The European Insomnia Guideline: An update on the diagnosis and treatment of insomnia 2023.

Progress in the field of insomnia since 2017 necessitated this update of the European Insomnia Guideline. Recommendations for the diagnostic procedure for insomnia and its comorbidities are: clinical interview (encompassing sleep and medical history); the use of sleep questionnaires and diaries (and physical examination and additional measures where indicated) (A). Actigraphy is not recommended for the routine evaluation of insomnia (C), but may be useful for differential-diagnostic purposes (A). Polysomnography should be used to evaluate other sleep disorders if suspected (i.e. periodic limb movement disorder, sleep-related breathing disorders, etc.), treatment-resistant insomnia (A) and for other indications (B). Cognitive-behavioural therapy for insomnia is recommended as the first-line treatment for chronic insomnia in adults of any age (including patients with comorbidities), either applied in-person or digitally (A). When cognitive-behavioural therapy for insomnia is not sufficiently effective, a pharmacological intervention can be offered (A). Benzodiazepines (A), benzodiazepine receptor agonists (A), daridorexant (A) and low-dose sedating antidepressants (B) can be used for the short-term treatment of insomnia (≤ 4 weeks). Longer-term treatment with these substances may be initiated in some cases, considering advantages and disadvantages (B). Orexin receptor antagonists can be used for periods of up to 3 months or longer in some cases (A). Prolonged-release melatonin can be used for up to 3 months in patients ≥ 55 years (B). Antihistaminergic drugs, antipsychotics, fast-release melatonin, ramelteon and phytotherapeutics are not recommended for insomnia treatment (A). Light therapy and exercise interventions may be useful as adjunct therapies to cognitive-behavioural therapy for insomnia (B).

Considerably Lower Levels of Hypocretin-1 in Cerebrospinal Fluid Is Revealed by a Novel Mass Spectrometry Method Compared with Standard Radioimmunoassay.

Low levels of hypocretin-1 (Hcrt1) in cerebrospinal fluid (CSF) are associated with narcolepsy type 1 (NT1). Although immunoassays are prone to antibody batch differences, detection methods and variation between laboratories, the standard method for Hcrt1 measurement is a radioimmunoassay (RIA). Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) is an antibody- and radioactive free alternative for precise measurement of Hcrt1. We developed an LC-MS/MS method for measurement of Hcrt1 in CSF with automated sample preparation by solid-phase extraction (SPE). The LC-MS/MS method was compared with the RIA method for Hcrt1 detection. CSF samples from healthy subjects and NT1 patients was obtained by lumbar puncture. NT1 patients were diagnosed according to the minimal criteria by the International Classification of Sleep Disorders (ICSD). The LC-MS/MS method showed linearity across the range of calibrators and had a limit of detection (LOD) of 2.5 pg/mL and a limit of quantitation (LOQ) of 3.6 pg/mL. Comparison of the LC-MS/MS method with RIA revealed a 19 times lower level in healthy controls and 22 times lower level in NT1 patients with the LC-MS/MS method than with RIA. Bland-Altman analysis demonstrated agreement between the methods. These results question what is detected by RIA and strongly suggest that the physiological concentrations of the peptide are much lower than previously believed. LC-MS/MS proves to be an alternative for detection of Hcrt1 for diagnosis of narcolepsy.

Excessive Daytime Sleepiness and REM Sleep Behavior Disorders in Parkinson's Disease: A Narrative Review on Early Intervention With Implications to Neuroprotection.

Sleep contributes to the consolidation of our memory and facilitates learning. Short term sleep deprivation temporarily reduces mnestic capacity, whereas long lasting sleep deprivation is associated with structural changes in the hippocampus and cortical areas. However, it is unknown whether early intervention and treatment of sleep disorders could have a neuroprotective effect. In neurodegenerative diseases sleep disorders can occur at preclinical stages and are frequently observed in patients with established Parkinson's disease (PD) and other α-synucleinopathies. REM sleep behavior disorder (RBD) is recognized as a hallmark for the development of α-synucleinopathies and may predict early cognitive decline, while excessive daytime sleepiness (EDS) is present in 12% of patients with PD before treatment initiation and increases continuously over time, causing substantial restrictions for the patients' social life. In more advanced disease, EDS is associated with dementia. Even though well recognized, limited attention has been given to genetics or the treatment of RBD and EDS in early PD. Systematic screening and early intervention can be expected to increase the patients' quality of life, but it remains unclear if this will also impact disease progression. Intervention studies in preclinical and early stages of α-synucleinopathies are needed to increase our understanding of the underlying pathomechanisms and may also provide important inroads to help clarify whether sleep disturbances are secondary to the neurodegenerative process or also contribute to disease exacerbation.

European guideline for the diagnosis and treatment of insomnia.

This European guideline for the diagnosis and treatment of insomnia was developed by a task force of the European Sleep Research Society, with the aim of providing clinical recommendations for the management of adult patients with insomnia. The guideline is based on a systematic review of relevant meta-analyses published till June 2016. The target audience for this guideline includes all clinicians involved in the management of insomnia, and the target patient population includes adults with chronic insomnia disorder. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) system was used to grade the evidence and guide recommendations. The diagnostic procedure for insomnia, and its co-morbidities, should include a clinical interview consisting of a sleep history (sleep habits, sleep environment, work schedules, circadian factors), the use of sleep questionnaires and sleep diaries, questions about somatic and mental health, a physical examination and additional measures if indicated (i.e. blood tests, electrocardiogram, electroencephalogram; strong recommendation, moderate- to high-quality evidence). Polysomnography can be used to evaluate other sleep disorders if suspected (i.e. periodic limb movement disorder, sleep-related breathing disorders), in treatment-resistant insomnia, for professional at-risk populations and when substantial sleep state misperception is suspected (strong recommendation, high-quality evidence). Cognitive behavioural therapy for insomnia is recommended as the first-line treatment for chronic insomnia in adults of any age (strong recommendation, high-quality evidence). A pharmacological intervention can be offered if cognitive behavioural therapy for insomnia is not sufficiently effective or not available. Benzodiazepines, benzodiazepine receptor agonists and some antidepressants are effective in the short-term treatment of insomnia (≤4 weeks; weak recommendation, moderate-quality evidence). Antihistamines, antipsychotics, melatonin and phytotherapeutics are not recommended for insomnia treatment (strong to weak recommendations, low- to very-low-quality evidence). Light therapy and exercise need to be further evaluated to judge their usefulness in the treatment of insomnia (weak recommendation, low-quality evidence). Complementary and alternative treatments (e.g. homeopathy, acupuncture) are not recommended for insomnia treatment (weak recommendation, very-low-quality evidence).

REM Sleep Behavior Disorder Is Not Associated with a More Rapid Cognitive Decline in Mild Dementia.

OBJECTIVES: REM sleep behavior disorder (RBD) is associated with cognitive dysfunctions and is a risk factor for development of mild cognitive impairment and dementia. However, it is unknown whether RBD is associated with faster cognitive decline in already established dementia. The main goal of this study was to determine if patients with mild dementia with and without RBD differ in progression rate and in specific neuropsychological measures over 4-year follow-up. METHODS: This longitudinal, prospective study based on data from the DemVest study compares neuropsychological measures in a mild dementia cohort. A diagnosis of probable RBD (pRBD) was made based on the Mayo Sleep Questionnaire. Neuropsychological domains were assessed by Mini Mental State Examination, total score and figure copying, California Verbal Learning Test-II, Visual Object and Space Perception Cube and Silhouettes, Boston Naming Test, Stroop test, Verbal Category Fluency, Trail Making Test A and B. RESULTS: Among the 246 subjects, 47 (19.1%) had pRBD at the baseline, and pRBD group was younger and with male predominance. During 4-year follow-up, we did not observe any significant differences in the rate of decline in neuropsychological measures. Patients with pRBD performed generally poorer in visuoconstructional, visuoperceptual, and executive/attention tests in comparison to RBD negative. CONCLUSION: We did not find any significant differences in progression rate of neurocognitive outcomes between dementia patients with and without RBD.

Changes in insomnia subtypes in early Parkinson disease.

OBJECTIVE: To examine the development of factors associated with insomnia in a cohort of originally drug-naive patients with incident Parkinson disease (PD) during the first 5 years after diagnosis. METHODS: One hundred eighty-two drug-naive patients with PD derived from a population-based incident cohort and 202 control participants were assessed for insomnia before treatment initiation and were repeatedly examined after 1, 3, and 5 years. Insomnia was diagnosed according to the Stavanger Sleepiness Questionnaire. The Parkinson's Disease Sleep Scale was used to differentiate sleep initiation problems from problems of sleep maintenance. Generalized estimating equation models were applied for statistical measures. RESULTS: The prevalence of insomnia in general was not higher in patients with PD compared to controls at the 5-year follow-up. There were changes in the prevalence of the different insomnia subtypes over the 5-year follow-up. The prevalence of solitary problems in sleep maintenance increased from 31% (n = 18) in the drug-naive patients at baseline to 49% (n = 29) after 1 year and were associated with the use of dopamine agonists and higher Montgomery-Åsberg Depression Rating Scale scores. The prevalence of solitary sleep initiation problems decreased continuously from 21% (n = 12) at baseline to 7.4% (n = 4) after 5 years; these were associated with less daytime sleepiness. CONCLUSIONS: The prevalence rates of the different insomnia subtypes changed notably in patients with early PD. The frequency of sleep maintenance problems increased, and these problems were associated with dopamine agonist use and depressive symptoms, while the total number of patients with insomnia remained stable. Our findings reflect the need for early individual assessments of insomnia subtypes and raise the possibility of intervention to reduce these symptoms in patients with early PD.

Higher Frequency and Complexity of Sleep Disturbances in Dementia with Lewy Bodies as Compared to Alzheimer's Disease.

BACKGROUND: Sleep disturbances (SDs) are common in patients with all forms of dementia. However, most studies focus on Alzheimer's disease (AD) and less is known about the prevalence and characteristics of SD in dementia with Lewy bodies (DLB). OBJECTIVE: The aims of this cross-sectional study were: (1) to examine the frequency of SD in DLB versus AD; (2) to compare patients with and without SD with regard to relevant clinical variables, and (3) to investigate the associations between SD and medication use. METHODS: Patients with a first-time diagnosis of probable or possible DLB or AD were selected from the Dementia Study of Western Norway and recruited from clinics for old age psychiatry from 2010 until the end of 2013. RESULTS: In all, 123 (55.7%) subjects with dementia suffered from at least one SD. Insomnia was present in 77 (34.8%), and 34 (20.7%) patients had probable REM-sleep behaviour disorder (RBD). All SDs were also significantly more frequent in patients with DLB than in AD, and DLB patients also more often had several co-occurring SDs. The presence of any SD was associated with more neuropsychiatric symptoms, higher morbidity, more parkinsonian symptoms and excessive daytime sleepiness. Antiparkinsonian medication was used more often in RBD, restless leg syndrome (RLS) and periodic limb movements, and benzodiazepines were also common in RLS. CONCLUSIONS: Sleep problems are more common in DLB patients compared to AD, and are associated with more clinical impairment. DLB patients frequently have several sleep problems occurring simultaneously, which suggests a need for screening and accurate assessment of sleep in DLB.

Variability in recording and scoring of respiratory events during sleep in Europe: a need for uniform standards.

Uniform standards for the recording and scoring of respiratory events during sleep are lacking in Europe, although many centres follow the published recommendations of the American Academy of Sleep Medicine. The aim of this study was to assess the practice for the diagnosis of sleep-disordered breathing throughout Europe. A specially developed questionnaire was sent to representatives of the 31 national sleep societies in the Assembly of National Sleep Societies of the European Sleep Research Society, and a total of 29 countries completed the questionnaire. Polysomnography was considered the primary diagnostic method for sleep apnea diagnosis in 10 (34.5%), whereas polygraphy was used primarily in six (20.7%) European countries. In the remaining 13 countries (44.8%), no preferred methodology was used. Fifteen countries (51.7%) had developed some type of national uniform standards, but these standards varied significantly in terms of scoring criteria, device specifications and quality assurance procedures between countries. Only five countries (17.2%) had published these standards. Most respondents supported the development of uniform recording and scoring criteria for Europe, which might be based partly on the existing American Academy of Sleep Medicine rules, but also take into account differences in European practice when compared to North America. This survey highlights the current varying approaches to the assessment of patients with sleep-disordered breathing throughout Europe and supports the need for the development of practice parameters in the assessment of such patients that would be suited to European clinical practice.

Development of excessive daytime sleepiness in early Parkinson disease.

OBJECTIVE: To examine the frequency, development, and risk factors of excessive daytime sleepiness (EDS) in a cohort of originally drug-naive patients with incident Parkinson disease (PD) during the first 5 years after diagnosis. METHODS: One hundred fifty-three drug-naive patients with early PD derived from a population-based incident cohort and 169 control participants were assessed for EDS and reevaluated after 1, 3, and 5 years on medication. EDS was diagnosed according to the Epworth Sleepiness Scale. Cutoff score above 10 was applied. Generalized estimating equation models for correlated data were used to examine associated and risk factors for EDS. RESULTS: Patients reported EDS more often than control participants at the time of diagnosis and during follow-up. The frequency of EDS in PD increased from 11.8% at baseline to 23.4% after 5 years. Associated factors were male sex, the use of dopamine agonists, and higher Montgomery-Åsberg Depression Rating Scale and Unified Parkinson's Disease Rating Scale-activities of daily living scores. Main risk factor for developing EDS was an increased Epworth Sleepiness Scale score at baseline. CONCLUSION: EDS is more frequent in PD even before treatment initiation compared with control participants and increases in occurrence with disease progression. The main risk factor for developing EDS with time is an early predisposition for sleepiness. In addition, the use of dopamine agonists was associated with the development of EDS. These findings necessitate caution in patients with PD and early increased sleep propensity and when using dopamine agonists.

Detection of hypoglycemia associated EEG changes during sleep in type 1 diabetes mellitus.

OBJECTIVE: Nocturnal hypoglycemia is a feared complication to insulin treated diabetes. Impaired awareness of hypoglycemia (IAH) increases the risk of severe hypoglycemia. EEG changes are demonstrated during daytime hypoglycemia. In this explorative study, we test the hypothesis that specific hypoglycemia-associated EEG-changes occur during sleep and are detectable in time for the patient to take action. RESEARCH DESIGN AND METHODS: Ten patients with type 1 diabetes (duration 23.7 years) with IAH were exposed to insulin-induced hypoglycemia during the daytime and during sleep. EEG was recorded and analyzed real-time by an automated multi-parameter algorithm. Participants received an auditory alarm when EEG changes met a predefined threshold, and were instructed to consume a meal. RESULTS: Seven out of eight participants developed hypoglycemia-associated EEG changes during daytime. During sleep, nine out of ten developed EEG changes (mean BG 2.0 mmol/l). Eight were awakened by the alarm. Four corrected hypoglycemia (mean BG 2.2 mmol/l), while four (mean BG 1.9 mmol/l) received glucose infusion. Two had false alarms. EEG-changes occurred irrespective of sleep stage. Post hoc improvement indicates the possibility of earlier detection of hypoglycemia. CONCLUSIONS: Continuous EEG monitoring and automated real-time analysis may constitute a novel technique for a hypoglycemia alarm in patients with IAH.

[Neuropsychiatric and cognitive symptoms in Parkinson disease]. / Nevropsykiatriske og kognitive symptomer ved Parkinsons sykdom.

BACKGROUND: A variety of neuropsychiatric symptoms commonly occur in Parkinson's disease. Extensive research the last 10 years has provided new knowledge in the field. MATERIAL AND METHODS: This review is based on literature retrieved from a Medline search and own research and clinical experience. RESULTS AND INTERPRETATION: Neuropsychiatric symptoms occur in the majority of patients with Parkinson's disease, and are associated with impaired quality of life for patients and relatives, additional deterioration of function and increased use of health resources. Medical and surgical therapies can induce or worsen such symptoms. Cognitive impairment and dementia are among the most common and severe complications to Parkinson's disease. No disease-modifying treatment is available, but rivastigmine was effective in one large randomised trial. Visual hallucinations are common and often persistent, but can be treated with klozapin if reducing the number and dose of antiparkinson agents are not helpful. Depression occurs frequently, usually mild, but there is little evidence of treatment efficacy. Apathy, anxiety and sleep disturbances are additional commonly occurring neuropsychiatric symptoms. Neuropsychiatric symptoms are so frequent in Parkinson's disease that they should be considered an integral part of the disease; it is important that clinicians are aware of these symptoms.

Epidemiology of Parkinson's disease.

Epidemiological research aims to provide information on the development, prevalence and progression of diseases, and their associated risk factors. Epidemiological research is thus the basis of increasing our understanding on the aetiology of diseases and as a consequence the starting point for identifying at risk groups in the population, development for novel prevention and treatment strategies, and health care planning. This review provides an overview of the epidemiology of Parkinson's disease, the second most common neurodegenerative disorder, with special emphasis on population-based data on the clinical progression of motor and non-motor features of the disease.

CSF hypocretin-1 levels and clinical profiles in narcolepsy and idiopathic CNS hypersomnia in Norway.

OBJECTIVE: To evaluate the relationship between CSF hypocretin-1 levels and clinical profiles in narcolepsy and CNS hypersomnia in Norwegian patients. METHOD: CSF hypocretin-1 was measured by a sensitive radioimmunoassay in 47 patients with narcolepsy with cataplexy, 7 with narcolepsy without cataplexy, 10 with idiopathic CNS hypersomnia, and a control group. RESULTS: Low hypocretin-1 values were found in 72% of the HLA DQB1*0602 positive patients with narcolepsy and cataplexy. Patients with low CSF hypocretin-1 levels reported more extensive muscular involvement during cataplectic attacks than patients with normal levels. Hypnagogic hallucinations and sleep paralysis occurred more frequently in patients with cataplexy than in the other patient groups, but with no correlation to hypocretin-1 levels. CONCLUSION: About three quarters of the HLA DQB1*0602 positive patients with narcolepsy and cataplexy had low CSF hypocretin-1 values, and appear to form a distinct clinical entity. Narcolepsy without cataplexy could not be distinguished from idiopathic CNS hypersomnia by clinical symptoms or biochemical findings.

Atrophy of foot muscles: a measure of diabetic neuropathy.

OBJECTIVE: Diabetic neuropathy is a length-dependent process that leads to reduced muscle strength and atrophy of leg muscles in some patients. We hypothesized that intrinsic foot muscles are atrophied in diabetic neuropathy and that the degree of atrophy is a measure of motor dysfunction closely related to the neuropathic process. RESEARCH DESIGN AND METHODS: Consecutive cross-sectional magnetic resonance images of the nondominant foot were obtained for stereological determination of the total volume of the intrinsic foot muscles (VFM) in 23 long-term diabetic patients with (n = 15) and without (n = 8) chronic neuropathy and in 23 matched healthy nondiabetic control subjects. Based on clinical examination, nerve conduction studies, and quantitative sensory examination, a neuropathy rank-sum score was calculated for each patient. RESULTS: Total VFM was 86 +/- 52, 165 +/- 34, and 168 +/- 42 cm3 in neuropathic patients, nonneuropathic patients, and healthy control subjects, respectively (P < 0.001). There was a close inverse relationship between the neuropathy rank-sum score and the VFM (r = -0.75, P < 1 x 10(-5)). CONCLUSIONS: Total volume of the foot muscles is halved in patients with diabetic neuropathy. Atrophy of foot muscles is closely related to the severity of neuropathy and reflects motor dysfunction.