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.     

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.     

Improved cognitive performance after dietary supplementation with a Pinus radiata bark extract formulation

Dietary interventions may have the potential to counter age-related cognitive decline. Studies have demonstrated an improvement in age-related cognitive impairment in animals after supplementation with plant extracts containing flavonoids but there are few human studies. This double-blind, controlled study examined the effects on cognitive performance of a 5 week supplementation with Enzogenol Pinus radiata bark extract containing flavonoids, in 42 males aged 50-65 years, with a body mass index >25. Participants were supplemented for 5 weeks either with Enzogenol plus vitamin C, or with vitamin C only. A battery of computerized cognitive tests was administered, and cardiovascular and haematological parameters were assessed prior to and following supplementation. The speed of response for the spatial working memory and immediate recognition tasks improved after supplementation with Enzogenol plus vitamin C, whereas vitamin C alone showed no improvements. A trend in a reduction of systolic blood pressure was observed with Enzogenol plus vitamin C, but not with vitamin C alone. The blood safety parameters were unchanged. The findings suggest a beneficial effect of supplementation with Enzogenol on cognition in older individuals. Larger studies are needed to ascertain its potential as a preventive treatment for age-related cognitive decline.     

军人失眠症患者睡眠的认知心理特点与个性特征的相关研究

目的探讨军人失眠症患者对睡眠的认知心理特点及与个性特征的关系。方法采用睡眠的个人信念和态度量表(DBAS)和艾森克个性问卷-成人版(EPQ)对48例军人失眠症患者(失眠症组)进行调查分析,并随机抽取某部50例官兵作为对照组。结果失眠症组患者的DBAS总分及各因子分和对照组比较,差异均有统计学意义(P<0.05,P<0.01);EPQ的内外向和神经质因子分与对照组比较差异有统计学意义(P<0.01);DBAS总分及各因子分和神经质呈正相关(r=0.159～0.234;P<0.05,P<0.01),与内外向呈负相关(r=-0.162～-0.238;P<0.05,P<0.01)。结论军人失眠症患者存在着大量与睡眠相关的错误认知,个性特征与这些错误认知有明显的相关性。     

血清铁死亡标记物与绝经后女性认知障碍的关系

目的 研究血清铁死亡标记物与绝经后女性认知障碍的关系。方法 选取2019年8月至2021年12月就诊的148例女性,其中生育期女性22例,围绝经期女性11例,绝经后女性115例。按照蒙特利尔认知评估量表(Montreal cognitive assessment, MoCA)将绝经后女性分为认知障碍组(n=77)和无认知障碍组(n=38),比较两组血清铁死亡标记物有无差异,应用Logistic进行多因素回归分析绝经后女性认知障碍的相关因素。通过受试者工作特征曲线(Receiver operating characteristic curve, ROC)评估相关因素对绝经后女性认知障碍的诊断价值。结果 与生育期和围绝经期女性相比,绝经后女性MoCA评分明显较低,血清ACSL4、System Xc-、GPX4、GSH、ROS、LPO及MDA水平均明显升高(均P<0.05)。与无认知障碍组相比,认知障碍组绝经后女性受教育年限短、患高血压的比例高,且血清ACSL4、System Xc_-^{、GPX4、GSH、ROS、LPO及MDA水平明显}升高 (均P<0.05)。多因素Logistic回归分析显示教育年限和血清谷胱甘肽(glutathione, GSH)与认知障碍独立相关(P<0.05),ROC曲线分析显示两者联合对预测女性是否患认知障碍具有中度诊断价值(AUC: 0.764, P<0.05)。结论 绝经后女性血清铁死亡标志物ACSL4、System Xc_-^{、GPX4、GSH、ROS、LPO及MDA水平}明显升高,其中GSH与女性认知障碍发生独立相关,与受教育年限联合有望成为绝经后女性认知障碍早期诊断的潜在标志物。     

非致残性缺血性脑血管事件患者早期淡漠与情感认知障碍的相关性研究

目的 探究非致残性缺血性脑血管事件（NICE）患者早期淡漠与情感认知障碍的关系。方法 收集2021年6月至2022年12月在上海长海医院收治的NICE患者244例,其中男性156例,女性88例,平均年龄为63.1±9.7岁。根据入院时淡漠评估量表-临床医师版（AES-C）评分分为情感淡漠（≥33分,n=64） 组和非淡漠（＜33分,n=180）组。收集患者的人口学资料、血检验结果以及影像学资料,于发病2周内完善匹兹堡睡眠质量指数量表(PSQI)、蒙特利尔认知评估量表（MoCA）、听觉语词学习测验（AVLT）、数字广度实验（DST）、数字符号转换测验（DSST）、数字连线测验（TMT）、汉密尔顿焦虑、抑郁量表（HAMD、HAMA）等评估。利用t检验或非参数检验比较两组之间资料的差异,多因素Logistic回归分析影响淡漠的因素。结果 NICE后早期淡漠的发生率为26.2%,与非淡漠组相比,淡漠组患者的年龄较高而 BMI和受教育年限较低（所有P<0.05）;两组患者的性别、吸烟、饮酒以及高血压病史无显著性差异（所有P>0.05）。入院时首次血检验结果提示两组患者甲状腺激素水平均无显著性差异（P>0.05）,同时TOAST病因分型未发现两组患者的病因存在差异（P>0.05）。使用Fazekas白质评分对白质损伤进行量化结果提示,淡漠组患者的脑白质损伤明显高于非淡漠组（P=0.004）。认知功能检测结果提示,与非淡漠组相比,淡漠组患者认知障碍发生率（MoCA＜26）明显更高（46% vs 59%, P＜0.05）。淡漠组患者的言语流畅性抽象能力、延迟回忆和定向能力均明显减退（所有P<0.05）,两组之间视空间、执行功能以及命名能力无显著差异（所有P>0.05）。此外,淡漠组PSQI、HAMA、HAMD得分均高于非淡漠组,且睡眠障碍、焦虑和抑郁的发生率显著增加（P<0.05）。Logistic回归分析发现HAMD得分、年龄以及TMT-A用时为卒中后淡漠的危险因素（P<0.05）。结论 早期淡漠的NICE患者认知功能障碍发生率更高,且更易出现睡眠障碍以及焦虑和抑郁状态。HAMD得分、年龄以及TMT-A用时为卒中后淡漠的危险因素。