Background(1)To investigate the association between age at diabetes diagnosis and the incidence of all-cause dementia(ACD),Alzheimer’s disease(AD),and vascular dementia(VD)in individuals with diabetes.(2)To assess th...Background(1)To investigate the association between age at diabetes diagnosis and the incidence of all-cause dementia(ACD),Alzheimer’s disease(AD),and vascular dementia(VD)in individuals with diabetes.(2)To assess the relationship among age at diabetes diagnosis,dementia polygenic risk score(PRS),APOEε4 carrier status,and risk of ACD.Methods In a large,population-based cohort with a median follow-up of 13.4 years,participants were stratified by age at diabetes diagnosis(<50,50–60,and>60 years).Cox proportional hazards models were used,adjusted for multiple covariates.Genetic risk was assessed using dementia PRS,and APOEε4 carrier status was considered in the analysis.Results(1)Individuals diagnosed at ages 50–60(hazard ratio(HR)=0.71,95%CI:0.55–0.93,P=0.0117)and>60 years(HR=0.59,95%CI:0.44–0.79,P<0.001)had significantly lower ACD risk compared to those diagnosed at age<50 years.(2)Genetic risk stratification:among participants with intermediate and high dementia PRS,diabetes diagnosis at age>60 years was associated with reduced ACD risk(intermediate PRS:HR=0.66,95%CI:0.44–0.97,P=0.0035;high PRS:HR=0.46,95%CI:0.26–0.83,P=0.009).(3)APOEε4 carrier analysis:in APOEε4 carriers,diagnosis of diabetes at>60 years(HR=0.43,95%CI:0.29–0.64,P<0.001)and at 50–60 years(HR=0.69,95%CI:0.40–0.85,P=0.005)was associated with a significantly reduced risk of ACD compared to diagnosis at age<50 years.Conclusion Later onset of diabetes(age≥50)is associated with a lower risk of ACD,particularly among individuals with higher genetic susceptibility to dementia,including APOEε4 carriers.These findings highlight the importance of early diabetes management and targeted lifestyle interventions in high-risk populations to potentially reduce dementia risk.展开更多
基金supported by Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Informatization(2021B1212040007)Special Projects for Scientific and Technological Research in Chinese Medicine and Ethnomedicine(QZYY-2024-035)+3 种基金Scientific and Technological Innovation 2030(2023ZD0505804,2023ZD0505800,and 2024YFF0507500)the National Key Research and Development Program of China(2021YFC2500100 and 2021YFC2500103)the National Natural Science Foundation of China(82471212,82071187,82360387,and 81870821)Key Project of Yunnan Provincial Department of Science and Technology(202301AS070037 and 202305AK340001).
文摘Background(1)To investigate the association between age at diabetes diagnosis and the incidence of all-cause dementia(ACD),Alzheimer’s disease(AD),and vascular dementia(VD)in individuals with diabetes.(2)To assess the relationship among age at diabetes diagnosis,dementia polygenic risk score(PRS),APOEε4 carrier status,and risk of ACD.Methods In a large,population-based cohort with a median follow-up of 13.4 years,participants were stratified by age at diabetes diagnosis(<50,50–60,and>60 years).Cox proportional hazards models were used,adjusted for multiple covariates.Genetic risk was assessed using dementia PRS,and APOEε4 carrier status was considered in the analysis.Results(1)Individuals diagnosed at ages 50–60(hazard ratio(HR)=0.71,95%CI:0.55–0.93,P=0.0117)and>60 years(HR=0.59,95%CI:0.44–0.79,P<0.001)had significantly lower ACD risk compared to those diagnosed at age<50 years.(2)Genetic risk stratification:among participants with intermediate and high dementia PRS,diabetes diagnosis at age>60 years was associated with reduced ACD risk(intermediate PRS:HR=0.66,95%CI:0.44–0.97,P=0.0035;high PRS:HR=0.46,95%CI:0.26–0.83,P=0.009).(3)APOEε4 carrier analysis:in APOEε4 carriers,diagnosis of diabetes at>60 years(HR=0.43,95%CI:0.29–0.64,P<0.001)and at 50–60 years(HR=0.69,95%CI:0.40–0.85,P=0.005)was associated with a significantly reduced risk of ACD compared to diagnosis at age<50 years.Conclusion Later onset of diabetes(age≥50)is associated with a lower risk of ACD,particularly among individuals with higher genetic susceptibility to dementia,including APOEε4 carriers.These findings highlight the importance of early diabetes management and targeted lifestyle interventions in high-risk populations to potentially reduce dementia risk.
