Altered resting-state functional connectivity patterns in late middle-aged and older adults with obstructive sleep apnea.

Introduction: Obstructive sleep apnea (OSA) is increasingly recognized as a risk factor for cognitive decline, and has been associated with structural brain alterations in regions relevant to memory processes and Alzheimer's disease. However, it is unclear whether OSA is associated with disrupted functional connectivity (FC) patterns between these regions in late middle-aged and older populations. Thus, we characterized the associations between OSA severity and resting-state FC between the default mode network (DMN) and medial temporal lobe (MTL) regions. Second, we explored whether significant FC changes differed depending on cognitive status and were associated with cognitive performance. Methods: Ninety-four participants [24 women, 65.7 ± 6.9 years old, 41% with Mild Cognitive Impairment (MCI)] underwent a polysomnography, a comprehensive neuropsychological assessment and a resting-state functional magnetic resonance imaging (MRI). General linear models were conducted between OSA severity markers (i.e., the apnea-hypopnea, oxygen desaturation and microarousal indices) and FC values between DMN and MTL regions using CONN toolbox. Partial correlations were then performed between OSA-related FC patterns and (i) OSA severity markers in subgroups stratified by cognitive status (i.e., cognitively unimpaired versus MCI) and (ii) cognitive scores in the whole sample. All analyzes were controlled for age, sex and education, and considered significant at a p < 0.05 threshold corrected for false discovery rate. Results: In the whole sample, a higher apnea-hypopnea index was significantly associated with lower FC between (i) the medial prefrontal cortex and bilateral hippocampi, and (ii) the left hippocampus and both the posterior cingulate cortex and precuneus. FC patterns were not associated with the oxygen desaturation index, or micro-arousal index. When stratifying the sample according to cognitive status, all associations remained significant in cognitively unimpaired individuals but not in the MCI group. No significant associations were observed between cognition and OSA severity or OSA-related FC patterns. Discussion: OSA severity was associated with patterns of lower FC in regions relevant to memory processes and Alzheimer's disease. Since no associations were found with cognitive performance, these FC changes could precede detectable cognitive deficits. Whether these FC patterns predict future cognitive decline over the long-term needs to be investigated.

Medial temporal lobe and obstructive sleep apnea: Effect of sex, age, cognitive status and free-water.

Medial temporal structures, namely the hippocampus, the entorhinal cortex and the parahippocampal gyrus, are particularly vulnerable to Alzheimer's disease and hypoxemia. Here, we tested the associations between obstructive sleep apnea (OSA) severity and medial temporal lobe volumes in 114 participants aged 55-86 years (35 % women). We also investigated the impact of sex, age, cognitive status, and free-water fraction correction on these associations. Increased OSA severity was associated with larger hippocampal and entorhinal cortex volumes in women, but not in men. Greater OSA severity also correlated with increased hippocampal volumes in participants with amnestic mild cognitive impairment, but not in cognitively unimpaired participants, regardless of sex. Using free-water corrected volumes eliminated all significant associations with OSA severity. Therefore, the increase in medial temporal subregion volumes may possibly be due to edema. Whether these structural manifestations further progress to neuronal death in non-treated OSA patients should be investigated.

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 during REM sleep and daytime cerebral functioning: A regional cerebral blood flow study using high-resolution SPECT.

Obstructive sleep apnea (OSA) predominantly during rapid eye movement (REM) sleep may have impacts on brain health, even in milder OSA cases. Here, we evaluated whether REM sleep OSA is associated with abnormal daytime cerebral functioning using high-resolution single-photon emission computed tomography (SPECT). We tested 96 subjects (25 F, age: 65.2 ± 6.4) with a wide range of OSA severity from no OSA to severe OSA (apnea-hypopnea index: 0-97 events/h). More respiratory events during REM sleep were associated with reduced daytime regional cerebral blood flow (rCBF) in the bilateral ventromedial prefrontal cortex and in the right insula extending to the frontal cortex. More respiratory events during non-REM (NREM) sleep were associated with reduced daytime rCBF in the left sensorimotor and temporal cortex. In subjects with a lower overall OSA severity (apnea-hypopnea index<15), more respiratory events during REM sleep were also associated with reduced daytime rCBF in the insula and extending to the frontal cortex. Respiratory events that characterized OSA during NREM versus REM sleep are associated with distinct patterns of daytime cerebral perfusion. REM sleep OSA could be more detrimental to brain health, as evidenced by reduced daytime rCBF in milder forms of OSA.

Disconnection Between Self-Reported and Objective Cognitive Impairment in Obstructive Sleep Apnea.

STUDY OBJECTIVES: Recent studies show that obstructive sleep apnea (OSA) is a possible contributor to abnormal cognitive decline in older adults. These new observations create the need to identify older adults with OSA who are at risk of the developing dementia if not treated. This study's goal was to verify whether self-reported cognitive complaints could become a useful tool to screen for objective cognitive deficits in late middle-aged and older adults with OSA. METHODS: Fifty-seven participants with OSA with an apnea-hypopnea index (AHI) ≥ 15 events/h (3% or arousal) and aged between 55 and 85 years were compared to 54 participants in a mild/non-OSA group on their ability to evaluate their objective cognitive functioning. They underwent overnight polysomnography followed by a comprehensive neuropsychological assessment. We recruited a similar proportion of participants with mild cognitive impairment (MCI) in both groups (OSA: 36.8%; mild/non-OSA: 35.2%). They filled out questionnaires assessing mood, sleep, and cognition. Group (OSA versus mild/non-OSA) × cognitive status (MCI versus non-MCI) analyses of variance were performed on cognitive complaint questionnaires. RESULTS: We found that among participants without objective cognitive deficits, participants in the OSA group reported more cognitive complaints compared to those in the mild/non-OSA group. Among participants with objective cognitive deficits, those in the OSA group reported less cognitive complaints compared to those in the mild/non-OSA group. CONCLUSIONS: Participants with OSA and MCI were less aware of their deficits compared to those in the mild/non-OSA group, possibly reflecting a distinctive OSA-associated cognitive impairment. Our results underscore the importance of referring patients with OSA for a comprehensive neuropsychological assessment when an abnormal cognitive decline is suspected.

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.

Learning-by-Concordance (LbC): introducing undergraduate students to the complexity and uncertainty of clinical practice.

BACKGROUND: A current challenge in medical education is the steep exposure to the complexity and uncertainty of clinical practice in early clerkship. The gap between pre-clinical courses and the reality of clinical decision-making can be overwhelming for undergraduate students. The Learning-by-Concordance (LbC) approach aims to bridge this gap by embedding complexity and uncertainty by relying on real-life situations and exposure to expert reasoning processes to support learning. LbC provides three forms of support: 1) expert responses that students compare with their own, 2) expert explanations and 3) recognized scholars' key-messages. METHOD: Three different LbC inspired learning tools were used by 900 undergraduate medical students in three courses: Concordance-of-Reasoning in a 1st-year hematology course; Concordance-of-Perception in a 2nd-year pulmonary physio-pathology course, and; Concordance-of-Professional-Judgment with 3rd-year clerkship students. Thematic analysis was conducted on freely volunteered qualitative comments provided by 404 students. RESULTS: Absence of a right answer was challenging for 1st year concordance-of-reasoning group; the 2nd year visual concordance group found radiology images initially difficult and unnerving and the 3rd year concordance-of-judgment group recognized the importance of divergent expert opinion. CONCLUSIONS: Expert panel answers and explanations constitute an example of "cognitive apprenticeship" that could contribute to the development of appropriate professional reasoning processes.

Treatment delays in non-small cell lung cancer and their prognostic implications.

INTRODUCTION: The impact of treatment delays on survival of patients with non-small cell lung cancer (NSCLC) is uncertain. Although later treatment could negatively affect psychological well-being, the maximum acceptable waiting time has not been determined. METHODS: We analyzed consecutive patients with NSCLC between January 2005 and May 2007 in our center. Treatment delay was calculated from the first abnormal radiographic study. Cox proportional hazards analysis was used to identify predictive factors and log-rank tests to compare survival. RESULTS: Four hundred ninety-five cases were identified; shorter treatment delays were associated with a poor prognosis. Conversely, for every week that the treatment could be delayed, the hazard ratio was improved at 0.97 (p = 0.05). Standard treatment was given to 319 of these patients who were separated in localized, regional, and advanced stages. The median treatment delay was 73 days and distributed as follows: 85, 94, and 50 days for localized, regional, and advanced stages, respectively (p < 0.01). For localized or regional stages, the association between treatment delay and survival was inconclusive. In the advanced group, each week of treatment delay had a hazard ratio of 0.93 (p = 0.009). Survival of advanced patients who began treatment earlier versus later than the group median was 6.8 versus 11.6 months (p = 0.027). CONCLUSIONS: For patients with advanced NSCLC receiving equivalent chemotherapy regimens, shorter treatment delays were associated with shorter survival. We hypothesize that urgent treatment carried a negative prognostic meaning, as this was preferentially offered to patients presenting with a higher symptom burden, which conferred them a worse outcome.