Cognitive impairment in obstructive sleep apnea.

Obstructive sleep apnea (OSA) is characterised by repetitive cessation or reduction of airflow due to upper airway obstructions. These respiratory events lead to chronic sleep fragmentation and intermittent hypoxemia. Several studies have shown that OSA is associated with daytime sleepiness and cognitive dysfunctions, characterized by impairments of attention, episodic memory, working memory, and executive functions. This paper reviews the cognitive profile of adults with OSA and discusses the relative role of altered sleep and hypoxemia in the aetiology of these cognitive deficits. Markers of cognitive dysfunctions such as those measured with waking electroencephalography and neuroimaging are also presented. The effects of continuous positive airway pressure (CPAP) on cognitive functioning and the possibility of permanent brain damage associated with OSA are also discussed. Finally, this paper reviews the evidence suggesting that OSA is a risk factor for developing mild cognitive impairment and dementia in the aging population and stresses the importance of its early diagnosis and treatment.

Executive dysfunction and memory impairment in idiopathic REM sleep behavior disorder.

BACKGROUND: Idiopathic REM sleep behavior disorder (iRBD) might be a stage in the development of neurodegenerative disorders, especially Parkinson disease and dementia with Lewy bodies. Recent studies showing a slowing of waking EEG in iRBD suggest that iRBD is associated with cognitive impairment. OBJECTIVE: To compare patients with iRBD on measures of cognitive function and quantitative waking EEG. METHODS: Fourteen patients with iRBD and 14 healthy control subjects matched for age and educational level were studied. Subjects underwent an extensive neuropsychological evaluation and waking EEG recordings. RESULTS: Compared to controls, patients with iRBD showed a lower performance on neuropsychological tests measuring attention, executive functions, and verbal memory. Moreover, patients with iRBD showed EEG slowing (higher delta and theta power) during wakefulness in all brain areas compared to controls. However, no correlation was found between performance on cognitive tests and quantitative waking EEG in patients with iRBD. CONCLUSION: This study shows a co-occurrence of impaired cognitive profile and waking EEG slowing in patients with idiopathic REM sleep behavior disorder similar to that observed in early stages of some synucleinopathies.

Effects of obstructive sleep apnea on cognitive function: a comparison between younger and older OSAS patients.

BACKGROUND AND PURPOSE: Patients with obstructive sleep apnea syndrome (OSAS) present cognitive deficits similar to those observed with aging. The aim of the study was to assess the effects of age on cognitive functions in OSAS patients. It was hypothesized that older OSAS patients will exhibit significant cognitive dysfunction relative to younger OSAS patients and controls. PATIENTS AND METHODS: Younger and older OSAS patients were compared to younger and older control subjects (age cut-off set at 50 yrs). Participants underwent a polysomnographic (PSG) and neuropsychological evaluation. Variables were analyzed by two-way analyses of variance (ANOVAs) with two factors: Group (control and OSAS) and Age (younger and older). Additionally, we evaluated the contribution of attentional deficits to cognitive dysfunction for each subgroup of patients by using Spearman correlation coefficients. RESULTS: No Group-by-Age interaction was found for any neuropsychological variables (p<0.05). However, main Group and Age effects were found. Correlations indicated that attentional deficits contributed importantly to a poorer cognitive performance in younger OSAS patients only (p<0.01). CONCLUSIONS: Our results are in agreement with those of the literature for both OSAS-related and aging-related cognitive deficits but did not demonstrate that age interacts with the effects of the OSAS condition to make those cognitive deficits worse.

REM sleep behavior disorder predicts cognitive impairment in Parkinson disease without dementia.

OBJECTIVE: To assess the relationship between the presence of REM sleep behavior disorder (RBD) and the cognitive profile of nondemented patients with Parkinson disease (PD). BACKGROUND: Cognitive impairment is an important nonmotor symptom in PD. Waking EEG slowing in nondemented PD has been related to the presence of RBD, a parasomnia affecting brainstem structures and frequently reported in PD. For this reason, RBD may be associated with cognitive impairment in PD. METHODS: Thirty-four patients with PD (18 patients with polysomnographic-confirmed RBD and 16 patients without RBD) and 25 healthy control subjects matched for age and educational level underwent sleep laboratory recordings and a comprehensive neuropsychological assessment. RESULTS: Patients with PD and concomitant RBD showed significantly poorer performance on standardized tests measuring episodic verbal memory, executive functions, as well as visuospatial and visuoperceptual processing compared to both patients with PD without RBD and control subjects. Patients with PD without RBD had no detectable cognitive impairment compared to controls. CONCLUSIONS: This study shows that cognitive impairment in nondemented patients with Parkinson disease (PD) is closely related to the presence of REM sleep behavior disorder, a sleep disturbance that was not controlled for in previous studies assessing cognitive deficits in PD.

Assessing whole brain perfusion changes in patients with REM sleep behavior disorder.

OBJECTIVE: To investigate the regional cerebral perfusion in patients with idiopathic REM behavior disorder (RBD) in order to establish the topography of networks involved. METHODS: We performed cerebral blood flow evaluation using (99m)Tc-Ethylene Cysteinate Dimer (ECD) SPECT on eight patients with polysomnographically confirmed RBD and nine age-matched controls. Comparisons were made using SPM2. RESULTS: We found increased perfusion in the pons and putamen bilaterally and in the right hippocampus. In addition, we observed a decreased perfusion in frontal (Brodmann area [BA] 4, 6, 10, 43, 44, 47 bilaterally and left BA 9, 46) and temporo-parietal (BA 13, 22, 43 bilaterally and left BA 7, 19, 20, 21, 39, 40, 41, 42) cortices. CONCLUSION: Perfusional abnormalities in patients with REM behavior disorder were located in the brainstem, striatum, and cortex. These abnormalities are consistent with the anatomic metabolic profile of Parkinson disease.

Association between waking EEG slowing and REM sleep behavior disorder in PD without dementia.

OBJECTIVE: To compare nondemented patients with Parkinson's disease (PD) with and without REM sleep behavior disorder (RBD) to healthy controls on quantitative EEG characteristics for both wakefulness and REM sleep. METHODS: Fifteen patients with PD (7 patients with polysomnographic-confirmed RBD [PD-RBD] and 8 patients without RBD [PD-NRBD]) and 15 healthy control subjects were studied. Each subject underwent a quantitative EEG analysis of both wakefulness and REM sleep. RESULTS: During wakefulness, patients with PD-RBD showed a higher theta power in frontal, parietal, temporal, and occipital regions in comparison to patients with PD-NRBD and control subjects. Moreover, a slowing of the dominant occipital frequency was observed only in patients with PD-RBD (p < 0.02). Patients with PD-NRBD did not present any slowing of the EEG. No between-group difference in quantitative REM sleep EEG was observed. CONCLUSIONS: This study demonstrates that the EEG slowing reported during wakefulness in nondemented patients with PD is strongly related to the presence of RBD.

Slow-wave activity in sleep apnea patients before and after continuous positive airway pressure treatment: contribution to daytime sleepiness.

STUDY OBJECTIVES: To estimate the course of slow-wave activity (SWA), its amount during the night, and its correlation with daytime sleepiness in sleep apnea syndrome (SAS) patients. This study also verified whether continuous positive airway pressure (CPAP) treatment also restores a normal pattern of SWA in severe SAS patients. PARTICIPANTS: Ten patients with a diagnosis of severe SAS who showed a good clinical response to CPAP after approximately 9 months of treatment were included in this study. These patients were matched for sex and age with 10 control subjects. DESIGN: All subjects underwent 1 night of polysomnography (PSG), followed by the multiple sleep latency test (MSLT) the next day. For the SAS patients only, the same procedure was repeated after 9 +/- 0.7 months of CPAP treatment. In addition to traditional scoring of sleep stages, apneas, hypopneas, and microarousals, the SWA, defined as the power in the 0.75- to 4.5-Hz frequency band, was evaluated. RESULTS: A positive correlation between SWA of the first cycle and the MSLT (r = 0.56; p = 0.045) was found before treatment. Moreover, SAS patients significantly increased their mean SWA after CPAP treatment in the first (p = 0.024) and second (p = 0.002) sleep cycles and restored a more physiologic decay of SWA across the night. CONCLUSIONS: These results suggest that daytime sleepiness in SAS patients may be the result of a lack of SWA during the first part of the night, and show that CPAP restores a more physiologic pattern of SWA across the night.

Daytime sleepiness and EEG spectral analysis in apneic patients before and after treatment with continuous positive airway pressure.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is characterized by recurrent apneas during sleep, resulting in repetitive hypoxemic episodes and interruptions of the normal sleep pattern. A previous study showed EEG slowing (ie, a higher ratio of delta + theta frequencies to alpha + beta frequencies on EEG) during rapid eye movement (REM) sleep and wakefulness in untreated OSAS patients. STUDY AND OBJECTIVES: To determine whether EEG slowing is reversible with continuous positive air pressure (CPAP) treatment and to verify whether the persistence of excessive daytime sleepiness (EDS) is correlated with residual slowing of the EEG. PATIENTS: Ten healthy subjects (9 men and 1 woman) and 14 patients with moderate-to-severe OSAS (13 men and 1 woman) were studied before and after 6 months of treatment with CPAP. RESULTS: Untreated OSAS patients showed EEG slowing in frontal and central cortical regions during both wakefulness and during REM sleep compared to healthy control subjects. This EEG slowing was found to be independent of time spent with arterial oxygen saturation < 90%, severity of OSAS, or mean sleep latency as determined by the multiple sleep latency test. CPAP treatment was found to correct the EEG slowing for both REM sleep and wakefulness. Daytime sleepiness also greatly improved with treatment, but some degree of somnolence remained. CONCLUSION: CPAP treatment was found to correct the EEG slowing that was observed in untreated OSAS patients. Persistent EDS may be related to persistent obesity after CPAP treatment.

Cognitive deficits associated with sleep apnea syndrome: a proposed neuropsychological test battery.

Numerous studies have assessed a wide range of cognitive deficits associated with obstructive sleep apnea syndrome (OSAS). The comparison of these various results, however, is hampered by the fact that different studies employ different neuropsychological tests, even when assessing the same function. The aim of this paper is to present a standardized neuropsychological test battery for the evaluation of OSAS patients. Following a description of the general characteristics of OSAS, we review the main cognitive functions reported as being impaired in OSAS patients. These include general intellectual functioning, attentional functioning, memory and learning abilities, executive functions, and motor performance. Based on this review, we propose a test battery designed to cover these cognitive processes while taking into account the time constraints present in most research and clinical centers. In addition to providing a comprehensive neuropsychological evaluation of OSAS patients, the proposed test battery should facilitate the comparison of results from different laboratories.

Sleep disturbances and eeg slowing in alzheimer's disease.

Changes in sleep structure, and especially REM sleep, and in EEG activation were studied in relation to the cholinergic deficit found in Alzheimer's Disease (AD). With respect to sleep architecture, only REM sleep percent was reduced in AD patients compared to controls as a result of a decrease in mean REM episode duration. Different results were obtained in patients with progressive supranuclear palsy (PSP). These results are discussed with respect to the role of brainstem and forebrain cholinergic populations in REM sleep generation in humans. More importantly, it was shown by means of spectral analyses that EEG slowing is much more prominent in REM sleep than in wakefulness in AD. Furthermore, there is a distinct topographical pattern of REM sleep EEG slowing in AD patients which is in agreement with findings from neuroradiological and neuropathological studies. Using the ratio of slow over fast frequencies from the temporal regions, a correct classification of 90.4% of subjects was obtained for the REM sleep EEG. This discrimination rate is the best marker of AD so far using a single measure. Quantitative REM sleep EEG was also used to evaluate patients' biological response to cholinergic treatments. Finally, we present here preliminary data on the progression of EEG slowing in wakefulness and in REM sleep. After six months on a placebo, there was only a decrease in alpha activity in wakefulness over all regions studied. No changes were observed for REM sleep.

Sleep and quantitative EEG in patients with progressive supranuclear palsy.

Sleep architecture and quantitative EEG from wakefulness and REM sleep were studied in six patients (mean age, 70.5 years) with progressive supranuclear palsy (PSP) and compared with that of six control subjects (mean age, 69.8 years). Particular attention was given to quantifying REM sleep variables because of the known PSP-associated degeneration of the pedunculopontine tegmentum (PPT)--a critical structure in REM sleep generation. Patients with PSP had a shorter total sleep time, a lower sleep efficiency, a drastic reduction in sleep spindles, an atonic slow-wave sleep, and a lower percentage of REM sleep. The lower percentage of REM sleep was the result of both a reduction in the number of REM periods and a reduction in mean period of duration. REM density was also reduced while REM efficiency, atonia, and phasic EMG were similar to control values. REM sleep findings are consistent with the known role of the PPT in REM sleep induction. A slowing of the awake EEG was found for the six frontal leads and for C4, P4, and T4 in PSP patients. The frontal EEG slowing found in wakefulness is in accord with imaging and neuropsychological studies showing impairment of the frontal lobes in these patients. REM sleep EEG was not significantly slower in any regions. Because all previous studies on PSP have relied on visual inspection of the EEG tracings, the present finding of EEG slowing in the frontal lobes (rather than in the temporal regions or diffusely) suggests that our quantitative EEG approach may be more useful in determining specific regions of impaired cortical activity.

Response selection deficits in frontal excisions.

We compared the performance of patients with frontal excisions, patients with temporal excisions and controls in tasks involving speeded choice responses in which a number of variables were manipulated including: perceptual difficulty, stimulus and response set-size, associative complexity, and spatial stimulus-response compatibility. Response times were sensitive to all manipulations but did not show any group differences. The error rates of the three groups were equally affected by perceptual difficulty and response set-size but frontals were preferentially affected by spatial S-R compatibility, associative complexity, and the number of stimuli per response. The results are consistent with a basic deficit in response selection processes which could underly many problems produced by frontal lesions.

Tardive dyskinesia and associated cognitive disorders: a convergent neuropsychological and neurophysiological approach.

This study sought to assess whether tardive dyskinesia (TD) related differentially to two types of cognitive functioning in schizophrenia. Thirteen schizophrenics with severe formal thought disorders (+FTD) were matched for age, sex, education, chronicity, dosage, hospital care, with 13 schizophrenics selected for absence of or minimal formal thought disorders (-FTD). TD and neuroleptic dosage were analyzed in relation to cognitive and motor tests of the Luria-Nebraska (L-N) battery and to attentional evoked potentials (EPs). EPs were recorded at electrodes Fz, Cz, and Pz, in a dichotic signal detection task (oddball paradigm), during attention and inattention conditions. Group differences on attentional EPs replicated published results with flatter and smaller positive waves in +FTD patients and larger late negative waves (FzN4-N7) in -FTD patients. Controlling for dosage, the following were the best groups discriminators. +FTD schizophrenics presented more severe dyskinesia in the orofacial area and poorer verbal scores on L-N. Severe TD correlated with smaller N1 amplitudes. +FTDs also presented distinct attentional EP deficits with abnormally small P3a, a correlate of deficient categorization and orienting. Neuroleptic dosage was not directly correlated to any single motor or cognitive measure, nor to TD indices. The hypothesis of a differential association of TD with distinct attentional/cognitive disorders was generally supported.

Target detection deficits in frontal lobectomy.

We examined the hypothesis of dorsomedial frontal lobe involvement in target detection through the effects of distractor interference and multiple target interference on unilateral lobectomy patients. Seven patients who underwent a unilateral frontal lobectomy for epilepsy involving dorsomedial cortex and variable amounts of lateral cortex were compared to 10 patients with a unilateral temporal lobectomy and to 10 normal adults on a visual character cancellation task. The task involved detecting occurrences of target characters embedded in rows of characters under three conditions: detection of one target character in the absence of distractors, detection of one target character among distractors, and detection of three targets among distractors. Visual detection performance was compared to that in the Stroop reading interference task. Frontals were predictably slower than the other groups in the baseline conditions of the character cancellation task and the Stroop task. After partialing out baseline detection performance in the character cancellation task, frontals showed an almost normal detection in the presence of distractors but were distinctly slower and made more errors than the other groups in multiple target detection. Frontals were also slower on the Stroop even after partialing out baseline naming performance. Temporals were normal on all tasks. Results suggest that frontal damage can affect selectivity in target detection as well as the Stroop and that this deficit is independent of the general psychomotor slowing observed in these patients.