Structural and functional neural correlates of visuospatial information processing in normal aging and amnestic mild cognitive impairment

Our understanding of cognitive changes related to human aging and their underlying neural processes is challenged by the distinction between normal and pathological aging. In our study, the neural correlates of visuospatial working memory (VSWM) in young persons (YC), healthy older adults (HC) and patients with amnestic mild cognitive impairment (aMCI) were investigated. Effects of the genetic risk factor apolipoprotein E (ApoE) ε4 on a VSWM task were analyzed for HC and aMCI patients. Higher cortical activation in extrastriate occipital regions and significantly decreased brain volumes in frontoparietal areas were observed in HC compared with young persons. Also, reduced cortical activation in the right middle frontal gyrus and superior frontal gyrus was observed in aMCI-patients compared with HC. Thus, attenuated cortical activation during VSWM tasks is related to the formation of aMCI and may serve as an early marker for cognitive decline. In contrast to previous studies, no significant apolipoprotein E-linked differences were found between HC and aMCI groups.     

Cerebral and blood correlates of reduced functional connectivity in mild cognitive impairment

Growing evidence suggests that decreased functional connectivity in cortical networks precedes clinical stages of Alzheimer’s disease (AD), although our knowledge about cerebral and biological correlates of this phenomenon is limited. To shed light on this issue, we have investigated whether resting-state oscillatory connectivity patterns in healthy older (HO) and amnestic mild cognitive impairment (aMCI) subjects are related to anatomical grey matter (GM) and functional (2-[18F]fluoro-2-deoxy-d-glucose (FDG)-PET) changes of neuroelectric sources of alpha rhythms, and/or to changes in plasma amyloid-beta (Aβ) and serum lipid levels, blood markers tied to AD pathogenesis and aging-related cognitive decline. We found that aMCI subjects showed decreased levels of cortical connectivity, reduced FDG-PET intake of the precuneus, and GM atrophy of the thalamus, together with higher levels of Aβ and apolipoprotein B (ApoB) compared to HO. Interestingly, levels of high-density lipoprotein (HDL) cholesterol were positively correlated with the strength of neural-phase coupling in aMCI subjects, and increased triglycerides accompanied bilateral GM loss in the precuneus of aMCI subjects. Together, these findings provide peripheral blood correlates of reduced resting-state cortical connectivity in aMCI, supported by anatomo-functional changes in cerebral sources of alpha rhythms. This framework constitutes an integrated approach to assess functional changes in cortical networks through neuroimaging and peripheral blood markers during early stages of neurodegeneration.     

Neural correlates of incidental memory in mild cognitive impairment: an fMRI study

Behaviour and fMRI brain activation patterns were compared during encoding and recognition tasks in mild cognitive impairment (MCI) (n=14) and normal controls (NC) (n=14). Deep (natural vs. man-made) and shallow (color vs. black and white) decisions were made at encoding and pictures from each condition were presented for yes/no recognition 20 min later. MCI showed less inferior frontal activation during deep (left only) and superficial encoding (bilaterally) and in both medial temporal lobes (MTL). When performance was equivalent (recognition of words encoded superficially), MTL activation was similar for the two groups, but during recognition testing of deeply encoded items NC showed more activation in both prefrontal and left MTL region. In a region of interest analysis, the extent of activation during deep encoding in the parahippocampi bilaterally and in left hippocampus correlated with subsequent recognition accuracy for those items in controls but not in MCI, which may reflect the heterogeneity of activation responses in conjunction with different degrees of pathology burden and progression status in the MCI group.     

Associations between sleep duration and cognitive impairment in mild cognitive impairment

The prevalence of mild cognitive impairment (MCI) increases among elderly people and is associated with a high risk of dementia. Identifying factors that may contribute to the progress of MCI to dementia is critical. The objective of this study was to examine the association of objective sleep with cognitive performance in MCI patients. A subsample of 271 participants with a diagnosis of probable Alzheimer's disease (AD; N = 50) or mild cognitive impairment (MCI; N = 121) and 100 persons who were not cognitively impaired (NI) were recruited from a large population‐based cohort in the island of Crete, Greece (3140 older adults aged >60 years). All participants underwent extensive neuropsychiatric/neuropsychological evaluation and a 3‐day 24‐hr actigraphy. Objective sleep variables and their association with neuropsychological performance were examined across the three groups, controlling for demographics, body mass index, depression, sleep apnea symptoms and psychotropic medications. Patients with AD had significantly longer 24‐hr total sleep time (TST) compared to the MCI and NI groups. Long 24‐hr TST was associated with reduced performance on tasks that placed significant demands on attention and processing speed in the MCI group and the AD group. Elderly patients with MCI have similar objective sleep duration to normal controls, whereas AD patients sleep longer. Long sleep duration in patients with multidomain subtypes of MCI is associated with critical non‐memory cognitive domains. It appears that within the MCI group those that sleep longer have more severe cognitive impairment.     

轻度认知障碍神经炎症机制的作用靶点

背景:临床上,轻度认知障碍是正常衰老认知下降与阿尔茨海默症早期之间的过渡状态,被认为是预防或改变阿尔茨海默症退行性变的最佳阶段.近年来,越来越多的研究表明,神经炎症是轻度认知障碍的核心发病机制和主要早期病理特征之一.目的:综述国内外神经炎症导致轻度认知障碍的机制研究进展.方法:英文检索词为neuroinflammat...     

Severity of insomnia correlates with cognitive impairment

INTRODUCTION AND METHODS: Cognitive deficits in insomnia have been already reported (5), however, a correlation between cognitive impairment and severity of insomnia was not as yet studied. Sixteen not medicated patients with primary insomnia according to DSM-IV (4), 7 men an 9 women, of mean age 40.8 year, were compared to 16 controls, matched according to age, sex and education. Standard polysomnographic data (PSG) were recorded. The next day all the subjects completed Athens Insomnia Scale (AIS) (7), Hyperarousal Scale (HS) (6), Hamilton Depression Rating Scale (HAM-D), Beck Depression Inventory (BDI), Multiple Sleep Latency Test (MSLT) (3), Continuous Attention Test (CAT) with simple reaction time (RT) (8) and Selective Reminding Test (SRT) (2). RESULTS AND DISCUSSION: The psychophysiological differences between patients and controls are shown in Table I. HAM-D and BDI scores were elevated in patients, although none of the patients met clinical criteria of depression. Insomniacs did not differ in the immediate recall, but the number of repetitions necessary to learn all the items of SRT was greater in patients. Insomniacs usually complain of poor performance, however, learning impairment has not been documented in insomnia. Degree of the learning impairment correlated with insomnia score (Fig. 1). Cognitive deficit cannot be due to a daytime sleepiness because sleep latency in all MSLT sessions was not shorter in insomniacs. No correlations between results of SRT and standard PSG parameters were found, in accordance with the thesis that subjective feeling of nonrestorative sleep and other accompanying deficits are only symptoms of an underlying 24-hour disorder (1).     

Cognitive correlates of HVOT performance differ between individuals with mild cognitive impairment and normal controls.

OBJECTIVE: To clinically characterize performance on the Hooper Visual Organization Test (HVOT) among participants with mild cognitive impairment (MCI) and to identify naming and executive functioning correlates associated with HVOT performance among MCI participants and normal controls (NC). BACKGROUND: The HVOT is a common neuropsychological instrument that measures visuospatial skills and agnosia. It has, however, been criticized for its multifactorial nature, as several studies have reported executive or language correlates of HVOT performance. To our knowledge, simultaneous comparison of executive functioning and language demands of the HVOT has never been performed among an older cohort. METHODS: The HVOT, two tests of executive functioning [Trail Making Test, Part B (TMT-B), Controlled Oral Word Association (COWA)] and two tests of naming [abbreviated Boston Naming Test (BNT), Animal Naming] were administered to 222 NC, 166 MCI, and 68 Alzheimer's disease (AD) individuals. RESULTS: HVOT scores were significantly different between all three groups in the expected direction (AD相似文献   

Reduced interhemispheric inhibition in mild cognitive impairment

In mild cognitive impairment (MCI), the corpus callosum is known to be affected structurally. We evaluated callosal function by interhemispheric inhibition (IHI) using transcranial magnetic stimulation (TMS) in MCI patients. We investigated 12 amnestic MCI patients and 16 healthy age-matched control subjects. The IHI was studied with a paired-pulse TMS technique. The conditioning TMS was given over the right primary motor cortex (M1) and the test TMS over the left M1. Motor evoked potentials were recorded from the relaxed first dorsal interosseous muscle. We also studied other motor cortical circuit functions; short-latency afferent inhibition (SAI), short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF). Both the amount of IHI and SAI were significantly reduced in MCI patients as compared with control subjects, whereas SICI or ICF did not differ between them. The degree of IHI significantly correlated with neither the mini-mental state examination score nor the degree of SAI. Our results suggest that transcallosal connection between bilateral M1 is primarily involved in MCI, regardless of SAI dysfunction.     

Cognitive estimation impairment in Alzheimer disease and mild cognitive impairment

Intact executive functioning is believed to be required for performance on tasks requiring cognitive estimations. This study used a revised version of a cognitive estimations test (CET) to investigate whether patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) were impaired on the CET compared with normal elderly controls (NECs). Neuropsychological tests were administered to determine the relationship between CET performance and other cognitive domains. AD patients displayed impaired CET performance when compared with NECs but MCI patients did not. Negative correlations between tests of working memory (WM) and semantic memory and the CET were found in NECs and AD patients, indicating that these cognitive domains were important for CET performance. Regression analysis suggests that AD patients were unable to maintain semantic information in WM to perform the task. The authors conclude that AD patients display deficits in working memory, semantic memory, and executive function, which are required for adequate CET performance.     

Vascular predictors of cognitive decline in patients with mild cognitive impairment

Our aim in this study was to assess the relationship between the state of cerebral vessels and the risk of conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD). We included 117 MCI patients. They underwent an ultrasonographic assessment of common carotid arteries intima-media thickness (IMT) and carotid plaque index. Cerebrovascular reactivity to hypercapnia in the middle cerebral arteries was calculated with the Breath-Holding Index (BHI). After a 12-month follow-up period, neuropsychological examinations demonstrated a progression to dementia in 21 patients. Pathological values of BHI and IMT significantly increased the risk of conversion (BHI: odds ratio, 5.80; 95% confidence interval, 1.83-18.37, p < 0.05; IMT: odds ratio, 3.08; 95% confidence interval, 1.02-9.33; p < 0.05, multinomial logistic regression analysis). Comparison between patients with all normal values and those with the simultaneous alteration of the 2 vascular indexes showed an increase in the risk of conversion from 9% to 33% (ordinal regression analysis). Our findings show that alterations of cerebral vessel functional and anatomic status increase the risk of conversion from MCI to dementia.     

Volumetric correlates of memory and executive function in normal elderly, mild cognitive impairment and Alzheimer's disease

In Alzheimer's disease (AD), atrophy negatively impacts cognition while in healthy adults, inverse relationships between brain volume and cognition may occur. We investigated correlations between gray matter volume and cognition in elderly controls, AD and mild cognitive impairment (MCI) patients with memory and executive deficits. AD demonstrated substantial loss in temporal, parietal and frontal regions while MCI exhibited moderate volume loss in temporal and frontal regions. In controls, memory and executive function were negatively correlated with frontal regions, while in AD, memory was positively correlated with temporal and frontal gyri, and executive function with frontal regions. The combination of the two patterns may explain the lack of correlations in MCI. Developmental versus pathological contributions to these relationships are discussed.     

轻度认知功能障碍患者的语义记忆损害与神经调控

文题释义：轻度认知障碍：是介于正常衰老与痴呆的过渡状态,是相对于年龄与教育程度的记忆或其他认知功能减退,记忆力、语言功能、注意力、执行能力等不同认知领域的减退,以记忆力减退为最常见的临床表现。国际轻度认知功能障碍工作组在2003年制定了轻度认知障碍的诊断标准：①有认知主诉,本人或知情者提供的认知功能障碍线索;②有认知功能损害的客观证据,选用蒙特利尔认知评估量表进行评分,高中及以上文化程度者≤26分,初中及以下文化程度者≤25分,且主要表现为记忆项异常者;③日常生活能力正常或仅有复杂日常能力轻度减退;④简易认知状态量表≥24分,不符合精神疾病的诊断和统计手册第四版诊断为痴呆的标准。语义记忆：包括对词语的意义、概念与事实的记忆。语义记忆涉及概念和实际知识是储存。广义上语义记忆包括对世界的所有认识。严格意义上的语义记忆,则是根据命名、分类任务判定。语义记忆障碍的患者表现为对熟悉的物品命名障碍。轻度的可能表现为语义分类词生成的减少,而严重的语义记忆障碍则表现为告知物品用途也不能进行命名,或给予名称也不能说出物品的用途,严重者可能表现为常识的缺失。 背景：阿尔茨海默病是一种进行性神经系统退化疾病,以认知下降为主要特点。认知力下降会导致老年人逐渐失去自我照料的能力,影响日常生活和活动。轻度认知障碍作为阿尔茨海默病的前驱状态,尽早对轻度认知障碍进行诊断和治疗,对预防阿尔茨海默病发展有重大的意义。 目的：针对轻度认知障碍语义记忆障碍评估与治疗的发展及未来前景做一综述。 方法：应用计算机在PubMed、Web of Science和中国知网、万方等数据库检索轻度认知障碍语义记忆评估、治疗的相关研究,检索关键词为“mild cognitive impairment,semantic memory impairment,semantic memory deficit,语义记忆,轻度认知功能障碍,轻度认知损害”,检索时间为2009年1月至2019年11月。结果与结论：语义记忆障碍为轻度认知障碍的主要临床症状之一,有一定的特异性。目前有不同类型的记忆量表可作为轻度认知障碍语义记忆障碍的神经心理学测量,颞叶、额叶和前运动区可能参与语义记忆环路。针对性的语义记忆神经生理学及辅助检查,靶向进行语义记忆康复训练,可利于早期识别轻度认知障碍的发生与转化。 ORCID: 0000-0002-2121-1523(关汉添) 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

Dietary ketosis enhances memory in mild cognitive impairment

We randomly assigned 23 older adults with mild cognitive impairment to either a high carbohydrate or very low carbohydrate diet. Following the 6-week intervention period, we observed improved verbal memory performance for the low carbohydrate subjects (p = 0.01) as well as reductions in weight (p < 0.0001), waist circumference (p < 0.0001), fasting glucose (p = 0.009), and fasting insulin (p = 0.005). Level of depressive symptoms was not affected. Change in calorie intake, insulin level, and weight were not correlated with memory performance for the entire sample, although a trend toward a moderate relationship between insulin and memory was observed within the low carbohydrate group. Ketone levels were positively correlated with memory performance (p = 0.04). These findings indicate that very low carbohydrate consumption, even in the short term, can improve memory function in older adults with increased risk for Alzheimer's disease. While this effect may be attributable in part to correction of hyperinsulinemia, other mechanisms associated with ketosis such as reduced inflammation and enhanced energy metabolism also may have contributed to improved neurocognitive function. Further investigation of this intervention is warranted to evaluate its preventive potential and mechanisms of action in the context of early neurodegeneration.     

Relationship between plasticity, mild cognitive impairment and cognitive decline.

A topic of great interest in gerontology research is the prediction of cognitive deterioration which marks the transition from mild cognitive impairment (MCI) to dementia. In this area the term plasticity is a construct of prime importance. Previous studies have demonstrated the existence of plasticity in healthy older persons, and it is thought that this is what discriminates between healthy individuals and those at risk for dementia. The aim of the present study is to demonstrate that plasticity exists in persons with MCI, and that a lack of plasticity may be one of the risk factors related to cognitive decline. An adapted version of the Auditory Verbal Learning Test-the AVLT of Learning Potential-was used to assess plasticity. Participants in the research were 203 older persons whose cognitive status had previously been determined using a cognitive screening test. The results show that plasticity exists in persons with MCI and that its presence is associated with less marked cognitive decline.     

Longitudinal change in cognitive performance among individuals with mild cognitive impairment

The authors used mixed-effects growth models to examine longitudinal change in neuropsychological performance over a 4-year period among 197 individuals who were either normal or had mild cognitive impairment (MCI) at baseline. At follow-up, the participants were divided into 4 groups: (a) controls: participants who were normal at both baseline and follow-up (n = 33), (b) stables: participants with MCI whose Clinical Dementia Rating-Sum of Boxes (CDR-SB) score did not differ between the first and last evaluations (n = 22), (c) decliners: participants with MCI whose CDR-SB score declined between the first and last evaluations (n = 95), and (d) converters: participants who received a clinical diagnosis of Alzheimer's disease during the follow-up period (n = 47). Only the Episodic Memory factor showed a significantly greater rate of decline over the follow-up period among the converters. Two other factors were significantly lower in converters at baseline in comparison with other groups (the executive function factor and the general knowledge factor), but the rate of decline over time did not differ. Individuals with an APOE epsilon4 allele scored lower on the episodic memory and executive function factors at baseline.