Cerebral grey matter may not explain sleep slow-wave characteristics after severe brain injury.

Sleep slow waves are the hallmark of deeper non-rapid eye movement sleep. It is generally assumed that grey matter properties predict slow-wave density, morphology, and spectral power in healthy adults. Here, we tested the association between grey matter volume (GMV) and slow-wave characteristics in 27 moderate to severe traumatic brain injury patients (TBI; 32.0 ± 12.2 years old, eight women) compared to 32 healthy controls (29.2 ± 11.5 years old, nine women). Participants underwent overnight polysomnography and cerebral MRI with a 3-tesla scanner. A whole-brain voxel-wise analysis was performed to compare GMV between groups. Slow-wave density, morphology, and spectral power (0.4-6  Hz) were computed, and GMV was extracted from the thalamus, cingulate, insula, precuneus, and orbitofrontal cortex to test the relationship between slow waves and grey matter in regions implicated in the generation and/or propagation of slow waves. Compared to controls, TBI patients had significantly lower frontal and temporal GMV and exhibited a subtle decrease in slow-wave frequency. Moreover, higher GMV in the orbitofrontal cortex, insula, cingulate cortex, and precuneus was associated with higher slow-wave frequency and slope, only in healthy controls. Higher orbitofrontal GMV was also associated with higher slow-wave density in healthy participants. While we observed the expected associations between GMV and slow-wave characteristics in healthy controls, no such associations were observed in the TBI group despite lower GMV. This finding challenges the presumed role of GMV in slow-wave generation and morphology.Significance Statement Because sleep slow waves play a key role in cognition, synaptic plasticity, and restorative sleep, understanding how they relate to cerebral matter integrity is especially important in the context of brain atrophy following moderate to severe traumatic brain injury (TBI). We found that higher grey matter volume (GMV) in regions involved in slow-wave generation and propagation was associated with faster and steeper slow waves in healthy individuals. However, these associations were not observed in TBI participants, raising questions about the degree of contribution of GMV to slow-wave properties in patients with lower grey matter relative to controls. These findings challenge our current understanding of the link between grey matter integrity and slow waves, highlighting the complexity of this relationship.

Unrefreshing naps and sleep architecture during the multiple sleep latency test in idiopathic hypersomnia.

Patients with idiopathic hypersomnia frequently report having unrefreshing naps. However, whether they have abnormal sleep architecture during naps that may explain their unrefreshing aspect is unknown. We compared sleep architecture during short daytime naps in patients with idiopathic hypersomnia reporting unrefreshing and refreshing naps. One-hundred and thirty-four patients tested with one-night polysomnography, followed by an adapted version of the Multiple Sleep Latency Test with four naps, were included. They were asked about the refreshing aspect of their habitual naps during a clinical interview. They were classified as having objective (Multiple Sleep Latency Test ≤ 8 min) or subjective idiopathic hypersomnia (Multiple Sleep Latency Test > 8 min), and as presenting refreshing or unrefreshing naps. We tested Group differences (refreshing versus unrefreshing naps) on nap sleep architecture in the whole sample and for subjective and objective idiopathic hypersomnia subgroups separately using ANCOVAs. No Group effects were observed in the Multiple Sleep Latency Test architecture in the whole sample and in objective and subjective idiopathic hypersomnia subgroups. This study provides preliminary evidence that reporting unrefreshing naps is not associated with clinically significant findings in Multiple Sleep Latency Test sleep architecture in patients with idiopathic hypersomnia. Given that naps taken by patients with idiopathic hypersomnia are typically long, future studies should investigate longer daytime sleep episodes.

Obstructive sleep apnea and cognitive functioning in the older general population: The moderating effect of age, sex, ApoE4, and obesity.

Research on the relationship between obstructive sleep apnea and cognitive functioning has yielded conflicting results, particularly in the older population, and moderators of this association have rarely been studied. Here we investigated the cross-sectional association between obstructive sleep apnea and cognitive functioning as well as the moderating effect of age, sex, apolipoprotein E4, and obesity on this association among community-dwelling older people. We analysed data from 496 participants (71.4 ± 4.4 years; 45.6% men) of the HypnoLaus study who underwent polysomnography and a battery of neuropsychological tests. The sample was categorised as no-to-mild obstructive sleep apnea (apnea-hypopnea index 0-14.9/h; reference), moderate obstructive sleep apnea (apnea-hypopnea index 15.0-29.9/h), or severe obstructive sleep apnea (apnea-hypopnea index ≥30/h). Regression and moderation analyses were performed with adjustment for confounders. Apolipoprotein E4 and obesity moderated the association between severe obstructive sleep apnea and processing speed, whereas no moderating effects were found for age and sex. In apolipoprotein E4 carriers only, severe obstructive sleep apnea was associated with lower performance in Stroop condition 1 (B = 3.13, p = 0.024). In obese participants only, severe obstructive sleep apnea was associated with lower performance in Stroop condition 1 (B = 3.02, p = 0.025) and Stroop condition 2 (B = 3.30, p = 0.034). Severe obstructive sleep apnea was also associated with lower executive function in the whole sample according to Stroop condition 3 (B = 3.44, p = 0.020) and Stroop interference score (B = 0.24, p = 0.006). Our findings support associations of severe obstructive sleep apnea (but not moderate obstructive sleep apnea) with lower performance in processing speed and executive function in the older general population. Apolipoprotein E4 and obesity appear to be vulnerability factors that strengthen the association between severe obstructive sleep apnea and lower performance in processing speed.

Use of actigraphy for monitoring agitation and rest-activity cycles in patients with acute traumatic brain injury in the ICU.

BACKGROUND: In traumatic brain injury patients (TBI) admitted to the intensive care unit (ICU), agitation can lead to accidental removal of catheters, devices as well as self-extubation and falls. Actigraphy could be a potential tool to continuously monitor agitation. The objectives of this study were to assess the feasibility of monitoring agitation with actigraphs and to compare activity levels in agitated and non-agitated critically ill TBI patients. METHODS: Actigraphs were placed on patients' wrists; 24-hour monitoring was continued until ICU discharge or limitation of therapeutic efforts. Feasibility was assessed by actigraphy recording duration and missing activity count per day. RESULTS: Data from 25 patients were analyzed. The mean number of completed day of actigraphy per patient was 6.5 ± 5.1. The mean missing activity count was 20.3 minutes (±81.7) per day. The mean level of activity measured by raw actigraphy counts per minute over 24 hours was higher in participants with agitation than without agitation. CONCLUSIONS: This study supports the feasibility of actigraphy use in TBI patients in the ICU. In the acute phase of TBI, agitated patients have higher levels of activity, confirming the potential of actigraphy to monitor agitation.

A window into the reality of families living long term with challenging behaviours after a TBI.

Challenging behaviours are a long-term burden for people with traumatic brain injury (TBI) and their families. Families frequently shoulder the responsibility alone, but little is known about the strategies they use to manage these behaviours. This study aimed to 1) identify the coping strategies used by people with TBI living in the community and their family caregivers to manage challenging behaviours; and 2) describe the similarities and differences between strategies used by people with TBI and caregivers. In this qualitative descriptive design, individual semi-structured interviews were conducted with adults with TBI and their caregivers and were inductively analyzed. The sample included 10 dyads and two triads, totalling 12 caregivers (8 women) and 14 individuals with TBI (6 women; 21.71 ± 10.84 years post-injury). Participants' strategies were proactive (prevention), reactive (response), or retroactive (aftercare). Most strategies were described by caregivers. Some of them were effective and lasting, others not, reflecting how they adapted their approaches over time. Families put in place various strategies in their life's journey, such as giving feedback or adapting the environment. Despite these strategies supporting long-term community living, the need for ongoing support is underscored, as crises may still occur, impacting families' quality of life.

Altered fornix integrity is associated with sleep apnea-related hypoxemia in mild cognitive impairment.

INTRODUCTION: The limbic system is critical for memory function and degenerates early in the Alzheimer's disease continuum. Whether obstructive sleep apnea (OSA) is associated with alterations in the limbic white matter tracts remains understudied. METHODS: Polysomnography, neurocognitive assessment, and brain magnetic resonance imaging (MRI) were performed in 126 individuals aged 55-86 years, including 70 cognitively unimpaired participants and 56 participants with mild cognitive impairment (MCI). OSA measures of interest were the apnea-hypopnea index and composite variables of sleep fragmentation and hypoxemia. Microstructural properties of the cingulum, fornix, and uncinate fasciculus were estimated using free water-corrected diffusion tensor imaging. RESULTS: Higher levels of OSA-related hypoxemia were associated with higher left fornix diffusivities only in participants with MCI. Microstructure of the other white matter tracts was not associated with OSA measures. Higher left fornix diffusivities correlated with poorer episodic verbal memory. DISCUSSION: OSA may contribute to fornix damage and memory dysfunction in MCI. HIGHLIGHTS: Sleep apnea-related hypoxemia was associated with altered fornix integrity in MCI. Altered fornix integrity correlated with poorer memory function. Sleep apnea may contribute to fornix damage and memory dysfunction in MCI.

Obstructive sleep apnoea and 5-year cognitive decline in the elderly.

BACKGROUND: The relationship between obstructive sleep apnoea (OSA) and cognitive decline remains controversial, especially in the elderly population. We used data from the HypnoLaus study to assess associations between OSA and longitudinal cognitive changes in a sample of community-dwelling elderly individuals. METHODS: We studied associations between polysomnographic OSA parameters (of breathing/hypoxaemia and sleep fragmentation) and cognitive changes over a 5-year period, after adjustment for potential confounders. The primary outcome was the annual change in cognitive scores. The moderating effects of age, sex and apolipoprotein E4 (ApoE4) status were also examined. RESULTS: 358 elderly individuals without dementia were included (mean±sd age 71.0±4.2 years; 42.5% males). A lower mean peripheral oxygen saturation (S pO2 ) during sleep was associated with a steeper decline in Mini-Mental State Examination (B= -0.12, p=0.004), Stroop test condition 1 (B=0.53, p=0.002) and Free and Cued Selective Reminding Test delayed free recall (B= -0.05, p=0.008). A longer time spent asleep with S pO2 <90% was associated with a steeper decline in Stroop test condition 1 (B=0.47, p=0.006). Moderation analysis showed that apnoea-hypopnoea index and oxygen desaturation index were associated with a steeper decline in global cognitive function, processing speed and executive function only in older participants, men and ApoE4 carriers. CONCLUSIONS: Our results provide evidence of the contribution of OSA and nocturnal hypoxaemia to cognitive decline in the elderly population.

The dual reality of challenging behaviours: Overlapping and distinct perspectives of individuals with TBI and their caregivers.

Challenging behaviours significantly impact the lives of people with traumatic brain injury (TBI) and their family caregivers. However, these behaviours are rarely defined from the perspectives of both individuals, a necessary step to developing interventions targeting meaningful goals for individuals and caregivers. This study aimed to (1) explore and confirm the perspective of individuals with TBI living in the community and their family caregivers on behaviours they consider challenging and, (2) identify overlapping or distinct views on challenging behaviours. A qualitative descriptive design was used. Twelve caregivers (8 females; 59.67 ± 11.64 years old) and 14 participants with mild-severe TBI (6 females; 43.21 ± 10.98 years old; time post-injury: 21.71 ± 10.84 years) were interviewed (10 dyads and two triads). Data were analysed using inductive qualitative analysis. Challenging behaviours most frequently reported by all participants were aggressive/impulsive behaviours, inappropriate social behaviours, and behavioural manifestations of cognitive impairments. Overlapping perspectives were identified regarding aggressive behaviours. Distinctions exist as inappropriate social behaviours and cognitive difficulties were mainly reported by caregivers. Our results confirm that perspectives may vary between dyad members. Interventions should include dyad inputs to formulate goals that are significant to the person with TBI and their caregiver.

Predictive Value of a New Brief Cognitive Test for Long-term Functional Outcome in Acute Traumatic Brain Injury.

OBJECTIVE: To determine how results on the EXAmen Cognitif abrégé en Traumatologie (EXACT), a new test specifically designed to briefly assess global cognitive functioning during the acute phase of traumatic brain injury (TBI), can predict long-term functional outcome compared with length of posttraumatic amnesia (PTA), a well-established predictor. DESIGN: Inception cohort. SETTINGS: Level 1 trauma center. PARTICIPANTS: A total of 90 patients (N=90) hospitalized for a moderate or severe TBI. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Performance on the EXACT in the first 3 months after injury and results on the Disability Rating Scale (DRS) at follow-up 1-2 years later. RESULTS: EXACT scores were all correlated with length of PTA and DRS result. Compared with length of PTA, the EXACT added significantly to the regression and improved prediction of functional outcome. More specifically, a total score ≤80 on the EXACT was associated with a higher rate of long-term disability because of more severe TBI consequences. Behavioral regulation and executive functions were the cognitive domains that showed the most impairment, followed by attention and working memory as well as episodic memory. Except for length of PTA and hospital stay, the DRS score was not correlated with other demographic (age, education) or clinical variables (Glasgow Coma Scale and maximum score on the Therapy Intensity Level Scale). CONCLUSIONS: The EXACT can be administered to most patients early in the acute phase of TBI, and results could be used, along with other predictors such as PTA, to estimate their long-term functional sequelae. The EXACT may be a promising brief cognitive instrument for future studies investigating recovery after TBI.

Longitudinal changes in regional cerebral blood flow in late middle-aged and older adults with treated and untreated obstructive sleep apnea.

Obstructive sleep apnea (OSA) is associated with abnormal cerebral perfusion at wakefulness, but whether these anomalies evolve over time is unknown. Here, we examined longitudinal changes in regional cerebral blood flow (rCBF) distribution in late middle-aged and older adults with treated or untreated OSA. Twelve controls (64.8 ± 8.0 years) and 23 participants with newly diagnosed OSA (67.8 ± 6.2 years) were evaluated with polysomnography and cerebral 99m Tc-HMPAO single-photon emission computed tomography during wakeful rest. OSA participants were referred to a sleep apnea clinic and 13 of them decided to start continuous positive airway pressure (CPAP). Participants were tested again after 18 months. Voxel-based analysis and extracted relative rCBF values were used to assess longitudinal changes. Untreated OSA participants showed decreased relative rCBF in the left hippocampus and the right parahippocampal gyrus over time, while treated participants showed trends for increased relative rCBF in the left hippocampus and the right parahippocampal gyrus. No changes were found over time in controls. Untreated OSA is associated with worsening relative rCBF in specific brain areas over time, while treated OSA shows the opposite. Considering that OSA possibly accelerates cognitive decline in older adults, CPAP treatment could help reduce risk for cognitive impairment.

Obstructive Sleep Apnea and the Brain: a Focus on Gray and White Matter Structure.

PURPOSE OF REVIEW: Obstructive sleep apnea is extremely prevalent in the elderly and may precipitate dementia. We review recent advances on gray and white matter structure in obstructive sleep apnea, the impact of treatment, and potential pathological and neurodegenerative processes underlying brain structural changes. RECENT FINDINGS: Two opposite patterns are observed in neuroimaging studies of obstructive sleep apnea. One may indicate cellular damage (gray matter atrophy, higher white matter hyperintensity burden, lower white matter fractional anisotropy, higher water diffusivities), while the other (gray matter hypertrophy, restricted white matter diffusivities) may reflect transitory responses, such as intracellular edema, reactive gliosis or compensatory structural changes. Treating obstructive sleep apnea could partly reverse these structural changes. Structural alterations related to obstructive sleep apnea may follow a multi-determined biphasic pattern depending on numerous factors (e.g. severity, symptomatology, age) that could tip the scale toward neurodegeneration and need to be investigated by longitudinal studies.

Cerebral white matter diffusion properties and free-water with obstructive sleep apnea severity in older adults.

Characterizing the effects of obstructive sleep apnea (OSA) on the aging brain could be key in our understanding of neurodegeneration in this population. Our objective was to assess white matter properties in newly diagnosed and untreated adults with mild to severe OSA. Sixty-five adults aged 55 to 85 were recruited and divided into three groups: control (apnea-hypopnea index ≤5/hr; n = 18; 65.2 ± 7.2 years old), mild (>5 to ≤15 hr; n = 27; 64.2 ± 5.3 years old) and moderate to severe OSA (>15/hr; n = 20; 65.2 ± 5.5 years old). Diffusion tensor imaging metrics (fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity, and mean diffusivity) were compared between groups with Tract-Based Spatial Statistics within the white matter skeleton created by the technique. Groups were also compared for white matter hyperintensities volume and the free-water (FW) fraction. Compared with controls, mild OSA participants showed widespread areas of lower diffusivity (p < .05 corrected) and lower FW fraction (p < .05). Participants with moderate to severe OSA showed lower AD in the corpus callosum compared with controls (p < .05 corrected). No between-group differences were observed for FA or white matter hyperintensities. Lower white matter diffusivity metrics is especially marked in mild OSA, suggesting that even the milder form may lead to detrimental outcomes. In moderate to severe OSA, competing pathological responses might have led to partial normalization of diffusion metrics.

Changes in Regional Cerebral Perfusion Over Time in Idiopathic REM Sleep Behavior Disorder.

BACKGROUND: Idiopathic rapid eye movement sleep behavior disorder is associated with increased risk of neurodegeneration, but the temporal evolution of regional perfusion, a marker of cerebral activity, has not been characterized. The objective of the current study was to study longitudinal regional perfusion in patients with idiopathic rapid eye movement sleep behavior disorder. METHODS: Thirty-seven patients and 23 controls underwent high-resolution single-photon emission computed tomography. After 17 months on average, scans were repeated for idiopathic rapid eye movement sleep behavior disorder patients. We compared regional cerebral blood flow between groups and over time. RESULTS: At baseline, patients showed lower relative regional perfusion in the anterior frontal and lateral parietotemporal cortex compared with controls. However, over time, patients showed an increase in relative regional perfusion in the anterior frontal, lateral parietal, and occipitotemporal cortex, reverting toward normal control levels. CONCLUSIONS: Patients with idiopathic rapid eye movement sleep behavior disorder showed significant areas of relative regional hypoperfusion, which disappeared over time to finally return to average levels, suggesting possible developing compensation in areas affected by neurodegeneration. © 2020 International Parkinson and Movement Disorder Society.

Brain white matter damage and its association with neuronal synchrony during sleep.

The restorative function of sleep partly relies on its ability to deeply synchronize cerebral networks to create large slow oscillations observable with EEG. However, whether a brain can properly synchronize and produce a restorative sleep when it undergoes massive and widespread white matter damage is unknown. Here, we answer this question by testing 23 patients with various levels of white matter damage secondary to moderate to severe traumatic brain injuries (ages 18-56; 17 males, six females, 11-39 months post-injury) and compared them to 27 healthy subjects of similar age and sex. We used MRI and diffusion tensor imaging metrics (e.g. fractional anisotropy as well as mean, axial and radial diffusivities) to characterize voxel-wise white matter damage. We measured the following slow wave characteristics for all slow waves detected in N2 and N3 sleep stages: peak-to-peak amplitude, negative-to-positive slope, negative and positive phase durations, oscillation frequency, and slow wave density. Correlation analyses were performed in traumatic brain injury and control participants separately, with age as a covariate. Contrary to our hypotheses, we found that greater white matter damage mainly over the frontal and temporal brain regions was strongly correlated with a pattern of higher neuronal synchrony characterized by slow waves of larger amplitudes and steeper negative-to-positive slopes during non-rapid eye movement sleep. The same pattern of associations with white matter damage was also observed with markers of high homeostatic sleep pressure. More specifically, higher white matter damage was associated with higher slow-wave activity power, as well as with more severe complaints of cognitive fatigue. These associations between white matter damage and sleep were found only in our traumatic brain injured participants, with no such correlation in controls. Our results suggest that, contrary to previous observations in healthy controls, white matter damage does not prevent the expected high cerebral synchrony during sleep. Moreover, our observations challenge the current line of hypotheses that white matter microstructure deterioration reduces cerebral synchrony during sleep. Our results showed that the relationship between white matter and the brain's ability to synchronize during sleep is neither linear nor simple.

Obstructive Sleep Apnea Severity Affects Amyloid Burden in Cognitively Normal Elderly. A Longitudinal Study.

RATIONALE: Recent evidence suggests that obstructive sleep apnea (OSA) may be a risk factor for developing mild cognitive impairment and Alzheimer's disease. However, how sleep apnea affects longitudinal risk for Alzheimer's disease is less well understood. OBJECTIVES: To test the hypothesis that there is an association between severity of OSA and longitudinal increase in amyloid burden in cognitively normal elderly. METHODS: Data were derived from a 2-year prospective longitudinal study that sampled community-dwelling healthy cognitively normal elderly. Subjects were healthy volunteers between the ages of 55 and 90, were nondepressed, and had a consensus clinical diagnosis of cognitively normal. Cerebrospinal fluid amyloid ß was measured using ELISA. Subjects received Pittsburgh compound B positron emission tomography scans following standardized procedures. Monitoring of OSA was completed using a home sleep recording device. MEASUREMENTS AND MAIN RESULTS: We found that severity of OSA indices (AHIall [F1,88 = 4.26; P < 0.05] and AHI4% [F1,87 = 4.36; P < 0.05]) were associated with annual rate of change of cerebrospinal fluid amyloid ß42 using linear regression after adjusting for age, sex, body mass index, and apolipoprotein E4 status. AHIall and AHI4% were not associated with increases in ADPiB-mask (Alzheimer's disease vulnerable regions of interest Pittsburg compound B positron emission tomography mask) most likely because of the small sample size, although there was a trend for AHIall (F1,28 = 2.96, P = 0.09; and F1,28 = 2.32, not significant, respectively). CONCLUSIONS: In a sample of cognitively normal elderly, OSA was associated with markers of increased amyloid burden over the 2-year follow-up. Sleep fragmentation and/or intermittent hypoxia from OSA are likely candidate mechanisms. If confirmed, clinical interventions for OSA may be useful in preventing amyloid build-up in cognitively normal elderly.

Detection of mild cognitive impairment in middle-aged and older adults with obstructive sleep apnoea.

Obstructive sleep apnoea increases the risk for mild cognitive impairment and dementia. The present study aimed to characterise the ability of two cognitive screening tests, the Mini-Mental State Examination and the Montreal Cognitive Assessment, to detect mild cognitive impairment in adults aged 55-85 years with and without obstructive sleep apnoea.We included 42 subjects with mild and 67 subjects with moderate-to-severe obstructive sleep apnoea. We compared them to 22 control subjects. Mild cognitive impairment was diagnosed by a comprehensive neuropsychological assessment. We used receiver operating characteristic curves to assess the ability of the two screening tests to detect mild cognitive impairment.The two screening tests showed similar discriminative ability in control subjects. However, among the mild and the moderate-to-severe obstructive sleep apnoea groups, the Mini-Mental State Examination was not able to correctly identify subjects with mild cognitive impairment. The Montreal Cognitive Assessment's discriminant ability was acceptable in both sleep apnoea groups and was comparable to what was observed in controls.The Mini-Mental State Examination should not be used to screen for cognitive impairment in patients with obstructive sleep apnoea. The Montreal Cognitive Assessment could be used in clinical settings. However, clinicians should refer patients for neuropsychological assessment when neurodegenerative processes are suspected.

Gray Matter Hypertrophy and Thickening with Obstructive Sleep Apnea in Middle-aged and Older Adults.

RATIONALE: Obstructive sleep apnea causes intermittent hypoxemia, hemodynamic fluctuations, and sleep fragmentation, all of which could damage cerebral gray matter that can be indirectly assessed by neuroimaging. OBJECTIVES: To investigate whether markers of obstructive sleep apnea severity are associated with gray matter changes among middle-aged and older individuals. METHODS: Seventy-one subjects (ages, 55-76 yr; apnea-hypopnea index, 0.2-96.6 events/h) were evaluated by magnetic resonance imaging. Two techniques were used: (1) voxel-based morphometry, which measures gray matter volume and concentration; and (2) FreeSurfer (an open source software suite) automated segmentation, which estimates the volume of predefined cortical/subcortical regions and cortical thickness. Regression analyses were performed between gray matter characteristics and markers of obstructive sleep apnea severity (hypoxemia, respiratory disturbances, and sleep fragmentation). MEASUREMENTS AND MAIN RESULTS: Subjects had few symptoms, that is, sleepiness, depression, anxiety, and cognitive deficits. Although no association was found with voxel-based morphometry, FreeSurfer revealed increased gray matter with obstructive sleep apnea. Higher levels of hypoxemia correlated with increased volume and thickness of the left lateral prefrontal cortex as well as increased thickness of the right frontal pole, the right lateral parietal lobules, and the left posterior cingulate cortex. Respiratory disturbances positively correlated with right amygdala volume, and more severe sleep fragmentation was associated with increased thickness of the right inferior frontal gyrus. CONCLUSIONS: Gray matter hypertrophy and thickening were associated with hypoxemia, respiratory disturbances, and sleep fragmentation. These structural changes in a group of middle-aged and older individuals may represent adaptive/reactive brain mechanisms attributed to a presymptomatic stage of obstructive sleep apnea.

BDNF Val66Met Polymorphism Interacts with Sleep Consolidation to Predict Ability to Create New Declarative Memories.

UNLABELLED: It is hypothesized that a fundamental function of sleep is to restore an individual's day-to-day ability to learn and to constantly adapt to a changing environment through brain plasticity. Brain-derived neurotrophic factor (BDNF) is among the key regulators that shape brain plasticity. However, advancing age and carrying the BDNF Met allele were both identified as factors that potentially reduce BDNF secretion, brain plasticity, and memory. Here, we investigated the moderating role of BDNF polymorphism on sleep and next-morning learning ability in 107 nondemented individuals who were between 55 and 84 years of age. All subjects were tested with 1 night of in-laboratory polysomnography followed by a cognitive evaluation the next morning. We found that in subjects carrying the BDNF Val66Val polymorphism, consolidated sleep was associated with significantly better performance on hippocampus-dependent episodic memory tasks the next morning (ß-values from 0.290 to 0.434, p ≤ 0.01). In subjects carrying at least one copy of the BDNF Met allele, a more consolidated sleep was not associated with better memory performance in most memory tests (ß-values from -0.309 to -0.392, p values from 0.06 to 0.15). Strikingly, increased sleep consolidation was associated with poorer performance in learning a short story presented verbally in Met allele carriers (ß = -0.585, p = 0.005). This study provides new evidence regarding the interacting roles of consolidated sleep and BDNF polymorphism in the ability to learn and stresses the importance of considering BDNF polymorphism when studying how sleep affects cognition. SIGNIFICANCE STATEMENT: Individuals with the BDNF Val/Val (valine allele) polymorphism showed better memory performance after a night of consolidated sleep. However, we observed that middle-aged and older individuals who are carriers of the BDNF Met allele displayed no positive association between sleep quality and their ability to learn the next morning. This interaction between sleep and BDNF polymorphism was more salient for hippocampus-dependent tasks than for other cognitive tasks. Our results support the hypothesis that reduced activity-dependent secretion of BDNF impairs the benefits of sleep on synaptic plasticity and next-day memory. Our work advances the field by revealing new evidence of a clear genetic heterogeneity in how sleep consolidation contributes to the ability to learn.

Effects of concomitant mild traumatic brain injury on resuming work after suffering from an isolated limb fracture: A cohort study.

BACKGROUND: The objective is to explore the effects of concomitant mild traumatic brain injury (mTBI) on return to work (RTW), among patients suffering from an isolated limb fracture. This follow-up study included a total of 170 working age subjects with an isolated limb fracture, and was conducted in a phone interview approximately 1-year post trauma. 41 had experienced an mTBI and 129 did not. METHODS: Data were obtained through a phone interview conducted on average 20.7 months (SD = 9.6 months) post-accident. The main outcome measure was the number of days taken to RTW after the injury. Demographic information was also gathered during the phone interview. Workers' compensation status was obtained through the hospitals' orthopaedic clinic data. RESULTS: The mTBI group took on average 329.7 days (SD = 298.0) to RTW after the injury, as opposed to 150.3 days (SD = 171.3) for the control group (p < 0.001). After excluding patients who received workers' compensation, the mTBI group still missed significantly more days of work (M = 299.4 days; SD = 333.0) than the control group (M = 105.2 days; SD = 121.6) (p < 0.0001). CONCLUSION: This study shows that mTBI increases work disability by preventing working-age individuals from rapidly returning to work.

Does age matter? A mixed methods study examining determinants of good recovery and resilience in young and middle-aged adults following moderate-to-severe traumatic brain injury.

AIM: To examine whether age contributes to functional recovery and resilience after moderate-to-severe traumatic brain injury. BACKGROUND: The ability to recover may change across the lifespan, but the influence of age on brain injury outcome is understudied. DESIGN: Mixed methods study. METHODS: All adults of working age (18-64 years) discharged from a level I trauma centre between 2010-2013 after sustaining a moderate-to-severe traumatic brain injury were considered. Functional recovery was assessed during a telephone interview with the Glasgow Outcome Scale-Extended 12-36 months postinjury. A subgroup completed the Connor-Davidson Resilience Scale and a face-to-face interview about resilience. RESULTS: Ninety-seven young (mean age: 27 years; 75% male) and 47 middle-aged brain trauma survivors (mean age: 53 years; 75% male) completed the telephone interview. Eight young and five middle-aged adults were also assessed for resilience. Overall, young participants experienced more severe head injuries. Yet, they achieved slightly higher levels of functional recovery compared with middle-aged ones as per the Glasgow Outcome Scale-Extended. Controlling for CT scan findings and posttraumatic amnesia duration, age was not found to be associated to functional recovery in adults of working age. Although both groups showed similar levels of resilience, young participants discussed the challenges related to "having more time on their hands" and "being a changed person", two elements perceived positively by middle-aged ones. CONCLUSION: While age does not appear to interfere with functional recovery in adults of working age, younger brain trauma survivors could benefit from nursing interventions to strengthen their resilience process related to re-employment orientation and identity.