Risk Factors And Clinical Characteristics Of Alzheimer's Disease With Depressive Symptoms

Purpose: Alzheimer's disease(AD)patients can be accompanied by a variety of psychiatric symptoms in the early stages,with depressive symptoms being the most common.Depressive symptoms not only seriously affected the quality of AD patients life,but also increased their cognitive dysfunction and the risk of death.Therefore,the correct diagnosis of AD with depressive symptoms is directly related to the treatment effect and prognosis of patients.Socio-economic factors and chronic diseases may affect the depressive symptoms of AD patients,but the mechanism of AD with depressive symptoms is not fully understood.In addition,in the case of AD with depressive symptoms,changes in the levels of amyloid-?(A?)in the brain and morphological changes of the nervous system are also unclear.This study provides a new strategy for the prevention and treatment of AD with depressive symptoms through clinical research on the risk factors and characteristics of AD with depressive symptoms and experimental research on APP / PS1 double transgenic mice with depressive symptoms.Methods:The clinical part of this research was a cross-sectional study.From January 2017 to January 2020,a total of 189 AD patients who met the inclusion and exclusion criteria were continuously collected from outpatient or inpatient treatment at the Third Affiliated Hospital of Army Military Medical University and completed relevant laboratory and neuroimaging examinations.We collected the general information and clinical data of patients,including hypertension,type 2 diabetes mellitus,ischemic heart disease in chronic disease history and related treatment,as well as smoking,alcohol consumption,economic level,education level,living status and negative life events,and so on and so forth,collected patients laboratory tests and imaging examination results,and Mini-mental State Examination(MMSE),Clinical Dementia Rating scale(CDR),Activities of daily living scale(ADL),Hamilton Depression scale(HAMD)were assessed the patient's cognitive function,daily living ability and depressive symptoms.Animal experiments used 8 APP / PS1 transgenic female mice of 32 weeks of age,among which 4 associated with depressive symptoms of APP/PS1 mice by continuous subcutaneous injection of corticosterone and dark solitary induction of depressive symptoms,not induced depressive symptoms 4 APP/PS1 mice as the control group.After the processing,the hippocampus,cortex,and plasma of the mice were collected(3 mice each with the depressive symptom group and the control group).Among them,the hippocampus and cortex were stained with Congo red and Tunel,the neurons and synaptic structures of the mice were observed by transmission electron microscopy,and the A?40 and A?42 levels in plasma samples of mice were detected by Elisa method.Results: One-way analysis of variance showed that the incidence of solitary,low income level,negative life events,type 2 diabetes mellitus,hypertension and white matter lesion in the AD group with depressive symptoms was statistically different from that of the AD group without depressive symptoms,and the scores of MMSE scale,CDR scale and ADL scale were worse(P<0.05 or 0.01).Multivariate Logistic regression analysis showed that AD patients with depressive symptoms were closely related to solitary(OR: 2.65,95% CI: 1.07-6.82),low income levels(OR: 1.94,95% CI: 1.05-3.48),negative life events(OR: 3.32,95% CI: 1.17-8.64),type 2 diabetes mellitus(OR: 1.85,95% CI: 1.06-3.31),hypertension(OR: 1.87,95% CI: 1.05-3.32),and white matter lesions(OR: 1.85,95% CI: 1.03-3.23).In addition,when AD patients with depressive symptoms were accompanied by solitary,low income level,negative life events,type 2 diabetes mellitus,hypertension and white matter lesions,their scores on MMSE scale and ADL scale decreased,and their scores on HAMD scale and CDR scale increased(P < 0.05 or 0.01).The anti-AD combined antidepressant treatment group had higher MMSE and ADL scores and lower HAMD scores than those of the anti-AD treatment group alone(P <0.01).APP/PS1 mice with depressive symptoms showed no significant differences from the control group in the area of cortical and hippocampal A? fiber plaques,the number of neuron apoptosis,and plasma A?40 and A?42 levels,and no difference or specific expression in the structure of neurons and synapses was observed under transmission electron microscopy.Conclusion:There were statistically significant differences in solitary,low income level,negative life events,type 2 diabetes mellitus,hypertension,and white matter lesions among AD patients with depressive symptoms compared with AD patients without depressive symptoms,and their scores on the MMSE scale,CDR scale,and ADL scale were worse.Solitary,low income levels,negative life events,type 2 diabetes mellitus,hypertension,and white matter lesions are risk factors for AD with depressive symptoms.Anti-AD combined with anti-depressant treatment can significantly improve cognitive function,depressive symptoms and daily living ability of AD patients with depressive symptoms.Compared with the control group,APP/PS1 mice with depressive symptoms showed no difference in brain A? fiber plaque area,number of neuron apoptosis,plasma A?40 and A?42 levels,and changes in neuron and synaptic structures.