Risk Factors For Subjective Cognitive Decline And Association Of Subjective Cognitive Decline With Cerebrospinal Fluid Biomarkers Of Alzheimer’s Disease Pathology In Cognitively Intact Older Adults:The CABLE Study

Objective:Increasing evidences supported that subjective cognitive decline（SCD）might be a potential first symptomatic manifestation of Alzheimer’s disease（AD）,which has great significance for the early intervention for AD.The rapidly growing number of SCD individuals who seek medical help and advice also makes it urgent to develop more precise strategy for SCD.Nowadays,only few studies reported the risk factors for SCD.What’s more,the association of subjective cognitive decline with cerebrospinal fluid biomarkers of Alzheimer’s disease pathology remains unclear.Therefore,this study aimed to explore the risk factors for SCD and the associations between SCD and CSF biomarkers of AD pathology.Methods:We enrolled non-demented participants without objective cognitive impairment and the study was divided into two parts.Firstly,we explored risk factors for SCD.Logistics and linear regression models were performed to investigate 41 factors.Cochran-Armitage trend test was used to confirm whether subjective cognition would be changed with an increasing number of risk factors.Then we conducted subgroup analysis to explore risk factors for SCD in populations of different ages,genders,and populations with SCD Plus characteristics.Secondly,we used linear regression to explore the associations between SCD and CSF biomarkers of AD pathology.Results:A high overall prevalence of SCD was found in total participants.SCD status and SCD severity were used to describe cognition of participants with SCD.In our analysis of risk factors for SCD,we analyzed 41 factors.Eight factors were eventually identified as risk factors for SCD,including four stable factors associated with both SCD statues and severity（older age,thyroid diseases,minimal anxiety symptoms[MAS]and day time dysfunction;odds ratio[OR]ranging from 1.74 to 2.29）as well as four suggestive factors associated with either SCD statues or severity（female sex,anemia,lack of physical exercises and living alone;OR ranging from 1.30 to 2.29）.The prevalence of SCD gradually increased with the number of risk factors clustering increased in individuals（p for trend<0.001）.The results of subgroup analysis showed that the risk factors for SCD were different in different ages and genders.Living alone,thyroid disease and daytime dysfunction are more likely to increase the risk of SCD in women,while lack of physical activity and MAS increase the risk of SCD in men.Advanced age is a risk factor for SCD in both men and women.Living alone,lack of physical activity,and MAS are risk factors for SCD in participants aged≥65 years,and thyroid disease increases the risk of SCD in middle age in participants<65 years.Five of these eight factors were further proved among individuals with SCD-plus features,which were considered more likely to have preclinical AD.In the analysis of association of SCD with CSF biomarkers of AD pathology,we mainly analyzed Aβ₄₂,T-tau,P-tau,T-tau/Aβ₄₂and T-tau/Aβ₄₂.After adjustments for covariates,SCD and SCD severity showed significant associations with CSF Aβ₄₂（SCD:β=-0.0003,p=0.0263;SCD severity:β=-0.0004,p=0.0046）,CSF T-tau/Aβ₄₂ ratio（SCD:β=0.1080,p=0.0064;SCD severity:β=0.1129,p=0.0009）and CSF P-tau/Aβ₄₂ratio（SCD:β=0.0167,p=0.0103;SCD severity:β=0.0193,p=0.0006）rather than T-tau and P-tau compared with cognitively normal individuals.Age,sex,years of education and APOEε4 genotype has no affection on the association.Conclusion:These findings revealed several risk factors for SCD.The results indicated that SCD was associated with CSF Aβ,but not with T-tau and P-tau.Our study provided some new clues for early prevention and intervention of AD.