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Background Neuropsychiatric symptoms (NPS) are common in individuals with Alzheimer’s disease (AD) dementia, but substantial heterogeneity exists in the manifestation of NPS. Sex differences may explain this clinical variability. We aimed to investigate the sex differences in the prevalence and severity of NPS in AD dementia. Methods Literature searches were conducted in Embase, MEDLINE/PubMed, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, PsycINFO, and Google Scholar from inception to February 2021. Study selection, data extraction, and quality assessment were conducted in duplicate. Effect sizes were calculated as odds ratios (OR) for NPS prevalence and Hedges’ g for NPS severity. Data were pooled using random-effects models. Sources of heterogeneity were examined using meta-regression analyses. Results Sixty-two studies were eligible representing 21,554 patients (61.2% females). The majority of the included studies had an overall rating of fair quality (71.0%), with ten studies of good quality (16.1%) and eight studies of poor quality (12.9%). There was no sex difference in the presence of any NPS ( k = 4, OR = 1.35 [95% confidence interval 0.78, 2.35]) and overall NPS severity ( k = 13, g = 0.04 [− 0.04, 0.12]). Regarding specific symptoms, female sex was associated with more prevalent depressive symptoms ( k = 20, OR = 1.60 [1.28, 1.98]), psychotic symptoms (general psychosis k = 4, OR = 1.62 [1.12, 2.33]; delusions k = 12, OR = 1.56 [1.28, 1.89]), and aberrant motor behavior ( k = 6, OR = 1.47 [1.09, 1.98]). In addition, female sex was related to more severe depressive symptoms ( k = 16, g = 0.24 [0.14, 0.34]), delusions ( k = 10, g = 0.19 [0.04, 0.34]), and aberrant motor behavior ( k = 9, g = 0.17 [0.08, 0.26]), while apathy was more severe among males compared to females ( k = 11, g = − 0.10 [− 0.18, − 0.01]). There was no association between sex and the prevalence and severity of agitation, anxiety, disinhibition, eating behavior, euphoria, hallucinations, irritability, and sleep disturbances. Meta-regression analyses revealed no consistent association between the effect sizes across studies and method of NPS assessment and demographic and clinical characteristics. Discussion Female sex was associated with a higher prevalence and greater severity of several specific NPS, while male sex was associated with more severe apathy. While more research is needed into factors underlying these sex differences, our findings may guide tailored treatment approaches of NPS in AD dementia.

ObjectivesDelirium is a serious complication following neurosurgical procedures. We hypothesise that the beneficial effect of music on a combination of delirium-eliciting factors might reduce delirium incidence following neurosurgery and subsequently improve clinical outcomes.DesignProspective randomised controlled trial.SettingSingle centre, conducted at the neurosurgical department of the Erasmus Medical Center, Rotterdam, the Netherlands.ParticipantsAdult patients undergoing craniotomy were eligible.InterventionsPatients in the intervention group received preferred recorded music before, during and after the operation until day 3 after surgery. Patients in the control group were treated according to standard of clinical care.Primary and secondary outcome measuresPrimary outcome was presence or absence of postoperative delirium within the first 5 postoperative days measured with the Delirium Observation Screening Scale (DOSS) and, in case of a daily mean score of 3 or higher, a psychiatric evaluation with the latest Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria. Secondary outcomes included anxiety, heart rate variability (HRV), depth of anaesthesia, delirium severity and duration, postoperative complications, length of stay and location of discharge.ResultsWe enrolled 189 patients (music=95, control=94) from July 2020 through September 2021. Delirium, as assessed by the DOSS, was less common in the music (n=11, 11.6%) than in the control group (n=21, 22.3%, OR:0.49, p=0.048). However, after DSM-5 confirmation, differences in delirium were not significant (4.2% vs 7.4%, OR:0.47, p=0.342). Moreover, music increased the HRV (root mean square of successive differences between normal heartbeats, p=0.012). All other secondary outcomes were not different between groups.ConclusionOur results support the efficacy of music in reducing the incidence of delirium after craniotomy, as found with DOSS but not after DSM-5 confirmation, substantiated by the effect of music on preoperative autonomic tone. Delirium screening tools should be validated and the long-term implications should be evaluated after craniotomy.Trial registration numberTrialregister.nl: NL8503 and ClinicalTrials.gov: NCT04649450.

IntroductionDelirium is a neurocognitive disorder characterised by an acute and temporary decline of mental status affecting attention, awareness, cognition, language and visuospatial ability. The underlying pathophysiology is driven by neuroinflammation and cellular oxidative stress.Delirium is a serious complication following neurosurgical procedures with a reported incidence varying between 4% and 44% and has been associated with increased length of hospital stay, increased amount of reoperations, increased costs and mortality.Perioperative music has been reported to reduce preoperative anxiety, postoperative pain and opioid usage, and attenuates stress response caused by surgery. We hypothesize that this beneficial effect of music on a combination of delirium eliciting factors might reduce delirium incidence following neurosurgery and subsequently improve clinical outcomes.MethodsThis protocol concerns a single-centred prospective randomised controlled trial with 6 months follow-up. All adult patients undergoing a craniotomy at the Erasmus Medical Center in Rotterdam are eligible. The music group will receive recorded music through an overear headphone before, during and after surgery until postoperative day 3. Patients can choose from music playlists, offered based on music importance questionnaires administered at baseline. The control group will receive standard of clinical careDelirium is assessed by the Delirium Observation Scale and confirmed by a delirium-expert psychiatrist according to the DSM-5 criteria. Risk factors correlated with the onset of delirium, such as cognitive function at baseline, preoperative anxiety, perioperative medication use, depth of anaesthesia and postoperative pain, and delirium-related health outcomes such as length of stay, daily function, quality of life (ie, EQ-5D, EORTC questionnaires), costs and cost-effectiveness are collected.Ethics and disseminationThis study is being conducted in accordance with the Declaration of Helsinki. The Medical Ethics Review Board of Erasmus University Medical Center Rotterdam, The Netherlands, approved this protocol. Results will be disseminated via peer-reviewed scientific journals and conference presentations.Trial registration numbersNL8503 and NCT04649450.

Background Neuropsychiatric symptoms (NPS) are prevalent in the early clinical stages of Alzheimer’s disease (AD) according to proxy-based instruments. Little is known about which NPS clinicians report and whether their judgment aligns with proxy-based instruments. We used natural language processing (NLP) to classify NPS in electronic health records (EHRs) to estimate the reporting of NPS in symptomatic AD at the memory clinic according to clinicians. Next, we compared NPS as reported in EHRs and NPS reported by caregivers on the Neuropsychiatric Inventory (NPI). Methods Two academic memory clinic cohorts were used: the Amsterdam UMC ( n  = 3001) and the Erasmus MC ( n  = 646). Patients included in these cohorts had MCI, AD dementia, or mixed AD/VaD dementia. Ten trained clinicians annotated 13 types of NPS in a randomly selected training set of n  = 500 EHRs from the Amsterdam UMC cohort and in a test set of n  = 250 EHRs from the Erasmus MC cohort. For each NPS, a generalized linear classifier was trained and internally and externally validated. Prevalence estimates of NPS were adjusted for the imperfect sensitivity and specificity of each classifier. Intra-individual comparison of the NPS classified in EHRs and NPS reported on the NPI were conducted in a subsample (59%). Results Internal validation performance of the classifiers was excellent (AUC range: 0.81–0.91), but external validation performance decreased (AUC range: 0.51–0.93). NPS were prevalent in EHRs from the Amsterdam UMC, especially apathy (adjusted prevalence = 69.4%), anxiety (adjusted prevalence = 53.7%), aberrant motor behavior (adjusted prevalence = 47.5%), irritability (adjusted prevalence = 42.6%), and depression (adjusted prevalence = 38.5%). The ranking of NPS was similar for EHRs from the Erasmus MC, although not all classifiers obtained valid prevalence estimates due to low specificity. In both cohorts, there was minimal agreement between NPS classified in the EHRs and NPS reported on the NPI (all kappa coefficients < 0.28), with substantially more reports of NPS in EHRs than on NPI assessments. Conclusions NLP classifiers performed well in detecting a wide range of NPS in EHRs of patients with symptomatic AD visiting the memory clinic and showed that clinicians frequently reported NPS in these EHRs. Clinicians generally reported more NPS in EHRs than caregivers reported on the NPI.

Background Neuropsychiatric symptoms (NPS) are very common in patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD) dementia and are associated with various disadvantageous clinical outcomes including a negative impact on quality of life, caregiver burden, and accelerated disease progression. Despite growing evidence of the efficacy of (non)pharmacological interventions to reduce these symptoms, NPS remain underrecognized and undertreated in memory clinics. The BEhavioural symptoms in Alzheimer’s disease Towards early Identification and Treatment (BEAT-IT) study is developed to (1) investigate the neurobiological etiology of NPS in AD and (2) study the effectiveness of the Describe, Investigate, Create, Evaluate (DICE) approach to structure and standardize the current care of NPS in AD. By means of the DICE method, we aim to improve the quality of life of AD patients with NPS and their caregivers who visit the memory clinic. This paper describes the protocol for the intervention study that incorporates the latter aim. Methods We aim to enroll a total of 150 community-dwelling patients with MCI or AD and their caregivers in two waves. First, we will recruit a control group who will receive care as usual. Next, the second wave of participants will undergo the DICE method. This approach consists of the following steps: (1) describe the context in which NPS occur, (2) investigate the possible causes, (3) create and implement a treatment plan, and (4) evaluate whether these interventions are effective. Primary outcomes are the quality of life of patients and their caregivers. Secondary outcomes include NPS change, caregiver burden, caregivers’ confidence managing NPS, psychotropic medication use, the experiences of patients and caregivers who underwent the DICE method, and the cost-effectiveness of the intervention. Conclusions This paper describes the protocol of an intervention study that is part of the BEAT-IT study and aims to improve current recognition and treatment of NPS in AD by structuring and standardizing the detection and treatment of NPS in AD using the DICE approach. Trial registration The trial was registered on the Netherlands Trial Registry ( NTR7459 ); registered 6 September 2018.

There are many types of cerebellar ataxia, including ataxia due to congenital or metabolic disorders and a paraneoplastic form in patients with gynecologic cancer, breast cancer, lung cancer, or Hodgkin's disease. 1 This paraneoplastic syndrome is the only type of cerebellar ataxia associated with autoantibodies against neuronal antigens. Often, the neuronal antigens are aberrantly expressed by the tumor cells. 2 – 4 The antineuronal autoantibodies are believed to cause cerebellar ataxia, but this is unproved. 5 , 6 In Hodgkin's disease, the lymphoma precedes the ataxia by months to years in 80 percent of patients, and ataxia often occurs during a prolonged complete remission. 4 Among . . .

Introduction:Behavioral and psychological symptoms in dementia (BPSD) have great impact on the daily lives of Alzheimer’s disease (AD) patients and their caregivers. Timely recognition and treatment of these symptoms may benefit quality of life, caregiver burden, and delay disease progression. In this qualitative study we examine the experiences of memory clinic physicians with the recognition and management of BPSD in early stages of AD.Methods:Semi-structured interviews were held with 8 physicians (5 neurologists, 3 geriatricians) employed at memory clinics of academic or general hospitals in the Netherlands. Two independent researchers coded verbatim transcripts of the interviews, followed by a consensus meeting on preliminary themes. In the upcoming months, additional interviews will be conducted until data saturation is reached.Results:Preliminary results indicate substantial variability in how memory clinic physicians recognize and diagnose BPSD in AD. Themes are: 1. Prevalence of BPSD in early stages of AD; e.g. ‘BPSD is more often present in late stages of AD […]’ vs. ‘I see this often, very often, I think these are the main problems people with AD face’). 2. Systematic assessment; some physicians consider it part of their clinical work-up to assess behavioral changes while other physicians do not touch upon BPSD. 3. Barriers for assessment; e.g. a lack of time, and not being able to observe BPSD occurring at home in a memory clinic setting. Treatment and management of BPSD in AD also differed greatly. Themes are 1. Treatment type; Two physicians discussed using a person-centered non-pharmacological approach, others refer patients with BPSD to daycare, a case manager or psychiatrist, or treat ‘problematic’ behaviors with psychotropic drugs. 2. Capabilities; some physicians experience managing BPSD in AD as very difficult, while others are confident about their capabilities. The majority suggests that collaboration with GPs or case managers may benefit treating these complex symptoms.Conclusion:There are remarkable differences in the recognition and management of BPSD in patients with AD visiting memory clinics in the Netherlands. Considering the potential benefit of early recognition and treatment, a first crucial step is discussing standardization of recognition and management of BPSD in memory clinics.