Longitudinal cerebrospinal fluid tau load increases in mild cognitive impairment

The aim of the study was to understand: (i), how far anticipatory postural adjustments (APA) participate in the sequences of a complex task; (ii), how, in the sagittal plane, horizontal and vertical progressions of the center of gravity (CG) are managed to achieve the prescribed goal. A posturo-kinetics sequence is identified during which forward CG progression is controlled in terms of a center of pressure (CP)-CG interaction. CP shifts and horizontal CG accelerations are correlated in timing and amplitude. There exists a control of whole body progression during the impulse, implying a braking of forwards movement. Vertical and horizontal CG accelerations are inter-dependent, and backward CP shift duration is related to its forward displacement. During the vertical jump initiation, whole body vertical propulsion and forward fall are linked. To increase impulse amplitude, initial whole body disequilibrium is lengthened and forward CG acceleration is greater. APA programming is probably elaborated on the basis of cognitive evaluation of the antero-posterior disturbance.     

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   

Longitudinal 1H MRS changes in mild cognitive impairment and Alzheimer's disease

Magnetic resonance (MR)-based volume measurements of atrophy are potential markers of disease progression in patients with amnestic mild cognitive impairment (MCI) and Alzheimer's disease (AD). Longitudinal changes in (1)H MR spectroscopy ((1)H MRS) metabolite markers have not been characterized in MCI subjects. Our objective was to determine the longitudinal (1)H MRS metabolite changes in patients with MCI, and AD, and to compare (1)H MRS metabolite ratios and ventricular volumes in tracking clinical disease progression in AD. The neuronal integrity marker N-acetylaspartate/creatine ratio declined in MCI and AD patients compared to cognitively normal elderly. The change in (1)H MRS metabolite ratios correlated with clinical progression about as strongly as the rate of ventricular expansion, suggesting that (1)H MRS metabolite ratios may be useful markers for the progression of AD. Choline/creatine ratio declined in stable MCI, compared to converter MCI patients and cognitively normal elderly, which may be related to a compensatory mechanism in MCI patients who did not to progress to AD.     

Naturalistic assessment of everyday functioning in individuals with mild cognitive impairment: The day-out task

Objective: The day-out task (DOT), a naturalistic task that requires multitasking in a real-world setting, was used to examine everyday functioning in individuals with mild cognitive impairment (MCI). Method: Thirty-eight participants with MCI and 38 cognitively healthy older adult controls prioritized, organized, initiated, and completed a number of subtasks in a campus apartment to prepare for a day out (e.g., determine and gather change for bus, bring a magazine). Participants also completed tests assessing cognitive constructs important in multitasking (i.e., retrospective memory, prospective memory, planning). Results: As compared with controls, the MCI group required more time to complete the DOT and demonstrated poorer task accuracy, performing more subtasks incompletely and inaccurately. Despite poorer DOT task accuracy, the MCI and control groups approached completion of the DOT in a similar manner. For the MCI group, retrospective memory was a unique predictor of the number of subtasks left incomplete and inaccurate, while prospective memory was a unique predictor of DOT sequencing. The DOT measures, but not the cognitive tests, were predictive of knowledgeable informant report of everyday functioning. Conclusions: These findings suggest that difficulty remembering and keeping track of multiple goals and subgoals may contribute to the poorer performance of individuals with MCI in complex everyday situations. (PsycINFO Database Record (c) 2012 APA, all rights reserved).     

Longitudinal CSF and MRI biomarkers improve the diagnosis of mild cognitive impairment

The diagnosis of Alzheimer's disease (AD) in patients with mild cognitive impairment (MCI) is limited because it is based on non-specific behavioral and neuroimaging findings. The lesions of Alzheimer's disease: amyloid beta (Abeta) deposits, tau pathology and cellular oxidative damage, affect the hippocampus in the earlier stages causing memory impairment. In a 2-year longitudinal study of MCI patients and normal controls, we examined the hypothesis that cerebrospinal fluid (CSF) markers for these pathological features improve the diagnostic accuracy over memory and magnetic resonance imaging (MRI)-hippocampal volume evaluations. Relative to control, MCI patients showed decreased memory and hippocampal volumes and elevated CSF levels of hyperphosphorylated tau and isoprostane. These two CSF measures consistently improved the diagnostic accuracy over the memory measures and the isoprostane measure incremented the accuracy of the hippocampal volume achieving overall diagnostic accuracies of about 90%. Among MCI patients, over 2 years, longitudinal hippocampal volume losses were closely associated with increasing hyperphosphorylated tau and decreasing amyloid beta-42 levels. These results demonstrate that CSF biomarkers for AD contribute to the characterization of MCI.     

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     

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.     

Hippocampal and cortical atrophy in amyloid-negative mild cognitive impairments: comparison with amyloid-positive mild cognitive impairment

Although patients with amnestic mild cognitive impairment (aMCI) are at higher risk of developing Alzheimer's disease (AD), their pathologies could be heterogeneous. We aimed to evaluate structural changes in amyloid-negative and amyloid-positive aMCI patients. Forty-eight aMCI patients who underwent Pittsburgh compound B (PiB) positron emission tomography were recruited. They were classified as PiB (−) aMCI (N = 16) and PiB (+) (N = 32). Hippocampal shape and regional cortical thickness were compared with 41 subjects with normal cognition (NC). Relative to NC, PiB(−) aMCI exhibited hippocampal deformity in the right cornu ammonis 1, whereas PiB(+) aMCI exhibited hippocampal deformity in bilateral subiculum and cornu ammonis 1 subregions. Relative to NC, PiB(−) aMCI showed cortical thinning in the left medial prefrontal and right anterior temporal regions, whereas PiB(+) aMCI exhibited cortical thinning in bilateral medial temporal regions, temporoparietal junctions and precuneus, and prefrontal cortices. Our findings suggest that structural changes in PiB(−) aMCI might be due to several possible pathologic changes, whereas structural changes in PiB(+) aMCI reflect AD-like structural changes.     

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.     

Structural correlates of mild cognitive impairment

The structural correlates of mild cognitive impairment (MCI) were examined in 105 elderly subjects whose cognitive function ranged from intact to demented, including 38 subjects with MCI. Hippocampal volumes (left and right HcV), brain volume (BV), and grey matter volume (GMV) and white matter volume (WMV) were segmented from high resolution magnetic resonance data sets and normalised to intracranial volume (ICV). Hippocampal volume reductions, but not global brain, white or grey matter atrophy, were associated with MCI. White matter lesion severity did not differ over cognitive states. In multiple logistic regression models, normalised HcV and ICV (indicating premorbid brain volume) were significant predictors of MCI versus normality. Normalised BV and ICV significantly predicted dementia versus MCI. Absolute volumetric measures of HcV and BV yielded comparable classification accuracies. Hippocampal atrophy may be the crucial step for the transition from normality to MCI. Widespread brain atrophy may be the step to determine the transition from MCI to dementia. Brain volume reserve effects appear to be involved in both of these steps.     

乌鲁木齐市轻度认知障碍老年人的抑郁情绪

老年轻度认知障碍(mild cognitive impairment,MCI)是介于正常衰老和老年痴呆之间的一种过渡状态,是痴呆的早期阶段[1].研究MCI老年认知功能的变化,特别是研究影响其变化的因素,对及时制定干预措施,预防、减缓老年痴呆的发病有实际意义.本文探讨MCI老年人的抑郁情绪状况,为针对MCI老人进行心理干预提供依据.     

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.     

Olfaction in patients with mild cognitive impairment and Alzheimer's disease

Understanding of olfactory dysfunction in Alzheimer's disease (AD) remains limited. In particular, it is not known how early in the course of the disease olfactory deficits occur, and whether they are restricted to identification or involve other aspects of olfaction. We studied olfactory (odor detection thresholds, quality discrimination, and identification) and cognitive (attention, reasoning, memory, naming and fluency) functioning in patients with AD, with mild cognitive impairment (MCI), and in normal elderly control (NEC) participants. MCI patients were impaired in olfactory sensitivity and identification, while a discrimination deficit was accounted for by abnormal thresholds. AD patients were impaired in all three domains, and were worse than the MCI group. Odor discrimination (OD) and identification performance correlated more prominently than detection thresholds with performance on neuropsychological tests. We concluded that deficits in olfactory detection thresholds and identification occur early in AD, before clinical symptoms are fully developed, and decline further over the course of the disease. High detection thresholds, together with impaired identification, may be useful as an early indicator of AD.     

Dual task performance in early Alzheimer's disease, amnestic mild cognitive impairment and depression

BACKGROUND: The dual task paradigm (Baddeley et al. 1986; Della Sala et al. 1995) has been proposed as a sensitive measure of Alzheimer's dementia, early in the disease process. METHOD: We investigated this claim by administering the modified dual task paradigm (utilising a pencil-and-paper version of a tracking task) to 33 patients with amnestic mild cognitive impairment (aMCI) and 10 with very early Alzheimer's disease, as well as 21 healthy elderly subjects and 17 controls with depressive symptoms. All groups were closely matched for age and pre-morbid intellectual ability. RESULTS: There were no group differences in dual task performance, despite poor performance in episodic memory tests of the aMCI and early Alzheimer's disease groups. In contrast, the Alzheimer patients were specifically impaired in the trail-making test B, another commonly used test of divided attention. CONCLUSIONS: The dual task paradigm lacks sensitivity for use in the early differential diagnosis of Alzheimer's disease.     

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.