Andrée-Ann Baril

Regional Cerebral Blood Flow during Wakeful Rest in Older Subjects with Mild to Severe Obstructive Sleep Apnea.

OBJECTIVES To evaluate changes in regional cerebral blood flow (rCBF) during wakeful rest in older subjects with mild to severe obstructive sleep apnea (OSA) and healthy controls, and to identify markers of OSA severity that predict altered rCBF. DESIGN High-resolution (99m)Tc-HMPAO SPECT imaging during wakeful rest. SETTING Research sleep laboratory affiliated with a University hospital. PARTICIPANTS Fifty untreated OSA patients aged between 55 and 85 years, divided into mild, moderate, and severe OSA, and 20 age-matched healthy controls. INTERVENTIONS N/A. MEASUREMENTS Using statistical parametric mapping, rCBF was compared between groups and correlated with clinical, respiratory, and sleep variables. RESULTS Whereas no rCBF change was observed in mild and moderate groups, participants with severe OSA had reduced rCBF compared to controls in the left parietal lobules, left precentral gyrus, bilateral postcentral gyri, and right precuneus. Reduced rCBF in these regions and in areas of the bilateral frontal and left temporal cortex was associated with more hypopneas, snoring, hypoxemia, and sleepiness. Higher apnea, microarousal, and body mass indexes were correlated to increased rCBF in the basal ganglia, insula, and limbic system. CONCLUSIONS While older individuals with severe obstructive sleep apnea (OSA) had hypoperfusion in the sensorimotor and parietal areas, respiratory variables and subjective sleepiness were correlated with extended regions of hypoperfusion in the lateral cortex. Interestingly, OSA severity, sleep fragmentation, and obesity correlated with increased perfusion in subcortical and medial cortical regions. Anomalies with such a distribution could result in cognitive deficits and reflect impaired vascular regulation, altered neuronal integrity, and/or undergoing neurodegenerative processes.

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.

Association between waking electroencephalography and cognitive event-related potentials in patients with obstructive sleep apnea.

OBJECTIVE Sleepiness, cognitive deficits, abnormal event-related potentials (ERP), and slowing of the waking electroencephalography (EEG) activity have been reported in patients with obstructive sleep apnea (OSA). Our study aimed at evaluating if an association exists between the severity of ERP abnormalities and EEG slowing to better understand cerebral dysfunctions in OSA. METHODS Twelve OSA patients and 12 age-matched controls underwent an overnight polysomnographic recording, an EEG recording of 10 min of wakefulness, and an auditory ERP protocol known to specifically recruit attention. P300 and P3a ERP components were measured as well as the spectral power in each frequency band of the waking EEG. Pearson product moment correlations were used to measure associations between ERP characteristics and EEG spectral power in OSA patients and control subjects. RESULTS A positive correlation between the late P300 amplitude and θ power in the occipital region was observed in OSA subjects (P<.01). A positive correlation was also found between P3a amplitude and β1 power in central region in OSA subjects (P<.01). No correlation was observed for control subjects. CONCLUSIONS ERP abnormalities observed in an attention task are associated with a slowing of the waking EEG recorded at rest in OSA.

Brain perfusion during rapid-eye-movement sleep successfully identifies amnestic mild cognitive impairment

INTRODUCTION Prodromal markers of Alzheimers disease (AD) have been derived from wakefulness. However, brain perfusion during rapid-eye movement (REM) sleep could be a sensitive marker of amnestic mild cognitive impairment (aMCI), as activation of REM sleep relies more on the cholinergic system. METHODS Eight subjects with aMCI, and 16 controls, underwent two single-photon emission computed tomography (SPECT) scans with tracer injected during REM sleep then wakefulness. RESULTS Perfusion in the anterior cingulate cortex was significantly decreased in aMCI cases compared to controls for both conditions. That defect was much larger and more severe in REM sleep (1795 voxels) compared to wakefulness (398 voxels), and extended to the middle cingulate cortex and the olfactory cortex. Hypoperfusion in the anterior cingulate cortex during REM sleep allowed better classification than hypoperfusion found in wakefulness (93.8 vs 81.3%). CONCLUSION REM sleep imaging is a valuable tool with which to identify individuals at risk of developing AD.

Biomarkers of dementia in obstructive sleep apnea

Epidemiologic and mechanistic evidence is increasingly supporting the notion that obstructive sleep apnea is a risk factor for dementia. Hence, the identification of patients at risk of cognitive decline due to obstructive sleep apnea may significantly improve preventive strategies and treatment decision-making. Cerebrospinal fluid and blood biomarkers obtained through genomic, proteomic and metabolomic approaches are improving the ability to predict incident dementia. Therefore, fluid biomarkers have the potential to predict vulnerability to neurodegeneration in individuals with obstructive sleep apnea, as well as deepen our understanding of pathophysiological processes linking obstructive sleep apnea and dementia. Many fluid biomarkers linked to Alzheimers disease and vascular dementia show abnormal levels in individuals with obstructive sleep apnea, suggesting that these conditions share common underlying mechanisms, including amyloid and tau protein neuropathology, inflammation, oxidative stress, and metabolic disturbances. Markers of these processes include amyloid-β, tau proteins, inflammatory cytokines, acute-phase proteins, antioxydants and oxidized products, homocysteine and clusterin (apolipoprotein J). Thus, these biomarkers may have the ability to identify adults with obstructive sleep apnea at high risk of dementia and provide an opportunity for therapeutic intervention. Large cohort studies are necessary to establish a specific fluid biomarker panel linking obstructive sleep apnea to dementia risk.

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

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 Assessments 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. The Montreal Cognitive Assessment performs better than the Mini-Mental State Examination in detecting cognitive impairment in individuals with obstructive sleep apnoea http://ow.ly/8gLS30lxjZk

Obstructive Sleep Apnea and the Risk of Cognitive Decline in Older Adults

Obstructive sleep apnea causes intermittent hypoxia and sleep fragmentation and affects at least 20% of individuals after the age of 65. There is accumulating evidence that obstructive sleep apnea may impact brain structure and function. Recent cohort studies suggest that it is a risk factor for stroke, mild cognitive impairment and Alzheimers disease. Because prevention through treatment of risk factors is currently the main intervention for reducing the incidence of dementia, how obstructive sleep apnea affects brain health and whether its treatment can slow neurodegeneration are relevant questions. This Perspective Article presents the most recent findings on the neurocognitive consequences of obstructive sleep apnea in the elderly. We focus on the aging brain and the link between obstructive sleep apnea, brain health, cognitive decline and dementia. We present how new discoveries from animal models, human sleep experiments, and Alzheimers disease biomarkers point to an active role of disturbed sleep in dementia pathogenesis. We show preliminary data on how sex, genetics, physical exercise and cognitive reserve can strengthen or weaken the association between obstructive sleep apnea and dementia. We present preliminary results of obstructive sleep apnea treatment, which can slow, stop or reverse neurodegenerative processes accentuated by obstructive sleep apnea, even in individuals already affected by a neurodegenerative disease. We propose future research directions that include studies on mild/moderate untreated obstructive sleep apnea, the evaluation of continuous positive airway pressure treatment to slow neurodegeneration and follow-up studies of older patients that measure predictors/markers of dementia.