Effects Of Smoking Status And Polygenic Risk Score On Cognitive Function In The Elderly

ObjectiveThe issue of impaired cognitive function in older people is of widespread concern in the context of an ageing population.Smoking is a common lifestyle habit and the findings of its relationship with cognitive function in existing studies are inconsistent.In this paper,we will investigate the association between smoking status and cognitive impairment in older adults,and construct a cognition-related polygenic risk score to explore its association with cognitive impairment.MethodsThe study was based on the"Survey of Factors Affecting the Healthy Longevity of the Elderly in China"project.26,372 elderly people aged 65 years and above were included in the study,after excluding those with missing information on smoking status.The Mini-Mental State Examination（MMSE）was used to assess the cognitive functioning of the participants.Count data were described using frequency and composition ratios,and between-group rates were compared using the Chi-Squared Test.A competing risk model was used to explore the association between smoking status and cognitive impairment.To investigate the influence of genetic factors on cognitive impairment,genetic data from this population were used to screen for cognitive-related genetic single nucleotide loci and construct a polygenic risk score（PRS）,which was categorised into quartiles（Q₁,Q₂,Q₃,Q₄）.The correlation between polygenic risk scores and cognitive impairment was assessed using the Q₁group as a reference.A restricted cubic spline model was used to further explore the dose-response relationship between duration of smoking and duration of smoking cessation and impaired cognitive function.In subgroup analyses,the association was based on age group（65-69 years,70-79 years,80-89 years,90-99 years,≥100 years）,sex（male and female）,BMI grouping（<18.5 kg/m² as low weight,18.5-23.9 kg/m² as normal weight,≥24 kg/m²-27.9 kg/m² as overweight,≥28 kg/m² as obese）,activity of daily living（ADL）,and cognitive function.(Activity of Daily Living（ADL）and alcohol consumption habits were stratified for the analysis of older people.Results（1）The prevalence of cognitive impairment in our elderly population in this study was relatively high（29.3%）,with a higher prevalence in women（16.2%）and higher than in men（13.4%）.The proportion of patients with impaired cognitive function was higher among never smokers（29.9%）than among current smokers（27.8%）and ex-smokers（29.3%）.（2）The results of the competing risks model suggest that current smoking is associated with a reduced risk of developing cognitive impairment.In the model adjusted for age and gender only,there was no statistical difference in impaired cognitive function among current smokers（HR=0.94,95%CI:0.89-1.01）and quitters（HR=0.97,95%CI:0.90-1.04）compared to never smokers;after adjusting for BMI,place of residence,whether or not they exercised and whether or not they drank alcohol based on model 1 After this,current smokers were less likely to have impaired cognitive function compared to never smokers（HR=0.93,95%CI:0.88-0.99）.In the fully adjusted model,current smokers were less likely to have impaired cognitive function compared to never smokers（HR=0.93,95%CI:0.88-0.99）.（3）The dose-response curve results from the restricted cubic spline model showed a non-linear dose-response relationship between duration of smoking and the risk of impaired cognitive function in older adults(P _non-linear<0.001).The risk of cognitive impairment decreased with increasing duration of smoking,increased after 45 years of smoking（OR=0.70,95%CI:0.57-0.87）and was not statistically significant after 56years of smoking（OR=0.80,95%CI:0.64-1.00）.（4）Stratified analysis showed that the association between smoking duration and cognitive impairment was not statistically significant.（4）Stratified analyses showed that current smoking was significantly associated with better cognitive function in older adults across age groups,BMI groups and gender.The results of the age-stratified analysis showed that smoking now was negatively associated with impaired cognitive function among older adults in the age range of 65-79 years compared to never smokers（HR=0.81,95%CI:0.71-0.92）,while quitters were not significantly associated with impaired cognitive function（HR=0.89,95%CI:0.76-1.05）.In the gender subgroup analysis,there were gender differences in the association between smoking status and impaired cognitive function,with no association found between current smoking（HR=0.93,95%CI:0.86-1.01）or smoking cessation（HR=0.96,95%CI:0.88-1.04）and impaired cognitive function in men.results for the BMI subgroup showed that in the normal weight group,compared to from non-smokers,there was a significant negative association between current smokers and impaired cognitive function（HR=0.90,95%CI:0.82-0.98）.In the group stratified according to ADL status,among participants with normal ADLs,there was a significant association between current smoking and impaired cognitive function compared to never smokers（HR=0.92,95%CI:0.86-0.98）and no significant association between quitters（HR=0.94,95%CI:0.87-1.01）and impaired cognitive function,which is consistent with our population-wide study results.Furthermore,after grouping according to drinking status,neither current smoking nor smoking cessation was significantly associated with impaired cognitive function in the drinking group,with risk ratios of（HR=0.96,95%CI:0.86-1.08）and（HR=0.92,95%CI:0.79-1.06）,respectively.（5）In the results of the association between PRS and impaired cognitive function,a significant positive association between PRS and impaired cognitive function was shown（OR=1.11,95%CI:1.08-1.13）;after dividing PRS into four groups according to quartiles,there was no significant association between PRS and impaired cognitive function in any of the Q₂ groups compared with the polygenic risk score in the Q₁ group,with OR and 95%CI were（OR=0.99,95%CI:0.86-1.16）;compared to the polygenic risk score in group Q₁,there was a significant association between PRS and impaired cognitive function in group Q₃,with an OR and 95%CI of（OR=1.17,95%CI:1.01-1.36）;compared to the polygenic risk score in group Q₁,there was a significant association between PRS and impaired cognitive function in group Q₄.There was a significant association between PRS and impaired cognitive function in the model,with an OR and 95%CI of（OR=1.67,95%CI:1.45-1.93）;this suggests that the risk of impaired cognitive function increases with increasing PRS in older people.Conclusions1.Current smoking is associated with better cognitive function in the elderly population,providing new and reliable evidence for the study,but we do not recommend smoking as a means of enhancing cognitive function.2.There was a non-linear dose-response relationship between duration of smoking and impaired cognitive function,with the risk of developing impaired cognitive function changing with duration of smoking.3.After stratified analysis,there was a significant association between smoking now and better cognitive function in older adults across age groups,gender,and BMI groups.In the stratified analysis by gender,smoking cessation was associated with a lower risk of cognitive impairment among women;in the age group 65-79 years,smoking now was associated with better cognitive function;and in the normal weight group,smoking now was associated with better cognitive function.4.Polygenic risk scores are risk factors for cognitive impairment and may predict the risk of developing cognitive impairment,which may provide a new direction for the diagnosis and screening of cognitive impairment.