Vincenza Castronovo

RATIONALE: Obstructive sleep apnea (OSA) is commonly associated with neurocognitive impairments that have not been consistently related to specific brain structure abnormalities. Knowledge of the brain structures involved in OSA and the corresponding functional implications could provide clues to the pathogenesis of cognitive impairment and its reversibility in this disorder. OBJECTIVES: To investigate the cognitive deficits and the corresponding brain morphology changes in OSA, and the modifications after treatment, using combined neuropsychologic testing and voxel-based morphometry. METHODS: A total of 17 patients treatment-naive to sleep apnea and 15 age-matched healthy control subjects underwent a sleep study, cognitive tests, and magnetic resonance imaging. After 3 months of treatment, cognitive and imaging data were collected to assess therapy efficacy. MEASUREMENTS AND MAIN RESULTS: Neuropsychologic results in pretreatment OSA showed impairments in most cognitive areas, and in mood and sleepiness. These impairments were associated with focal reductions of gray-matter volume in the left hippocampus (entorhinal cortex), left posterior parietal cortex, and right superior frontal gyrus. After treatment, we observed significant improvements involving memory, attention, and executive-functioning that paralleled gray-matter volume increases in hippocampal and frontal structures. CONCLUSIONS: The cognitive and structural deficits in OSA may be secondary to sleep deprivation and repetitive nocturnal intermittent hypoxemia. These negative effects may be recovered by consistent and thorough treatment. Our findings highlight the importance of early diagnosis and successful treatment of this disorder.

OBJECTIVE: To evaluate the cognitive performance of patients with idiopathic REM sleep behavior disorder (RBD). METHODS: The authors studied 17 consecutive patients with idiopathic RBD vs 17 age- and education-matched control subjects. Tests given to each patient and control included Mini-Mental State Examination, verbal and spatial short-term memory, visual selective attention, verbal fluency, prose memory, visuoconstructional abilities, spatial learning, and executive function tests. A self-administered depression rating scale was also used. RESULTS: RBD patients had significantly lower scores than control subjects in two tests: copy of Rey-Osterrieth Figure and Corsi Supraspan Learning. No correlation was found between the results of neuropsychological tests and RBD duration or with polysomnographic findings. CONCLUSIONS: Visuospatial constructional dysfunction and altered visuospatial learning may be present in idiopathic RBD. A neuropsychological assessment may be indicated in RBD patients.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is commonly associated with cognitive and functional deficits, some of which are resolved after continuous positive airway pressure (CPAP) treatment. The investigation of brain structural changes before and after treatment could provide deep insights into the pathogenesis and the reversibility of this disorder. We hypothesized that severe OSA patients would have altered white matter (WM) integrity and cognition and that treatment would improve both the structural damage and the cognitive impairment. DESIGN: Prospective clinical study. SETTING: The Sleep Disorders Center and the Center of Excellence in High-Field Magnetic Resonance Imaging at Vita-Salute San Raffaele University, Milan, Italy. PARTICIPANTS: Seventeen never-treated consecutive OSA patients were evaluated before and after treatment (after 3 and 12 months) and compared to 15 matched healthy controls. INTERVENTION: CPAP. MEASUREMENTS: WM integrity measured by diffusion tensor imaging (DTI) and cognitive performance (measured with neuropsychological testing) before and after 3 and 12 months of CPAP. RESULTS: Results in pre-treatment OSA patients showed impairments in most cognitive areas, mood and sleepiness that were associated with diffuse reduction of WM fiber integrity reflected by diminished fractional anisotropy (FA) and mean diffusivity (MD) in multiple brain areas. After 3 months of CPAP, only limited changes of WM were found. However, over the course of 12 months CPAP treatment, an almost complete reversal of WM abnormalities in all the affected regions was observed in patients who were compliant with treatment. Significant improvements involving memory, attention, and executive-functioning paralleled WM changes after treatment. CONCLUSIONS: Changes of WM DTI "signatures" of brain pathology in OSA patients are appreciable over the course of 12-month treatment with CPAP in most of the regions involved. Recovery of cognitive deficits after treatment is consistent with the presence of a reversible structural neural injury in OSA in patients who were compliant with treatment.