Pathological involvement of the noradrenergic locus coeruleus occurs early in Parkinson’s disease, and widespread noradrenaline reductions are found at post-mortem. Rapid eye movement sleep behaviour disorder (RBD) accompanies Parkinson’s disease and its presence predicts an unfavourable disease course with a higher propensity to cognitive impairment and orthostatic hypotension. MRI can detect neuromelanin in the locus coeruleus while ¹¹C-MeNER PET is a marker of noradrenaline transporter availability. Here, we use both imaging modalities to study the association of RBD, cognition and autonomic dysfunction in Parkinson’s disease with loss of noradrenergic function. Thirty non-demented Parkinson’s disease patients [16 patients with RBD and 14 without RBD, comparable across age (66.6 ± 6.7 years), sex (22 males), and disease stage (Hoehn and Yahr, 2.3 ± 0.5)], had imaging of the locus coeruleus with neuromelanin sensitive MRI and brain noradrenaline transporter availability with ¹¹C-MeNER PET. RBD was confirmed with polysomnography; cognitive function was assessed with a neuropsychological test battery, and blood pressure changes on tilting were documented; results were compared to 12 matched control subjects. We found that Parkinson’s disease patients with RBD showed decreased locus coeruleus neuromelanin signal on MRI (P < 0.001) and widespread reduced binding of ¹¹C-MeNER (P < 0.001), which correlated with amount of REM sleep without atonia. Parkinson’s disease with RBD was also associated with a higher incidence of cognitive impairment, slowed EEG activity, and orthostatic hypotension. Reduced ¹¹C-MeNER binding correlated with EEG slowing, cognitive performance, and orthostatic hypotension. In conclusion, reduced noradrenergic function in Parkinson’s disease was linked to the presence of RBD and associated with cognitive deterioration and orthostatic hypotension. Noradrenergic impairment may contribute to the high prevalence of these non-motor symptoms in Parkinson’s disease, and may be of relevance when treating these conditions in Parkinson’s disease.

Insomnia is two to three times more prevalent in cancer survivors than in the general population, where it is estimated to be 10% to 20%. Cognitive-behavioral therapy for insomnia (CBT-I) is the recommended treatment for chronic insomnia, but meeting survivor needs remains a challenge. Internet-delivered CBT-I (iCBT-I) has been shown efficacious in otherwise healthy adults. We tested the efficacy of iCBT-I in breast cancer survivors with clinically significant sleep disturbance. Women from a national sample of Danish breast cancer survivors who experienced clinically significant sleep disturbance were randomly allocated to iCBT-I or waitlist control (55:45). The fully automated iCBT-I program consisted of six cores. Online measures of insomnia severity, sleep quality, and fatigue were collected at baseline, postintervention (nine weeks), and follow-up (15 weeks). Online sleep diaries were completed over two-week periods pre- and postintervention. Intention-to-treat analyses (time × group interactions) were conducted with mixed linear models and corrected for multiple outcomes. All statistical tests were two-sided. A total of 255 women were randomly allocated to iCBT-I (n = 133) or waitlist control (n = 122). Statistically significant (P ≤ .02) time × group interactions were found for all sleep-related outcomes from pre- to postintervention. Effect sizes (Cohen’s d) ranged from 0.33 (95% confidence interval [CI] = 0.06 to 0.61) for wake after sleep onset to 1.17 (95% CI = 0.87 to 1.47) for insomnia severity. Improvements were maintained for outcomes measured at follow-up (d = 0.66–1.10). iCBT-I appears to be effective in breast cancer survivors, with additional benefit in terms of reduced fatigue. This low-cost treatment could be incorporated in cancer rehabilitation programs.

Background Cognitive complaints are common amongst breast cancer survivors, and no standard treatment exists. The present study evaluates whether web-based cognitive training can alleviate subjectively reported and objectively assessed cognitive complaints in a sample of breast cancer survivors. The primary and secondary outcomes were an objective measure of working memory and a measure of perceived cognitive functioning. Additional outcomes were neuropsychological tests of memory, executive function, working memory and questionnaire-based assessment of anxiety, depression and somatization. Methods A total of 157 female breast cancer survivors were recruited from an existing cohort and through announcements in open access cancer-related Internet fora and randomly allocated to either web-based cognitive training (eCogT) with telephone support (n = 94) or a waitlist control (WLC) condition (n = 63). eCogT encompassed 30 training sessions over 6 weeks. Neuropsychological assessments were undertaken over the telephone, and questionnaire data was collected online. Data was collected at baseline, post-intervention and at 5-month follow-up. Results Mixed linear models revealed no statistically significant change in primary or secondary outcome at follow-up in either group. Statistically significant improvements (p 0.040–0.043) were found in the eCogT group for verbal learning and on a working memory test. Conclusions Web-based cognitive training did not result in improvements of the primary or secondary outcome. Improved performance was observed on verbal learning and working memory. These effects were observed at 5-month follow-up, indicating long-term effects of training. The intervention may be applied in a clinical setting at low cost and without risk of adverse effects. © 2016 The Authors. Psycho-Oncology Published by John Wiley & Sons Ltd.

Non-alcoholic fatty liver disease (NAFLD) has emerged as the hepatic component of the metabolic syndrome and now seemingly affects one-fourth of the world population. Features associated with NAFLD and the metabolic syndrome have frequently been linked to cognitive dysfunction, i.e. systemic inflammation, vascular dysfunction, and sleep apnoea. However, emerging evidence suggests that NAFLD may be a cause of cognitive dysfunction independent of these factors. NAFLD in addition exhibits dysbiosis of the gut microbiota and impaired urea cycle function, favouring systemic ammonia accumulation and further promotes systemic inflammation. Such disruption of the gut–liver–brain axis is essential in the pathogenesis of hepatic encephalopathy, the neuropsychiatric syndrome associated with progressive liver disease. Considering the growing burden of NAFLD, the morbidity from cognitive impairment is expected to have huge societal and economic impact. The present paper provides a review of the available evidence for cognitive dysfunction in NAFLD and outlines its possible mechanisms. Moreover, the clinical challenges of characterizing and diagnosing cognitive dysfunction in NAFLD are discussed.