Background:The combinatorial efect of multiple genetic factors calculated as a polygenic risk score(PRS)has been studied to predict disease progression to Alzheimer’s disease(AD)from mild cognitive impairment(MCI).Pr...Background:The combinatorial efect of multiple genetic factors calculated as a polygenic risk score(PRS)has been studied to predict disease progression to Alzheimer’s disease(AD)from mild cognitive impairment(MCI).Previous studies have investigated the performance of PRS in the prediction of disease progression to AD by including and excluding single nucleotide polymorphisms within the region surrounding the APOE gene.These studies may have missed the APOE genotype-specifc predictability of PRS for disease progression to AD.Methods:We analyzed 732 MCI from the Alzheimer’s Disease Neuroimaging Initiative cohort,including those who progressed to AD within 5 years post-baseline(n=270)and remained stable as MCI(n=462).The predictability of PRS including and excluding the APOE region(PRS_(+APOE) and PRS_(−APOE))on the conversion to AD and its interaction with the APOEε4 carrier status were assessed using Cox regression analyses.Results:PRS_(+APOE)(hazard ratio[HR]1.468,95%CI 1.335-1.615)and PRS_(−APOE)(HR 1.293,95%CI 1.157-1.445)were both associated with a signifcantly increased risk of MCI progression to dementia.The interaction between PRS_(+APOE) and APOEε4 carrier status was signifcant with a P-value of 0.0378.The association of PRSs with the progression risk was stronger in APOEε4 non-carriers(PRS_(+APOE):HR 1.710,95%CI 1.244-2.351;PRS_(−APOE):HR 1.429,95%CI 1.182-1.728)than in APOEε4 carriers(PRS_(+APOE):HR 1.167,95%CI 1.005-1.355;PRS_(−APOE):HR 1.172,95%CI 1.020-1.346).Conclusions:PRS could predict the conversion of MCI to dementia with a stronger association in APOEε4 noncarriers than APOEε4 carriers.This indicates PRS as a potential genetic predictor particularly for MCI with no APOEε4 alleles.展开更多
BACKGROUND Metabolic syndrome(MetS)is related to poor cognitive function.However,the results of previous studies were inconsistent,and whether the ApoEε4 allele modifies the association remains unclear.AIM To elucida...BACKGROUND Metabolic syndrome(MetS)is related to poor cognitive function.However,the results of previous studies were inconsistent,and whether the ApoEε4 allele modifies the association remains unclear.AIM To elucidate the relationships among MetS,ApoEε4,and cognitive dysfunction in an elderly population in China.METHODS One hundred elderly patients with MetS and 102 age-and gender-matched controls were included in the study.Baseline clinical characteristics and biochemical index for glucose and lipid metabolism were obtained.The distribution of ApoEε4 was assessed with PCR restriction fragment length polymorphism analysis.Cognitive function was evaluated by mini-mental status examination at the 1-year follow-up examination.RESULTS Compared with controls,MetS patients had worse cognitive function and decreased ability to participate in activities of daily life(P=0.001 and 0.046,respectively).Patients with cognitive dysfunction had higher prevalence of MetS(62.1%vs 36.4%,P<0.001)and were more likely to carry the ApoEε4 allele(22.3%vs 10.1%,P=0.019).Multivariate logistic regression analyses showed that diagnosis with MetS,severe insulin resistance,status as an ApoEε4 carrier,higher systolic blood pressure,and larger waist circumference were risk factors for cognitive dysfunction(P<0.05).Repeated-measures analysis of variance,performed with data collected at the 1-year follow-up,revealed continuous influences of MetS and ApoEε4 on the deterioration of cognitive function(time×team,P<0.001 for both).CONCLUSION Diagnosis of MetS and ApoEε4 carrier status were persistently associated with cognitive dysfunction among an elderly population in China.展开更多
基金Alzheimer’s Disease Neuroimaging Initiative(National Institutes of Health Grant U01 AG024904)and DOD ADNI(Department of Defense award number W81XWH-12–2-0012).ADNI is funded by the National Institute on Agingthe National Institute of Biomedical Imaging and Bioengineering,and through generous contributions from the following:AbbVie,Alzheimer’s Association+28 种基金Alzheimer’s Drug Discovery FoundationAraclon BiotechBioClinica,Inc.BiogenBristol-Myers Squibb CompanyCereSpir,Inc.CogstateEisai Inc.Elan Pharmaceuticals,Inc.Eli Lilly and CompanyEuroImmunF.Hofmann-La Roche Ltd and its afliated company Genentech,Inc.FujirebioGE HealthcareIXICO Ltd.Janssen Alzheimer Immunotherapy Research&Development,LLC.Johnson&Johnson Pharmaceutical Research&Development LLC.LumosityLundbeckMerck&Co.,Inc.Meso Scale Diagnostics,LLC.NeuroRx ResearchNeurotrack TechnologiesNovartis Pharmaceuticals CorporationPfzer Inc.Piramal ImagingServierTakeda Pharmaceutical Companyand Transition Therapeutics.The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada.Private sector contributions are facilitated by the Foundation for the National Institutes of Health(www.fnih.org).The grantee organization is the Northern California Institute for Research and Education,and the study is coordinated by the Alzheimer’s Therapeutic Research Institute at the University of Southern California.ADNI data are dis‑seminated by the Laboratory for Neuro Imaging at the University of Southern California.
文摘Background:The combinatorial efect of multiple genetic factors calculated as a polygenic risk score(PRS)has been studied to predict disease progression to Alzheimer’s disease(AD)from mild cognitive impairment(MCI).Previous studies have investigated the performance of PRS in the prediction of disease progression to AD by including and excluding single nucleotide polymorphisms within the region surrounding the APOE gene.These studies may have missed the APOE genotype-specifc predictability of PRS for disease progression to AD.Methods:We analyzed 732 MCI from the Alzheimer’s Disease Neuroimaging Initiative cohort,including those who progressed to AD within 5 years post-baseline(n=270)and remained stable as MCI(n=462).The predictability of PRS including and excluding the APOE region(PRS_(+APOE) and PRS_(−APOE))on the conversion to AD and its interaction with the APOEε4 carrier status were assessed using Cox regression analyses.Results:PRS_(+APOE)(hazard ratio[HR]1.468,95%CI 1.335-1.615)and PRS_(−APOE)(HR 1.293,95%CI 1.157-1.445)were both associated with a signifcantly increased risk of MCI progression to dementia.The interaction between PRS_(+APOE) and APOEε4 carrier status was signifcant with a P-value of 0.0378.The association of PRSs with the progression risk was stronger in APOEε4 non-carriers(PRS_(+APOE):HR 1.710,95%CI 1.244-2.351;PRS_(−APOE):HR 1.429,95%CI 1.182-1.728)than in APOEε4 carriers(PRS_(+APOE):HR 1.167,95%CI 1.005-1.355;PRS_(−APOE):HR 1.172,95%CI 1.020-1.346).Conclusions:PRS could predict the conversion of MCI to dementia with a stronger association in APOEε4 noncarriers than APOEε4 carriers.This indicates PRS as a potential genetic predictor particularly for MCI with no APOEε4 alleles.
基金Supported by Basic and Clinical Cooperation Project of Capital Medical University,No.16JL82.
文摘BACKGROUND Metabolic syndrome(MetS)is related to poor cognitive function.However,the results of previous studies were inconsistent,and whether the ApoEε4 allele modifies the association remains unclear.AIM To elucidate the relationships among MetS,ApoEε4,and cognitive dysfunction in an elderly population in China.METHODS One hundred elderly patients with MetS and 102 age-and gender-matched controls were included in the study.Baseline clinical characteristics and biochemical index for glucose and lipid metabolism were obtained.The distribution of ApoEε4 was assessed with PCR restriction fragment length polymorphism analysis.Cognitive function was evaluated by mini-mental status examination at the 1-year follow-up examination.RESULTS Compared with controls,MetS patients had worse cognitive function and decreased ability to participate in activities of daily life(P=0.001 and 0.046,respectively).Patients with cognitive dysfunction had higher prevalence of MetS(62.1%vs 36.4%,P<0.001)and were more likely to carry the ApoEε4 allele(22.3%vs 10.1%,P=0.019).Multivariate logistic regression analyses showed that diagnosis with MetS,severe insulin resistance,status as an ApoEε4 carrier,higher systolic blood pressure,and larger waist circumference were risk factors for cognitive dysfunction(P<0.05).Repeated-measures analysis of variance,performed with data collected at the 1-year follow-up,revealed continuous influences of MetS and ApoEε4 on the deterioration of cognitive function(time×team,P<0.001 for both).CONCLUSION Diagnosis of MetS and ApoEε4 carrier status were persistently associated with cognitive dysfunction among an elderly population in China.
