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Background Parkinson's disease (PD), the second most common neurodegenerative disease with notable clinical heterogeneity, has Parkinson disease dementia (PDD) that severely impacts patients' quality of life. As no effective treatment exists, this study aimed to find potential drug targets for PD cognitive disorders. Methods Two-sample Mendelian randomization (MR) and transcriptome analysis were used to identify PD biomarkers. Protein-protein interaction (PPI), gene ontology (GO), and KEGG pathway analyses explored biological effects. A nomogram model was developed. Results 76 Mendelian randomization genes (MRGs) from MR and 1771 differentially expressed genes (DEGs) from the transcriptome were obtained. Three significant shared DEGs (S-DEGs) were identified, with USP8 and STXBP6 having strong diagnostic value for PDD. The nomogram model with these two genes showed enhanced predictive ability. These genes had physical interactions, co-localization, and correlated with ODC and NEU immune cells. USP8 was linked to five diseases, and STXBP6 to one. Conclusion USP8, STXBP6, and immune cells (ODC and NEU) associated with PDD were identified, offering new insights into PD progression.

The demonstration that dopamine loss is the key pathological feature of Parkinson's disease (PD), and the subsequent introduction of levodopa have revolutionalized the field of PD therapeutics. This review will discuss the significant progress that has been made in the development of new pharmacological and surgical tools to treat PD motor symptoms since this major breakthrough in the 1960s. However, we will also highlight some of the challenges the field of PD therapeutics has been struggling with during the past decades. The lack of neuroprotective therapies and the limited treatment strategies for the nonmotor symptoms of the disease (ie, cognitive impairments, autonomic dysfunctions, psychiatric disorders, etc.) are among the most pressing issues to be addressed in the years to come. It appears that the combination of early PD nonmotor symptoms with imaging of the nigrostriatal dopaminergic system offers a promising path toward the identification of PD biomarkers, which, once characterized, will set the stage for efficient use of neuroprotective agents that could slow down and alter the course of the disease.

Memory problems are generally quite prominent in dementia and they have a significant impact on everyday functioning. Medication developed for Alzheimer's disease, for example, acetylcholinesterase inhibitors, can slow down the increase of cognitive impairment for a while. In addition to pharmacotherapy, psychosocial treatment methods are also used, some of which have a positive effect on cognition, for example, cognitive rehabilitation, cognitive stimulation therapy and movement therapy. However, more research is needed. This article first describes the consequences of memory problems on the everyday life of people with dementia and summarizes research findings on how people with dementia experience and cope with their illness. We then discuss the most frequently applied psychosocial treatments for cognitive problems in dementia.

Dysfunctional cognitions can contribute to depression and its maintenance. They may be related to a higher relapse rate and a longer duration of the depressive episode. The relevance of dysfunctional cognitions for acute inpatient treatment of unipolar depression is examined in this study and its variability by cognitive behavioural therapy (CBT). 222 patients suffering from Major Depressive Disorder (MDD) were evaluated during their inpatient treatment by assessing admission and discharge depression scores and their relationship to dysfunctional cognitions, using the Dysfunctional Attitude Scale (DAS). The relationship between dysfunctional cognitions and treatment outcome was examined. Primary outcome measures were the Hamilton-Rating-Scale (HRSD) and the Beck Depression Inventory (BDI). Higher age, depression severity at admission, comorbid personality disorders and recurrent depressive disorders are related with higher DAS-scores at admission. DAS-Scores declined during treatment but to a lower extend than depressive symptom scales (effect size dDAS-G t1-t2 = .31; dHRSD t1-t2 = 2.88; dBDI t1-t2 = 1.38). Higher DAS-scores at admission correlated negatively with the improvement of depressive symptoms during treatment (HRSD: r = −.62; p < .01; BDI: r = −.54; p < .01) and remission rates (HRSD: r = −.65; p < .01; BDI: r = −.48; p < .01). CBT did not additionally reduce DAS-scores compared to pharmacotherapy only. Dysfunctional cognitions are relatively stable compared to other depressive symptoms and are associated with poorer treatment outcome even in combined treatment of antidepressant medication and CBT during inpatient treatment. Changes of dysfunctional cognitions seem to be a long-term treatment goal, especially because of their association with comorbid personality disorders and recurrent depressive disorders.

Background Alzheimer’s disease (AD), as the most common cause of dementia, brings huge economic burden for patients and social health care systems, which motivates researchers to study multiple protective factors, among which physical activity and exercise have been proven to be both effective and economically feasible. Methods A systematic literature search was performed for eligible studies published up to November 1st 2018 on three international databases (PubMed, Cochrane Library, and Embase) and two Chinese databases (Wanfang Data, China National Knowledge Infrastructure). All analyses were conducted using Stata 14.0. Due to heterogeneity between studies, a random-effects model was used for this meta-analysis. Meta-analysis was used to explore if physical activity and exercise can exert positive effects on cognition of elderly with AD and subgroup analyses were conducted to find out if there are dose-response effects. Results A total of 13 randomized controlled trials were included with a sample size of 673 subjects diagnosed with AD. Intervention groups showed a statistically significant improvement in cognition of included subjects measured by the MMSE score (SMD = 1.12 CI:0.66~1.59) compared to the control groups. Subgroup analyses showed different amounts of physical activity and exercise can generate different effects. Conclusions As one of few meta-analyses comparing different quantities of physical activity and exercise interventions for AD in details, our study suggests that physical activity and exercise can improve cognition of older adults with AD. While the concomitant effects on cognition functions of high frequency interventions was not greater than that of low frequency interventions, the threshold remains to be settled. However, more RCTs with rigorous study design are needed to support our findings.

AbstractCognitive impairment is a debilitating side effect experienced by patients with cancer treated with systemically administered anticancer therapies. With around 19.3 million new cases of cancer worldwide in 2020 and the five year survival rate growing from 50% in 1970 to 67% in 2013, an urgent need exists to understand enduring side effects with severe implications for quality of life. Whereas cognitive impairment associated with chemotherapy is recognized in patients with breast cancer, researchers have started to identify cognitive impairment associated with other treatments such as immune, endocrine, and targeted therapies only recently. The underlying mechanisms are diverse and therapy specific, so further evaluation is needed to develop effective therapeutic interventions. Drug and non-drug management strategies are emerging that target mechanistic pathways or the cognitive deficits themselves, but they need to be rigorously evaluated. Clinically, consistent use of objective diagnostic tools is necessary for accurate diagnosis and clinical characterization of cognitive impairment in patients treated with anticancer therapies. This should be supplemented with clinical guidelines that could be implemented in daily practice. This review summarizes the recent advances in the mechanisms, clinical characterization, and novel management strategies of cognitive impairment associated with treatment of non-central nervous system cancers.

Background Aging-related cognitive decline and cognitive impairment greatly impacts older adults’ daily life. The worldwide ageing of the population and associated wave of dementia urgently calls for prevention strategies to reduce the risk of cognitive decline. Physical activity (PA) is known to improve cognitive function at older age through processes of neuroplasticity. Yet, emerging studies suggest that larger cognitive gains may be induced when PA interventions are combined with cognitive activity (CA). This meta-analysis evaluates these potential synergistic effects by comparing cognitive effects following combined PA + CA interventions to PA interventions (PA only), CA interventions (CA only) and control groups. Methods Pubmed, Embase, PsycInfo, CINAHL and Sportdiscus were searched for English peer-reviewed papers until April 2018. Data were extracted on cognition and factors potentially influencing the cognitive effects: mode of PA + CA combination (sequential or simultaneous), session frequency and duration, intervention length and study quality. Differences between older adults with and without mild cognitive impairments were also explored. Results Forty-one studies were included. Relative to the control group, combined PA + CA intervention showed significantly larger gains in cognition ( g  = 0.316; 95% CI 0.188–0.443; p  < .001). Studies that compared combined PA + CA with PA only, showed small but significantly greater cognitive improvement in favor of combined interventions ( g  = 0.160; 95% CI 0.041–0.279; p  = .008). No significant difference was found between combined PA + CA and CA only interventions. Furthermore, cognitive effects tended to be more pronounced for studies using simultaneous designs ( g  = 0.385; 95%CI 0.214–0.555; p  < .001) versus sequential designs ( g  = 0.114; 95%CI -0.102- 0.331, p  = .301). Effects were not moderated by session frequency, session duration, intervention length or study quality. Also, no differences in effects were found between older adults with and without mild cognitive impairments. Conclusion Findings of the current meta-analysis suggest that PA programs for older adults could integrate challenging cognitive exercises to improve cognitive health. Combined PA + CA programs should be promoted as a modality for preventing as well as treating cognitive decline in older adults. Sufficient cognitive challenge seems more important to obtain cognitive effects than high doses of intervention sessions.

  [...]called \"asymptomatic\" malaria infections have been recognized for many years, and result from partial immunity (sometimes referred to as \"premunition\"), which controls but does not completely eliminate the infection. [...]persistent or repeated \"asymptomatic\" infection is sometimes viewed as beneficial to the individual, as it helps to maintain this state of premunition, thereby reducing the risk of severe disease [1]. [...]to ensure the prevention of future malaria infection, approaches must be instigated with concomitant vector control measures.

Extracellular vesicles (EVs) secreted by cells present an attractive strategy for developing new therapies, but progress in the field is limited by several issues: The quality of the EVs varies with the type and physiological status of the producer cells; protocols used to isolate the EVs are difficult to scale up; and assays for efficacy are difficult to develop. In the present report, we have addressed these issues by using human mesenchymal stem/stromal cells (MSCs) that produce EVs when incubated in a protein-free medium, preselecting the preparations of MSCs with a biomarker for their potency in modulating inflammation, incubating the cells in a chemically defined protein-free medium that provided a stable environment, isolating the EVs with a scalable chromatographic procedure, and developing an in vivo assay for efficacy of the cells in suppressing neuroinflammation after traumatic brain injury (TBI) in mice. In addition, we demonstrate that i.v. infusion of the isolated EVs shortly after induction of TBI rescued pattern separation and spatial learning impairments 1 mo later.

Patients with glioma present with complex palliative care needs throughout their disease trajectory. The life-limiting nature of gliomas and the presence of specific symptoms related to neurological deterioration necessitate an appropriate and early palliative care approach. The multidisciplinary palliative care task force of the European Association of Neuro-Oncology did a systematic review of the available scientific literature to formulate the best possible evidence-based recommendations for the palliative care of adult patients with glioma, with the aim to reduce symptom burden and improve the quality of life of patients and their caregivers, particularly in the end-of-life phase. When recommendations could not be made because of the scarcity of evidence, the task force either used evidence from studies of patients with systemic cancer or formulated expert opinion. Areas of palliative care that currently lack evidence and thus deserve attention for further research are fatigue, disorders of behaviour and mood, interventions for the needs of caregivers, and timing of advance care planning.