Alzheimer's disease (AD) is a significant public health concern. The incidence continues to rise, and it is set to be over one million in the UK by 2025. The processes involved in the pathogenesis of AD have been shown to overlap with those found in cognitive decline in patients with Obstructive Sleep Apnoea (OSA). Currently, the standard treatment for OSA is Continuous Positive Airway Pressure. Adherence to treatment can, however, be an issue, especially in patients with dementia. Also, not all patients respond adequately, necessitating the use of additional treatments. Based on the body of data, we here suggest that excessive and prolonged neuronal activity might contribute to genesis and acceleration of both AD and OSA in the absence of appropriately structured sleep. Further, we argue that external factors, including systemic inflammation and obesity, are likely to interfere with immunological processes of the brain, and further promote disease progression. If this hypothesis is proven in future studies, it could have far-reaching clinical translational implications, as well as implications for future treatment strategies in OSA.

Obstructive sleep apnea (OSA) is a chronic, multisystem disorder that has a bidirectional relationship with several major neurological disorders, including Alzheimer's dementia. Treatment with Continuous Positive Airway Pressure (CPAP) offers some protection from the effects of OSA, although it is still unclear which populations should be targeted, for how long, and what the effects of treatment are on different organ systems. We investigated whether cognitive improvements can be achieved as early as one month into CPAP treatment in patients with OSA. 55 patients (mean (SD) age: 47.6 (11.1) years) with newly diagnosed moderate-severe OSA (Oxygen Desaturation Index: 36.6 (25.2) events/hour; Epworth sleepiness score (ESS): 12.8 (4.9)) and 35 matched healthy volunteers were studied. All participants underwent neurocognitive testing, neuroimaging and polysomnography. Patients were randomized into parallel groups: CPAP with best supportive care (BSC), or BSC alone for one month, after which they were re-tested. One month of CPAP with BSC resulted in a hypertrophic trend in the right thalamus [mean difference (%): 4.04, 95% CI: 1.47 to 6.61], which was absent in the BSC group [-2.29, 95% CI: -4.34 to -0.24]. Significant improvement was also recorded in ESS, in the CPAP plus BSC group, following treatment [mean difference (%): -27.97, 95% CI: -36.75 to -19.19 vs 2.46, 95% CI: -5.23 to 10.15; P=0.012], correlated to neuroplastic changes in brainstem (r=-0.37; P=0.05), and improvements in delayed logical memory scores [57.20, 95% CI: 42.94 to 71.46 vs 23.41, 95% CI: 17.17 to 29.65; P=0.037]. One month of CPAP treatment can lead to adaptive alterations in the neurocognitive architecture that underlies the reduced sleepiness, and improved verbal episodic memory in patients with OSA. We propose that partial neural recovery occurs during short periods of treatment with CPAP.

Poor sleep and daytime sleepiness are common in people with epilepsy. Sleep disorders can disrupt seizure control and in turn sleep and vigilance problems can be exacerbated by seizures and by antiepileptic treatments. Nevertheless, these aspects are frequently overlooked in clinical practice and a clear agreement on the evidence-based guidelines for managing common sleep disorders in people with epilepsy is lacking. Recently, recommendations to standardize the diagnostic pathway for evaluating patients with sleep-related epilepsies and comorbid sleep disorders have been presented. To build on these, we adopted the Delphi method to establish a consensus within a group of experts and we provide practical recommendations for identifying and managing poor night-time sleep and daytime sleepiness in people with epilepsy. We recommend that a comprehensive clinical history of sleep habits and sleep hygiene should be always obtained from all people with epilepsy and their bed partners. A psychoeducational approach to inform patients about habits or practices that may negatively influence their sleep or their vigilance levels should be used, and strategies for avoiding these should be applied. In case of a suspected comorbid sleep disorder an appropriate diagnostic investigation should be performed. Moreover, the possible presence of sleep fragmentation induced by sleep-related seizures should be ruled out. Finally, the dose and timing of antiepileptic medications and other co-medications should be optimized to improve nocturnal sleep and avoid daytime sedation.

Objective: Using narrative review techniques, this paper evaluates the evidence for separable underlying patho-mechanisms of periodic limb movements (PLMs) to separable PLM motor patterns and phenotypes, in order to elucidate potential new treatment modalities. Background: Periodic limb movement disorder (PLMD) is estimated to occur in 5–8% of the paediatric population and 4–11% of the general adult population. Due to significant sleep fragmentation, PLMD can lead to functional impairment, including hyperactivity and delayed language development in children, and poor concentration and work performance in adults. Longitudinal data demonstrate that those with PLMD are at greater risk of depression and anxiety, and a 4-fold greater risk of developing dementia. PLMD has been extensively studied over the past two decades, and several key insights into the genetic, pathophysiological, and neural correlates have been proposed. Amongst these proposals is the concept of separable PLM phenotypes, proposed on the basis of nocturnal features such as the ratio of limb movements and distribution throughout the night. PLM phenotype and presentation, however, varies significantly depending on the scoring utilized and the nocturnal features examined, across age, and co-morbid clinical conditions. Furthermore, associations between these phenotypes with major neurologic and psychiatric disorders remain controversial. Methods: In order to elucidate potential divergent biological pathways that may help clarify important new treatment modalities, this paper utilizes narrative review and evaluates the evidence linking PLM motor patterns and phenotypes with hypothesised underlying patho-mechanisms. Distinctive, underlying patho-mechanisms include: a pure motor mechanism originating in the spinal cord, iron deficiency, dopamine system dysfunction, thalamic glutamatergic hyperactivity, and a more cortical-subcortical interplay. In support of the latter hypothesis, PLM rhythmicity appears tightly linked to the microarchitecture of sleep, not dissimilarly to the apnoeic/hypopneic events seen in obstructive sleep apnea (OSA). Conclusions: This review closes with a proposal for greater investigation into the identification of potential, divergent biological pathways. To do so would require prospective, multimodal imaging clinical studies which may delineate differential responses to treatment in restless legs syndrome (RLS) without PLMS and PLMS without RLS. This could pave the way toward important new treatment modalities.

Early studies posited a relationship between sleep and the basal ganglia, but this relationship has received little attention recently. It is timely to revisit this relationship, given new insights into the functional anatomy of the basal ganglia and the physiology of sleep, which has been made possible by modern techniques such as chemogenetic and optogenetic mapping of neural circuits in rodents and intracranial recording, functional imaging, and a better understanding of human sleep disorders. We discuss the functional anatomy of the basal ganglia, and review evidence implicating their role in sleep. Whilst these studies are in their infancy, we suggest that the basal ganglia may play an integral role in the sleep-wake cycle, specifically by contributing to a thalamo-cortical-basal ganglia oscillatory network in slow-wave sleep which facilitates neural plasticity, and an active state during REM sleep which enables the enactment of cognitive and emotional networks. A better understanding of sleep mechanisms may pave the way for more effective neuromodulation strategies for sleep and basal ganglia disorders.