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 Alzheimer’s 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 Alzheimer’s 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.

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.

Based on associations between sleep spindles, cognition, and sleep-dependent memory processing, here we evaluated potential relationships between levels of CSF Aβ42, P-tau, and T-tau with sleep spindle density and other biophysical properties of sleep spindles in a sample of cognitively normal elderly individuals. One-night in-lab nocturnal polysomnography (NPSG) and morning to early afternoon CSF collection were performed to measure CSF Aβ42, P-tau and T-tau. Seven days of actigraphy were collected to assess habitual total sleep time. Spindle density during NREM stage 2 (N2) sleep was negatively correlated with CSF Aβ42, P-tau and T-tau. From the three, CSF T-tau was the most significantly associated with spindle density, after adjusting for age, sex and ApoE4. Spindle duration, count and fast spindle density were also negatively correlated with T-tau levels. Sleep duration and other measures of sleep quality were not correlated with spindle characteristics and did not modify the associations between sleep spindle characteristics and the CSF biomarkers of AD. Reduced spindles during N2 sleep may represent an early dysfunction related to tau, possibly reflecting axonal damage or altered neuronal tau secretion, rendering it a potentially novel biomarker for early neuronal dysfunction. Given their putative role in memory consolidation and neuroplasticity, sleep spindles may represent a mechanism by which tau impairs memory consolidation, as well as a possible target for therapeutic interventions in cognitive decline.

S and full research articles published in SLEEP, the official journal of the APSS. Sleep and sleep disorder scientific findings.