Brief Report: Adenosine A2A receptor blockade prevents cisplatin-induced impairments in neurogenesis and cognitive function

Chemotherapy-induced cognitive impairment (CICI) has emerged as a significant medical problem without therapeutic options. Using the platinum-based chemotherapy cisplatin to model CICI, we revealed robust elevations in the adenosine A_2A receptor (A_2AR) and its downstream effectors, cAMP and CREB, by cisplatin in the adult mouse hippocampus, a critical brain structure for learning and memory. Notably, A_2AR inhibition by the Food and Drug Administration–approved A_2AR antagonist KW-6002 prevented cisplatin-induced impairments in neural progenitor proliferation and dendrite morphogenesis of adult-born neurons, while improving memory and anxiety-like behavior, without affecting tumor growth or cisplatin’s antitumor activity. Collectively, our study identifies A_2AR signaling as a key pathway that can be therapeutically targeted to prevent cisplatin-induced cognitive impairments.     

Identification of Nordic Berries with Beneficial Effects on Cognitive Outcomes and Gut Microbiota in High-Fat-Fed Middle-Aged C57BL/6J Mice

High-fat diets are associated with neuronal and memory dysfunction. Berries may be useful in improving age-related memory deficits in humans, as well as in mice receiving high-fat diets. Emerging research has also demonstrated that brain health and cognitive function may be related to the dynamic changes in the gut microbiota. In this study, the impact of Nordic berries on the brain and the gut microbiota was investigated in middle-aged C57BL/6J mice. The mice were fed high-fat diets (60%E fat) supplemented with freeze-dried powder (6% dwb) of bilberry, lingonberry, cloudberry, blueberry, blackcurrant, and sea buckthorn for 4 months. The results suggest that supplementation with bilberry, blackcurrant, blueberry, lingonberry, and (to some extent) cloudberry has beneficial effects on spatial cognition, as seen by the enhanced performance following the T-maze alternation test, as well as a greater proportion of DCX-expressing cells with prolongation in hippocampus. Furthermore, the proportion of the mucosa-associated symbiotic bacteria Akkermansia muciniphila increased by 4–14 times in the cecal microbiota of mice fed diets supplemented with lingonberry, bilberry, sea buckthorn, and blueberry. These findings demonstrate the potential of Nordic berries to preserve memory and cognitive function, and to induce alterations of the gut microbiota composition.     

Depressive symptoms in amnesic mild cognitive impairment: an FDG-PET/CT study

IntroductionThe detection in mild cognitive impairment (MCI) of metabolic alterations suggestive of depression and/or of evolution to dementia.MethodsSixty-nine MCI patients underwent clinical and imaging evaluation including position emission tomography/computed tomography with fluorodeoxy-glucose (FDG-PET/CT).ResultsThe metabolism mean values in parietal, temporal and pre-cuneus areas were lower in subjects who evolved to dementia, and in frontal and in anterior cingulate areas in depressed subjects. Abnormal metabolism values were higher in the frontal and parietal lobes, and in the precuneus in subjects who evolved to dementia independently from depression.ConclusionsIn MCI FDG-PET/CT abnormality patterns suggest the presence of depression or the evolution to dementia.     

The past,present, and future of sleep measurement in mild cognitive impairment and early dementia—towards a core outcome set: a scoping review

Study ObjectivesSleep abnormalities emerge early in dementia and may accelerate cognitive decline. Their accurate characterization may facilitate earlier clinical identification of dementia and allow for assessment of sleep intervention efficacy. This scoping review determines how sleep is currently measured and reported in Mild Cognitive Impairment (MCI) and early dementia, as a basis for future core outcome alignment.MethodsThis review follows the PRISMA Guidelines for Scoping Reviews. CINAHL, Embase, Medline, Psychinfo, and British Nursing Index databases were searched from inception—March 12, 2021. Included studies had participants diagnosed with MCI and early dementia and reported on sleep as a key objective/ outcome measure.ResultsNineteen thousand five hundred and ninety-six titles were returned following duplicate removal with 188 studies [N] included in final analysis. Sleep data was reported on 17 139 unique, diagnostically diverse participants (n). “Unspecified MCI” was the most common diagnosis amongst patients with MCI (n = 5003, 60.6%). Despite technological advances, sleep was measured most commonly by validated questionnaires (n = 12 586, N = 131). Fewer participants underwent polysomnography (PSG) (n = 3492, N = 88) and actigraphy (n = 3359, N = 38) with little adoption of non-PSG electroencephalograms (EEG) (n = 74, N = 3). Sleep outcome parameters were reported heterogeneously. 62/165 (37.6%) were described only once in the literature (33/60 (60%) in interventional studies). There was underrepresentation of circadian (n = 725, N = 25) and micro-architectural (n = 360, N = 12) sleep parameters.ConclusionsAlongside under-researched areas, there is a need for more detailed diagnostic characterization. Due to outcome heterogeneity, we advocate for international consensus on core sleep outcome parameters to support causal inference and comparison of therapeutic sleep interventions.     

The sexual brain,genes, and cognition: A machine‐predicted brain sex score explains individual differences in cognitive intelligence and genetic influence in young children

Sex impacts the development of the brain and cognition differently across individuals. However, the literature on brain sex dimorphism in humans is mixed. We aim to investigate the biological underpinnings of the individual variability of sexual dimorphism in the brain and its impact on cognitive performance. To this end, we tested whether the individual difference in brain sex would be linked to that in cognitive performance that is influenced by genetic factors in prepubertal children (N = 9,658, ages 9–10 years old; the Adolescent Brain Cognitive Development study). To capture the interindividual variability of the brain, we estimated the probability of being male or female based on the brain morphometry and connectivity features using machine learning (herein called a brain sex score). The models accurately classified the biological sex with a test ROC–AUC of 93.32%. As a result, a greater brain sex score correlated significantly with greater intelligence (p _fdr < .001, ηp2 = .011–.034; adjusted for covariates) and higher cognitive genome‐wide polygenic scores (GPSs) (p _fdr < .001, ηp2 < .005). Structural equation models revealed that the GPS‐intelligence association was significantly modulated by the brain sex score, such that a brain with a higher maleness score (or a lower femaleness score) mediated a positive GPS effect on intelligence (indirect effects = .006–.009; p = .002–.022; sex‐stratified analysis). The finding of the sex modulatory effect on the gene–brain–cognition relationship presents a likely biological pathway to the individual and sex differences in the brain and cognitive performance in preadolescence.     

Copper Biology in Health and Disease: The accumulation of copper in the brain of Down syndrome promotes oxidative stress: possible mechanism underlying cognitive impairment

Individuals with Down syndrome (DS), which is caused by triplication of human chromosome 21 (Hsa21), show numerous characteristic symptoms, such as intellectual disability, an impaired cognitive function, and accelerated aging-like phenotypes. Enhanced oxidative stress is assumed to be implicated as a mechanism underlying many of these symptoms of DS. Some genes coded in Hsa21, such as App, Sod1, and Ets2, are suggested as being involved in the exacerbation of oxidative stress. In addition, enhanced oxidative stress has been recently shown to be caused by dyshomeostasis of the redox-active bio-metal copper in the brain of a mouse model of DS. This review aims to summarize the current knowledge on enhanced oxidative stress in DS and suggest a possible molecular mechanism underlying the cognitive impairment of DS mediated by enhanced oxidative stress.     

Teach-Back健康教育模式对学龄期手足口病患儿家属疾病认知水平及防护行为的影响

目的:探讨Teach-Back健康教育模式对学龄期手足口病(HFMD)患儿家属疾病认知水平及防护行为的影响。方法:2018年7月—2020年11月选取我院学龄期113名HFMD患儿家属为研究对象,按照随机数字表法分为对照组56例与观察组57例,对照组给予常规健康教育干预,观察组给予Teach-Back健康教育模式干预,观察两组患儿家属疾病认知水平、行为干预遵从率、患儿症状改善状况。结果:干预后,观察组患儿家属发病原因、传播途径、隔离治疗、并发症预防认知评分高于对照组(P<0.05);观察组患儿家属消毒隔离措施、饭前便后洗手、勤晒衣被、居家开窗通风遵从率高于对照组(P<0.05);观察组患儿发热、口腔溃疡、皮疹、食欲减退改善时间短于对照组(P<0.05)。结论:对学龄期HFMD患儿家属开展Teach-Back健康教育模式,可明显提高家属对疾病认知水平,提高行为干预遵从率,促进患儿恢复。     

Supplementation with NAD+ and Its Precursors to Prevent Cognitive Decline across Disease Contexts

The preservation of cognitive ability by increasing nicotinamide adenine dinucleotide (NAD⁺) levels through supplementation with NAD⁺ precursors has been identified as a promising treatment strategy for a number of conditions; principally, age-related cognitive decline (including Alzheimer’s disease and vascular dementia), but also diabetes, stroke, and traumatic brain injury. Candidate factors have included NAD⁺ itself, its reduced form NADH, nicotinamide (NAM), nicotinamide mononucleotide (NMN), nicotinamide riboside (NR), and niacin (or nicotinic acid). This review summarises the research findings for each source of cognitive impairment for which NAD⁺ precursor supplementation has been investigated as a therapy. The findings are mostly positive but have been made primarily in animal models, with some reports of null or adverse effects. Given the increasing popularity and availability of these factors as nutritional supplements, further properly controlled clinical research is needed to provide definitive answers regarding this strategy’s likely impact on human cognitive health when used to address different sources of impairment.     

脑电生物反馈治疗注意缺陷多动障碍儿童的疗效

目的 探讨脑电生物反馈治疗对注意缺陷多动障碍(ADHD)患儿临床症状和认知功能的疗效.方法 对20例经主治医师以上精神科医师确诊符合<美国精神障碍诊断与统计手册>4版中ADHD诊断标准、年龄(10.4±2.2)岁的患儿,应用Autogenic A620型脑电生物反馈仪进行40次脑电生物反馈治疗,以抑制4～8 Hz的0波、强化12～15 Hz的感觉运动节律波为治疗方案.治疗前后应用Conners父母问卷评估临床表现,韦氏记忆量表(WMS)评定长时记忆、短时记忆和瞬时记忆,数字划消测验和斯特鲁普(Stroop)测试评估认知加工速度和选择性注意力,持续性操作能力测试(CPT)评估注意力和冲动性.健康对照组儿童来自医院附近的中小学,性别和年龄与ADHD组配对,配对年龄相差不超过6个月,仅进行一次上述评估.结果 ADHD组治疗后,Conners父母问卷调查患儿行为因子评分明显降低(P＜0.05),WMS测试的短时记忆评分明显增加(P＜0.05).Stroop色测验时间和词义干扰时明显缩短(Pa＜0.05),数字划消测试的第1、2、3段净分均明显增加(Pa＜0.05).ADHD组治疗后与健康对照组儿童比较,Conners父母问卷调查患儿躯体因子、多动因子和焦虑因子、韦氏记忆测试的瞬时记忆、Stroop色测验时间、词测验时间和颜色干扰时、数字划消测试的第1、2、3段净分、CPT的遗漏率均无统计学差异(Pa≥0.05).结论脑电生物反馈治疗40次可显著改善ADHD患儿的临床症状、注意力、记忆力、选择性注意力和认知加工速度,部分指标可达到健康儿童水平.     

右美托咪定对老年患者经尿道前列腺电切术后早期认知功能的影响

目的：探讨右美托咪定（Dex）对老年患者经尿道前列腺电切术（TURP）早期认知功能的影响.方法：择期拟行TURP患者76例,美国麻醉师协会（ASA）分级Ⅰ或Ⅱ级,年龄65～81岁,术前简易智力状态检查量表（MMSE）评分＞23分,采用随机数字表法,将其随机分为2组：Dex组（D组）和生理盐水组（C组）,每组38例.全麻诱导前D组静脉输注负荷量Dex 1μg/kg,10 min后改为恒速静脉输注Dex 0.5 μg＆#183;kg-1＆#183;h-1至术毕前30 min,C组采用同样方法静脉输注等容量生理盐水.记录气管插管前（T0）、气管插管即刻（T1）、手术开始时（T2）、手术开始30 min（T3）时的MAP和HR以及手术时间、苏醒时间,并分别于术前24 h、术后24 h采用MMSE评分进行神经心理学评估.结果：两组患者一般资料和术中情况比较差异无统计学意义.C组患者在T1、Tz时的MAP明显高于D组（P＜0.05）.与C组比较,D组术后24 h的MMSE评分明显升高,术后认知功能障碍（POCD）的发生率明显降低（P＜0.05）.结论：Dex可减少老年患者TURP术后早期POCD的发生率,术中麻醉平稳且不影响患者的苏醒.