神经行为认知状态检查介绍(NCSE)

随着各种脑损害的存活率的提高和康复医学的发展 ,认知功能障碍越来越受到重视 ,对认知功能障碍的诊断 ,依靠的不是神经影像学检查而是有效的神经心理评估[1] 。《神经行为认知状态检查》(Theneurobehavioralcognitivestatusexamination ,NCSE) ,由Mueller等编制于 1983年[2 ] 。该量表采用分量表和分量表分的形式对各认知领域进行分析而被称为第二代认知功能检查法。1　NCSE的内容及评测方法NCSE评估认知功能的三个一般因素 (意识水平、注意力和定向能力 )和五个主要的认知功能区域(语言能力、结构能力、记忆力、计算能力和推理能力 …     

A method for detection of Alzheimer's disease using ICA-enhanced EEG measurements

OBJECTIVE: Many researchers have studied automatic EEG classification and recently a lot of work has been done on artefact-removal from EEG data using independent component analyses (ICA). However, demonstrating that a ICA-processed multichannel EEG measurement becomes more interpretable compared to the raw data (as is usually done in work on ICA-processing of EEG data) does not yet prove that detection of (incipient) anomalies is also better possible after ICA-processing. The objective of this study is to show that ICA-preprocessing is useful when constructing a detection system for Alzheimer's disease. METHODS AND MATERIAL: The paper describes a method for detection of EEG patterns indicative of Alzheimer's disease using automatic pattern recognition techniques. Our method incorporates an artefact removal stage based on ICA prior to automatic classification. The method is evaluated on measurements of a length of 8s from two groups of patients, where one group is in an initial stage of the disease (28 patients), whereas the other group is in a more progressed stage (15 patients). Both setups include a control group that should be classified as normal (10 and 21, respectively). RESULTS: Our final classification results for the group with severe Alzheimer's disease are comparable to the best results from literature. We show that ICA-based reduction of artefacts improves classification results for patients in an initial stage. CONCLUSION: We conclude that a more robust detection of Alzheimer's disease related EEG patterns may be obtained by employing ICA as ICA based pre-processing of EEG data can improve classification results for patients in an initial stage of Alzheimer's disease.     

Cognitive components of deficit awareness in Alzheimer's disease

Awareness of deficit was examined in 24 patients with Alzheimer's disease (AD) and their spouses (for a total of 48 participants) using performance prediction-postdiction and questionnaire discrepancy (QD) paradigms. Participants estimated their own memory performances as well the performances of spouses and of a fictional, memory-disordered patient observed on videotape. Patients overpredicted self-performances, but the extent of overestimation decreased for postdictions. Patients and caregivers accurately estimated caregiver performances but overestimated performances of the fictional patient. QD data revealed that patients underestimated their difficulties performing daily functioning tasks as compared with caregiver reports. Awareness of deficit is a complex ability, involving dissociable cognitive processes. AD patients may display intact immediate awareness of memory dysfunction but fail to incorporate incidents of memory failure into generalized self-belief systems.     

Desamino-D-arginine-vasopressin (DDAVP) in Alzheimer's disease

Fourteen Alzheimer subjects participated in a parallel group study of desamino-D-arginine-vasopressin (DDAVP, desmopressin). All subjects received one week of single-blind placebo. Then on a double-blind basis, the active group received DDAVP intranasally in doses starting at 30 micrograms per day and increasing over a 3 week period to 180 micrograms per day; the control group received an identical placebo. Using a repeated measures ANOVA, three measures out of thirty-one were found to be statistically significant for DDAVP treatment: the Hamilton depression scale and the affect and interpersonal subscales of the SCAG. However, the magnitude of these changes was probably too small to be clinically significant. Except for one subject who transiently became hyponatremic (Na of 120) and confused while receiving 180 micrograms of DDAVP, there were no adverse effects. There were no significant group changes in sodium, potassium, plasma osmolality, blood pressure, and weight.     

Cognitive correlates of alterations in acetylcholinesterase in Alzheimer's disease

We recently reported findings of modest loss of cortical acetylcholinesterase (AChE) activity in patients with overall mild Alzheimer's disease (AD) using N-[11C]methyl-pi-peridin-4-yl propionate ([11C]PMP) AChE positron emission tomography (PET). To determine cognitive correlates of in vivo cortical AChE activity in patients with mild to moderate AD (n=15), and in normal controls (NC, n=12) using [11C]PMP AChE PET imaging. Mean cortical AChE activity in the AD subjects was mildly reduced (-11.1%) compared to the control subjects (P<0.05). Analysis of the cognitive data showed that mean cortical AChE activity was significantly associated with performance on a test of attention and working memory (WAIS-III Digit Span, R=0.46, P=0.01) but not with tests of delayed short or long-term memory functions. Similar findings were present when the analysis was limited to the temporal cortex. Cortical AChE activity is more robustly associated with functions of attention and working memory compared to performance on primary memory tests in AD.     

SVM-based CAD system for early detection of the Alzheimer's disease using kernel PCA and LDA

Single-photon emission tomography (SPECT) imaging has been widely used to guide clinicians in the early Alzheimer's disease (AD) diagnosis challenge. However, AD detection still relies on subjective steps carried out by clinicians, which entail in some way subjectivity to the final diagnosis. In this work, kernel principal component analysis (PCA) and linear discriminant analysis (LDA) are applied on functional images as dimension reduction and feature extraction techniques, which are subsequently used to train a supervised support vector machine (SVM) classifier. The complete methodology provides a kernel-based computer-aided diagnosis (CAD) system capable to distinguish AD from normal subjects with 92.31% accuracy rate for a SPECT database consisting of 91 patients. The proposed methodology outperforms voxels-as-features (VAF) that was considered as baseline approach, which yields 80.22% for the same SPECT database.     

Cognitive impairment in preclinical Alzheimer's disease: a meta-analysis

To determine the size of the impairment across different cognitive domains in preclinical Alzheimer's disease (AD), a meta-analysis based on 47 studies involving 9,097 controls and 1,207 preclinical AD cases was conducted. There were marked preclinical deficits in global cognitive ability, episodic memory, perceptual speed, and executive functioning; somewhat smaller deficits in verbal ability, visuospatial skill, and attention; and no preclinical impairment in primary memory. Younger age (< 75 years) and shorter follow-up intervals (< 3 years) were associated with larger effect sizes for both global cognitive ability and episodic memory. For global cognitive ability, studies that used population-based sampling yielded larger effect sizes; for episodic memory, larger differences were seen in studies that preidentified groups in terms of baseline cognitive impairment. Within episodic memory, delayed testing and recall-based assessment resulted in the largest effect sizes. The authors conclude that deficits in multiple cognitive domains are characteristic of AD several years before clinical diagnosis. The generalized nature of the deficit is consistent with recent observations that multiple brain structures and functions are affected long before the AD diagnosis.     

Hypocretin (orexin) loss in Alzheimer's disease

Sleep disturbances in Alzheimer's disease (AD) patients are associated with the severity of dementia and are often the primary reason for institutionalization. These sleep problems partly resemble core symptoms of narcolepsy, a sleep disorder caused by a general loss of the neurotransmitter hypocretin. AD is a neurodegenerative disorder targeting different brain areas and types of neurons. In this study, we assessed whether the neurodegenerative process of AD also affects hypothalamic hypocretin/orexin neurons. The total number of hypocretin-1 immunoreactive neurons was quantified in postmortem hypothalami of AD patients (n = 10) and matched controls (n = 10). In addition, the hypocretin-1 concentration was measured in postmortem ventricular cerebrospinal fluid of 24 AD patients and 25 controls (including the patients and controls in which the hypothalamic cell counts were performed). The number of hypocretin-1 immunoreactive neurons was significantly decreased by 40% in AD patients (median [25th-75th percentiles]); AD 12,935 neurons (9972-19,051); controls 21,002 neurons (16,439-25,765); p = 0.049). Lower cerebrospinal fluid (CSF) hypocretin-1 levels were found in AD patients compared with controls (AD: 275 pg/mL [197-317]; controls: 320 pg/mL [262-363]; p = 0.038). Two AD patients with documented excessive daytime sleepiness showed the lowest CSF hypocretin-1 concentrations (55 pg/mL and 76 pg/mL). We conclude that the hypocretin system is affected in advanced AD. This is reflected in a 40% decreased cell number, and 14% lower CSF hypocretin-1 levels.     

Early Alzheimer's disease blocks responses to accelerating self-movement

We assessed the cortical processing of self-movement stimuli in aging and Alzheimer's disease (AD). Our goal was to identify distinguishing effects on neural mechanisms related to driving and navigation. Young (YNC) and older (ONC) normal controls, and early AD patients (EAD) viewed real-world videos and dot motion stimuli simulating self-movement scenes. We recorded visual motion event related potentials (VMERPs) to stimulus motion coherence and speed. Aging delays motion evoked N200s, whereas AD diminishes response amplitudes. Early Alzheimer's disease patients respond to increments in motion coherence, but they are uniquely unresponsive to increments in motion speed that simulate accelerating self-movement. AD-related impairments of self-movement processing may have grave consequences for driving safety and navigational independence.     

Cognitive and behavioral heterogeneity in Alzheimer's disease: seeking the neurobiological basis

Alzheimer’s disease (AD) is manifested by core features of progressive memory impairment, visuospatial decline, aphasia, and loss of executive function. In addition, patients may evidence a variety of other cognitive and behavioral features. The neurobiological basis for this clinical heterogeneity is uncertain but corresponding abnormalities on functional imaging suggest that variations in the distribution of the pathogenic changes in AD account for some of the observed clinical differences. Behavioral as well as cognitive variability has been correlated with disturbances on positron emission tomography and single photon emission computerized tomography. Functional imaging can reveal characteristic brain activity changes in AD, distinguish AD from other dementia syndromes, assess the integrity of transmitter systems in AD, determine the effect of cognitive enhancing and psychotropic drugs on metabolism and transmitter system function in AD, and possibly predict treatment responsiveness. Animal models of AD may improve our understanding of clinical variations in human AD. Thus far, development of cognitive tests for transgenic mice with AD pathology has been limited. Evaluations paralleling human neuropsychological tests are needed. In addition, technologies facilitating behavioral observations relevant to psychosis, depression, apathy, and agitation in AD have not been developed for transgenic models. Application of experiments inducing animal equivalents of depression and psychosis to determine the vulnerability of animal models of AD to these conditions may provide additional insights into human neuropsychiatric symptoms in AD. The efficacy of psychotropic drugs can be assessed in animal models of AD subjected to the provocative stimuli used in experimental models of psychopathology. There are a plethora of opportunities for basic scientists to offer insights, develop strategies, and provide techniques and technologies relevant to understanding the clinical manifestations of AD.     

Cognitive and neuropathologic correlates of Stroop Color-Word Test performance in Alzheimer's disease

The Stroop Color-Word Test (SCWT; C. Golden, 1978) was examined in 59 patients with probable Alzheimer's disease (AD) and in 51 demographically comparable normal control (NC) participants. AD patients produced significantly larger Stroop interference effects than NC participants, and level of dementia severity significantly influenced SCWT performance. Principal-components analyses demonstrated a dissociation in the factor structure of the Stroop trials between NC participants and AD patients, suggesting that disruption of semantic knowledge and speeded verbal processing in AD may be a major contributor to impairment on the incongruent trial. Results of clinicopathologic correlations in an autopsy-confirmed AD subgroup further suggest the invocation of a broad network of integrated cortical regions and executive and language processes underlying successful SCWT performance.     

Elevated 4-hydroxyhexenal in Alzheimer's disease (AD) progression

Multiple studies have demonstrated elevations of α, β-unsaturated aldehydes including 4-hydroxynonenal (HNE) and acrolein, in vulnerable regions of mild cognitive impairment (MCI), preclinical Alzheimer's disease (PCAD), and late stage Alzheimer's disease (LAD) brain. However, there has been limited study of a third member, 4-hydroxyhexenal (HHE), a diffusible lipid peroxidation product of the ω-3 polyunstataturated fatty acids (PUFAs). In the present study levels of extractable and protein-bound HHE were quantified in the hippocampus/parahippocampal gyrus (HPG), superior and middle temporal gyri (SMTG), and cerebellum (CER) of MCI, PCAD, LAD, and normal control (NC) subjects. Levels of extractable and protein-bound HHE were increased in multiple regions in the progression of Alzheimer's disease (AD). Extractable HHE was significantly elevated in the hippocampus/parahippocampal gyrus (HPG) of PCAD and LAD subjects and protein-bound HHE was significantly higher in MCI, PCAD, and LAD HPG. A time- and concentration-dependent decrease in survival and a concentration-dependent decrease in glucose uptake were observed in primary cortical cultures treated with HHE. Together these data support a role for lipid peroxidation in the progression of Alzheimer's disease.     

Complement receptor 1 (CR1) and Alzheimer's disease

Alzheimer's disease (AD) is the most common neurodegenerative disease and it poses an ever-increasing burden to an aging population. Several loci responsible for the rare, autosomal dominant form of AD have been identified (APP, PS1 and PS2), and these have facilitated the development of the amyloid cascade hypothesis of AD aetiology. The late onset form of the disease (LOAD) is poorly defined genetically, and up until recently the only known risk factor was the ε4 allele of APOE. Recent genome-wide association studies (GWAS) have identified common genetic variants that increase risk of LOAD. Two of the genes highlighted in these studies, CLU and CR1, suggest a role for the complement system in the aetiology of AD. In this review we analyse the evidence for an involvement of complement in AD. In particular we focus on one gene, CR1, and its role in the complement cascade. CR1 is a receptor for the complement fragments C3b and C4b and is expressed on many different cell types, particularly in the circulatory system. We look at the evidence for genetic polymorphisms in the gene and the possible physiological effects of these well-documented changes. Finally, we discuss the possible impact of CR1 genetic polymorphisms in relation to the amyloid cascade hypothesis of AD and the way in which CR1 may lead to AD pathogenesis.