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

Abstract

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.

The Prevalence of Obstructive Sleep Apnea in Mild Cognitive Impairment: A Systematic Review

“…Whilst there is an adverse impact of OSA on the healthy young brain, and this is greater with the aging middle-aged brain [41], the natural assumption is that the additive burden of OSA may exert greater deleterious effects especially to the elderly brain. Untreated OSA can potentially accentuate the progression of MCI and Alzheimer's disease [2] in cognitively intact individuals due the accumulation of Alzheimer's disease biomarkers (amyloid beta and tau proteins) [42,43], through hypoxic insults and/or disrupted sleep architecture [39].…”

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

“…Recent meta‐analyses concluded that OSA is a risk factor for cognitive decline and incident dementia (Leng, McEvoy, Allen, & Yaffe, ; Shi et al, ; Zhu & Zhao, ). These epidemiological findings have given rise to several mechanistic hypotheses linking OSA to neurodegeneration: OSA is associated with amyloid‐β generation and altered clearance, tau hyperphosphorylation, inflammation, oxidative stress, and metabolic and vascular deregulation (Baril, Carrier, et al, ; Baril, Gagnon, et al, ; Gosselin, Baril, Osorio, Kaminska, & Carrier, ; Polsek et al, ; Rosenzweig et al, ). In addition, OSA in late middle‐aged and older adults could precipitate the progression toward dementia by creating microstructural cerebral changes, especially white matter damage.…”

The Prevalence of Obstructive Sleep Apnea in Mild Cognitive Impairment: A Systematic Review

“…37,38 Long-standing OSA leads to recurrent intermittent hypoxia and alters sleep architecture, which may lead gradually to brain neurodegenerative processes. 39 A recent review proposed several possible mechanisms linking OSA to dementia, highlighting the important roles chronic sleep architecture impairments may play in neurogenesis, synaptic plasticity and memory consolidation. 39 A neuroimaging meta-analysis assessing the neuro-structural differences between patients with OSA and healthy controls reported significant grey matter reductions in the bilateral parahippocampus, left temporal and right frontal lobes of OSA patients.…”

“…39 A recent review proposed several possible mechanisms linking OSA to dementia, highlighting the important roles chronic sleep architecture impairments may play in neurogenesis, synaptic plasticity and memory consolidation. 39 A neuroimaging meta-analysis assessing the neuro-structural differences between patients with OSA and healthy controls reported significant grey matter reductions in the bilateral parahippocampus, left temporal and right frontal lobes of OSA patients. 40 Whilst there is an adverse impact of OSA on the healthy young brain, and this is greater with the aging middle-aged brain 41 , the natural assumption is that the additive burden of OSA may exert greater deleterious effects especially to the elderly brain.…”