BACKGROUND & AIMS: INTRODUCTION:Shared-housing arrangements (SHAs) are small, home-like care environments in Germany. Residents are predominantly people with dementia. The risk for all-cause hospitalisation is consistently higher for people with dementia compared with people without dementia and there is currently no evidence-based intervention to reduce the risk of hospitalisation. Thus, the DemWG study investigates whether a complex intervention is effective in reducing hospitalisation (primary outcome), behavioural and psychological symptoms of dementia and falls and for stabilising cognitive functioning and quality of life in people with dementia and mild cognitive impairment (MCI) in German SHAs. METHODS AND ANALYSIS:Based on the UK Medical Research Council framework 'Developing and evaluating complex interventions', a prospective, mixed-methods, multicentre, cluster-randomised controlled trial combining primary and secondary data analyses as well as quantitative and qualitative research methods is being conducted. The intervention consists of three parts: (A) education of nursing staff in SHAs; (B) awareness raising and continuing medical education (CME) of general practitioners; (C) multicomponent non-pharmacological group intervention MAKS-mk+ ('m'=motor training; 'k'=cognitive training; '+'=fall prevention) for people with dementia and MCI. Randomisation is stratified by the German federal states and type of setting (rural vs urban). Neither the trained professionals nor the participants are blinded. Data are collected at baseline and after 6, 12 and 18 months with standardised instruments. Quantitative data will be analysed by multivariate analyses according to the general linear model, qualitative data using qualitative content analysis. Recruitment is still ongoing until 31 December 2020. ETHICS AND DISSEMINATION:All procedures were approved by the Ethics Committee of the University of Bremen (Ref. 2019-18-06-3). Informed consent will be obtained before enrolment of participants. Due to findings of previous randomised controlled trials, serious adverse events are not expected. Results will be disseminated in peer-reviewed journal publications and conference presentations. TRIAL REGISTRATION NUMBER:ISRCTN89825211.

背景与目标：

BACKGROUND & AIMS: :This study aimed to validate the TICS and modified TICS (TICSm) in Korean elderly population and to compare MCI and dementia screening ability between TICS and TICSm. TICS and TICSm were administered to 70 cognitively normal (CN), 75 MCI, and 85 dementia subjects, with mini-mental state examination (MMSE) and other cognitive and functional measures. TICS and TICSm scores were highly correlated with other global cognitive and functional scores. The CN vs. dementia discrimination ability of both instruments was as excellent as that of MMSE (sensitivity/specificity at optimal cutoff: 87.1/90.1 for TICS; 88.2/90.0 for TICSm). Although their CN vs. MCI discrimination performances were comparable to that of MMSE, they were far from perfect (sensitivity/specificity: 69.3/68.6 for TICS; 73.3/67.1 for TICSm). There was no significant difference in dementia or MCI screening accuracy between TICS and TICSm. Both of them also showed high test-retest reliability. Our findings indicate that TICS and TICSm are reliable and as valid as MMSE in regard of screening cognitively impaired elderly. In terms of the comparison between TICSm and TICS, however, TICSm has little advantage over TICS for screening dementia and even MCI, in spite of longer administration time and more efforts required.

背景与目标： : 本研究旨在验证韩国老年人群的TICS和改良TICS (TICSm)，并比较TICS和TICSm之间的MCI和痴呆症筛查能力。对70名认知正常 (CN)，75名MCI和85名痴呆症受试者进行了TICS和TICSm，并进行了迷你精神状态检查 (MMSE) 和其他认知和功能测量。TICS和TICSm评分与其他全球认知和功能评分高度相关。两种仪器的CN与痴呆鉴别能力与MMSE一样出色 (最佳临界点的敏感性/特异性: TICS的87.1/90.1; TICSm的88.2/90.0)。尽管它们的CN与MCI区分性能与MMSE相当，但它们远非完美 (敏感性/特异性: TICS的69.3/68.6; TICSm的73.3/67.1)。TICS和TICSm在痴呆或MCI筛查准确性方面没有显着差异。两者也都显示出很高的重测可靠性。我们的发现表明，在筛查认知受损的老年人方面，TICS和TICSm是可靠的，并且与MMSE一样有效。然而，就TICSm和TICS之间的比较而言，TICSm在筛查痴呆症甚至MCI方面比TICS没有什么优势，尽管给药时间更长，需要更多的努力。

BACKGROUND & AIMS: :Data support the evidence that neuropsychological rehabilitation is effective in Alzheimer disease (AD), to strengthen the pharmacological treatment to delay the progression of dementia. At moment, a few studies have examined the efficacy of non-pharmacological treatment in MCI. This is a controlled study that assesses the effectiveness of neuropsychological rehabilitation on cognitive and behavioral symptoms and functional status in a group of community-dwelling subjects with MCI and MD. Our results demonstrate that a systematic rehabilitation, that provides a computerized cognitive program training, produces an improvement in cognitive and affective status of patients with MCI and MD, while a rehabilitation program not providing a punctual stimulation of cognitive functions, does not have significant effects.

背景与目标： : 数据支持神经心理康复对阿尔茨海默病 (AD) 有效的证据，以加强药物治疗以延缓痴呆症的进展。目前，一些研究已经检查了MCI中非药物治疗的功效。这是一项对照研究，旨在评估一组患有MCI和MD的社区居民中神经心理康复对认知和行为症状以及功能状态的有效性。我们的结果表明，提供计算机化认知程序训练的系统康复可以改善MCI和MD患者的认知和情感状态，而康复程序不提供准时的认知功能刺激，则没有显着效果。

BACKGROUND & AIMS: BACKGROUND:The timed up and go (TUG) is a test used to assess mobility in older adults and patients with neurological conditions. This study aims to compare brain gray matter (GM) correlates and structural covariance networks associated with the TUG time in cognitively healthy individuals (CHI) and in patients with mild cognitive impairment (MCI). METHODS:The TUG time was measured in 326 non-demented older community-dwellers (age 71.3 ± 4.5; 42% female) - 156 CHI and 170 MCI. GM covariance networks were computed using voxel-based morphometry with the main neural correlates of TUG for each group as seed regions. RESULTS:Increased TUG time (i.e., poor performance) was associated with distinct brain volume reductions between CHI and MCI. The covariance analysis showed cortical regions involving the default mode network in CHI and bilateral cerebellar regions in MCI. CONCLUSIONS:GM networks associated with the TUG vary between CHI and MCI, suggesting distinct brain control for locomotion between CHI and MCI patients.

背景与目标：

BACKGROUND & AIMS: OBJECTIVES:To use a Machine Learning (ML) approach to compare Neuropsychiatric Symptoms (NPS) in participants of a longitudinal study who developed dementia and those who did not. DESIGN:Mann-Whitney U and ML analysis. Nine ML algorithms were evaluated using a 10-fold stratified validation procedure. Performance metrics (accuracy, recall, F-1 score, and Cohen's kappa) were computed for each algorithm, and graphic metrics (ROC and precision-recall curves) and features analysis were computed for the best-performing algorithm. SETTING:Primary care health centers. PARTICIPANTS:128 participants: 78 cognitively unimpaired and 50 with MCI. MEASUREMENTS:Diagnosis at baseline, months from the baseline assessment until the 3rd follow-up or development of dementia, gender, age, Charlson Comorbidity Index, Neuropsychiatric Inventory-Questionnaire (NPI-Q) individual items, NPI-Q total severity, and total stress score and Geriatric Depression Scale-15 items (GDS-15) total score. RESULTS:30 participants developed dementia, while 98 did not. Most of the participants who developed dementia were diagnosed at baseline with amnestic multidomain MCI. The Random Forest Plot model provided the metrics that best predicted conversion to dementia (e.g. accuracy=.88, F1=.67, and Cohen's kappa=.63). The algorithm indicated the importance of the metrics, in the following (decreasing) order: months from first assessment, age, the diagnostic group at baseline, total NPI-Q severity score, total NPI-Q stress score, and GDS-15 total score. CONCLUSIONS:ML is a valuable technique for detecting the risk of conversion to dementia in MCI patients. Some NPS proxies, including NPI-Q total severity score, NPI-Q total stress score, and GDS-15 total score, were deemed as the most important variables for predicting conversion, adding further support to the hypothesis that some NPS are associated with a higher risk of dementia in MCI.

背景与目标：

BACKGROUND & AIMS: OBJECTIVE:Although visual memory has been shown to be impaired in amnestic mild cognitive impairment (aMCI), the differences between MCI subtypes are not well defined. The current study attempted to investigate visual memory profiles in different MCI subtypes. METHODS:One hundred and seventy volunteers aged older than 50 years performed several visual memory tests included in the CANTAB battery. Participants were classified into four groups: (1) multiple domain aMCI (mda-MCI) (32 subjects); (2) single domain aMCI (sda-MCI)(57 subjects); (3) multiple domain non amnestic MCI (mdna-MCI) (32 subjects); and (4) controls (54 healthy individuals without cognitive impairment). Parametric and non parametric analyses were performed to compare the groups and to obtain their corresponding memory profiles. RESULTS:The mda-MCI group exhibited impairments in both dimensions of episodic memory (recognition and recollection/recall), and also in learning and working memory, whereas the sda-MCI only showed impairment in recollection-delayed recall and learning. The mdna-MCI group displayed impairment in working memory but good preservation of learning and episodic memory. CONCLUSION:The CANTAB visual memory profiles may contribute to better cognitive characterization of patients with different MCI subtypes, allowing comparison across several processes involved in visual memory such as attention, recognition, recollection and working memory.

背景与目标：

BACKGROUND & AIMS: OBJECTIVE:The multicenter prospective cohort study (Japan Cooperative SPECT Study on Assessment of Mild Impairment of Cognitive Function: J-COSMIC) aimed to examine the value of (123)I-N-isopropyl-4-iodoamphetamine cerebral blood flow (IMP-CBF) SPECT in regards to early diagnosis of Alzheimer's disease (AD) in patients with mild cognitive impairment (MCI). METHODS:Three hundred and nineteen patients with amnestic MCI at 41 participating institutions each underwent clinical and neuropsychological examinations and (123)I-IMP-CBF SPECT at baseline. Subjects were followed up periodically for 3 years, and progression to dementia was evaluated. SPECT images were classified as AD/DLB (dementia with Lewy bodies) pattern and non-AD/DLB pattern by central image interpretation and automated region of interest (ROI) analysis, respectively. Logistic regression analyses were used to assess whether baseline (123)I-IMP-CBF SPECT was predictive of longitudinal clinical outcome. RESULTS:Ninety-nine of 216 amnestic MCI patients (excluding 3 cases with epilepsy (n = 2) or hydrocephalus (n = 1) and 100 cases with incomplete follow-up) converted to AD within the observation period. Central image interpretation and automated ROI analysis predicted conversion to AD with 56 and 58 % overall diagnostic accuracy (sensitivity, 76 and 81 %; specificity, 39 and 37 %), respectively. Multivariate logistic regression analysis identified SPECT as a predictor, which distinguished AD converters from non-converters. The odds ratio for a positive SPECT to predict conversion to AD with automated ROI analysis was 2.5 and combining SPECT data with gender and mini-mental state examination (MMSE) further improved classification (joint odds ratio 20.08). CONCLUSIONS:(123)I-IMP-CBF SPECT with both automated ROI analysis and central image interpretation was sensitive but relatively nonspecific for prediction of clinical outcome during the 3-year follow-up in individual amnestic MCI patients. A combination of statistically significant predictors, both SPECT with automated ROI analysis and neuropsychological evaluation, may increase predictive utility.

背景与目标：

BACKGROUND & AIMS: OBJECTIVE:Cognitive impairment is prevalent among individuals with Parkinson's disease (PD). Effort has been made to identify individuals at risk for cognitive decline and dementia. Objectively-defined subtle cognitive decline (Obj-SCD) is a novel classification that may identify individuals at risk for cognitive decline prior to a diagnosis of mild cognitive impairment (MCI). We examined the utility of Obj-SCD criteria to predict future cognitive decline and difficulties with activities of daily living (ADLs) among individuals with PD. METHOD:The sample included 483 individuals newly diagnosed with PD. Participants were followed for a five-year span with yearly visits where they completed neuropsychological tests. Participants were categorized as cognitively normal (CN), the newly proposed Obj-SCD, PD-MCI or Parkinson's disease dementia (PDD). Analyses determined if utilization of Obj-SCD criteria predicted subsequent cognitive impairment and difficulties with ADLs. RESULTS:At baseline, 372 (77%) participants were classified as CN, 40 (8.3%) classified as Obj-SCD, and 71 (14.7%) classified as PD-MCI. Analyses revealed that relative to the CN group, participants classified as Obj-SCD at baseline, were more likely to develop PD-MCI or PDD within 5 years (odds ratio 2.413; 95% confidence interval 1.215-4.792). Furthermore, the Obj-SCD represented an intermediate level of impairment, relative to the CN and PD-MCI groups, on an independent measure of cognition (Montreal Cognitive Assessment) and ADL. CONCLUSIONS:Findings provide evidence that Obj-SCD criteria can identify individuals at risk for cognitive decline and impairments in ADL. Obj-SCD criteria may identify individuals at risk for cognitive impairment who are not detected by PD-MCI criteria.

背景与目标：

BACKGROUND & AIMS: :Limited research has investigated the effects of executive dysfunction on semantic memory deterioration among patients with amnestic mild cognitive impairment (aMCI). This study examined the cognitive performance of 181 participants from various MCI subgroups, a group of mildly impaired individuals with dementia of the Alzheimer type (DAT) and a group of individuals with subjective memory impairment on various semantic memory tasks. The aMCI-single domain (aMCI-sd) group displayed poor performance on a semantic memory task requiring relatively higher degrees of effortful retrieval, and participants in the aMCI-multiple domain (aMCI-md) group, who also suffered with mild executive dysfunction displayed poor performance on all semantic memory tasks, similar to the DAT group. The nonamnestic MCI (non-a-MCI)-single domain group displayed normal performance across all semantic tasks, whereas the non-a-MCI-multiple domain group displayed a pattern similar to that of the aMCI-sd group. aMCI-sd patients who displayed poor performance on the semantic memory task had higher risk of conversion to DAT, whereas poor performance on tasks requiring relatively less effortful retrieval was associated with higher risk of conversion in the aMCI-md group. Thus, executive function may relate to deterioration of semantic memory retrieval processes. Such patterns of semantic memory impairment could be valuable for characterization of cognitive differences among MCI patients.

背景与目标： : 有限的研究调查了执行功能障碍对遗忘型轻度认知障碍 (aMCI) 患者语义记忆恶化的影响。这项研究检查了来自各个MCI亚组的181名参与者的认知表现，一组轻度受损的阿尔茨海默氏痴呆症 (DAT) 个体和一组主观记忆障碍个体在各种语义记忆任务上的认知表现。aMCI-单域 (amci-sd) 组在需要相对较高程度的努力检索的语义记忆任务上表现不佳，而aMCI-多域 (amci-md) 组的参与者也患有轻度执行功能障碍在所有语义记忆任务上表现不佳，类似于DAT组。非遗忘MCI (non-a-MCI)-单域组在所有语义任务中显示正常性能，而非a-MCI-多域组显示的模式类似于amci-sd组。在语义记忆任务上表现不佳的amci-sd患者转换为DAT的风险较高，而在需要相对较少的努力检索的任务上表现不佳与amci-md组的转换风险较高相关。因此，执行功能可能与语义记忆检索过程的恶化有关。这种语义记忆障碍的模式对于表征MCI患者之间的认知差异可能很有价值。

BACKGROUND & AIMS: BACKGROUND:We explored the presence of both reserve and resilience in late-converter mild cognitive impairment due to Alzheimer's disease (MCI-AD) and in patients with slowly progressing amyloid-positive MCI by assessing the topography and extent of neurodegeneration with respect to both "aggressive" and typically progressing phenotypes and in the whole group of patients with MCI, grounding the stratification on education level. METHODS:We analyzed 94 patients with MCI-AD followed until conversion to dementia and 39 patients with MCI who had brain amyloidosis (AMY+ MCI), all with available baseline 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) results. Using a data-driven approach based on conversion time, patients with MCI-AD were divided into typical AD and late-converter subgroups. Similarly, on the basis of annual rate of Mini Mental State Examination score reduction, AMY+ MCI group was divided, obtaining smoldering (first tertile) and aggressive (third tertile) subgroups. Finally, we divided the whole group (MCI-AD and AMY+ MCI) according to years of schooling, obtaining four subgroups: poorly educated (Low-EDUC; first quartile), patients with average education (Average-EDUC; second quartile), highly educated (High-EDUC; third quartile), and exceptionally educated (Except-EDUC; fourth quartile). FDG-PET of typical AD, late converters, and aggressive and smoldering AMY+ MCI subgroups, as well as education level-based subgroups, were compared with healthy volunteer control subjects (CTR) and within each group using a two-samples t test design (SPM8; p < 0.05 family-wise error-corrected). RESULTS:Late converters were characterized by relatively preserved metabolism in the right middle temporal gyrus (Brodmann area [BA] 21) and in the left orbitofrontal cortex (BA 47) with respect to typical AD. When compared with CTR, the High-EDUC subgroup demonstrated a more extended bilateral hypometabolism in the posterior parietal cortex, posterior cingulate cortex, and precuneus than the Low- and Average-EDUC subgroups expressing the same level of cognitive impairment. The Except-EDUC subgroup showed a cluster of significant hypometabolism including only the left posterior parietal cortex (larger than the Low- and Average-EDUC subgroups but not further extended with respect to the High-EDUC subgroup). CONCLUSIONS:Middle and inferior temporal gyri may represent sites of resilience rather than a hallmark of a more aggressive pattern (when hypometabolic). These findings thus support the existence of a relatively homogeneous AD progression pattern of hypometabolism despite AD heterogeneity and interference of cognitive reserve. In fact, cortical regions whose "metabolic resistance" was associated with slower clinical progression had different localization with respect to the regions affected by education-related reserve.

背景与目标：

BACKGROUND & AIMS: :The neuropathological and cognitive changes preceding Alzheimer's disease (AD) appear to begin decades before disease symptoms make the clinical diagnosis obvious. Clinical trials have begun to focus on preventive treatments aimed to slow cognitive decline in people with only subjective memory complaints. However, it is not clear how many years before clinical diagnosis of Alzheimer's disease is possible to recognize early signs of neurodegeneration. We report evidence from the literature showing feasibility to diagnose AD at the stage of mild cognitive impairment (MCI) and also a few years before the MCI stage with imaging markers. However, we showed that neuroimaging brain changes evidenced decades before MCI are not early signs of neurodegeneration but expression of genetic risk states for AD or markers of inter-individual variability of cognitive performance due to genetic or environmental factors.

背景与目标： 阿尔茨海默病 (AD) 之前的神经病理和认知变化似乎在疾病症状使临床诊断变得明显之前的几十年就开始了。临床试验已经开始集中于预防性治疗，旨在减缓只有主观记忆主诉的人的认知能力下降。但是，尚不清楚在阿尔茨海默氏病的临床诊断之前有多少年可以识别神经变性的早期迹象。我们报告了文献中的证据，表明在轻度认知障碍 (MCI) 阶段以及在MCI阶段之前几年使用成像标记物诊断AD的可行性。然而，我们发现，在MCI之前数十年，神经影像学的大脑变化证明不是神经变性的早期迹象，而是AD的遗传风险状态的表达或由于遗传或环境因素导致的认知表现的个体间变异性的标记。

BACKGROUND & AIMS: MCI-154 (6-[4-(4'-pyridylamino)phenyl]-4,5-dihydro-3(2H)pyridazinone hydrochloride trihydrate) is a potent novel cardiotonic agent whose positive inotropism is shown to be mainly based on an increase in Ca2+ sensitivity of the contractile apparatus. To elucidate the exact mechanism through which this drug acts, we investigated the movement of the reconstituted thin filament on a myosin layer in vitro. Cardiac thin filaments were reconstituted from actin and tropomyosin-troponin complex purified from rat cardiac acetone powder separately. Double staining of the filament showed that tropomyosin-troponin complex was integrated along actin filament homogeneously. Thin filaments thus prepared were fluorescently labeled and made to slide on rat cardiac myosin fixed on a glass coverslip while varying the [Ca2+] of the medium (control, pH 7.2 at 25 degrees C). When [Ca2+] was low, the filaments showed only brownian motion. However, above a certain level of [Ca2+] (the threshold [Ca2+]), the filaments started to slide, and the velocity increased, reaching the maximum velocity within a very narrow range of [Ca2+]. The regulation was completely abolished by using simple actin filaments without tropomyosin-troponin complex, demonstrating that the regulatory proteins are responsible for this Ca2+ regulation of the movement of the reconstituted thin filament. Under the control condition, addition of MCI-154 shifted the threshold [Ca2+] to a lower level (sensitization) in a concentration-related manner. And 10(-4) mol/L of MCI-154 reversed the desensitization effect induced by either acidosis (pH 6.8), low temperature (15 degrees C), or the addition of inorganic phosphate (10 mmol/L).(ABSTRACT TRUNCATED AT 250 WORDS)

背景与目标： MCI-154 (6-[4-(4 '-吡啶基) 苯基]-4，5-二氢-3(2H) 盐酸哒嗪酮三水合物) 是一种有效的新型强心剂，其正性肌力作用主要基于收缩装置的Ca2敏感性的增加。为了阐明这种药物起作用的确切机制，我们研究了重构的细丝在体外肌球蛋白层上的运动。由肌动蛋白和分别从大鼠心脏丙酮粉末中纯化的原肌球蛋白-肌钙蛋白复合物重构心脏细丝。细丝的双重染色表明原肌球蛋白-肌钙蛋白复合物沿肌动蛋白细丝均匀整合。这样制备的细丝被荧光化标记并在固定在玻璃盖玻片上的大鼠心脏肌球蛋白上滑动，同时改变培养基的 [Ca2] (对照，pH 7.2在25 ℃)。当 [Ca2 +] 低时，细丝仅显示布朗运动。然而，超过一定水平的 [Ca2 +] (阈值 [Ca2 +])，细丝开始滑动，并且速度增加，在非常窄的 [Ca2 +] 范围内达到最大速度。通过使用没有原肌球蛋白-肌钙蛋白复合物的简单肌动蛋白丝完全取消了调节，表明调节蛋白负责重构细丝运动的Ca2 + 调节。在控制条件下，MCI-154的加入以浓度相关的方式将阈值 [Ca2 +] 转移到较低的水平 (敏化)。并且10(-4) mol/L的MCI-154逆转了酸中毒 (pH 6.8) 、低温 (15 ℃) 、或添加无机磷酸盐 (10 mmol/L)。(摘要截短于250字)

BACKGROUND & AIMS: :Cognitive training in MCI may stimulate pre-existing neural reserves or recruit neural circuitry as "compensatory scaffolding" prompting neuroplastic reorganization to meet task demands (Reuter-Lorenz & Park, 2014). However, existing systematic reviews and meta-analytic studies exploring the benefits of cognitive interventions in MCI have been mixed. An updated examination regarding the efficacy of cognitive intervention in MCI is needed given improvements in adherence to MCI diagnostic criteria in subject selection, better defined interventions and strategies applied, increased use of neuropsychological measures pre- and post-intervention, as well as identification of moderator variables which may influence treatment. As such, this meta-analytic review was conducted to examine the efficacy of cognitive intervention in individuals diagnosed with mild cognitive impairment (MCI) versus MCI controls based on performance of neuropsychological outcome measures in randomized controlled trials (RCT). RCT studies published from January 1995 to June 2017 were obtained through source databases of MEDLINE-R, PubMed, Healthstar, Global Health, PSYCH-INFO, and Health and Psychological Instruments using search parameters for MCI diagnostic category (mild cognitive impairment, MCI, pre-Alzheimer's disease, early cognitive decline, early onset Alzheimer's disease, and preclinical Alzheimer's disease) and the intervention or training conducted (intervention, training, stimulation, rehabilitation, or treatment). Other inclusion and exclusion criteria included subject selection based on established MCI criteria, RCT design in an outpatient setting, MCI controls (active or passive), and outcomes based on objective neuropsychological measures. From the 1199 abstracts identified, 26 articles met inclusion criteria for the meta-analyses completed across eleven (11) countries; 92.31% of which have been published within the past 7 years. A series of meta-analyses were performed to examine the effects of cognitive intervention by cognitive domain, type of training, and intervention content (cognitive domain targeted). We found significant, moderate effects for multicomponent training (Hedges' g observed = 0.398; CI [0.164, 0.631]; Z = 3.337; p = 0.001; Q = 55.511; df = 15; p = 0.000; I 2  = 72.978%; τ 2  = 0.146) as well as multidomain-focused strategies (Hedges' g = 0.230; 95% CI [0.108, 0.352]; Z = 3.692; p  < 0.001; Q = 12.713; df = 12; p = 0.390; I 2  = 5.612; τ 2  = 0.003). The effects for other interventions explored by cognitive domain, training type, or intervention content were indeterminate due to concerns for heterogeneity, bias, and small cell sizes. In addition, subgroup and meta-regression analyses were conducted with the moderators of MCI category, mode of intervention, training type, intervention content, program duration (total hours), type of control group (active or passive), post-intervention follow-up assessment period, and control for repeat administration. We found significant overall effects for intervention content with memory focused interventions appearing to be more effective than multidomain approaches. There was no evidence of an influence on outcomes for the other covariates examined. Overall, these findings suggest individuals with MCI who received multicomponent training or interventions targeting multiple domains (including lifestyle changes) were apt to display an improvement on outcome measures of cognition post-intervention. As such, multicomponent and multidomain forms of intervention may prompt recruitment of alternate neural processes as well as support primary networks to meet task demands simultaneously. In addition, interventions with memory and multidomain forms of content appear to be particularly helpful, with memory-based approaches possibly being more effective than multidomain methods. Other factors, such as program duration, appear to have less of an influence on intervention outcomes. Given this, although the creation of new primary network paths appears strained in MCI, interventions with memory-based or multidomain forms of content may facilitate partial activation of compensatory scaffolding and neuroplastic reorganization. The positive benefit of memory-based strategies may also reflect transfer effects indicative of compensatory network activation and the multiple-pathways involved in memory processes. Limitations of this review are similar to other meta-analysis in MCI, including a modest number studies, small sample sizes, multiple forms of interventions and types of training applied (some overlapping), and, while greatly improved in our view, a large diversity of instruments used to measure outcome. This is apt to have contributed to the presence of heterogeneity and publication bias precluding a more definitive determination of the outcomes observed.

背景与目标： : MCI中的认知训练可能会刺激预先存在的神经储备或招募神经回路作为 “补偿支架”，促使神经可塑性重组以满足任务需求 (Reuter-Lorenz & Park，2014)。然而，现有的系统评价和荟萃分析研究探讨了认知干预对MCI的益处。需要对认知干预对MCI的有效性进行更新检查，因为在受试者选择中遵守MCI诊断标准的情况有所改善，应用了更好的定义干预措施和策略，干预前后神经心理学措施的使用增加以及识别可能影响治疗的调节变量。因此，在随机对照试验 (RCT) 中，基于神经心理学结局指标的表现，进行了这项荟萃分析评价，以检查认知干预对被诊断为轻度认知障碍 (MCI) 的个体与MCI对照组的疗效。1995年1月至2017年6月发表的RCT研究是通过MEDLINE-R、PubMed、Healthstar、全球健康、心理信息以及健康和心理工具的源数据库获得的，使用MCI诊断类别 (轻度认知障碍、MCI、阿尔茨海默氏病前、早期认知衰退、早发性阿尔茨海默病和临床前阿尔茨海默病) 以及进行的干预或训练 (干预、训练、刺激、康复或治疗)。其他纳入和排除标准包括基于既定MCI标准的受试者选择，门诊患者的RCT设计，MCI对照 (主动或被动) 以及基于客观神经心理学指标的结果。从确定的1199篇摘要中，有26篇文章符合11个国家/地区完成的荟萃分析的纳入标准; 其中92.31% 篇已在过去7年内发表。进行了一系列荟萃分析，以通过认知领域，训练类型和干预内容 (目标认知领域) 来检查认知干预的效果。我们发现多组分训练有显著的中等效果 (hedges的g observed  =   0.398; CI [0.164，0.631]; Z =   3.337; P =   0.001; Q =   55.511; df  =   15; P =   0.000; I 2   =   72.978%; Τ 2   =   0.146) 以及多域聚焦策略 (hedges的g   =   0.230; 95% CI [0.108，0.352]; Z   =   3.692; P   < 0.001; Q   =   12.713; df  =   12; P   =   0.390; I 2   =   5.612; Τ 2   =   0.003)。由于对异质性，偏倚和小细胞大小的担忧，通过认知领域，训练类型或干预内容探索的其他干预措施的效果是不确定的。此外，还对MCI类别，干预方式，培训类型，干预内容，计划持续时间 (总小时数)，对照组类型 (主动或被动)，干预后随访评估期和重复给药控制进行了亚组和荟萃回归分析。我们发现，以记忆为重点的干预措施对干预内容的整体效果似乎比多领域方法更有效。没有证据表明其他协变量对结果有影响。总体而言，这些发现表明接受多组分训练或针对多个领域 (包括生活方式改变) 的干预措施的MCI患者易于在干预后的认知结果指标上显示出改善。因此，多组分和多域形式的干预可能会促使替代神经过程的招募以及支持主要网络以同时满足任务需求。此外，对记忆和多域形式的内容的干预似乎特别有帮助，基于记忆的方法可能比多域方法更有效。其他因素，如项目持续时间，似乎对干预结果的影响较小。鉴于此，尽管在MCI中创建新的主要网络路径似乎很紧张，但对基于记忆或多域形式的内容进行干预可能会促进补偿性支架的部分激活和神经整形重组。基于记忆的策略的积极好处还可以反映出指示补偿性网络激活和记忆过程中涉及的多个路径的转移效应。本综述的局限性与MCI中的其他荟萃分析相似，包括数量适中的研究，小样本量，多种形式的干预措施和应用的培训类型 (有些重叠)，尽管我们认为有很大的改善，但用于测量结果的工具种类繁多。这容易导致异质性和发表偏见的存在，从而无法对观察到的结果进行更明确的确定。

BACKGROUND & AIMS: :The biological mechanisms that link Beta-amyloid (Aβ) plaque deposition, neurodegeneration, and clinical decline in Alzheimer's disease (AD) dementia, have not been completely elucidated. Here we studied whether amyloid accumulation and neurodegeneration, independently or interactively, predict clinical decline over time in a group of memory impaired older individuals [diagnosed with either amnestic mild cognitive impairment (MCI), or mild AD dementia]. We found that baseline Aβ-associated cortical thinning across clusters encompassing lateral and medial temporal and parietal cortices was related to higher baseline Clinical Dementia Rating Sum-of-Boxes (CDR-SB). Baseline Aβ-associated cortical thinning also predicted CDR-SB over time. Notably, the association between CDR-SB change and cortical thickness values from the right lateral temporo-parietal cortex and right precuneus was driven by individuals with high Aβ burden. In contrast, the association between cortical thickness in the medial temporal lobe (MTL) and clinical decline was similar for individuals with high or low Aβ burden. Furthermore, amyloid pathology was a stronger predictor for clinical decline than MTL thickness. While this study validates previous findings relating AD biomarkers of neurodegeneration to clinical impairment, here we show that regions outside the MTL may be more vulnerable and specific to AD dementia. Additionally, excluding mild AD individuals revealed that these relationships remained, suggesting that lower cortical thickness values in specific regions, vulnerable to amyloid pathology, predict clinical decline already at the prodromal stage.

背景与目标： : 尚未完全阐明将 β-淀粉样蛋白 (a β) 斑块沉积，神经变性和阿尔茨海默氏病 (AD) 痴呆的临床下降联系起来的生物学机制。在这里，我们研究了淀粉样蛋白积累和神经变性是否独立或交互预测一组记忆受损的老年人 [被诊断为遗忘型轻度认知障碍 (MCI) 或轻度AD痴呆] 的临床随时间推移而下降。我们发现，包括外侧和内侧颞叶和顶叶皮质在内的簇的基线a β 相关皮质变薄与较高的基线临床痴呆评分盒总和 (CDR-SB) 有关。基线a β 相关的皮质变薄也预测了CDR-SB随时间的推移。值得注意的是，CDR-SB变化与右颞顶叶皮层和右前皮层的皮层厚度值之间的关联是由a β 负担高的个体驱动的。相反，对于a β 负荷高的或低的个体，内侧颞叶 (MTL) 的皮质厚度与临床下降之间的关联相似。此外，与MTL厚度相比，淀粉样蛋白病理是临床下降的更强预测指标。尽管这项研究证实了先前将神经退行性变的AD生物标志物与临床损害相关的发现，但在这里我们表明，MTL以外的区域可能更容易受到AD痴呆的影响。此外，排除轻度AD个体后，这些关系仍然存在，这表明易受淀粉样蛋白病理影响的特定区域的皮质厚度值较低，预示着前驱阶段的临床下降。

BACKGROUND & AIMS: :Capturing the dynamics of gray matter (GM) atrophy in relation to the conversion from mild cognitive impairment (MCI) to clinically probable Alzheimer's disease (AD) would be of considerable interest. In this prospective study we have used a novel longitudinal voxel-based method to map the progression of GM loss in MCI patients over time and compared converters to non-converters. Eighteen amnestic MCI patients were followed-up for a predefined fixed period of 18 months and conversion was judged according to NINCDS-ADRDA criteria for probable AD. Each patient underwent a high-resolution T1-weighted volume MRI scan both at entry in the study and 18 months later. We used an optimal VBM protocol to compare baseline imaging data of converters to those of non-converters. Moreover, to map GM loss from baseline to follow-up assessment, we used a modified voxel-based morphometry (VBM) procedure specially designed for longitudinal studies. At the end of the follow-up period, seven patients had converted to probable AD. Areas of lower baseline GM value in converters mainly included the hippocampus, parahippocampal cortex, and lingual and fusiform gyri. Regions of significant GM loss over the 18-month follow-up period common to both converters and non-converters included the temporal neocortex, parahippocampal cortex, orbitofrontal and inferior parietal areas, and the left thalamus. However, there was significantly greater GM loss in converters relative to non-converters in the hippocampal area, inferior and middle temporal gyrus, posterior cingulate, and precuneus. This accelerated atrophy may result from both neurofibrillary tangles accumulation and parallel pathological processes such as functional alteration in the posterior cingulate. The ability to longitudinally assess GM changes in MCI offers new perspectives to better understand the pathological processes underlying AD and to monitor the effects of treatment on brain structure.

背景与目标： : 捕捉与从轻度认知障碍 (MCI) 到临床可能的阿尔茨海默氏病 (AD) 的转化有关的灰质 (GM) 萎缩的动力学将引起极大的兴趣。在这项前瞻性研究中，我们使用了一种新颖的基于纵向体素的方法来绘制MCI患者随时间推移的GM损失进展图，并将转换器与非转换器进行了比较。对18例遗忘型MCI患者进行了预定义的固定时间18个月的随访，并根据NINCDS-ADRDA标准对可能的AD进行了判断。每位患者在进入研究阶段和18个月后均接受了高分辨率T1-weighted体积MRI扫描。我们使用了最佳VBM协议来比较转换器与非转换器的基线成像数据。此外，为了将GM的损失从基线到后续评估进行映射，我们使用了专门为纵向研究设计的改进的基于体素的形态计量学 (VBM) 程序。在随访期结束时，有7名患者转化为可能的AD。转化器中基线GM值较低的区域主要包括海马，海马旁皮质以及舌和梭形回。在18个月的随访期内，转化者和非转化者共有的显着GM损失区域包括颞新皮质，海马旁皮质，眶额叶和顶叶下区域以及左丘脑。然而，相对于海马区，颞下回和中回，扣带回后和神经前的非转换器，转换器中的GM损失明显更大。这种加速萎缩可能是由于神经原纤维缠结的积累和平行的病理过程 (例如后扣带回的功能改变) 引起的。纵向评估MCI中GM变化的能力为更好地理解AD的病理过程和监测治疗对大脑结构的影响提供了新的视角。