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

IntroductionObstructive 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.MethodsNinety-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.ResultsIn 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.DiscussionOSA 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

Obstructive Sleep Apnea and Cognitive Decline: A Review of Potential Vulnerability and Protective Factors

Around 40% of dementia risk is attributable to modifiable risk factors such as physical inactivity, hypertension, diabetes and obesity. Recently, sleep disorders, including obstructive sleep apnea (OSA), have also been considered among these factors. However, despite several epidemiological studies investigating the link between OSA and cognitive decline, there is still no consensus on whether OSA increases the risk of dementia or not. Part of the heterogeneity observed in previous studies might be related to some individual characteristics that modulate the association between OSA and cognitive decline. In this narrative review, we present these individual characteristics, namely, age, sex, menopause, obesity, diabetes mellitus, hypertension, cardiovascular diseases, smoking, excessive alcohol consumption, depression, air pollution, Apolipoprotein E ε4 allele, physical activity, and cognitive reserve. To date, large cohort studies of OSA and cognitive decline tended to statistically control for the effects of these variables, but whether they interact with OSA to predict cognitive decline remains to be elucidated. Being able to better predict who is at risk of cognitive decline when they have OSA would improve clinical management and treatment decisions, particularly when patients present relatively mild OSA

REM sleep is associated with the volume of the cholinergic basal forebrain in aMCI individuals

Abstract Background Rapid-eye movement (REM) sleep highly depends on the activity of cholinergic basal forebrain (BF) neurons and is reduced in Alzheimer’s disease. Here, we investigated the associations between the volume of BF nuclei and REM sleep characteristics, and the impact of cognitive status on these links, in late middle-aged and older participants. Methods Thirty-one cognitively healthy controls (66.8 ± 7.2 years old, 13 women) and 31 participants with amnestic Mild Cognitive Impairment (aMCI) (68.3 ± 8.8 years old, 7 women) were included in this cross-sectional study. All participants underwent polysomnography, a comprehensive neuropsychological assessment and Magnetic Resonance Imaging examination. REM sleep characteristics (i.e., percentage, latency and efficiency) were derived from polysomnographic recordings. T1-weighted images were preprocessed using CAT12 and the DARTEL algorithm, and we extracted the gray matter volume of BF regions of interest using a probabilistic atlas implemented in the JuBrain Anatomy Toolbox. Multiple linear regressions were performed between the volume of BF nuclei and REM sleep characteristics controlling for age, sex and total intracranial volume, in the whole cohort and in subgroups stratified by cognitive status. Results In the whole sample, lower REM sleep percentage was significantly associated to lower nucleus basalis of Meynert (Ch4) volume (β = 0.32, p = 0.009). When stratifying the cohort according to cognitive status, lower REM sleep percentage was significantly associated to both lower Ch4 (β = 0.48, p = 0.012) and total BF volumes (β = 0.44, p = 0.014) in aMCI individuals, but not in cognitively unimpaired participants. No significant associations were observed between the volume of the BF and wake after sleep onset or non-REM sleep variables. Discussion These results suggest that REM sleep disturbances may be an early manifestation of the degeneration of the BF cholinergic system before the onset of dementia, especially in participants with mild memory deficits