Increased prediction value of biomarker combinations for the conversion of mild cognitive impairment to Alzheimer''''s dementia

摘要

Background:Progression of mild cognitive impairment(MCI)to Alzheimer''s disease(AD)dementia can be predicted by clinical features and a combination of biomarkers may increase the predictive power.In the present study,we investigated whether the combination of olfactory function and plasma neuronal-derived exosome(NDE)Aβ1-42 can best predict progression to AD dementia.Methods:Eighty-seven MCI patients were enrolled and received cognitive assessment at 2-year and 3-year follow-up to reevaluate cognition.In the meanwhile,80 healthy controls and 88 AD dementia patients were enrolled at baseline as well to evaluate the diagnose value in cross-section.Olfactory function was evaluated with the sniffin sticks(SS-16)and Aβ142 levels in NDES were determined by ELISA.Logistic regression was performed to evaluate the risk factors for cognitive decline in MCI at 2-year and 3-year revisits.Results:In the cross cohort,lower SS-16 scores and higher AB142 levels in NDES were found in MCI and AD dementia compared to healthy controls.For the longitudinal set,8 MCI individuals developed AD dementia within 2 years,and 16 MCI individuals developed AD dementia within 3 years.The two-parameter combination of SS-16 scores and Aβ1-42 level in NDEs showed better prediction in the conversion of MCI to AD dementia at 2-year and 3-year revisits.Moreover,after a 3-year follow-up,SS-16 scores also significantly predicted the conversion to AD dementia,where lower scores were associated with a 10-fold increased risk of developing AD dementia(p=0.006).Similarly,higher AB1-42 levels in NDES in patients with MCI increased the risk of developing AD dementia by 8.5-fold(p=0.002).Conclusion:A combination of two biomarkers NDE AB1-42 and SS-16 predicted the conversion of MCI to AD dementia more accurately.These findings have critical implications for understanding the pathophysiology of AD dementia and for developing preventative treatments for cognitive decline.