Associations Of Lifestyles And ApoE Gene With Frailty,and Mortality Risk Among The Chinese Elderly

ObjectiveThis study aimed to investigate the impact of lifestyles,ApoE gene,and their interaction on the risks of frailty and mortality among the Chinese elderly based on a prospective cohort design.MethodsThe data for this study was obtained from the China Health and Retirement Longitudinal Study(CHARLS)conducted between 2002 and 2018.The author participated in investigation for a total of 1094 participants across seven cities in Guangdong province in 2018,as well as data collection for 320 participants in longevity villages in Guangdong province in 2021.The specific lifestyle factors included in this study were smoking status,alcohol consumption,dietary diversity,physical activity,cognitive activities,and social activities.A lifestyle score was constructed based on above lifestyles,and the study participants were categorized into three groups:unhealthy,moderate,and healthy lifestyle.The ApoE genotype was assessed by rs429358 and rs7412 and divided into ApoEε4 carriers and non-carriers.Frailty status was assessed using the frailty index consisting of 39 variables.Cox proportional hazards models were used to assess the association of lifestyle and ApoE gene with the risks of frailty and mortality,as well as the possible interaction effects.Results(1)In the analysis of frailty outcomes,a total of 6059 participants were included,with a cumulative follow-up of 43164 person-years.Among them,2321 individuals experienced frailty.High levels of dietary diversity,physical activity,cognitive activity,and social activity were associated with respective reductions in frailty risk:18%(HR:0.82,95%CI:0.74-0.92),14%(HR:0.86,95%CI:0.76-0.98),19%(HR:0.81,95%CI:0.68-0.95),and 22%(HR:0.78,95%CI:0.69-0.89).Participants who maintained 5-6 specific healthy lifestyle factors had a 41%reduction in frailty risk compared to those who did not maintain any specific healthy lifestyle factors(HR:0.59,95%CI:0.45-0.76).Moreover,individuals with healthy lifestyles had a 27%lower risk of frailty compared to those with unhealthy lifestyles(HR:0.73,95%CI:0.63-0.85).Carrying the ApoEε4 allele increased the risk of frailty by 21%(HR:1.21,95%CI:1.08-1.35).There was no significant interaction between the ApoE gene and lifestyle;however,among ApoEε4 carriers,a healthy lifestyle did not provide significant protection against frailty risk.Compared to ApoE non-carriers with a healthy lifestyle,ApoEs4 carriers with poor lifestyle habits had a further 88%increase in frailty risk(HR:1.88,95%CI:1.43-2.46).(2)In the analysis of mortality outcomes,a total of 8641 subjects were included,with a cumulative follow-up of 58842 person-years,resulting in 4872 deaths.Never smoking,as well as high levels of dietary diversity,physical activity,cognitive activity,and social activity,were associated with respective reductions in mortality risk:18%(HR:0.82,95%CI:0.75-0.89),15%(HR:0.85,95%CI:0.78-0.92),20%(HR:0.80,95%CI:0.74-0.87),21%(HR:0.79,95%CI:0.70-0.89),and 10%(HR:0.90,95%CI:0.82-1.00).Participants who maintained 5-6 specific healthy lifestyle factors had a 57%reduction in mortality risk compared to those who did not maintain any specific healthy lifestyle factors(HR:0.43,95%CI:0.35-0.53).Moreover,individuals with a healthy lifestyle had a 30%lower risk of mortality compared to those with unhealthy lifestyles(HR:0.70,95%CI:0.63-0.78).Carrying the ApoEε4 allele increased the risk of mortality by 9%(HR:1.09,95%CI:1.01-1.18).There was no significant interaction between the ApoE gene and lifestyle,and a healthy lifestyle had a protective effect against mortality risk regardless of ApoEε4 allele carriage.Compared to ApoE noncarriers with a healthy lifestyle,ApoEε4 carriers with poor lifestyle habits had a further 72%increase in mortality(HR:1.72,95%CI:1.43-2.06).ConclusionsHigh levels of dietary diversity,physical activity,cognitive engagement,and social interactions have protective effects against frailty and mortality risks.Nonsmoking is associated with a reduced risk of mortality,while there is no significant association between alcohol consumption and frailty or mortality risks.Adopting an overall healthy lifestyle can reduce the occurrence of frailty and mortality to varying degrees.The ApoEε4 allele is positively correlated with increased risks of frailty and mortality,and there is no interaction effect with lifestyle factors.Compared to ApoEε4 non-carriers with a healthy lifestyle,individuals carrying the ApoEε4 allele with an unhealthy lifestyle have further increased risks of frailty and mortality.