Low body weight in Alzheimer's disease is associated with mesial temporal cortex atrophy

There are reports of weight loss and low body mass index (BMI) in patients with AD. The mesial temporal cortex (MTC) is involved in feeding behavior and memory and is preferentially involved in AD. We studied 74 subjects, including 58 AD patients and 16 control subjects, to determine whether BMI is associated with atrophy of the MTC or other brain regions. We used MRI morphometric analysis to provide measures of regional brain atrophy. AD patients had significant brain atrophy in all measured brain regions, except the white matter, compared with normal control subjects. The MTC was the only brain region significantly associated with BMI in AD patients (r = 0.39, p = 0.003). Multiple-regression analysis indicated that addition of brain regions other than the MTC to the model did not significantly add to the prediction of BMI. We conclude that low BMI correlates best and specifically with MTC atrophy. This finding supports a connection between limbic system damage and low body weight in AD.     

Accumulation of alpha-synuclein/NACP is a cytopathological feature common to Lewy body disease and multiple system atrophy

A recently developed chitosan-EDTA conjugate, neutralized with sodium hydroxide (NaChito-EDTA), has been tested for possible topical use. The technical properties and microbial stability of NaChito-EDTA have been compared with those of carmellose sodium (NaCMC), hydroxypropylmethylcellulose (HPMC), sodium polycarbophil (NaPCP) and sodium carbopol 980 (NaC980), well established gelatinizing agents. NaChito-EDTA forms stable, colourless, completely transparent hydrogels at a polymer concentration of 0.5%. Of the polymers tested the novel polymer had the lowest incompatibility with multivalent cations and with ethanol, and much the best swelling properties. After 28 days of incubation at room temperature the rates of growth of the complete bacterial spectrum occurring in demineralized water and of Escherichia coli, serving as model strain representative of gram-negative bacteria, were at least 2 log and 5.7 log, respectively, lower in NaChito-EDTA gels than in the other hydrogels. This antimicrobial activity of NaChito-EDTA can be explained by its highest binding affinity towards magnesium, which stabilizes the outer membrane of gram-negative bacteria. However, this antimicrobial effect is insufficient to guarantee microbial stability. Further results showed that the antimicrobially acting polypeptide nisin can be recommended as an alternative novel preservative for NaChito-EDTA gels, because its antimicrobial spectrum could also be increased towards gram-negative bacteria in combination with chelating excipients. NaChito-EDTA seems, therefore, to be a promising novel polymer for topically-used gels, with advantages over well established gelatinizing agents.     

Hippocampal and entorhinal cortex atrophy in frontotemporal dementia and Alzheimer's disease

Transient unilateral forebrain hypoxia-ischaemia (HI) in 14-day-old rats produces infarction and delayed neuronal death in the frontal cortex. Cell death can also be observed in regions distant from the primary injury, a phenomenon known as diaschisis. While apoptosis is involved in selective neuronal death, its role in infarction and diaschisis remains poorly understood. Here, we have investigated the proteolytic cleavage of poly(ADP ribose) polymerase (PARP) and the occurrence of apoptosis in the hippocampus and the cerebellum following either HI or traumatic brain injury. We demonstrate that: (i) in vitro, PARP is cleaved during apoptosis but not necrosis in cultured neuronal (N1E) cells and Swiss 3T3 fibroblasts; (ii) following HI, apoptotic cells can be detected by 4 h after injury in the hippocampus; (iii) in the ipsilateral hippocampus the appearance of cells with apoptotic morphology is preceded by a dramatic increase in PARP cleavage in the same region, starting immediately following HI and persisting for 24 h; (iv) HI also induces apoptosis in the cerebellum and, as in the hippocampus, the appearance of cells with apoptotic morphology is preceded by PARP cleavage that is greater on the side ipsilateral to forebrain injury; and (v) similarly, traumatic brain injury to the forebrain leads to PARP cleavage and apoptosis in the cerebellum. We conclude that HI injury or traumatic injury to the developing rat forebrain leads to PARP cleavage in directly affected areas and in sites distant from the primary injury that precedes the appearance of cells with apoptotic morphology. Our results are consistent with a role for apoptotic cell death in infarction and in diaschisis resulting from forebrain injury to the developing brain.     

Airways remodeling is a distinctive feature of asthma and is related to severity of disease

PURPOSE: Airways remodeling, evaluated as the subepithelial layer thickness, was compared in asthmatic patients with that of healthy subjects, and was related to clinical grading of disease, presence of atopy, and length of asthmatic history. SUBJECTS AND METHODS: Thirty-four patients with stable asthma (mean age+/-SD: 26.5+/-9.2 years; 10 female) treated with only inhaled beta2-agonists and eight healthy volunteers (mean age+/-SD: 24.6+/-2.5 years; four female) were recruited for the study. Twenty-seven of 34 asthmatics had atopy. Eleven patients had newly diagnosed conditions (duration of disease < or = 1 year), nine patients had long asthmatic history (> 1 year and < or = 10 years), and 14 had prolonged asthmatic history (> 10 years). Bronchial responsiveness to methacholine (M) was expressed as provocative concentration of M causing a 20% fall in FEV1 (PC20) (mg/mL). Degree of asthma severity was assessed using a 0- to 12-point score based on symptoms, bronchodilator use, and daily peak expiratory flow variability over a 3-week period. Bronchoscopy and bronchial biopsy were performed successfully for all subjects; the subepithelial layer thickness, in biopsy samples, was measured from the base of bronchial epithelium to the outer limit of reticular lamina. RESULTS: In asthmatics, baseline FEV1 values (percent of predicted) ranged from 75.7 to 137.0%, and PC20 M ranged from 0.15 to 14.4 mg/mL. According to the asthma severity score, 14 asthmatics were classified as having mild disease, 14 as having moderate disease, and six as having severe disease. The mean values of subepithelial layer thickness were 12.4+/-3.3 microm (range, 6.8 to 22.1 microm) in asthmatics, and 4.4+/-0.5 microm (range, 3.8 to 5.2 microm) in healthy subjects (p<0.001). Subepithelial layer thickness of those with severe asthma differed significantly from that of patients with moderate and mild asthma (16.7+/-3.1 microm vs 12.1+/-2.7 microm and 10.8+/-2.4 microm, p<0.01 and p<0.003, respectively). Moreover, in asthmatics, degree of thickening was positively correlated to asthma severity score (Spearman rank correlation coefficient [rs]=0.581; p<0.001), and negatively correlated with baseline FEV1 (rs=-0.553; p<0.001) and PC20 M (rs=-0.510; p<0.01). No difference was found between degree of thickening observed in atopic asthmatics, compared with that of nonatopic asthmatics, or between degree of thickening in patients with different lengths of asthmatic history. Lastly, multiple regression analysis revealed that asthma severity score was the significant predictive factor for thickness of subepithelial layer. CONCLUSIONS: We confirmed that airways remodeling is a very distinctive and characteristic pathologic finding of asthma. We also demonstrated that it is related to the clinical and functional severity of asthma, but not to atopy or length of asthmatic history.     

Visual attention deficits in Alzheimer's disease: Simple versus conjoined feature search.

The authors investigated selective attention in patients with Alzheimer's disease (AD), using a well-known visual search procedure. In simple feature search, the deficit observed in AD patients represented a baseline shift in the median hit reaction time (RT). On the conjoined feature search task, the median hit RT for AD patients increased disproportionately with increasing array size, indicating an additional cognitive impairment on this task. Of particular importance, the cognitive deficit observed in conjunction search was more profound than that predicted on the basis of previous reports of global cognitive slowing in AD. There was some evidence that the performance of AD patients improved more than the performance of controls over the duration of the experimental test session. Patients also had more difficulty in detecting targets on the right side of hemispace and in more peripheral locations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

脑血管病危险因素

近年来,每到冬季就有很多老年患者到医院或者社区诊所点滴,原因是得了心脑血管病.本文主要针对常见的脑血管病进行论述.     

Brain atrophy progression measured from registered serial MRI: validation and application to Alzheimer's disease

In this paper, we validate the brain boundary shift integral (BBSI) as a measure of brain atrophy and demonstrate its application in Alzheimer's disease (AD). Nineteen normal subjects and nine patients with AD underwent serial three-dimensional MRI (6- to 30-month scan intervals). Repeat studies were registered to the baseline studies. The accuracy of the BBSI was assessed by comparison with simulated atrophy and with segmentation; it was also tested for reproducibility, linearity, and its ability to discriminate patients with AD from healthy controls. The BBSI correlated closely with simulated volumes of atrophy (r = 1.000). The mean absolute difference between repeat measures was 1.51 ml or .13% of mean brain volume. Rates of atrophy from all 18 AD scan pairs were widely separated from those of all 31 control pairs. In matched subgroups, the mean (SD) annual rate of brain atrophy in nine controls was .24% (.32%), compared with 2.78% (.92%) in nine patients with AD. We conclude that the BBSI is a linear and highly reproducible measure of atrophy with potential uses in the early diagnosis and measurement of progression in Alzheimer's disease.     

Cerebrovascular occlusive disease: hydatidosis

We reviewed six patients with cerebral hydatid embolism from the heart. Although hydatid disease is becoming less common in the world as a whole, it should be considered in the differential diagnosis of embolic stroke in children, especially in the infested areas where hydatidosis is endemic.     

Comprehension of grammatical and emotional prosody is impaired in Alzheimer's disease.

Previous research has demonstrated impairment in comprehension of emotional prosody in individuals diagnosed with Alzheimer's disease (AD). The present pilot study further explored the prosodic processing impairment in AD, aiming to extend our knowledge to encompass both grammatical and emotional prosody processing. As expected, impairments were seen in emotional prosody. AD individuals were also found to be impaired in detecting sentence modality, suggesting that impairments in affective prosody processing in AD may be ascribed to a more general prosodic processing impairment, specifically in comprehending prosodic information signaled across the sentence level. AD participants were at a very mild stage of the disease, suggesting that prosody impairments occur early in the disease course. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neuroendocrine differentiation is a common feature of thymic carcinoma

Immunohistochemical evidence of neuroendocrine differentiation in the form of reactivity for synaptophysin, neuron-specific enolase, and/or chromogranin was found in 11 of 19 (58%) thymic carcinomas having the typical morphologic features of that tumor type. Four of these 19 cases were studied ultrastructurally, and neuroendocrine-type cytoplasmic dense-core granules were found in two. In contrast, 84 thymomas were negative for these markers, except for a focal immunoreactivity for neuron-specific enolase in areas of medullary differentiation in half of the lymphocyte-rich tumors. The results of this study show that in the thymus, similar to most other organs, neuroendocrine differentiation is not limited to tumors with an identifiable neuroendocrine appearance in hematoxylin-eosin-stained slides, such as carcinoid tumor and small cell carcinoma, but rather that it represents a common event shared by the major types of malignant epithelial tumors of that organ.     

Atypical form of Alzheimer's disease with prominent posterior cortical atrophy: a review of lesion distribution and circuit disconnection in cortical visual pathways

In recent years, the existence of visual variants of Alzheimer's disease characterized by atypical clinical presentation at onset has been increasingly recognized. In many of these cases post-mortem neuropathological assessment revealed that correlations could be established between clinical symptoms and the distribution of neurodegenerative lesions. We have analyzed a series of Alzheimer's disease patients presenting with prominent visual symptomatology as a cardinal sign of the disease. In these cases, a shift in the distribution of pathological lesions was observed such that the primary visual areas and certain visual association areas within the occipito-parieto-temporal junction and posterior cingulate cortex had very high densities of lesions, whereas the prefrontal cortex had fewer lesions than usually observed in Alzheimer's disease. Previous quantitative analyses have demonstrated that in Alzheimer's disease, primary sensory and motor cortical areas are less damaged than the multimodal association areas of the frontal and temporal lobes, as indicated by the laminar and regional distribution patterns of neurofibrillary tangles and senile plaques. The distribution of pathological lesions in the cerebral cortex of Alzheimer's disease cases with visual symptomatology revealed that specific visual association pathways were disrupted, whereas these particular connections are likely to be affected to a less severe degree in the more common form of Alzheimer's disease. These data suggest that in some cases with visual variants of Alzheimer's disease, the neurological symptomatology may be related to the loss of certain components of the cortical visual pathways, as reflected by the particular distribution of the neuropathological markers of the disease.     

Naming from definition, semantic relevance and feature type: The effects of aging and Alzheimer's disease.

Objective: The principal aim of the present study was to evaluate the impact of semantic relevance and feature type on the ability to name from definition. Method: Thirty-two normal young subjects (Study 1) and 20 probable Alzheimer's disease patients (pAD) with 20 matched older controls (Study 2) were tested with verbal definitions consisting of 4 features, combining feature type (sensory vs. nonsensory) and semantic relevance (high vs. low). The subjects were asked to provide a name corresponding to the definition and to select which individual features they considered most important in justifying their answer. Results: Feature selection results showed that high-relevance features first (d = 2.13 in Study 1; d = 1.44 in Study 2) and nonsensory features second (d = 0.81 in Study 1; d = 0.36 in Study 2) were the main dimensions driving correct performance. Overall, naming performance was affected by the age of acquisition (AoA) of the concept, and differences between the groups in all measures were mainly quantitative. Conclusions: These findings suggest that semantic relevance and feature type are important feature dimensions in conceptual representation and in conceptual access and retrieval. Moreover, results suggest that the former dimension may be more important than the latter, at least in the case of naming from definition. Finally, these results extend previous findings with other tasks, supporting the importance of AoA for correct performance and suggesting that the poorer performance of pAD patients on semantic tasks may represent an exaggeration of difficulties found also in normal older subjects. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The Cystatin-C gene is not linked to early onset familial Alzheimer's disease

The APP717 mutations discovered in only a few early onset Alzheimer's disease (AD) families have confirmed the genetic heterogeneity of this disorder. To identify the other gene(s) involved in the disease we selected the protease inhibitor, Cystatin-C, as a candidate gene. Cystatin-C is an amyloidogenic protein causing hereditary cerebral haemorrhage with amyloidosis-Icelandic type (HCHWA-I). It is localised with the beta-amyloid peptide in the arterial walls of AD brains. We have analysed the segregation of a polymorphic marker in this gene in 8 early onset AD families. Two early onset families showed clear non-segregation of the marker with the disease. When the 8 families are analysed together (assuming only one other gene is involved), they present exclusion linkage criteria. These data indicate that Cystatin-C is not the site of the defect in 2 families and is not likely to be in the other families analysed. We conclude that the deposition of Cystatin-C in AD is a secondary event in the disease process, and that this gene is not pathogenic in familial AD.     

Memory enhancement for emotional stimuli is impaired in early Alzheimer's disease.

Emotional arousal is associated with enhanced memory in neurologically intact individuals, but it is unknown whether this effect is obtained in Alzheimer's disease (AD). The current study compared emotional memory and emotional reactions in patients with early AD and in older controls. Participants viewed emotionally arousing (both pleasant and unpleasant) and neutral photographs while cognitive and electrophysiological reactions were assessed. Memory was tested by free recall and recognition. Emotional reactions were normal in the AD group, but the emotional memory effect (enhanced memory for emotional vs. neutral stimuli) was impaired. Recall results indicated that this effect was normal for pleasant stimuli but abnormal for unpleasant stimuli. These results suggest that the neural basis for the emotional memory effect may be disrupted in AD. Findings are discussed in terms of the role of the amygdala in mediating emotional memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)