Correlation Between Insulin Resistance And Urinary Level Of AD7c-NTP And The Degree Of Cognitive Impairment In Alzheimer’s Disease

Objective:Our study was aimed to explore the method of early diagnosis of mild cognitive impairment(MCI)by analyzing the correlation between insulin resistance and the expression level of Alzheimer’s disease-associated neurofilament protein(AD7C-NTP)in urine and the degree of cognitive impairment in patients with Alzheimer’s disease(AD).Method:28 patients with mild cognitive impairment(MCI group)and 52 patients with probable AD were recruited in Nanchong Central Hospital from October 2019 to October 2021.According to the Clinical Dementia Rating Scale(CDR),AD patients were divided into mild AD group(CDR=1 point)(27 cases),moderate-severe AD group(CDR≥2 points)(25 cases),and 30 healthy controls matched by age and gender were included in the physical examination in our hospital.Glucose metabolism-related indexes[fasting blood glucose(FPG),fasting insulin(FINS),C-peptide,glycosylated hemoglobin(HbA1c),Homeostasis model of assessment for insulin resistance index(HOMA-IR),referred to as insulin resistance index],urinary AD7c-NTP levels,Montreal Cognitive Assessment(MOCA)and Mini-mental State Scale(MMSE)were compared among MCI group,mild AD group,moderate-severe AD group and control group.Analyze the correlation of glucose metabolism index,urinary AD7c-NTP expression level with MOCA score and MMSE score in each group of subjects,and evaluate the early diagnosis value of each index for MCI.Result:(1)The MOCA score and MMSE score of the case groups(MCI group,mild AD group,moderate-severe AD group)were significantly lower than those of the control group(P<0.001).The more severe the group,the lower the MOCA score and the MMSE score,the higher the urinary AD7c-NTP level(P<0.001).(2)There were no significant difference in FPG,FINS,C-peptide and HbA1c between the MCI group and the control group(P>0.05),while the HOMA-IR of the MCI group was higher than that of the control group[(4.25±3.57)vs(2.47±2.28),P=0.019].The glucose metabolism-related indexes in AD group were higher than those in MCI group and control group(P<0.05);FPG,FINS,HOMA-IR in moderate-severe AD group were significantly higher than those in mild AD group,but the differences were not statistically significant.(3)In the case group,FINS,HOMA-IR,HbA1c and urinary AD7c-NTP were negatively correlated with MOCA score and MMSE score(r<0,P<0.05);while FPG and C-peptide had no correlation with MOCA score and MMSE score(P>0.05).In the MCI group and the mild AD group,further analysis of the correlation between the urinary AD7c-NTP expression level and the glucose metabolism indexes showed that the urinary AD7c-NTP level was positively correlated with the glucose metabolism indexes(r>0,P<0.05).In moderate to severe AD group,there was no correlation between urinary AD7c-NTP expression level and glucose metabolism indexes(P>0.05).(4)According to the ROC curve,1.131ng/mL was determined as the best cut-off value for urinary AD7c-NTP to diagnose MCI,and its corresponding sensitivity and specificity were 87.27%and 92.24%,respectively,and the area under the ROC curve was 0.9333,the 95%confidence interval is 0.8695～0.9667,which is of high value for clinical diagnosis.The HOMA-IR index is a mathematical model established to reflect the interaction between plasma glucose and insulin in different organs.Compared with the blood glucose clamp method,it has a good correlation.Therefore,for people with normal fasting blood glucose,it could reflect the situation of insulin resistance more sensatively than single index.Combining with the ROC curve of HOMA-IR,it can be inferred that the area under the ROC curve of HOMA-IR is 0.7405.When the cut-off value of HOMA-IR is 3.16,it can diagnose MCI.The sensitivity was 82.14%and the specificity was 64.67%.HOMA-IR has certain auxiliary diagnostic value for MCI,but its specificity and sensitivity are not as good as that of urinary AD7c-NTP,but it may have predictive value for the risk of MCI progression to AD.Conclusion:(1)Attention should be paid to the transitional period of normal fasting plasma glucose and elevated insulin resistance index during the screening of patients at high risk of AD.Early intervention of insulin resistance may delay the occurrence and development of AD.(2)In the stage of MCI and mild AD,abnormal glucose metabolism can increase the risk of cognitive impairment and progression to dementia,but the body’s insulin resistance reaches a certain level during the course of the disease.Due to the non-regeneration of neurons and the saturation of insulin-related receptors,urinary AD7c-NTP levels may decline.(3)Urinary AD7c-NTP has certain diagnostic value for MCI stage,HOMA-IR index may have predictive value for the risk of MCI progression to AD,and insulin resistance as an early intervention target for AD has certain clinical value.