Hippocampal Hypertrophy and Sleep Apnea: A Role for the Ischemic Preconditioning?

Abstract

The full impact of multisystem disease such as obstructive sleep apnoea (OSA) on regions of the central nervous system is debated, as the subsequent neurocognitive sequelae are unclear. Several preclinical studies suggest that its purported major culprits, intermittent hypoxia and sleep fragmentation, can differentially affect adult hippocampal neurogenesis. Although the prospective biphasic nature of chronic intermittent hypoxia in animal models of OSA has been acknowledged, so far the evidence for increased ‘compensatory’ neurogenesis in humans is uncertain. In a cross-sectional study of 32 patients with mixed severity OSA and 32 non-apnoeic matched controls inferential analysis showed bilateral enlargement of hippocampi in the OSA group. Conversely, a trend for smaller thalami in the OSA group was noted. Furthermore, aberrant connectivity between the hippocampus and the cerebellum in the OSA group was also suggested by the correlation analysis. The role for the ischemia/hypoxia preconditioning in the neuropathology of OSA is herein indicated, with possible further reaching clinical implications.

Structural and functional neural adaptations in obstructive sleep apnea: An activation likelihood estimation meta-analysis

“…Moreover, an aberrant connectivity between the hippocampus and the cerebellum has been reported in OSA patients, with view that this may lead to alterations in a distributed memory system for associative learning (Rosenzweig et al, 2013a). In addition, bilateral enlargement of hippocampus in OSA patients has been reported previously (Rosenzweig et al, 2013b)…”

Sleep apnoea and the brain: a complex relationship

“…CPAP treatment of OSA has been shown to partially reverse the damage in hippocampal regions, and to ameliorate some of the associated cognitive deficits, possibly also by modulating adult neurogenesis 46 . In a recent neuroimaging study, co-existence of hypotrophic and hypertrophic changes in brains of OSA patients was taken to reflect the evolving nature of OSA-associated brain injury 30 . It was proposed that at any given time ongoing maladaptive neuroinflammatory processes likely exist alongside adaptive mechanisms of increased brain plasticity and ischemic preconditioning 30,83,[91][92][93] .…”

“…In a recent neuroimaging study, co-existence of hypotrophic and hypertrophic changes in brains of OSA patients was taken to reflect the evolving nature of OSA-associated brain injury 30 . It was proposed that at any given time ongoing maladaptive neuroinflammatory processes likely exist alongside adaptive mechanisms of increased brain plasticity and ischemic preconditioning 30,83,[91][92][93] . As a corollary to these findings, in a recent study that compared the cognitive performance of patients with high and low hypoxemia after controlling for demographic factors and other aspects of OSA severity, an unexpected advantage of higher hypoxemia on memory was demonstrated in a carefully matched clinical cohort 94 .…”

“…Their overall net result depends on the stage of this dynamic process, effects on other body systems, cognitive reserve and the idiosyncratic susceptibility of each particular patient (for in depth reviews please refer to 2,15,17,[27][28][29][30][31] ). This is important as different therapeutical approaches might benefit different stages and conversely might…”

Emerging co-morbidities of obstructive sleep apnea: cognition, kidney disease, and cancer

“…It is possible that aberrant functional connectivity of amygdala and hippocampus in patients with OSA may further impact already dysfunctional intrinsic network activity in MDD, and that this may underlie some of the psychological disturbances in patients with OSA (10). In a similar vein, an aberrant connectivity between the hippocampus and the cerebellum, which has been previously reported in OSA patients, may lead to alterations in a distributed memory system for associative learning (59). On the other hand, an atypical engagement of the insula within the salience network appears to be common feature of OSA as well as of several neuropsychiatric disorders, including AD and MDD (10).…”