Hypoxemia correlates with attentional dysfunction in patients with obstructive sleep apnea.

PURPOSE: Obstructive sleep apnea is associated with cognitive impairment, but whether hypoxemia or repeated arousals and sleepiness are the underlying mechanism is controversial. Studies using a wide range of attention and executive functions tests in patients with severe sleep apnea are lacking. METHODS: In a prospective cohort study, 40 patients aged 30-70 years, diagnosed with obstructive sleep apnea (apnea-hypopnea index ≥5) were recruited. Patients with known cardiovascular, pulmonary, psychiatric, or neurological disease, and or patients receiving anti-psychotic, sedatives, or stimulant medications were excluded. Patients underwent full overnight polysomnography including continuous oxygen saturation measurements followed by extensive neuropsychological testings in attention and executive function domains. The correlation between sleep apnea severity and patients' performance on the neuropsychological tests was examined. RESULTS: The patients' performance on measures of attention and executive function was significantly worse compared to the average in a normal population. Attention, as reflected by the number of omissions and by the reaction time on the Conners' Continuous Performance Test correlated significantly with the apnea-hypopnea index (r = 0.6, p < 0.001 and r = 0.48, p = 0.003, respectively) and with parameters of hypoxemia, namely the average SpO(2) (r = -0.51, p = 0.002 and r = -0.39, p = 0.02, respectively) and the percent time spent with SpO(2) < 90% (r = 0.57, p < 0.001 and r = 0.39, p = 0.02, respectively), but not with the degree of sleepiness. Executive dysfunction did not correlate with sleep parameters. DISCUSSION: Attention is the predominant cognitive function affected in patients with obstructive sleep apnea and correlates primarily with nocturnal hypoxemia rather than daytime sleepiness or sleep fragmentation. Executive functions, while below average in some patients, do not correlate with polysomnographic parameters.

Beneficial effect of repetitive transcranial magnetic stimulation combined with cognitive training for the treatment of Alzheimer's disease: a proof of concept study.

The current drug treatment for Alzheimer's disease (AD) is only partially and temporary effective. Transcranial magnetic stimulation (TMS) is a non-invasive technique that generates an electric current inducing modulation in cortical excitability. In addition, cognitive training (COG) may improve cognitive functions in AD. Our aim was to treat AD patients combining high-frequency repetitive TMS interlaced with COG (rTMS-COG). Eight patients with probable AD, treated for more than 2 months with cholinesterase inhibitors, were subjected to daily rTMS-COG sessions (5/week) for 6 weeks, followed by maintenance sessions (2/week) for an additional 3 months. Six brain regions, located individually by MRI, were stimulated. COG tasks were developed to fit these regions. Primary objectives were average improvement of Alzheimer Disease Assessment Scale-Cognitive (ADAS-cog) and Clinical Global Impression of Change (CGIC) (after 6 weeks and 4.5 months, compared to baseline). Secondary objectives were average improvement of MMSE, ADAS-ADL, Hamilton Depression Scale (HAMILTON) and Neuropsychiatric Inventory (NPI). One patient abandoned the study after 2 months (severe urinary sepsis). ADAS-cog (average) improved by approximately 4 points after both 6 weeks and 4.5 months of treatment (P < 0.01 and P < 0.05) and CGIC by 1.0 and 1.6 points, respectively. MMSE, ADAS-ADL and HAMILTON improved, but without statistical significance. NPI did not change. No side effects were recorded. In this study, rTMS-COG (provided by Neuronix Ltd., Yokneam, Israel) seems a promising effective and safe modality for AD treatment, possibly as good as cholinesterase inhibitors. A European double blind study is underway.