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Abstract: Objective:: Although epidemiological and clinical studies suggest that hormone replacement therapy (HRT) may protect against cognitive disorders and neurodegenerative diseases, the relation between estrogen and cognition in postmenopausal women remains controversial. Methods:: In a double-blind placebo-controlled, parallel group design study the effects of HRT with the estrogen–progestogen combination Presomen 1.25 compositum® (1.25mg equine conjugated estrogens administered for 21 days plus the progestogen 5mg medrogeston given for 11 days) on event-related potentials (ERPs) in postmenopausal patients with age-related cognitive decline (DSM-IV code 780.9, ICD-10 code R 41.8) were investigated. After a pre-drug comparison with age-matched normal postmenopausal controls, 48 psychotropic drug-free patients aged 60 ± 6 years were randomized to receive either placebo or verum for 4 months. ERPs were recorded before as well as on the 91–92 days of the study, which thus fell into the estrogen phase of the treatment during the fourth cycle. Results:: At baseline, patients showed a lengthening of P300 latency and an attenuation of P300 amplitudes as compared with normal controls. After HRT with Presomen, a significant shortening of P300 latency as compared with placebo was observed. Conclusions:: The baseline P300 differences suggest that in the patient group the aging process was advanced, while after HRT with Presomen a significant improvement and normalization of information processing as indexed by P300 was observed. [Copyright &y& Elsevier]

Unlabelled: The aim of the double-blind, placebo-controlled study was to investigate the effects of a continuous combined estrogen-progestogen treatment (Climodien, Lafamme) as compared with estrogen alone on vigilance in insomniac postmenopausal syndrome patients, objectified by EEG mapping.Methods: In a 3-arm, 2-month parallel group design phase, patients received a combination of estradiol valerate 2 mg and the novel progestogen dienogest 3 mg (Climodien 2/3) or estradiol valerate 2 mg alone or placebo. In a subsequent open-label phase, all patients received estradiol valerate 2 mg+dienogest 2 mg (Climodien 2/2). EEG mapping was carried out before and after the 2-month double-blind phase as well as after the 2-month open-label treatment.Results: As compared with placebo, Climodien 2/3 induced a marked and highly significant increase in absolute power in all frequency bands, specifically in alpha-2 activity. Moreover, a significant increase in relative alpha-2 power, a decrease in relative delta and beta power as well as an acceleration of the dominant frequency and of the delta and alpha centroids suggested a marked improvement in vigilance. In contrast, under estradiol valerate 2 mg alone, only a slight augmentation of alpha and attenuation of relative delta and beta power occurred, suggesting only a slight vigilance improvement as compared with placebo. Thus, dienogest 2 mg increased the estrogen effect, which was also confirmed by a statistical evaluation of the differences between Climodien 2/3 and estradiol valerate alone (augmentation of alpha-2, attenuation of relative beta, acceleration of the dominant frequency). Moreover, Climodien 2/2 also markedly increased alpha-2 power, decreased relative beta-2 power and accelerated the alpha centroid. Finally, comparing Climodien 2/3 with Climodien 2/2, there was even a dose-efficacy relation.Conclusions: Estradiol valerate 2 mg improves vigilance slightly, thereby confirming previous findings. The additional administration of dienogest does not minimize the effect of estrogen, but on the contrary increases it, which makes the combination superior to both placebo and estradiol valerate alone. Vigilance improvement may be of great therapeutic benefit to menopausal syndrome patients at a time when increased adaptability is needed to adjust to increasing sexual, marital, occupational and social difficulties known to occur specifically in this period of life. [ABSTRACT FROM AUTHOR]

Background: S-Adenosyl-L-methionine (SAMe, or ademetionine) is a naturally occurring molecule used as both a nutraceutical and a pharmaceutical to treat depression. Objective: The central mode of action of SAMe was investigated in 20 healthy volunteers by mapping of electroencephalograms (EEGs) and event-related potentials (ERPs) and low-resolution brain electromagnetic tomography (LORETA). Design: In an acute and subacute, double-blind, placebo-controlled, crossover study, subjects received in random order infusions of 800 mg SAMe and placebo for 7 d, with a washout period of 3 wk between the 2 treatment periods. EEG recordings were made 0, 1, 3, and 6 h after and ERP recordings were made 0 and 1 h after the drug infusions on days 1 and 7. Results: Multivariate analyses of variance and Hotelling T2 tests showed significant acute and subacute encephalotropic effects of SAMe compared with placebo. Acute pharmaco-EEG changes were typical of classic antidepressants of the thymoleptic type; subacute alterations were typical of cognition enhancers. Regarding ERPs, standard N1 and P2 latencies were shortened, and target P300 latencies were lengthened. N1 amplitudes increased after subacute treatment, and temporooccipital P300 amplitudes increased after the acute dose. Similar changes were described for antidepressants. LORETA showed that the N2 source strength increased in both the left and the right temporal lobes, whereas the P300 source strength increased in the dorsolateral prefrontal regions and decreased in the ventral limbic regions. Conclusion: EEG-ERP mapping identified SAMe as an antidepressant. LORETAtargeted brain regions crucial in the therapeutic efficacy of antidepressants. [ABSTRACT FROM AUTHOR]

The influence of a combined estrogen-progestin regimen (Climodien®, Lafamme®) on auditory event-related potentials (ERPs) was investigated in a double-blind, placebo-controlled, comparative, randomized 3-arm trial phase (Climodien 2/3=estradiol valerate 2 mg+the progestin dienogest 3 mg, EV=estradiol valerate 2 mg, and placebo), followed by an open-label phase in which all patients received Climodien 2/2 (estradiol valerate 2 mg+dienogest 2 mg). Both the double-blind and the open-label phase lasted 2 months. ERPs were recorded from 19 EEG leads in a two-tone odd-ball paradigm in 49 patients aged between 46 and 67 yr with the diagnosis of insomnia (G 47.0) related to postmenopausal syndrome (N 95.1). Climodien reduced standard N1 and target P300 latencies as compared to placebo, while EV did not affect N1 latency but similarly reduced P300 latency. Climodien increased N1, P2 and P300 amplitudes dose-dependently, predominantly at frontal leads. Estrogen alone had only minor effects on ERP amplitudes. The shortening of standard N1 latency and enhancement of N1 and P2 amplitudes indicates a positive effect of Climodien on perceptual processing, most likely due to vigilance improvements also observed in EEG mapping. Concerning target P300, it seems that estradiol is responsible for the improvement in stimulus evaluation time, as reflected by the shortening of the peak latency, while dienogest seems to account for the improvement in cognitive information processing capacity, whereby 3 mg induced a more pronounced augmentation of P300 amplitudes than 2 mg. Based on the spatial distribution of this increase, it can be speculated that Climodien mainly affects the more frontally distributed P3a subcomponent, which is associated with attention and orientation. Furthermore, the observed changes in ERP-components are consistent with recent studies showing significant positive effects of hormone replacement therapy on cholinergic functions. Thus, Climodien seems to be of interest in preventing cognitive decline and treating cognitive disorders in postmenopausal women. Indeed, there is increasing evidence of beneficial effects of estrogen in dementia. Our present findings suggest that the estrogen effects may be augmented by dienogest. [Copyright &y& Elsevier]

Restless legs syndrome (RLS) is a sensorimotor movement and sleep disorder with a high prevalence. While the sleep disturbance due to RLS has been studied quite well polysomnographically, little is known about the electrophysiological function during daytime. The aim of the present study was to investigate the diurnal quantitative EEG and clinical symptomatology in 33 drug-free RLS patients as compared with age- and sex-matched normal controls. Investigations comprised brain mapping of the vigilance-controlled EEG as well as completion of the Zung Self-Rating Depression Scale, the Zung Self-Rating Anxiety Scale, the Quality of Life Index, the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale for evaluation of clinical symptomatology. Statistical analysis demonstrated an increase in absolute delta and absolute and relative alpha-2 power, a decrease in absolute and relative alpha-1 power, an acceleration of the dominant frequency and the alpha centroid, and a slowing of the delta/theta centroid, as well as a non-significant attenuation in total power. These findings are characteristic of dissociated vigilance changes described in depression. Indeed, RLS patients demonstrated significantly higher depression and anxiety scores, lower quality of life and deteriorated sleep quality. The score of the Epworth Sleepiness Scale was not elevated, in contrast to the increased daytime sleepiness observed in other highly prevalent organic sleep disorders (e.g. sleep apnea). In conclusion, daytime EEG mapping revealed neurophysiological correlates of depression in RLS, which was confirmed by self-ratings at the symptomatological level. [Copyright &y& Elsevier]

Objective: Obstructive sleep apnea (OSA) impacts stroke recovery and outcome negatively. Although its identification and treatment are part of the current stroke guidelines, standard management with positive airway pressure (PAP) therapy is not routinely performed and adherence rates are very low. The purpose of this study was to determine whether PAP adherence can be improved by a PAP training strategy during in-hospital rehabilitation combined with a telemedicine monitoring system after discharge.Methods: In this study, we performed a controlled trial (RCT) on standard PAP treatment (SG) as compared with proactive telemonitored PAP treatment (TG). After three months and one year, PAP adherence (min of use per day) and clinical outcome variables were compared.Results: In 33 (47.1%) out of 70 patients diagnosed with therapy-relevant OSA [70% male, 62 (5) years, body mass index (BMI) 30 (4) kg/m2, Barthel Index 90 (20), NIHSS 3 (3)] in-hospital PAP titration was performed. Subsequently, they were randomized to SG or TG. Drop-out rates after three months and after one year were 12% and 30%, respectively, with no differences between the groups. After three months, telemonitored patients used the PAP device 76 min longer per night (SG: 299 (76), TG: 375 (86) minutes per night; p = 0.017), after one year there was no significant difference.Conclusion: People with stroke and therapy-relevant OSA who accept PAP therapy should receive additional telemedicine monitoring at least for three months. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov; Unique identifier: NCT02748681. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To elucidate the relationship between excessive daytime sleepiness (EDS) in obstructive sleep apnea (OSA) and carotid atherosclerosis determined by ultrasonography and serum surrogate markers. Methods: One hundred and forty-seven patients (102 males) with snoring and sleep-disordered breathing were investigated. Carotid atherosclerosis was evaluated by serum analysis of high-sensitivity C-reactive protein and fibrinogen and four sonographic indices: intima media thickness (IMT) of the common carotid artery (CCA), IMT from the bulb to the internal carotid artery (ICA), combined IMT measurements from all segments and a plaque score. EDS was assessed by the Epworth Sleepiness Scale (ESS). Pearson correlation analysis, intergroup comparison (ANOVA) and two multiple regression models explored associations between confounders, surrogate markers and EDS. Results: Forty-four patients had no OSA (apnea–hypopnea index AHI<5h−1), 27 mild (5–15), 25 moderate (15–30) and 51 severe OSA (>30). The ESS significantly distinguished severe OSA from non-OSA patients (p =0.003). It showed significant correlations with the BMI, HbA1c, systolic RR, the AHI, sleep time spent with an oxygen saturation <90%, the respiratory arousal index, IMT of the CCA and combined IMT measurements, but no correlation with serum markers. The ESS was found to be an independent predictor of CCA-IMT in the pre-polysomnographic multiple regression model (p =0.008), but not in the post-polysomnographic model after including respiratory variables. Conclusion: EDS is associated with obesity, diabetes and all respiratory variables in OSA patients and may serve as an independent predictor of carotid atherosclerosis before polysomnography. [Copyright &y& Elsevier]

Abstract: We reported earlier that overnight change in explicit memory is positively related to the change in sleep spindle activity (between a control and a learning night). However, it remained unclear whether this effect was restricted to good memory performers and whether a general association of sleep spindles and a “sleep-related learning trait” may not account for this effect. Here we now present a secondary and more detailed analysis of our randomized multicenter study. Subjects were studied over a 4-week study period (including actigraphy and daily sleep diaries), including three overnight stays in the sleep laboratory. In the course of the study, subjects completed test-batteries of memory (Wechsler-Memory-Scale-revised; WMS) and other cognitive abilities (Raven''s Advanced-Progressive-Matrices; APM) and were asked to study 160 word pairs in the evening before being tested by cued-recall. Afterwards, subjects went to bed in the laboratory with full polysomnographic montages. Additionally, subjects participated on another occasion in a non-learning control (perceptual priming) task that was counterbalanced either before or after the learning condition. Slow as well as fast spindle activities were analyzed at frontopolar and central topographies. Although it was found that spindle activity is generally (in learning as well as control nights) elevated in highly gifted subjects, spindle analyses revealed that spindle increase (control to learning night) is specifically related to explicit memory improvement overnight, independent of individual learning traits. Together these findings suggest that the spindle increase after learning is related to elaborate encoding before sleep, whereas an individual''s general learning ability is well reflected in interindividual (and trait-like) differences of absolute sleep spindle activity. [Copyright &y& Elsevier]

Abstract: Low-resolution brain electromagnetic tomography (LORETA) showed a functional deterioration of the fronto-temporo-parietal network of the right hemispheric vigilance system in narcolepsy and a therapeutic effect of modafinil. The aim of this study was to determine the effects of modafinil on cognitive and thymopsychic variables in patients with narcolepsy and investigate whether neurophysiological vigilance changes correlate with cognitive and subjective vigilance alterations at the behavioral level. In a double-blind, placebo-controlled crossover design, EEG-LORETA and psychometric data were obtained during midmorning hours in 15 narcoleptics before and after 3 weeks of placebo or 400 mg modafinil. Cognitive investigations included the Pauli Test and complex reaction time. Thymopsychic/psychophysiological evaluation comprised drive, mood, affectivity, wakefulness, depression, anxiety, the Symptom Checklist 90 and critical flicker frequency. The Multiple Sleep Latency Test (MSLT) and the Epworth Sleepiness Scale (ESS) were performed too. Cognitive performance (Pauli Test) was significantly better after modafinil than after placebo. Concerning reaction time and thymopsychic variables, no significant differences were observed. Correlation analyses revealed that a decrease in prefrontal delta, theta and alpha-1 power correlated with an improvement in cognitive performance. Moreover, drowsiness was positively correlated with theta power in parietal and medial prefrontal regions and beta-1 and beta-2 power in occipital regions. A less significant correlation was observed between midmorning EEG LORETA and the MSLT; between EEG LORETA and the ESS, the correlation was even weaker. In conclusion, modafinil did not influence thymopsychic variables in narcolepsy, but it significantly improved cognitive performance, which may be related to medial prefrontal activity processes identified by LORETA. [Copyright &y& Elsevier]

The aim of the study was to investigate abnormalities of event-related potentials (ERPs) in social phobia patients indicating deficits in speed and amount of perceptual and cognitive resources as well as relationships between ERPs and cognitive functioning. ERPs were recorded from 19 EEG leads in a two-tone oddball paradigm in medication-free patients with DSM-IV social phobia (n=25) and in age- and sex-matched healthy controls (HC). Neuropsychological test performance was administered. Compared with the HC group, patients with social phobia showed reductions in N1 at temporal leads, N2 and P300 amplitudes, predominantly centroparietally, and longer P300 latencies. The observed P300 latency prolongation was associated with reduced Non-Verbal Learning Test (NVLT) but not the Wisconsin Card Sorting Test (WCST) scores. The reduction in N1 amplitude indicates an impairment in perceptual processing. The reduced P300 amplitudes may reflect reduced cognitive resources for the evaluation of relevant information. The increased P300 latency, indicating longer stimulus evaluation time, was correlated to deficits in learning processes as measured by the Non-Verbal Learning Test but not to executive function as measured by the Wisconsin Card Sorting Test. It may therefore be concluded that social phobia patients show deficits in cognitive information processing as reflected by ERPs. [Copyright &y& Elsevier]

Recent studies have suggested an information-processing bias in social phobia (SP). Little is known about the electrophysiological correlates of anxiety in SP. The aim of the present study was to investigate the quantitative electroencephalogram (EEG) in 25 drug-free patients with SP as compared with age- and sex-matched normal controls and to correlate anxiety and depressive symptoms with EEG data. EEG was recorded under vigilance-controlled and resting conditions. The Spielberger State and Trait Anxiety Scale (STAI) and the Beck Depression Inventory (BDI) were administered to assess anxiety and depression levels. Multivariate analysis of variance revealed significant differences between patients and controls, specifically frontopolarly and right centrally. Statistical analysis demonstrated a decrease in absolute and relative delta, theta power, alpha-adjacent slow-beta and fast beta power and an increase in absolute and relative intermediate beta power, as well as an acceleration of the total centroid and a slowing in beta centroid and its variability. Trait anxiety and depression scores correlated positively with the dominant alpha frequency and the alpha centroid, and negatively with absolute theta and slow alpha power as well as with the centroid of the delta/theta frequency band. In conclusion, EEG mapping in patients with SP revealed significant differences from normal controls suggesting a hyperarousal as a pathogenetic factor of anxiety. [Copyright &y& Elsevier]