Abstract
Obstructive sleep apnea (OSA) is accompanied by brain injury, perhaps resulting from apnea-related hypoxia or periods of impaired cerebral perfusion. Perfusion changes can be determined indirectly by evaluation of cerebral blood volume and oxygenation alterations, which can be measured rapidly and non-invasively with the global blood oxygen level dependent (BOLD) signal, a magnetic resonance imaging procedure. We assessed acute BOLD responses in OSA subjects to pressor challenges that elicit cerebral blood flow changes, using a two-group comparative design with healthy subjects as a reference. We separately assessed female and male patterns, since OSA characteristics and brain injury differ between sexes. We studied 94 subjects, 37 with newly-diagnosed, untreated OSA (6 female (age mean ± std: 52.1±8.1 yrs; apnea/hypopnea index [AHI]: 27.7±15.6 events/hr and 31 male 54.3±8.4 yrs; AHI: 37.4±19.6 events/hr), and 20 female (age 50.5±8.1 yrs) and 37 male (age 45.6±9.2 yrs) healthy control subjects. We measured brain BOLD responses every 2 s while subjects underwent cold pressor, hand grip, and Valsalva maneuver challenges. The global BOLD signal rapidly changed after the first 2 s of each challenge, and differed in magnitude between groups to two challenges (cold pressor, hand grip), but not to the Valsalva maneuver (repeated measures ANOVA, p<0.05). OSA females showed greater differences from males in response magnitude and pattern, relative to healthy counterparts. Cold pressor BOLD signal increases (mean ± adjusted standard error) at the 8 s peak were: OSA 0.14±0.08% vs. Control 0.31±0.06%, and hand grip at 6 s were: OSA 0.08±0.03% vs. Control at 0.30±0.02%. These findings, indicative of reduced cerebral blood flow changes to autonomic challenges in OSA, complement earlier reports of altered resting blood flow and reduced cerebral artery responsiveness. Females are more affected than males, an outcome which may contribute to the sex-specific brain injury in the syndrome.
Highlights
Obstructive sleep apnea (OSA) is present in approximately 10% of the adult population, and is accompanied by symptoms related to central nervous system dysfunction, including excessive daytime sleepiness, high levels of depression and anxiety, elevated sympathetic tone, and memory deficits [1,2]
To address the question of whether cerebral blood volume and oxygenation responses within brain tissue in OSA were impaired, we described whole-brain changes in global blood oxygen level dependent (BOLD) signal to transient blood pressure increases that normally elicit changes in cerebral blood flow and volume
Time trends and time points of within- and between-group differences are shown for OSA and control groups in Figs 1–6, and corresponding raw data are in file S1, S2, and S3 (Valsalva)
Summary
Obstructive sleep apnea (OSA) is present in approximately 10% of the adult population, and is accompanied by symptoms related to central nervous system dysfunction, including excessive daytime sleepiness, high levels of depression and anxiety, elevated sympathetic tone, and memory deficits [1,2] These symptoms likely derive from changes to brain structure and function in the condition [3,4,5,6,7,8,9,10]. Other challenges demonstrate similar patterns of reduced heart rate changes and altered neural responses in OSA [3,6,8] Such autonomic impairments could contribute to cerebral injury. The presence of impaired acute cerebral perfusion changes has only been shown in surface cerebral arteries, but not directly within brain tissue
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