We report behavioral and cognitive characteristics of 12 patients with caudate nuclei lesions, 11 unilateral and one bilateral. These patients developed an acute behavioral change characterized by apathy, disinhibition, or a major affective disturbance. The pattern of personality change correlated with size and location of lesion within the caudate but not the laterality. Seven patients were further compared with matched controls on a series of neuropsychological tests. Their performance was impaired on tasks requiring planning and sequencing. They had short attention spans and decreased free recall of episodic and semantic items with good recognition memory scores. Similar behavioral and cognitive changes also occur in early Huntington's disease, frontal-lesioned patients, and caudate-lesioned animals, and correspond to disturbances of specific frontal-caudate circuits. These results implicate the caudate nuclei in mediating prefrontal behaviors and possibly in the conceptual integration of memories.

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The aim of this randomized controlled trial was to assess the effects of treatment with continuous positive airway pressure versus conservative therapy (CT) on well-being, mood, and functional status in subjects with mild sleep-disordered breathing (SDB). One hundred and eleven subjects, aged 25 to 65 yr, with a respiratory disturbance index (RDI) of 5 to 30 and without subjective pathologic sleepiness, were randomized to nasal CPAP or to CT. Ninety-seven subjects were followed-up after 8 wk. Treatment response was assessed from changes between baseline and follow-up measures of mood, energy/fatigue, and functional status/general health. Of the 51 subjects randomized to CPAP, 25 (49%) experienced an improved outcome, as compared with 12 of 46 of subjects (26%) randomized to CT (p < 0.05). The odds of experiencing a treatment response in the CPAP as compared with the CT group were 2.72 (OR: 1.18 to 6.58, 95% CI). A beneficial effect of CPAP over CT was most evident among individuals without sinus problems and among subjects with hypertension or diabetes. Differential treatment responses were not related to degree of baseline sleepiness or SDB. This suggests that middle-aged snorers with relatively low levels of SDB (RDI < 30) may benefit more from nasal CPAP than from less specific therapy directed at improving breathing during sleep. CPAP therapy may be beneficial to a broader group of subjects than previously appreciated.

Although a broad range of neuropsychological deficits has been reported in patients with severe sleep disordered breathing (SDB), little is known about the impact of mild SDB on neuropsychological performance. In this study, we compared neuropsychological test performance in two groups of carefully screened volunteers who differed clearly according to the respiratory disturbance index (RDI). Controls (n = 20) were identified on the basis of an RDI < 5; cases (n = 32) had an RDI in the range of 10-30. Cases and controls were well matched with regard to IQ, age, and sex. Cases had significantly more self-reported snorting and apneas and a higher body mass index than controls but did not differ according to sleepiness as measured by either the multiple sleep latency test or the Epworth sleepiness scale. An extensive battery of neuropsychological and performance tests was administered after an overnight sleep study. Cases performed significantly more poorly on a visual vigilance task (perceptual sensitivity, d': 2.24 +/- 0.64 vs. 2.70 +/- 0.53, p = 0.01, for cases and controls, respectively) and a test of working memory, the Wechsler adult intelligence scale-revised digits backwards test (6.12 +/- 2.20 vs. 7.55 +/- 2.22, p = 0.02), than controls. The groups did not differ in their performance on other tests of memory, information processing, and executive functioning. In summary, subjects with mild SDB may manifest a vigilance deficit in the absence of substantial sleepiness. Subjects with a mildly elevated RDI (10-30) without sleepiness do not appear to suffer appreciable deficits in more complex neuropsychological processes (e.g. executive functions).

Sleep-disordered breathing (SDB) has been associated with neuropsychological (NP) deficits. The extent to which such effects are attributable to unmeasured confounders or selection biases, or are manifest across a range of SDB is unclear. The relationship of SDB with a broad range of NP functions was examined in 100 volunteers with a spectrum of SDB and without underlying comorbidity. Factor analysis suggested that the NP tests could be summarized as four constructs: declarative memory, signal discrimination, working memory, and set shifting. These factors plus vigilance were dependent variables. Independent variables were age, the respiratory disturbance index (RDI), a sleepiness score, the arousal index, and sleep-associated hypoxemia. Factors "declarative memory" (measuring 25% of the common variance, alpha = 0.95), "signal discrimination" (10% variance, alpha = 0.70), and "working memory" (9% variance, alpha = 0.52) were each significantly, linearly predicted by hypoxemia and/or the RDI, with no evidence for significant threshold effects. SDB measures accounted for 4-6% of the variance in NP constructs. In contrast, sleepiness best predicted vigilance. Thus, adverse exposures (hypoxemia or RDI) during sleep may negatively influence NP functions in a dose-response relationship, and, other than vigilance, these effects may not be directly attributable to sleepiness.