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The Relationship Between Advanced Glycosylation End Products And Cognitive Function Among Elders

Posted on:2012-09-01Degree:MasterType:Thesis
Country:ChinaCandidate:X ChenFull Text:PDF
GTID:2214330368975602Subject:Neurology
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1. ObjectiveAlzheimer Disease is central nervous system degenerative diseases with the progressive cognitive impairment as major clinical manifestation. The typical pathological mechanisms are senile plaques, neurofibrillary tangles and loss of neurons. The etiological mechanisms underlying the neuropathological changes in AD remain unclear, but are probably affected by both environmental and genetic factors. An estimated 24 million people worldwide have dementia, the majority of whom are thought to have Alzheimer's disease. Thus, Alzheimer's disease represents a major public health concern and has been identified as a research priority. Although there are licensed treatments that can alleviate symptoms of Alzheimer's disease, there is a pressing need to improve our understanding of pathogenesis to enable development of disease-modifying treatments. Methods for improving diagnosis are also moving forward, but a better consensus is needed for development of a panel of biological and neuroimaging biomarkers that support clinical diagnosis.Advanced glycosylation end products have a very important influence on the AD incidence. Under non-enzymatic condition, the AGEs is a group of brown, fluorescence active, high cross-linking and irreversible end products after the condense, rearrange, split, and oxidative modification on the aldehyde group of reducing sugar and the free amino from the macromolecular such as protein, amino acid, lipid and nucleic acid.The AGEs can exchange the protein, activate glia, stabilize neuritic plaque and enhance the inflammatory responses. Saccharificatized Aβand AGEs receptor can mutually activate small and astrocytes glia, promote the oxidative stress, secrete mass of inducible nitric oxide synthase and mass of proinflammatory cytokine, and reflect the expression from AGE receptor; It can worsen the AD pathological mechanisms by neuron damage caused by the Oxidative Stress and cytokine.This research probes the relationship between the AGEs among elders and the cognitive impairment, so as to establish specific lab index which can bring convenience to diagnose AD in the early stage.2. MethodsAll the testees, totally 270 cases, were elders above 60 years old from our hospital's neurological department and medical examination center, who had capacities of listening, saying, writing and who have stable emotion, so that they coordinated with the survey scale well.Montreal Cognitive Assessment(MoCA, Beijing Version) and the MoCA (Guangdong Version) were applied to assess the patients'cognitive impairment and their illness history were enquired.2 millilitre fasting whole blood was drawn from each testee and separated serum by centrifugation. Then serum was diluted within given concentration. Molecular fluorescence analysis was applied with 365nm excitation wavelengths and with 435nm emission wavelengths to detect the serum's fluorescence intensity, namely relative content.According to the results from the MoCA, all the patients were divided into two groups, group of elderly people with normal cognitive function (≥26 points) and group of cognitive impairment(<26 points),then we compared the difference among the AGEs, ages, education, gender and other factors. Moreover, according to the illness history, we also divided the patient into two groups, diabetic mellitus group and control group, so as to analyze the relationship between the AGEs and cognitive impairment, and to compare the detection rate from these two groups. The test data were processed by the SPSS 17.0 statistic software. Independent-samples T test and One-way ANOVA were used in the comparisons of MoCA scores between each groups; binary comparison:if equal variances assumed, used LSD; if equal variances not assumed, used DunnettT3; while Independent-samples T test was used in the comparisons of AGEs between the cognitive impairment group and the normal cognitive group. Chi-Square test was used in the comparisons on the detection rate of cognitive impairment; the level of significant difference isα=0.05.3. Results①Total 270 patients undertook this test, among which 131 patients were detected as cognitive impairment,48.52% of all test receivers.77 patients were Mild cognitive impairment, while 54 patients were dementia. The detection rate is 28.52% and 20.00% respectively.②The relationship between the various age groups and the MoCA scores: Grouping from young age to elder age, the MoCA score is 25.23±4.12,21.68±5.78,17.00±6.51 respectively, which had significant differences (F=24.149, P=0.000);60 to 69 years old group was significantly different from the other groups (P=0.000, P=0.000),70 to 79 years old group was also significantly different from the over 80 years old group (P=0.040). The detection rate for the cognitive impairment is 35.17%,61.47%,81.25% respectively, which had significant differences from each other (χ2=24.520, P=0.000)③The relationship between the education and the MoCA scores:the average MoCA scores in different education level groups had significant differences (F=59.352, P=0.000). The MoCA score for the groups of the illiterate and the primary school were 13.50±4.11 and 21.62±4.76, while the groups of junior high school, senior high school and the university had significant differences from them (P=0.000) and their MoCA score was 24.86±4.38,26.24±3.1726.35±2.97 respectively. But the MoCA score for the groups of junior high school, senior high school and the university had no significant differences from each other (P=0.322, P=0.343, P=1.000). As the higher education, the MoCA score were increasing and the detection rate of cognitive impairment was obvious decreasing with significant differences (x2=84.936, P=0.000).④The relationship between the gender and the MoCA scores:the MoCA scores for male was 24.45±4.65, and for female was 22.63±5.86, which had significant differences from each other (t=-2.806, P=0.005). The detection rate for the male and female cognitive impairment were 42.57% and 52.07%, the female have higher percentage than the male, but had no distinguished differences (X2=2.283, P=0.131).⑤The relationship between the AGEs result and the MoCA scores:AGEs content:normal cognitive group:55.14±15.15; cognitive impairment group: 57.95±16.01. No significant differences existed in these two groups (t=-1.479, P=0.140)⑥The comparison between AGEs and the detection rate of the cognitive impairment for group of diabetic mellitus and group of the health:AGEs content: group of diabetic mellitus was 65.54±21.05 while the group of the health was 49.81±9.30, which were significantly different from each other(t=-5.487, P=0.000). AGEs content for the group of diabetic mellitus:normal cognitive group was 67.66±23.90, and group of cognitive impairment was 63.98±18.89. Both groups had no significant differences(t=0.688, P=0.494). The detection rate of the cognitive impairment:group of diabetic mellitus was 57.81% while the group of the health was 34.33%, the former was higher than the latter, and they had significant differences (X2=7.272, P=0.007), which suggested diabetes patients than healthy patients were more likely to have cognitive dysfunction.4. ConclusionFrom the research, the conclusion could be drawn that the cognitive impairment was proportional with the ages, and was inversely proportional with education level. The female had higher incidence rate than male, which coincided with most of the current research results of epidemiology. Moreover, in this research, group of diabetic mellitus had obviously higher detection rate of cognitive impairment than the group of no diabetic mellitus, which conformed to the findings of other medical literature. There were no distinguished differences of AGEs between the cognitive impairment and normal cognitive. The groups of cognitive impairment and normal cognitive within diabetic mellitus, had no distinguished differences on the AGEs, so the AGEs couldn't be acted as the Alzheimer Disease's lab index to diagnose AD in the early stage. As for the diagnosis of AD in the early stage, it still needs to enhance all the social recognition and make early diagnosis and precaution.
Keywords/Search Tags:Alzheimer's disease(AD), Advanced glycosylation end products(AGEs), Montreal Cognitive Assessment(MoCA), Risk factors
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