Obstructive sleep apnea and cognitive impairment: Addressing the blood–brain barrier

Abstract

SUMMARY Increasing data support a connection between obstructive sleep apnea (OSA) and cognitive impairment but a causal link has yet to be established. Although neuronal loss has been linked to cognitive impairment, emerging theories propose that changes in synaptic plasticity can cause cognitive impairment. Studies demonstrate that disruption to the blood–brain barrier (BBB), which is uniquely structured to tightly maintain homeostasis inside the brain, leads to changes in the brain’s microenvironment and affects synaptic plasticity. Cyclical intermittent hypoxia is a stressor that could disrupt the BBB via molecular responses already known to occur in either OSA patients or animal models of intermittent hypoxia. However, we do not yet know if or how intermittent hypoxia can cause cognitive impairment by mechanisms operating at the BBB. Therefore, we propose that initially, adaptive homeostatic responses at the BBB occur in response to increased oxygen and nutrient demand, specifically through regulation of influx and efflux BBB transporters that alter microvessel permeability. We further hypothesize that although these responses are initially adaptive, these changes in BBB transporters can have long-term consequences that disrupt the brain’s microenvironment and alter synaptic plasticity leading to cognitive impairment.

Sleep disturbances and cognitive decline in the Northern Manhattan Study

“…20,23,24 Continuous positive airway pressure, the main therapy for SDB, delayed the progression of dementia in patients with SDB. 25 The NOMAS sample consists mostly of Caribbean Hispanics.…”

Intermittent Hypoxia-Induced Spinal Inflammation Impairs Respiratory Motor Plasticity by a Spinal p38 MAP Kinase-Dependent Mechanism

“…Ketoprofen inhibits prostaglandin and leukotriene synthesis (Netter et al, 1985;Walker, 1995;Cabré et al, 1998) by inhibiting the enzymatic activities of both COX-1 and COX-2 peripherally (Gynther et al, 2010;Kokki, 2010), though some work suggests that it can have direct effects centrally (Netter et al, 1985;Mannila et al, 2006) or when modified to increase blood-brain barrier permeability (Gynther et al, 2010). As such, pLTF rescue by ketoprofen most likely results from (1) directly diminishing CNS inflammation; (2) altering systemic inflammation, thereby decreasing transduction of systemic inflammatory signals via the vagus nerve (Hansen et al, 1998); (3) decreasing systemic expression of cytokines that cross the blood-brain barrier (Carson et al, 2006); and/or (4) preventing blood-brain barrier disruption and alteration of the brain's microenvironment (Lim and Pack, 2013). Although systemic NSAIDs do not localize the relevant inflammation, pLTF rescue by ketoprofen confirms that IH-1-induced inflammation undermines pLTF.…”

Hypomyelination, memory impairment, and blood–brain barrier permeability in a model of sleep apnea

“…Even controlling for performance in the first test, no significant differences were observed in novel object recognition test variables, indicating that performance of hypoxia and control groups were similar over time. Lim and Pack, (2014) sugge…”