| Background:Cognitive impairment(CI)is a kind of clinical syndrome which includes remote and recent memory loss, disorientation, aphasia, Poor judgment, calculation dysfunctions, visuospatial deficits and other cognitive functional disturbances with different degree caused by various kinds of reasons.Dementia is a group of severe cognitive impairments, which interferes with occupation, social function and activities of daily living. Data from Chinese epidemiological investigation indicated that the prevalence of dementia in the population above 65 years were 6.9%(AD4.2%, VD1.9%)in the north area, and3.9%(AD2.8%, VD 0.9%)in the south area. With the aging of the population, the incidence of CI has an obvious uptrend. CI has been recognized as a major cause of morbidity and mortality in the aging population world wide, which will bring about heavy economic burden on society and family. Accordingly, we should make an emphasis on the study of cognitive impairment.Mild cognitive impairment (MCI) describes a pre-clinical stage of AD, applied to a transitional period between normal aging and early AD. MCI at present likely represents the best opportunity for pharmacologic interventions. The clinical criteria for the diagnosis of amnestic MCI are those described by Petersen.and include:(i) memory complaints, (ii) objective memory impairment for age and education, (iii) intact general cognitive function, (iv) intact activities of daily living (ADLs), and (v) the subject is not demented. The metabolic syndrome is a constellation of cardiovascular risk factors that has been associated with increased risk of developing cardiovascular disease, diabetes. The metabolic syndrome is comprised of five cardiovascular risk factors that include abdominal obesity, dyslipidemia,hyperglycemia, hypertension. Recent evidence suggests that metabolic syndrome also affects cognitive decline.The vascular risk factors may be related to the occurrence and development of AD. One time vacular event may promote AD from preclinical phase to clinical phase, or aggravate the clinical manifestation of AD.Hypothesis of brain aging in combination with ischemia injury indicated that brain aging incombination with ischemia injury was the fundamental pathological process of CI, vascular harmful factors and neural degeneration may promote the occurrence of CI in common.Vascular and degenerative pathology were two frequently pathological changes in the process of aging. In conclusion, metabolic syndrome was the risk factors for MCI. Therefore,Identification of these risk factors may shed some light on the pathophysiology of Alzheimer's disease and also provide new potential avenues for its prevention and treatment.A chronic inflammatory process has been implicated in the neuropathology of Alzheimer's disease. Increasing evidence suggests that peripheral modification of inflammatory factors may occur early during the development of AD.Characterizing similar immune alterations in subjects with MCI, which represents a preclinical stage of AD, will help identify potential biomarkers for MCI in easily accessible peripheral blood cells. Identification of the inflammatory factors may provide new potential avenues for prevention and treatment of AD.PART ONE Relationship between metabolic syndrome and mild cognitive impairment in elderly patientsObjective:To evaluate the cognition of Senile Metabolic Syndrome(MS) patients and to investigate the relationship between metabolism-related indices and MCI. Methods:74 cases with MS(MS group),45 patients with vascular risk factors (NMS group)and 32 normal controls were enrolled. Mini-mental state examination (MMSE), Montreal cognitive assessment (MoCA), Digit-Symbol Test (DST), Auditory verbal memory test (AVMT), Trail making test (TMT), Sunderland clock drawing test (CDT), verbal Fluency test (VFT) were applied to evaluate cognitive function. Biochemical variables were measured by routine methods.Results:1,The incidences of MCI in the MS and NMS groups were 52.7% and 33.3% respectively. There was statistical difference in incidence between the two groups (P< 0.01).2,The levels of waist circumference, body-mass index(BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), triglycerides (TG) in the MCI group were higher than those in the non-MCI group. (P<0.05)3,The general cognition function in MS and NMS groups was significantly lower than that in the control group (P< 0.001). MS cases achieved significantly lower scores than NMS cases in memory,orientation,attention and executive function. (P<0.01).4,The scores of MoCA,DST,AVMT,TMT in MS group were lower than those in NMS group (P<0.05)5,The four most related risk factors affecting cognitive domain of MCI patients were FBG,blood lipids,SBP and waist circumference. The severity of cognitive impairment was directly associated with the level of metabolic indexes.Conclusions:Elderly patients with metabolic syndrome show a deterioration in memory,calculation,attention and visuospatial perception. Patients with MCI often accompany metabolic dysregulation, and there is positive correlation between the number of abnormal metabolism-related indices and the degree of cognitive impairment. PART TWO The change of serum adiponectin and inflammatory factors in senile metabolic syndrome patients with mild cognitive impairment and their clinical significanceObjective:To evaluate the cognition of senile metabolic syndrome(MS) patients and to investigate the relationship of the levels of serum intercellular adhesion molecule-1 (ICAM-1),matrix metalloproteinase-9(MMP-9),adiponectin with cognitive function in senile metabolic syndrome patients.Methods:74 cases with MS and 32 normal controls were enrolled. mini- mental state examination (MMSE), montreal cognitive assessment (MoCA), digit-symbol test (DST), auditory verbal memory test (AVMT), trail making test (TMT), sunderland clock drawing test (CDT), verbal fluency test (VFT) were applied to evaluate cognitive function. Based on the cognitive assessment, metabolic syndrome patients were divided into two groups:one group with 39 cases of mild cognitive impairment (MS+MCI group) and the other with 35 cases of non-cognitive impairment(MS group). ICAM-1,MMP-9,adiponectin were measured by ELISA.Biochemical variables were measuresd by routine methods in all subjects.Results:1,Subjects with MCI had significantly higher values of body-mass index(BMI), systolic blood pressure (SBP), fasting blood glucose(FBG), MMP-9 (P<0.05) and lower adiponectin-levels (P<0.05) compared with subjects without MCI. Subjects with MS had significantly higher values of MMP-9,ICAM-1(P<0.01) and lower adiponectin-levels (P<0.01) compared with controls.2,Spearman's correlation analysis showed that the serum levels of MMP-9(r=-0.794, P< 0.001) and ICAM-l(r=-0.501, P<0.001) were negatively correlated with adiponectin.However,MMP-9 was positively correlated with ICAM-1(r=0.48,P=0.006).3,Multiple linear regression analysis indicated that there was linear relationship between MoCA and MMP-9(β=-3.438, P=0.001), adiponectin (β=1.337, P=0.006),SBP(β=-0.058, P=0.003) and FBGG(β=-0.227, P=0.049)4,Stepwise logistic analysis showed that influence factors of cognitive function of the elderly were MMP-9(OR=1.007) and adiponectin(OR=0.359).Conclusions:Elderly patients with metabolic syndrome show a deterioration in memory,calculation,attention and visuospatial perception.Elevated inflammatory factors might contribute, in combination with metabolism, to the inflammatory disorder in mild cognitive impairment.MMP-9 might contribute to neuronal degeneration.However, adiponectin could strongly counteract the most of the risk factors for cognitive impairment. |
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