中文修订版智能筛查检测在阿尔茨海默病和轻度认知损害评估中的作用

目的:探讨智能筛查测验(CASI)在不同严重度的阿尔茨海默病(AD)患者中的表现及与MMSE总分的关系。方法:使用2.0版本的CASI、MMSE及临床痴呆量表等对30名正常中老年人、20例轻度认知损害(MCI)和53例不同严重度的AD患者(20例轻度、19例中度、14例重度)进行评估。结果:根据CASI因子分分析发现,MCI组新记忆和概念判断受损、完成测验的耗时数延长,AD组在从轻至重度组中依次出现定向障碍、心算障碍,直到所有因子分均显著减退。除"概判"因子外,其余因子分都随着病情严重度而逐渐降低。除了重度AD组以外,MCI组、轻度AD组和中度AD组均较前一组下降约10分。CASI总分以≤85分为界:识别MCI的敏感度为70.6%;识别轻度AD的敏感度为82.7%;特异度均为73.9%。对于大学及以上文化者,CASI难度过低,容易出现假阴性。结论:CASI可有效判断AD认知损害的严重度,并能从组成项目中获得MMSE总分。     

Visual feedback has differential effects on reaching movements in Parkinson’s and Alzheimer’s disease

We examine the role of visual feedback in the programming and execution of reaching movement in patients with Parkinson’s disease without cognitive impairment and patients with Alzheimer’s disease without extrapyramidal signs. Controls were normally aging subjects. All subjects moved a cursor to targets on a digitizing tablet without seeing their limb. Starting and target positions were always visible on a screen while, during movement, cursor position was either visible or blanked. They were instructed to make uncorrected movements, as fast and as accurate as possible without minimizing reaction time. In absence of visual feedback, movement accuracy in patients with AD was severely impaired. Hand paths of parkinsonian patients were as accurate as normal subjects’ with similar temporal velocity profiles and movement speed. With cursor feedback, accuracy was the same in the three groups, although movement speed and transport phase in patients with Alzheimer’s disease were significantly reduced compared to the other groups. Also, movements of parkinsonian patients showed shorter transport phase and lower mean velocity than controls’. The different characteristics of the motor performance suggests that in the two diseases visual information is used differently for both motor programming and execution: patients with Alzheimer’s disease, while scarcely using feed forward commands, relied on continuous on-line external cues. The correlation of motor performance with cognitive impairment argues against the hypothesis of basal ganglia involvement in AD. The motor abnormalities we found may represent early subclinical manifestation of apraxic disturbance. Parkinsonian patients showed higher reliance on feedback commands only with cursor feedback: this could be explained by their difficulty in engaging effectively automatic routines when distractors are present.     

Inflammation in Alzheimer’s disease

Alzheimer’s disease (AD) is the most common neurodegenerative disorder to date. Next to its classical histopathological characteristics such as deposition of fibrillogenic amyloid β peptides and neurofibrillary tangles, an inflammatory component of the disease has been identified. This article will review which cell types contribute to this phenomenon and which pro- and anti-inflammatory mediators are being released in the AD brain. Further, it will be discussed whether there are any known pathogenetic factors that may facilitate the induction and persistence of neuroinflammatory mechanisms. While neuroinflammation has mostly been quoted as a reaction to neurodegenerative events, more recent evidence suggests that it can feedback stimulate on neurodegenerative pathomechanisms including the generation of amyloid β peptides, thereby establishing a vicious and self-perpetuating cycle. Along this line, pro- and anti-inflammatory mechanisms may also contribute to the chronicity and duration of the disease. Therefore, anti-inflammatory treatment strategies should be evaluated as possible future therapeutics for AD.     

Serum heme oxygenase‐1 levels are increased in Parkinson’s disease but not in Alzheimer’s disease

Mateo I, Infante J, Sánchez‐Juan P, García‐Gorostiaga I, Rodríguez‐Rodríguez E, Vázquez‐Higuera JL, Berciano J, Combarros O. Serum heme oxygenase‐1 levels are increased in Parkinson’s disease but not in Alzheimer’s disease.
Acta Neurol Scand: 2010: 121: 136–138.
© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objective – Oxidative stress is implicated in Parkinson’s disease (PD) and Alzheimer’s disease (AD), and heme oxygenase‐1 (HO‐1) is a potent antioxidant overexpressed in PD substantia nigra and AD cerebral cortex and hippocampus, indicating a possible up‐regulation of antioxidant defenses in both neurodegenerative diseases. The role of HO‐1 in peripheral blood of PD and AD patients remains unresolved. Methods – We measured serum HO‐1 levels in 107 patients with PD, 105 patients with AD, 104 controls for PD and 120 controls for AD. Results – The median serum concentration of HO‐1 was significantly higher in PD patients (2.04 ng/ml) compared with that of PD controls (1.69 ng/ml, P = 0.016), with PD patients predominating over controls in the upper tertile of serum HO‐1 levels, whereas there was more PD controls than PD patients in the lower tertile (P = 0.006). Median serum levels of HO‐1 did not differ significantly between AD patients and AD controls. Conclusion – The increase of serum HO‐1 levels in PD patients could indicate a systemic antioxidant reaction related to a chronic oxidative stress state in PD brain.     

Altered expression of the synuclein family mRNA in Lewy body and Alzheimer’s disease

The main objective of this study was to determine if levels of α-, β- and/or γ-synuclein mRNAs are differentially affected in brains of Lewy body disease (LBD) and Alzheimer’s disease (AD) patients, compared to controls. In control cases, highest levels of expression were observed in the neocortex and the lowest in basal ganglia and substantia nigra. β-Synuclein was the most abundant message (75–80%), followed by γ-synuclein (10–15%) and α-synuclein (8–10%). Analysis of the superior temporal cortex, a region selectively affected in LBD and AD, showed that compared to controls, levels of α-synuclein were increased in cases of diffuse LBD (DLBD), levels of β-synuclein were decreased in AD and DLBD, and levels of γ-synuclein were increased in AD cases. This study suggests that a critical balance among products of the synuclein gene is important to maintain normal brain function and that alterations in this balance might be associated with neurodegenerative disorders.     

Memory with emotional content,brain amygdala and Alzheimer’s disease

Objectives – A highly adaptive aspect of human memory is the enhancement of explicit, consciously accessible memory by emotional stimuli. We studied the performance of Alzheimer’s disease (AD) patients and elderly controls using a memory battery with emotional content, and we correlated these results with the amygdala and hippocampus volume. Methods – Twenty controls and 20 early AD patients were subjected to the International Affective Picture System (IAPS) and to magnetic resonance imaging‐based volumetric measurements of the medial temporal lobe structures. Results – The results show that excluding control group subjects with 5 or more years of schooling, both groups showed improvement with pleasant or unpleasant figures for the IAPS in an immediate free recall test. Likewise, in a delayed free recall test, both the controls and the AD group showed improvement for pleasant pictures, when education factor was not controlled. The AD group showed improvement in the immediate and delayed free recall test proportional to the medial temporal lobe structures, with no significant clinical correlation between affective valence and amygdala volume. Conclusion – AD patients can correctly identify emotions, at least at this early stage, but this does not improve their memory performance.     

Zinc takes the center stage: its paradoxical role in Alzheimer’s disease

There is compelling evidence that the etiology of Alzheimer’s disease (AD) involves characteristic amyloid-β (Aβ) deposition, oxidative stress, and anomalous metal–Aβ protein interaction. New studies have implicated redox active metals such as copper, iron, and zinc as key mediating factors in the pathophysiology of Alzheimer’s disease. There is also evidence that drugs with metal chelating properties could produce a significant reversal of amyloid-β plaque deposition in vitro and in vivo. This paper reviews current observations on the etiologic role of zinc in AD. We also discuss the interactions of zinc and copper with Aβ, a factor that purportedly facilitates disease processes. Finally, we review the protective role of zinc against Aβ cytotoxicity and hypothesize how the apparent effect of zinc on AD pathology may be paradoxical, The Zinc Paradox. Indeed, complex pathologic stressors inherent to the Alzheimer’s diseased brain dictate whether or not zinc will be neuroprotective or neurodegenerative. Further research on the zinc paradox in AD is needed in order to elucidate the exact role zinc plays in AD pathogenesis.     

Gesture comprehension,knowledge and production in Alzheimer’s disease

Background and purpose: Although apraxia is a typical consequence of Alzheimer’s disease (AD), the profile of apraxic impairments is still subject to debate. Here, we analysed apraxia components in patients with AD with mild‐to‐moderate or moderately severe dementia. Methods: Thirty‐one patients were included. We first evaluated simple gestures, that is, the imitation of finger and hand configurations, symbolic gestures (recognition, production on verbal command and imitation), pantomimes (recognition, production on verbal command, imitation and production with the object), general knowledge and complex gestures (tool–object association, function–tool association, production of complex actions and knowledge about action sequences). Tests for dementia (Mini Mental State Examination and the Dementia Rating Scale), language disorders, visual agnosia and executive function were also administered. Results: Compared with controls, patients showed significant difficulties (P ≤ 0.01) in subtests relating to simple gestures (except for the recognition and imitation of symbolic gestures). General knowledge about tools, objects and action sequences was less severely impaired. Performance was frequently correlated with the severity of dementia. Multiple‐case analyses revealed that (i) the frequency of apraxia depended on the definition used, (ii) ideomotor apraxia was more frequent than ideational apraxia, (iii) conceptual difficulties were slightly more frequent than production difficulties in the early stage of AD and (iv) difficulties in gesture recognition were frequent (especially for pantomimes). Conclusion: Patients with AD can clearly show gesture apraxia from the mild–moderate stage of dementia onwards. Recognition and imitation disorders are relatively frequent (especially for pantomimes). We did not find conceptual difficulties to be the main problem in early‐stage AD.     

Hippocampal estrogen β-receptor immunoreactivity is increased in Alzheimer’s disease

Post-menopausal estrogen use reduces the risk and severity of Alzheimer’s disease (AD). The present study investigates the distribution of both estrogen receptors ERα and ERβ in the human hippocampus in aged controls and in AD cases with immunohistochemistry. No ERα immunoreactivity was observed both in controls and in AD cases. On the other hand, ERβ was observed in some neuronal cells in the hippocampal subfields CA1–4, in astrocytes and in extracellular deposits both in controls and AD cases. The ERβ immunoreactivity was distinctly increased in all AD cases in cellular and extracellular localizations indicating a role for ERβ-mediated estrogen effects in AD-related neuropathology. This study provides the first demonstration of ERβ in human hippocampus in aged controls compared to AD cases.