose, we performed experiments measuring the mean DNA extension and its standard deviation while varying the channel geometry, dye intercalation ratio, and ionic strength of the buffer. The experimental results agree very well with theory at high ionic strengths, indicating that the model parameters are reliable. At low ionic strengths, the agreement is less good. We discuss possible reasons. In principle, our approach allows us to measure the Kuhn length and the effective width of a single DNA molecule and more generally of semiflexible polymers in solution.

COBRA: A prospective multimodal imaging study of dopamine, brain structure and function, and cognition.

Cognitive decline is a characteristic feature of normal human aging. Previous work has demonstrated marked interindividual variability in onset and rate of decline. Such variability has been linked to factors such as maintenance of functional and structural brain integrity, genetics, and lifestyle. Still, few, if any, studies have combined a longitudinal design with repeated multimodal imaging and a comprehensive assessment of cognition as well as genetic and lifestyle factors. The present paper introduces the Cognition, Brain, and Aging (COBRA) study, in which cognitive performance and brain structure and function are measured in a cohort of 181 older adults aged 64 to 68 years at baseline. Participants will be followed longitudinally over a 10-year period, resulting in a total of three equally spaced measurement occasions. The measurement protocol at each occasion comprises a comprehensive set of behavioral and imaging measures. Cognitive performance is evaluated via computerized testing of working memory, episodic memory, perceptual speed, motor speed, implicit sequence learning, and vocabulary. Brain imaging is performed using positron emission tomography with [(11)C]-raclopride to assess dopamine D2/D3 receptor availability. Structural magnetic resonance imaging (MRI) is used for assessment of white and gray-matter integrity and cerebrovascular perfusion, and functional MRI maps brain activation during rest and active task conditions. Lifestyle descriptives are collected, and blood samples are obtained and stored for future evaluation. Here, we present selected results from the baseline assessment along with a discussion of sample characteristics and methodological considerations that determined the design of the study. This article is part of a Special Issue entitled SI: Memory & Aging.

The Anticipated Positive Psychosocial Impact of Present Web-Based E-Health Services and Future Mobile Health Applications: An Investigation among Older Swedes.

This study investigates the anticipated psychosocial impact of present web-based e-health services and future mobile health applications among older Swedes. Random sample's of Swedish citizens aged 55 years old and older were given a survey containing two different e-health scenarios which respondents rated according to their anticipated psychosocial impact by means of the PIADS instrument. Results consistently demonstrated the positive anticipation of psychosocial impacts for both scenarios. The future mobile health applications scored more positively than the present web-based e-health services. An increase in age correlated positively to lower impact scores. These findings indicate that from a psychosocial perspective, web-based e-health services and mobile health applications are likely to positively impact quality of life. This knowledge can be helpful when tailoring and implementing e-health services that are directed to older people.

Perceptions of participating in high-intensity functional exercise among older people dependent in activities of daily living (ADL).

The purpose of the study was to evaluate how older people, dependent in ADL perceive their participation in a high-intensity, functional exercise program compared to the perceptions of those participating in a control activity. Forty-eight older people living in residential care facilities answered a questionnaire about their perceptions of participating in an activity for three months. They were aged 65-98, had a mean score of 24 on Mini Mental State Examination (MMSE) and 14 on Barthel ADL Index. The participants had been randomized to exercise (n=20) or control activity (n=28). Differences in responses between exercise and control activity were evaluated using logistic and ordinal regression analyses. The results show that a majority of the exercise group perceived positive changes in lower limb strength, balance, and in the ability to move more safely and securely compared to a minority of the control group (p<0.001). Significantly more respondents in the exercise activity answered that they felt less tired due to the activity (p=0.027) and that they prioritized this activity above other activities (p=0.010). More exercise participants reported that meeting for three months was too short, and fewer that it was too long compared to the control group (p=0.038). This study shows that older people living in residential care facilities, dependent in ADL, and with mild or no cognitive impairment had positive perceptions about participating in high-intensity functional exercise. The findings support the use of a high-intensity exercise program in this population of older people.

Randomized multicenter clinical trial of myofascial physical therapy in women with interstitial cystitis/painful bladder syndrome and pelvic floor tenderness.

PURPOSE: We determined the efficacy and safety of pelvic floor myofascial physical therapy compared to global therapeutic massage in women with newly symptomatic interstitial cystitis/painful bladder syndrome. MATERIALS AND METHODS: A randomized controlled trial of 10 scheduled treatments of myofascial physical therapy vs global therapeutic massage was performed at 11 clinical centers in North America. We recruited women with interstitial cystitis/painful bladder syndrome with demonstrable pelvic floor tenderness on physical examination and a limitation of no more than 3 years' symptom duration. The primary outcome was the proportion of responders defined as moderately improved or markedly improved in overall symptoms compared to baseline on a 7-point global response assessment scale. Secondary outcomes included ratings for pain, urgency and frequency, the O'Leary-Sant IC Symptom and Problem Index, and reports of adverse events. We compared response rates between treatment arms using the exact conditional version of the Mantel-Haenszel test to control for clustering by clinical center. For secondary efficacy outcomes cross-sectional descriptive statistics and changes from baseline were calculated. RESULTS: A total of 81 women randomized to the 2 treatment groups had similar symptoms at baseline. The global response assessment response rate was 26% in the global therapeutic massage group and 59% in the myofascial physical therapy group (p=0.0012). Pain, urgency and frequency ratings, and O'Leary-Sant IC Symptom and Problem Index decreased in both groups during followup, and were not significantly different between the groups. Pain was the most common adverse event, occurring at similar rates in both groups. No serious adverse events were reported. CONCLUSIONS: A significantly higher proportion of women with interstitial cystitis/painful bladder syndrome responded to treatment with myofascial physical therapy than to global therapeutic massage. Myofascial physical therapy may be a beneficial therapy in women with this syndrome.

Comparison of real-life accidental falls in older people with experimental falls in middle-aged test subjects.

Falling is a common accident among older people. Automatic fall detectors are one method of improving security. However, in most cases, fall detectors are designed and tested with data from experimental falls in younger people. This study is one of the first to provide fall-related acceleration data obtained from real-life falls. Wireless sensors were used to collect acceleration data during a six-month test period in older people. Data from five events representing forward falls, a sideways fall, a backwards fall, and a fall out of bed were collected and compared with experimental falls performed by middle-aged test subjects. The signals from real-life falls had similar features to those from intentional falls. Real-life forward, sideways and backward falls all showed a pre impact phase and an impact phase that were in keeping with the model that was based on experimental falls. In addition, the fall out of bed had a similar acceleration profile as the experimental falls of the same type. However, there were differences in the parameters that were used for the detection of the fall phases. The beginning of the fall was detected in all of the real-life falls starting from a standing posture, whereas the high pre impact velocity was not. In some real-life falls, multiple impacts suggested protective actions. In conclusion, this study demonstrated similarities between real-life falls of older people and experimental falls of middle-aged subjects. However, some fall characteristics detected from experimental falls were not detectable in acceleration signals from corresponding heterogeneous real-life falls.

Cognitive status in persons with amalgam-related complaints.

Self-reported cognitive symptoms are frequent in persons with amalgam-related complaints, but few studies have focused on their cognitive function. The aim was to examine a symptom profile and whether participants with amalgam-related complaints have cognitive deficits in comparison with control individuals. We drew 342 participants with amalgam-related complaints and 342 one-to-one matched control individuals from a longitudinal population-based study. For 81 of the participants with amalgam-related complaints and controls, data were available approximately five years before the onset of complaints, making a longitudinal analysis possible. All participants were assessed by a self-reported health questionnaire and a comprehensive cognitive test battery. The participants with amalgam-related complaints reported more symptoms, mainly musculoskeletal and neuropsychological, compared with control individuals (p < 0.001). The results revealed no significant difference between the amalgam and control group, either cross-sectionally or longitudinally, for any of the cognitive tests. These results suggest that cognitive decline is not associated with amalgam-related complaints.

Motor imagery: if you can't do it, you won't think it.

Since long, motor imagery has been recognized as a method for studying motor representations. In the last few years, important advances regarding the use of motor imagery have been made. In particular, issues concerning the functional equivalence between imagery and action have been addressed, and how equivalence affects the use of imagery to study motor representations. In this paper, we review recent findings in order to highlight the current state of knowledge about motor imagery and its relation to motor action. Three topics are discussed: (i) the imagery perspective, (ii) task complexity, and (iii) the importance of physical experience. It is shown how theses factors are closely related and how previous studies may have underestimated to what extent these factors affect the interpretation of results. Practical implications for imagery interventions are considered. It is concluded that if you cannot perform an action physically, you cannot imagine it in a way that is necessary for a high degree of functional equivalence.

Age-related differences in white matter microstructure: region-specific patterns of diffusivity.

We collected MRI diffusion tensor imaging data from 80 younger (20-32 years) and 63 older (60-71 years) healthy adults. Tract-based spatial statistics (TBSS) analysis revealed that white matter integrity, as indicated by decreased fractional anisotropy (FA), was disrupted in numerous structures in older compared to younger adults. These regions displayed five distinct region-specific patterns of age-related differences in other diffusivity properties: (1) increases in both radial and mean diffusivity; (2) increases in radial diffusivity; (3) no differences in parameters other than FA; (4) a decrease in axial and an increase in radial diffusivity; and (5) a decrease in axial and mean diffusivity. These patterns suggest different biological underpinnings of age-related decline in FA, such as demyelination, Wallerian degeneration, gliosis, and severe fiber loss, and may represent stages in a cascade of age-related degeneration in white matter microstructure. This first simultaneous description of age-related differences in FA, mean, axial, and radial diffusivity requires histological and functional validation as well as analyses of intermediate age groups and longitudinal samples.

Grapefruit juice interaction with oral budesonide: equal effect on immediate-release and delayed-release formulations.

Grapefruit juice (GFJ) inhibits CYP3A activity in the gut wall, thereby decreasing first-pass metabolism of CYP3A substrates. In this study be evaluated the influence of GFJ on the systemic availability of budesonide, a CYP3A-metabolised drug, both from an extended-release (ER) formulation and plain capsules. Eight healthy men participated in this open crossover study. Three mg budesonide as ER capsules or plain capsules was swallowed with or without previous intake of GFJ. Regular-strength GFJ 200 ml was given three times a day for four days. Budesonide was administered immediately after the first intake on the fourth day. A simultaneous intravenous low dose of deuterium-labelled budesonide enabled estimation of bioavailability and absence of hepatic inhibition. Concentrations of labelled and unlabelled budesonide in plasma were measured. GFJ did not affect systemic clearance of budesonide. Although absorption of the ER formulation to a great extent occurs from ileum and proximal colon where CYP3A activity is lower than in the upper small intestine, GFJ about doubled bioavailability after both ER and plain capsules. In conclusion, regular intake of grapefruit juice doubled the bioavailability of both plain and delayed-release budesonide, probably because of inhibition of all mucosal CYP3A activity.

Importance of enjoyment when promoting physical exercise.

The purpose of this study was to investigate the importance of enjoyment of exercise in a health care-based intervention aimed at promoting physical exercise in primary health care patients. In a controlled study design, the intervention group was offered a wide range of group exercises over 3 months, followed by support in designing their own exercise program. The control group received usual care. Enjoyment of exercise and exercise level were measured. Associations between enjoyment and exercise level were analyzed using Spearman's rank correlation coefficients. Changes in enjoyment between and within study groups were analyzed by the independent and paired t-test. Associations were found between enjoyment and exercise level (r=0.36, P<0.01), as well as between changes in enjoyment and changes in exercise level (r=0.34, P<0.01). At the 12-month follow-up, enjoyment of exercise was 25% higher in the intervention group than in the control group (P<0.01). In this group of primary health care patients, enjoyment of exercise was associated with exercise level. Enjoyment of exercise seems to be a mediator of exercise level. Furthermore, health care-based interventions seem to be able to affect enjoyment of exercise. Enjoyment of exercise may be important for the long-term effectiveness, of health care-based interventions.

Altered deactivation in individuals with genetic risk for Alzheimer's disease.

Regions that show task-induced deactivations may be part of a default-mode network related to processes that are more engaged during passive than active task conditions. Alteration of task-induced deactivations with age and dementia is indicated by atypical engagement of default-mode network regions. Genetic studies show a relation between the apolipoprotein E4 (APOE4) allele and the common form of Alzheimer's disease (AD), and altered functional brain activation has been observed in non-demented APOE4 carriers compared to non-carriers. Here we investigate the hypothesis of altered default-mode network brain responses in individuals with genetic risk for AD. Functional MRI was used to assess task-induced deactivation in 60 subjects of which 30 carried at least one copy of the APOE4 allele, and 30 non-carriers. Subjects were scanned while performing a semantic categorization task shown to promote episodic memory encoding. The results show patterns of deactivation consistent with the default-mode network. We also found reduced deactivation in non-demented APOE4 carriers compared to non-carriers, suggesting alterations in the default-mode network in the absence of dementia. These results implicate possibilities for investigating altered properties of task-induced deactivations in individuals with genetic risk for AD, and may prove useful for pre-clinical identification of individuals susceptible to memory problems and AD.