Homocysteine and B vitamins in mild cognitive impairment and dementia.

Elderly subjects with mild cognitive impairment have a high risk for conversion to Alzheimer's disease or are already in a preclinical dementia stage. By cross-sectionally comparing subjects in prodromal and early phases of dementia with non-demented controls, we tested the hypothesis whether low serum vitamin B12 and folate and high plasma total homocysteine concentrations precede or are a consequence of dementia onset. From a large population of 623 consecutive subjects seen at the Memory Clinic (Ospedale Beata Vergine, Mendrisio, Switzerland), 433 subjects could be included in the analyses: 79 elderly controls, 218 Clinical Dementia Rating 0.5 subjects, and 136 demented patients (111 with Alzheimer's disease and 25 with vascular dementia). As in an earlier report on a smaller sample of the same population (n=228), the lowest folate tertile was strongly associated with mild cognitive impairment (adjusted OR=3.1) and Alzheimer's disease (adjusted OR=4.0). Hyperhomocysteinemia showed a significant association not only with Alzheimer's disease (adjusted OR=3.1) but, at variance with the previous report, also with mild cognitive impairment (adjusted OR=2.6). Present reanalysis results suggest that subclinical folate deficiency and hyperhomocysteinemia might predate dementia onset, findings to be confirmed by longitudinal studies.     

Alzheimer's disease.

Alzheimer's disease is one of the most severe and most common chronic diseases of older persons. Because occurrence of the disease is strongly related to age, its public health impact is likely to continue to increase as the population ages. As with many other diseases, a diagnosis of Alzheimer's disease is made through a combination of clinical history, physical, and neurologic examination, and laboratory evaluation. Because the dominant feature of this disease is its effect on cognition, its diagnosis requires careful evaluation of cognitive function usually with formal neuropsychological performance testing. Clinical evaluation of persons for Alzheimer's disease has four objectives: (1) to determine as accurately as possible if the person has dementia; (2) if dementia is present, to determine whether its presentation and course are consistent with a diagnosis of Alzheimer's disease; (3) to assess evidence for any alternate diagnoses, especially if the presentation and course are atypical for Alzheimer's disease; and (4) to evaluate evidence of other, coexisting, diseases that may contribute to the dementia, with strong emphasis on conditions that might respond to treatment. There is no reliable antemortem diagnostic test for Alzheimer's disease; the main purpose of laboratory testing is to identify other conditions that might cause or exacerbate dementia. Pathologically, Alzheimer's disease is characterized by the presence of two lesions on microscopic examination of the brain: neuritic plaques and neurofibrillary tangles. Both lesions can be seen in the brains of older persons without dementia. However, they are found in greater numbers in the neocortex and hippocampus with Alzheimer's disease. Caring for patients with Alzheimer's disease is demanding and requires compassion and skills that go beyond the choices among sophisticated and effective therapies that characterize much of modern medical practice. The current lack of effective pharmacotherapy for cognitive dysfunction in Alzheimer's disease should not obscure that there are many areas in which intervention can improve quality of life for both the patient and the caregiver. Achieving success in these areas typically requires that the physician work effectively with providers of many other medical and nonmedical services. Community resources, advocacy, behavior management, and experimental therapies and procedures, should be discussed with the family of each patient. In addition, persons with mild disease should be promptly informed of their diagnosis in order to obtain their wishes regarding life prolonging measures and extended care options.     

Neural correlates of Alzheimer's disease and mild cognitive impairment: A systematic and quantitative meta-analysis involving 1351 patients

Alzheimer's disease is the most common form of dementia. Its prodromal stage amnestic mild cognitive impairment is characterized by deficits of anterograde episodic memory. The development of standardized imaging inclusion criteria has to be regarded as a prerequisite for future diagnostic systems. Moreover, successful treatment requires isolating imaging markers predicting the disease. Accordingly, we conducted a systematic and quantitative meta-analysis to reveal the prototypical neural correlates of Alzheimer's disease and its prodromal stage. To prevent any a priori assumptions and enable a data-driven approach only studies applying quantitative automated whole brain analysis were included. Finally, 40 studies were identified involving 1351 patients and 1097 healthy control subjects reporting either atrophy or decreases in glucose utilization and perfusion. The currently most sophisticated and best-validated of coordinate-based voxel-wise meta-analyses was applied (anatomical likelihood estimates). The meta-analysis reveals that early Alzheimer's disease affects structurally the (trans-)entorhinal and hippocampal regions, functionally the inferior parietal lobules and precuneus. Results further may suggest that atrophy in the (trans-)entorhinal area/hippocampus and hypometabolism/hypoperfusion in the inferior parietal lobules predicts most reliably the progression from amnestic mild cognitive impairment to Alzheimer's disease, whereas changes in the posterior cingulate cortex and precuneus are unspecific. Fully developed Alzheimer's disease involved additionally a frontomedian-thalamic network. In conclusion, the meta-analysis characterizes the prototypical neural substrates of Alzheimer's disease and its prodromal stage amnestic mild cognitive impairment. By isolating predictive markers it enables successful treatment strategies in the future and contributes to standardized imaging inclusion criteria for Alzheimer's disease as suggested for future diagnostic systems.     

Sleep and cognition in people with Alzheimer's disease

It is important that we identify factors that could lead to interventions to slow cognitive decline in people with Alzheimer's disease. One potentially modifiable factor in Alzheimer's disease is disturbed sleep. The effect of disturbed sleep on cognition is of profound importance in people with Alzheimer's disease because disturbed sleep may worsen memory complaints. Therefore, the purpose of this article is to provide an updated review of literature that describes the impact of disturbed sleep on cognition in healthy populations and discuss the implications that this relationship has for people with Alzheimer's disease and their formal and informal caregivers.     

模拟家庭照护对阿尔茨海默病患者认知功能和行为能力的影响

目的 探讨模拟家庭照护对阿尔茨海默病(AD)怠者认知功能和行为能力的影响.方法 AD患者68例,按入院顺序分为研究组和对照组各34例.研究组采用模拟家庭照护,进行模拟家庭生活能力训练;对照组采用老年科常规护理.两组分别在干预前和干预后3个月、6个月后进行简易精神状态检查评分、日常生活能力量表评分的测评.结果 研究组干预后认知功能的改善较对照组明显(t=2.31,P=0.026);行为能力的改善也较对照组明显(t=2.59,P=0.012).结论 模拟家庭照护对AD患者认知、行为能力有显著改善作用.     

Neuropsychological correlates of amyloid precursor protein in Alzheimer's disease

The comprehensive cognitive screens for dementia, the Cambridge Cognitive screen (CAMCOG) and the Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE) were used for assessing use of the putative Alzheimer's disease biological marker, plasma amyloid precursor protein (APP), in Alzheimer's disease and Down syndrome. The analysis suggested that there were significant correlations between amyloid precursor protein and cognitive decline as assessed by the IQCODE. Preliminary investigations of Down syndrome suggest amyloid precursor protein levels are associated with duration of dementia in the group. The findings imply circulating amyloid precursor protein has a more central role in the pathogenesis of Alzheimer's disease.     

益智训练对老年痴呆患者认知功能改善的效果观察

目的 探讨益智训练对提高早中期老年性痴呆(AD)患者认知功能、生活自理能力和生活质量的效果.方法 应用临床痴呆评定量表(CDR)测评出轻、中度AD患者38例,对其进行益智训练1年,期问,家属参与及饮食指导.采用简明精神量表(MMSE),常识、记忆、注意测量量表(IMCT)、日常生活能力量表(ADL)做训练前及训练后效果评价.结果 患者的缺陷程度在训练前和训练后1～3个月比较筹异尢统计学意义(P＞0.05),训练6个月后缺陷程度显著改善(P＜0.05),1年后改善程度更为显著(P＜0.01).结论 有效的益智训练可提高老年痴呆患者认知能力,改善其症状,延缓痴呆的进程,提高生存和生命质量.     

Salvia officinalis extract in the treatment of patients with mild to moderate Alzheimer's disease: a double blind,randomized and placebo-controlled trial

BACKGROUND: Alzheimer's disease is characterized by a slow, progressive decline in cognitive function and behaviour. Acetylcholine esterase inhibitors are the only agents approved by the Food and Drug Administration for the treatment of Alzheimer's disease. All other agents prescribed for the treatment of Alzheimer's disease are used on an off-label basis. Current research into new drugs is focused on agents that will prevent, slow down and/or halt the progress of the disease process. Salvia officinalis has been used in herbal medicine for many centuries. It has been suggested, on the basis of traditional medicine, its in vitro cholinergic binding properties and modulation of mood and cognitive performance in humans, that Salvia officinalis might potentially provide a novel natural treatment for Alzheimer's disease. The objective of this study was to assess the efficacy and safety of Salvia officinalis extract using a fixed dose (60 drops/day), in patients with mild to moderate Alzheimer's disease, over a 4-month period. METHODS: This was a 4-month, parallel group, placebo-controlled trial undertaken in three centres in Tehran, Iran. Patients with mild to moderate Alzheimer's disease aged between 65 and 80 years (n = 42, 18 women) with a score of > or = 12 on the cognitive subscale of Alzheimer's Disease Assessment Scale (ADAS-cog) and < or = 2 on the Clinical Dementia Rating (CDR) were randomized to placebo or fixed dose of S. officinalis extract. Over the 16 weeks, the main efficacy measures were the change in the ADAS-cog and CDR-Sum of Boxes scores compared with baseline. In addition, side-effects were systematically recorded throughout the study using a checklist. RESULTS: At 4 months, S. officinalis extract produced a significant better outcome on cognitive functions than placebo (ADAS-cog: F = 4.77, d.f. = 1, P = 0.03) (CDR-SB: F = 10.84, d.f. = 1, P < 0.003). There were no significant differences in the two groups in terms of observed side-effects except agitation that appears to be more frequent in the placebo group (P = 0.09). CONCLUSIONS: The results of this study indicate the efficacy of S. officinalis extract in the management of mild to moderate Alzheimer's disease. Moreover, S. officinalis may well reduce agitation of patients but this needs to be confirmed.     

快速老化小鼠SAMP8 在阿尔茨海默病研究中的应用

阿尔茨海默病以进行性认知功能障碍、记忆能力下降为主要特征。脑内β-淀粉样蛋白(Aβ)异常沉积、神经原纤维缠结、胆碱能神经元功能减退、突触和树突棘缺失等为阿尔茨海默病特征性病理改变。快速老化小鼠SAMP8 在早期即出现学习记忆功能障碍、Aβ异常沉积、tau 蛋白磷酸化、神经递质改变、突触结构和功能障碍、生理节律紊乱,以及基因表达等多方面的特征性改变,与人类阿尔茨海默病病理改变较为一致,可以作为较理想的动物模型,用于阿尔茨海默病防治药物的研究。     

Automatic morphometry in Alzheimer's disease and mild cognitive impairment

This paper presents a novel, publicly available repository of anatomically segmented brain images of healthy subjects as well as patients with mild cognitive impairment and Alzheimer's disease. The underlying magnetic resonance images have been obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. T1-weighted screening and baseline images (1.5T and 3T) have been processed with the multi-atlas based MAPER procedure, resulting in labels for 83 regions covering the whole brain in 816 subjects. Selected segmentations were subjected to visual assessment. The segmentations are self-consistent, as evidenced by strong agreement between segmentations of paired images acquired at different field strengths (Jaccard coefficient: 0.802±0.0146). Morphometric comparisons between diagnostic groups (normal; stable mild cognitive impairment; mild cognitive impairment with progression to Alzheimer's disease; Alzheimer's disease) showed highly significant group differences for individual regions, the majority of which were located in the temporal lobe. Additionally, significant effects were seen in the parietal lobe. Increased left/right asymmetry was found in posterior cortical regions. An automatically derived white-matter hypointensities index was found to be a suitable means of quantifying white-matter disease. This repository of segmentations is a potentially valuable resource to researchers working with ADNI data.     

认知功能训练对老年痴呆患者的影响

目的 探讨认知功能训练对老年痴呆患者病情改善的影响.方法 对30例老年痴呆患者均在接受常规药物治疗的基础上进行认知功能训练,训练前后采用简易精神状态检查量表和功能独立性评定量表进行评定,并进行t检验.结果 训练后患者的认知功能及生活自理能力较治疗前有显著提高.结论 认知功能训练能改善老年痴呆患者的认知功能和生活自理能力,有助于提高患者的生活质量.     

A holistic approach to caring for people with Alzheimer's disease

This article adopts a holistic view of Alzheimer's disease. Biomedical, psychological and social aspects of the condition are discussed, and aetiology, epidemiology, diagnosis and treatment explored. A range of approaches to working with people with Alzheimer's disease, based on a psychological model of dementia, is described including reminiscence and cognitive stimulation therapy.     

Cognitive rehabilitation combined with drug treatment in Alzheimer's disease patients: a pilot study

OBJECTIVE: To study the efficacy of cognitive rehabilitation combined with acetylcholinesterase inhibitor (AChE-I) treatment in patients with mild Alzheimer's disease and their relatives. METHOD: Thirteen patients with mild Alzheimer's disease treated with rivastigmine 6-12 mg/day for more than two months started cognitive rehabilitation training. Before and after the cognitive rehabilitation training patients were assessed through cognitive tests, activities of daily living scale, neuropsychological battery and scales to evaluate caregivers' depressive and anxiety symptoms. Six patients were randomized to a combined treatment group (AChE-I plus cognitive rehabilitation and caregiver support) and seven patients to a control group (AChE-I only) and followed up for five months. RESULTS: Mini-Mental State Examination (MMSE) scores (p = 0.047) and backward digit span scores (p = 0.018) were significantly different between the groups on follow-up. The combined treatment group showed a better positive treatment effect on cognitive and neuropsychological tests applied to patients and reduction of psychiatric symptoms was observed in their caregivers (nonsignificant). CONCLUSION: Cognitive rehabilitation associated with AChE-I treatment can potentially be useful to stabilize or improve cognitive and functional performance of patients with mild Alzheimer's disease and can reduce caregivers' psychiatric symptoms.     

Homocysteine, vascular dementia and Alzheimer's disease.

There is some evidence from recent observational studies that hyperhomocysteinemia is a risk factor for cognitive dysfunction, including Alzheimer's disease and vascular dementia. There are only a few intervention studies, and the results are disappointing for such a frequent disease. Prospective double-blind and placebo-controlled intervention studies are not available. If homocysteine-lowering therapy will be in the running for the prevention and treatment of dementia, we must be able to diagnose the disease at a preclinical stage (i.e. 5 or 10 or 20 years before the disease becomes clinically overt for Alzheimer's disease). At the moment, there are insufficient data to support a vitamin B12, B6 or folate therapy in the prevention or treatment of patients with dementia.     

Multi-region analysis of longitudinal FDG-PET for the classification of Alzheimer's disease

Imaging biomarkers for Alzheimer's disease are desirable for improved diagnosis and monitoring, as well as drug discovery. Automated image-based classification of individual patients could provide valuable diagnostic support for clinicians, when considered alongside cognitive assessment scores. We investigate the value of combining cross-sectional and longitudinal multi-region FDG-PET information for classification, using clinical and imaging data from the Alzheimer's Disease Neuroimaging Initiative. Whole-brain segmentations into 83 anatomically defined regions were automatically generated for baseline and 12-month FDG-PET images. Regional signal intensities were extracted at each timepoint, as well as changes in signal intensity over the follow-up period. Features were provided to a support vector machine classifier. By combining 12-month signal intensities and changes over 12 months, we achieve significantly increased classification performance compared with using any of the three feature sets independently. Based on this combined feature set, we report classification accuracies of 88% between patients with Alzheimer's disease and elderly healthy controls, and 65% between patients with stable mild cognitive impairment and those who subsequently progressed to Alzheimer's disease. We demonstrate that information extracted from serial FDG-PET through regional analysis can be used to achieve state-of-the-art classification of diagnostic groups in a realistic multi-centre setting. This finding may be usefully applied in the diagnosis of Alzheimer's disease, predicting disease course in individuals with mild cognitive impairment, and in the selection of participants for clinical trials.     

Inhibition of neprilysin by infusion of thiorphan into the hippocampus causes an accumulation of amyloid Beta and impairment of learning and memory

An imbalance between anabolism and catabolism causes an accumulation of amyloid beta-peptide (Abeta), which is a proposed trigger of the onset of Alzheimer's disease. Neprilysin is a rate-limiting peptidase that participates in the catabolism of Abeta in the brain. We examined whether rats continuously infused with thiorphan, a specific neprilysin inhibitor, into the hippocampus develop cognitive impairments through accumulation of Abeta. Thiorphan infusion elevated hippocampal Abeta40 and Abeta42 levels in the insoluble but not the soluble fraction. Thiorphan-infused rats displayed cognitive impairments in the ability to discriminate in the object recognition test, associative learning in the conditioned fear learning test, and spatial memory in the water maze test, tasks that depend on the hippocampus. These cognitive abilities in the battery of behavioral tasks inversely correlated with insoluble Abeta contents in the hippocampus. The nicotine-stimulated release of acetylcholine in the hippocampus of thiorphan-infused rats was significantly lower than that in vehicle-infused rats. These results indicate that continuous infusion of thiorphan into the hippocampus causes cognitive dysfunction and reduces cholinergic activity by raising the level of Abeta in the hippocampus and suggest that a reduction of neprilysin activity contributes to the deposition of Abeta and development of Alzheimer's disease.     

护理干预对老年痴呆患者的影响

目的 对老年痴呆患者进行护理健康指导及干预,观察其对生活质量的影响.方法 对我院2007年3月-2008年9月共收治的45例老年痴呆患者施行基础护理、心理护理和安全护理措施等,观察患者的自理能力和认知能力.结果 老年痴呆患者的误吸、误服、跌倒、自伤、走失的发生率明显下降,生活自理人数增加,患者自理能力、认知能力和社交能力有所提高.结论 加强饮食和日常生活护理,重视心理及安全护理具有提高老年痴呆患者生活质量的效果,值得医院、社区及家庭的推广.     

多模态MRI在阿尔茨海默病早期诊断中的研究进展

阿尔茨海默病(Alzheimer's disease,AD)是发生于中老年人中最常见的中枢神经系统退行性疾病,以进行性认知障碍和行为非认知功能能力的减低为主要症状。近年来,随着磁共振成像(magnetic resonance imaging,MRI)多种序列的逐渐成熟,多模态MRI诊断在AD早期诊断中占有越来越重要的角色;作者就磁共振成像中结构性磁共振(structural magnetic resonance imaging,s MRI)、磁共振波谱成像(magnetic resonance spectroscopy,MRS)、磁共振弥散张量成像(diffusion tensor imaging,DTI)和磁共振扩散峰度成像(diffusion kurtosis imaging,DKI)、磁敏感加权成像(susceptibility weighted imaging,SWI)和定量磁敏感成像(quantitative susceptibility mapping,QSM)及静息态功能磁共振(functional MRI,f MRI)在AD早期诊断中的应用进行综述。     

New drug therapy possibilities of Alzheimer disease

New drugs are available now for the specific treatment of Alzheimer's disease. The lack of acetylcholine plays an important role in the pathophysiology of this disease. Centrally acting cholinesterase-inhibitors may prolong the action of acetylcholine and thus induce a temporary improvement or stabilization of cognitive performance. The disease progression continues; however, to a lesser extent than without therapy. The need for a patient to enter a nursing home can be delayed by one year on average. Nootropica may also have some modest success in treating cognitive dysfunctions, but the effect size is relatively small. Several agents, such as estrogens, anti-inflammatory drugs and antioxidants, are being investigated for their potential use in Alzheimer's disease, and additional drugs might be available for the treatment of this disease in the near future.     

轻度认知功能障碍脑结构与功能MRI研究进展

轻度认知功能障碍（MCI）患者被认为是阿尔茨海默病的高危人群，并且在MCI阶段进行干预治疗，有利于延缓病情进展甚至逆转认知功能破坏，故对于MCI的研究，具有重要的临床意义。MRI技术包含多个序列成像，可从不同角度发现MCI的大脑结构和功能异常，有利于早期诊断、预测病情进展情况和揭示病理机制，促进MCI和阿尔茨海默病的防治。本文主要对于近些年来结构磁共振成像、功能磁共振成像、扩散张量成像、动脉自旋标记和质子磁共振波谱分析在MCI的诊断、分类、预测病情方面的研究现状进行了论述，希望为今后的临床诊疗及科研提供借鉴。