Dysfonctions cérébrales et changements neuroanatomiques dans l’apnée obstructive du sommeil chez les personnes âgées

Obstructive sleep apnea (OSA) is a sleep disorder especially common in the older population, which can present itself at different levels of severity. Recent epidemiological studies showed an association between OSA and incident dementia. In addition, AOS was repeatedly identified as a risk factor for stroke. These potential consequences of OSA on the brain could be caused by intermittent hypoxemia and sleep fragmentation, which is observed following repeated respiratory obstructions. Although OSA has been implicated in the incidence of serious consequences on brain health, its impact on the function and structure of the aging brain remains unclear. Thus, the objective of this thesis was to evaluate the association between OSA as well as its severity with cerebral functioning and structure in adults aged 55 years old and over. We hypothesized that cerebral changes in individuals with OSA would be similar to profiles observed in preclinical stages of cognitive decline. In order to achieve this goal, various neuroimaging methods were used to characterize the brain of individuals with OSA as a whole. Cerebral functioning during wakeful rest was evaluated with single-photon emission computed tomography by measuring regional cerebral blood flow. Grey matter and white matter structure were evaluated with magnetic resonance imaging. Grey matter structure was assessed with structural techniques that measure grey matter volume and cortical thickness. White matter was assessed with diffusion tensor imaging that measures water molecules diffusion.  In our first study, we observed that severe OSA as well as many markers associated with OSA severity were correlated with hypoperfused regions during wakeful rest. These regions of reduced cerebral perfusion could present altered neuronal and glial functioning. In our second study, we showed that the daytime regional pattern of cerebral hypoperfusion was different whether apneas and hypopneas were observed during rapid eye movement sleep or non-rapid eye movement sleep. In individuals with a milder OSA severity, respiratory events during rapid eye movement sleep were still associated with regions of hypoperfusion. This suggests that respiratory events during rapid eye movement sleep may be more detrimental to brain health than those in non-rapid eye movement sleep. Overall, these results suggest that OSA leads to an altered cerebral functioning as evidenced by decreased regional cerebral perfusion. In addition, these studies also suggest that many factors contribute differently to cerebral dysfunction in OSA. In our third study, we observed that respiratory disturbances, sleep fragmentation, and mostly hypoxemia all contributed to grey matter hypertrophy. We suggest that oedema or other reactive or acute processes could cause these increased in grey matter structure. These processes may also explain our results observed in our last study. In that fourth study, we showed that OSA is associated with reduced white matter diffusivities, especially in milder OSA cases. An intracellular oedema process may restrict the diffusion of water molecules inside cells.  The results of this thesis clarify the cerebral changes observed in the aging population with OSA. Although reduced regional brain perfusion suggests cerebral dysfunctions, OSA was also associated with grey and white matter structural changes that suggest reactive and acute processes. Because this pattern was reported previously in preclinical stages of cognitive decline and dementia, our results highlight the importance of identifying individuals at higher risk of negative outcomes to brain health. In addition, our results also emphasize the importance of understanding the efficiency of treating OSA in order to prevent or slow its impact on cerebral functioning and structure.

Keyphrases: Obstructive sleep apnea, Aging, Biomarkers, Dementia, Neuroimaging, White matter, Grey matter, Magnetic resonance imaging, Regional cerebral blood flow, Single-photon emission computed tomography