In October 2014,we conducted a community population-based cohort study on cognitive impairment in two villages in Huyi district of Xi'an.All the village residents aged 40 years and above received a face-to-face questionnaire survey and were followed up every two years for cognitive changes.In this special issue,we used this cohort data to explore the relationships between vascular risk factors and cognitive impairment,investigated the predictive value of plasma biomarkers for cognitive impairment,and the effects of vascular risk factors intervention on cognitive impairment.We believe these are important for comprehensively understanding the risk factors for cognitive impairment and guiding its prevention and treatment.

Objective To explore the relationship between blood pressure at baseline and significant decline in cognitive function after 4 years in middle-aged and elderly people in rural Xi'an,and the potential effect of age on the relationship.Methods Data were collected from a cohort of middle-aged and elderly people with cognitive impairment in rural Xi'an,Shaanxi Province.The cohort consisted of people aged≥40 years from a village in Huyi District,Xi'an.The baseline survey was completed between October 2014 and March 2015,and two follow-up visits were conducted in 2016 and 2018.Blood pressure parameters studied included hypertension and high systolic blood pressure(≥140 mmHg vs.＜140 mmHg),and high diastolic blood pressure(≥90 mmHg vs.＜90 mmHg).The Mini-Mental State Examination(MMSE)was used to assess the whole cognitive function,and the decline of MMSE score ≥4 points in 4 years was defined as significant decline of cognitive function.Multivariate Logistic regression was used to analyze the relationship between blood pressure and cognitive function at baseline.Subgroup analysis was used to study the effect of age(＜65 vs.≥65 years)on the relationship.Results We recruited a total of 1 350 subjects in the analysis,including 235 subjects(17.4％)with baseline age ≥65 years and 533 male subjects(39.5％);671 subjects(49.7％)had hypertension,with systolic blood pressure of(131.71±17.79)mmHg;840 subjects(62.2％)had high systolic blood pressure,with diastolic blood pressure of(82.18±10.56)mmHg;395(29.3％)had high diastolic blood pressure.During the 4-year follow-up,56 cases(4.2％)met the criteria for significant decline of cognitive function.We did not find significant association of hypertension and high systolic blood pressure with cognitive decline in the general population,＜65-year-old subgroup,or ≥ 65-year-old subgroup.The incidence of significant cognitive decline was not statistically significant in the total population(3.6％vs.5.6％,P=0.092),the ≥65-year-old subgroup(7.5％vs.8.2％,P=0.855),the normal diastolic blood pressure group,or the high diastolic blood pressure group.However,in the subgroup＜65 years,the incidence of cognitive decline was higher in the high diastolic blood pressure group than in the normal diastolic blood pressure group(2.7％vs.5.1％,P=0.043).Multivariate analysis showed that high diastolic blood pressure was not found to be associated with significant cognitive decline in the total population(OR=1.744,95％CI:0.953-3.192,P=0.071),the subgroup of ≥65 years old(OR=0.858,95％CI:0.221-3.338,P=0.825),or the subgroup of ≥65 years old.In the＜65 age group,high diastolic blood pressure was significantly associated with cognitive decline(OR=2.051,95％CI:1.005-4.186,P=0.048).Conclusion High diastolic blood pressure is associated with 4-year cognitive decline in people aged 40-65 years,but not in those aged ≥65.No association is found between hypertension or high systolic blood pressure and significant cognitive decline.

Objective By comparing the prevalence and mortality of dementia among rural people in Xi'an in 1997 and 2014 to clarify the epidemiological changes of dementia among rural people in the city over 17 years.Methods In 1997 and 2014,people aged 55 and above in villages in Xi'an were selected by random cluster sampling method,and face-to-face questionnaire survey was conducted by combining centralized and home visits.Dementia and its subtypes were diagnosed by"the three-step method";the changes of dementia prevalence and mortality were compared between the two surveys.Results The prevalence of dementia among rural residents aged 55 and above in Xi'an was 3.49％in 1997,with age-gender standardized prevalence of 2.08％.In 2014,the prevalence of dementia was 4.25％,with age-gender standardized prevalence of 2.78％.Over the 17 years,the prevalence of dementia increased by 1.79 times(OR=1.79,95％CI:1.20-2.65,P=0.004),with a 1.9-fold increase in females and a 1.67-fold increase in males.The mortality of dementia patients was 61.76‰ and age-gender standardized mortality was 60.20‰ in 1997,while the mortality was 35.71‰ and age-gender standardized mortality was 34.18‰ in 2014.The mortality of dementia decreased by 33％over the 17 years(HR=0.33,95％CI:0.15-0.74,P=0.007).Conclusion The prevalence of dementia in rural areas of Xi'an increased significantly over the 17 years,but the mortality rate decreased,and this trend was more obvious in women.

Objective To investigate the relationship between baseline serum lipid levels and cognitive decline after a 4-year follow-up in a cohort of middle-aged and elderly people in rural Xi'an.Methods The data were collected from the cognitive impairment cohort of middle-aged and elderly people in rural areas of Xi'an,Shaanxi Province.The cohort selected the population ≥40 years old in two villages of Huyi District,Xi'an,as the research subjects.The baseline survey was completed from October 2014 to March 2015,and two follow-up visits were conducted in 2016 and 2018.The Mini-Mental State Examination(MMSE)was applied to assess the overall cognitive function.The MMSE score dropping between the 2014 and 2018(△MMSE)≥2 points were defined as cognitive decline.Baseline lipid levels[total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-c),low-density lipoprotein cholesterol(LDL-c)]were converted into three classification data based on 25％quantile and 75％quantile[Q1(≤25％)vs.Q2-Q3(25％-75％)vs.Q4(≥75％)],and using the Q2-Q3 group as the reference group.The relationship between serum lipid levels and cognitive decline at baseline was analyzed by multivariate Logistic regression.Interaction effect analysis and subgroup analysis were made to investigate the interaction effect of age(＜65 years vs.≥65 years)on the relationship between serum lipid and cognitive decline.Results There were 1 349 participants with complete baseline data,and 235(17.42％)were ≥65 years old at baseline;230 cases(17.05％)had cognitive decline.No significant association was found between TC,TG,LDL-c,HDL-c and cognitive decline in subgroups＜65 years of age.In the subgroup ≥65 years of age,the Q1(≤4.37 mmol/L)group of TC was not significantly associated with the risk of cognitive decline compared with the Q2-Q3(4.37-5.61 mmol/L)group of TC,but the Q,(≥5.61 mmol/L)group of TC was significantly associated withan increased risk of cognitive decline(OR=2.519,95％CI:1.217-5.214,P=0.013).Age had an interactive effect on the relationship between the Q4 group of TC and cognitive decline(OR=2.202,95％CI:1.111-4.363,P=0.024).Compared with the Q2-Q3(1.03-2.01 mmol/L)group of TG,the Q,(≤ 1.03 mmol/L)group of TG was associated with a lower risk of cognitive decline(OR=0.318,95％CI:0.120-0.838,P=0.020).Age had an interactive effect on the relationship between the Q1 group of TG and cognitive decline(OR=0.344,95％CI:0.132-0.896,P=0.029).However,there was no significant correlation between the Q4(≥2.01 mmol/L)group of TG and the risk of cognitive decline.Compared with the Q2-Q3(2.70-3.81 mmol/L)group of LDL-c,the Q1(≤ 2.70 mmol/L)group of LDL-c was not significantly associated with the risk of cognitive decline,but the Q4(≥3.81 mmol/L)group of LDL-c had significant association with an increased risk of cognitive decline(OR=2.367,95％CI:1.143-4.900,P=0.020).Age had an interactive effect on the relationship between the Q4 group of LDL-c and cognitive decline(OR=2.237,95％CI:1.134-4.415,P=0.020).No significant association was found between HDL-c and cognitive decline.Conclusion No significant association was found between HDL-c and cognitive decline at baseline.The relationship of TC,TG and LDL-c with cognitive decline was affected by age.Only in participants over 65 years old,the risk of cognitive decline was higher in those with high baseline levels of TC and LDL-c.Those with low baseline serum TG levels had a lower risk of cognitive decline.

Objective To investigate the relationship between type 2 diabetes mellitus(T2DM)and cognitive decline.Methods Data were obtained from the cognitive impairment cohort of middle-aged and elderly population in rural areas of Xi'an City.The cohort consisted of residents aged 40 years and older in two villages of Huyi District,Xi'an.The baseline survey was completed between October 2014 and March 2015,with two follow-up visits in 2016 and 2018.The present study was conducted on cognitively normal people at baseline.Individual characteristics,lifestyle,and medical history were collected;physical and biochemical examinations were completed.According to medical history of T2DM and fasting blood glucose,the study population was divided into non-T2DM group,pre-existing T2DM group,and new-onset T2DM group.The Mini-Mental State Examination(MMSE)was used to assess global cognitive function.Participants with a drop of≥2 points in MMSE score from baseline after 4 years were defined as having cognitive decline.Chi-square test and multivariate Logistic regression analysis were employed to analyze the effect of T2DM status on the risk of cognitive decline.Results A total of 1 350 subjects completed the follow-up.In the follow-up population,1 096(81.2％)were free of T2DM,158(11.7％)already had T2DM at baseline,and 96(7.1％)developed new-onset T2DM during the follow-up.Cognitive decline was observed in 230 individuals after 4 years,representing 17.0％of the study population.The new-onset T2DM group had the highest 4-year incidence of cognitive decline(non-T2DM group vs.pre-existing T2DM group vs.new-onset T2DM group:15.7％vs.20.9％vs.26.0％,P=0.014),and the incidence of cognitive decline in the newly-onset T2DM group was significantly higher than that in the non-T2DM group(P=0.009).Multivariate Logistic regression analysis showed that the new-onset T2DM group had an increased risk of cognitive decline compared with the non-T2DM group within 4 years(OR=1.726,95％CI:1.029-2.896,P=0.039).However,no significant difference in 4-year risk of cognitive decline in the pre-existing T2DM group was observed(OR=1.402,95％CI:0.890-2.210,P=0.145).Conclusion Through the 4-year follow-up study of cognitively normal adults aged 40 and above in rural Xi'an,it was found that new-onset T2DM patients face a significantly elevated risk of cognitive decline,suggesting that cognitive decline may occur in the early stage of T2DM.

Objective To explore the relationship between plasma amyloid-β(Aβ)and cognitive impairment.Methods A total of all villagers(aged 40 years and above)from two villages of Xi'an,China,were enrolled.A validated Chinese version of the Mini-Mental State Examination and neuropsychological battery were used to assess cognition.Levels of fasting plasma Aβ1-42 and Aβ1-40 were tested using commercial enzyme-linked immunosorbent assay(ELISA).Relationship between plasma Aβ and cognitive impairment was analyzed using Logistic regression analysis.Results Of the 1 314 enrolled subjects,1 180(89.80％)had normal cognition,85(6.47％)had suspected cognitive impairment,and 49(3.73％)had probable cognitive impairment.Univariate analysis showed that plasma Aβ1-42/Aβ1-40 ratio was higher in the suspected cognitive impairment group than in the probable cognitive impairment group(P＜0.05)and normal cognitive group(P＜0.05);plasma Aβ1-42 level in the suspected cognitive impairment group was higher than that in normal cognitive group(P＜0.05).The level of Aβ1-40 did not differ between the three groups.After correcting for confounding factors(including age,gender,degree of education,cognitive impairment risk factors,habits of living)in the multivariate Logistic regression analysis,the results were consistent with those in the univariate analysis.Conclusion Levels of plasma Aβ1-42 and Aβ1-42/Aβ1-40 ratio were elevated in patients with suspected cognitive impairment,indicating that elevated plasma Aβ1-42 and Aβ1-42/Aβ1-40 ratio may be more pronounced in early stage of cognitive impairment.They may be early biomarkers for cognitive impairment,which can help identify and intervene the disease earlier.

Objective To investigate the relationship between plasma homocysteine(Hcy)levels and cognitive impairment(CI).Methods From November 2018 to January 2019,baseline data and cognitive function were collected from the participants aged≥40 years who lived in two villages in Huyi District,Xi'an,China.Their global cognitive function was assessed by Mini-Mental State Examination(MMSE)and the diagnosis of cognitive impairment was based on international guidelines.Fasting blood was collected in the morning,and plasma Hcy level was measured by the chemiluminometric assay.Multivariate Logistic regression analysis,subgroup analysis,and interaction analysis were performed to investigate the relationship between plasma Hcy and CI.Results A total of 1 805 subjects were included in the analysis.There were 1 056 females(58.5％),age ranged from 40 to 88 years[mean(58.99±9.52)years],and 145 participants(8.0％)were diagnosed as CI.The median plasma Hcy level in the overall population was 14.1(11.6,17.8)μmol/L.There were 729(40.4％)subjects in the HHcy group(＞15.0 μmol/L)and 1 076(59.6％)in the normal group(≤15.0 μmol/L).Univariate analysis showed that the prevalence of CI was higher in the HHcy group than in the normal Hcy group(11.4％vs.5.8％,P＜0.001).In multivariable Logistic regression fully adjusted for potential confounders,each 1 μmol/L increase in plasma Hcy level was associated with a 3.0％increased risk of CI(OR=1.030,95％CI:1.012-1.048,P=0.001).Interaction analysis indicated that sex,age,BMI,systolic blood pressure,history of stroke,and diabetes did not significantly modify this association.Conclusion Elevated plasma Hcy levels are associated with an increased risk of CI in people aged≥40 years.This indicates that HHcy may be a risk factor for CI.

Objective To study the age-dependent relationship between body mass index(BMI)and cognitive impairment in rural population aged 40 years and above.Methods From October 2014 to March 2015,people aged 40 years and above,who lived in two natural villages in Huyi District of Xi'an,were selected as the research subjects.Their general demographic information,lifestyle,medical history,family history,physical examination,and biochemical examination were collected.Mini-Mental State Examination(MMSE)was used to evaluate global cognitive function.Cognitive impairment was defined as an MMSE score lower than the cutoff value,specifically,scores ≤17 for subjects who were illiterate,scores ≤20 for subjects with primary school education,and scores ≤24 for subjects with junior high school education or above.The age-dependent relationship between BMI and cognitive impairment was discussed using stratified analysis,restricted cubic spline(RCS),and multivariate Logistic regression.Results We included a total of 1 792 subjects in the analysis,of whom 230(12.8％)were diagnosed with cognitive impairment.There were 726 males(40.5％);the average age was(55.53±9.92)years,ranging from 40 to 85 years,1 193 subjects aged 40-59 years(66.6％),and 599 subjects aged ≥60 years(33.4％).The average BMI was(25.29±3.14)kg/m2.In the total population,BMI index was fitted as restricted cubic splines in the Logistic regression model,and other confounding factors were corrected.The results showed that BMI index was significantly correlated with cognitive impairment(Poverall=0.023),and there was a trend of nonlinear relationship(P nonlinear=0.097).The specific relationship was that with BMI=25 kg/m2 as the reference(OR=1),when BMI index was＜25 kg/m2,the OR value increased as BMI index decreased.However,when BMI index was ≥25 kg/m2,the OR value did not change significantly as BMI index increased.The population was divided into two subgroups according to age(40-59 years vs.≥60 years).Stratified analysis showed that in the ≥60 years old subgroup,cognitive impairment had significant correlation with BMI index(Poverall=0.038,Pnonlinear=0.097),and the changing trend of the correlation was similar to that of the overall population.By contrast,in the 40-59 years old subgroup,BMI index was not significantly associated with cognitive impairment(Poverall=0.722,Pnonlinear=0.738).Conclusion The relationship between BMI and cognitive impairment is affected by age.No significant association is found in the middle-aged population of 40-59 years old,but there may be a nonlinear association in the elderly population over 60 years old.Specifically,with BMI=25 kg/m2 as the boundary,as BMI decreases,the risk of cognitive impairment gradually increases.As BMI further increases,the risk of cognitive impairment does not change significantly even though it reaches the obesity level.

Objective This study examined the association between smoking and cognitive decline through a cohort in rural population in Xi'an.Methods Data were collected from the cognitive impairment cohort of middle-aged and elderly people in rural areas of Xi'an.The cohort selected the population aged 40 years and above in rural Xi'an.The baseline survey was completed between October 2014 and March 2015,and two follow-up visits were conducted in 2016 and 2018.This study took the baseline cognitively normal population of this cohort as the research subjects.According to the survey results in 2018,the population was divided into three groups according to smoking status:smoking,quitting and non-smoking.Cognitive function was assessed by Mini-Mental State Examination(MMSE).△MMSE(2014 rating-2018 rating)≥2 was defined as cognitive decline,and △MMSE＜2 was defined as cognitive stability.Binary Logistic regression model and stratified analysis were used to analyze the relationship between smoking and cognitive decline and the influence of age on the relationship.Results A total of 1 289 subjects were included in this study.According to smoking status in 2018,they were divided into non-smokers(910,70.6％),smokers(335,26.0％),and ex-smokers(44,3.4％).In the total population,there was no significant difference in the incidence of cognitive decline among non-smokers,smokers and ex-smokers(17.3％vs.16.1％vs.15.9％,P=0.880).When stratified by age,there was no significant difference in the incidence of cognitive decline among the three groups in the subgroup of age＜65 years(16.5％vs.13.2％vs.12.1％,P=0.365).In the subgroup of age≥65 years,no significant difference was found in the incidence of cognitive decline among non-smokers,smokers and ex-smokers(20.8％vs.30.9％vs.27.3％,P=0.306).After adjusting for confounding factors,smokers had a significantly higher risk of cognitive decline than non-smokers(OR=14.139;95％CI:1.541-129.705;P=0.019).There was a trend of cognitive decline in the ex-smokers group,but with no statistical significance(OR=8.252;95％CI:0.630-108.175;P=0.108).Conclusion Smoking is positively associated with cognitive decline in the elderly,suggesting that smoking may accelerate cognitive decline in this population.

Objective To investigate the effect of lifestyle on cognitive decline in rural people aged 40 years and older in Xi'an.Methods This was a prospective cohort study.People aged 40 years and older in two villages in Huyi District were selected as the study population.They completed the baseline survey from October 2014 to March 2015 as well as two follow-up visits in 2016 and 2018,respectively.A comprehensive score of lifestyle was calculated based on factors including smoking,drinking,exercise,and diet collected at the baseline.The Mini-Mental State Examination(MMSE)was used to evaluate global cognitive function at both baseline and follow-up;a≥4-point decrease in MMSE score from the baseline was defined as marked cognitive decline.Multivariable Logistic regression,propensity score correction,and propensity score matching were used to investigate the relationship between lifestyle and cognitive decline.Results A total of 1 348 participants were ultimately enrolled and 56(4.2％)of them met the criteria for marked cognitive decline(△MMSE≥4-points).Among them,386(28.6％)people had smoking history,184(13.6％)were drinkers,214(15.9％)lacked physical activity,and 400(29.7％)ate a diet high in oil and salt.Generally,304(22.6％)met the definition of the unhealthy lifestyle(comprehensive score＜6),which means more than one of the four subscales was unhealthy or more than two were relatively unhealthy.Multivariable Logistic regression analysis showed that unhealthy lifestyle was positively associated with marked cognitive decline(OR=2.838,95％CI:1.302-5.525,P=0.005).Propensity-score adjusted model yielded very similar results(OR=2.786,95％CI:1.371-5.661,P=0.005).Propensity score matching was performed to further balance the differences in covariates between the two groups.Multivariate Logistic regression analysis conducted in the matched population revealed that the risk of marked cognitive decline was still higher in those with unhealthy lifestyle(OR=3.994,95％CI:1.582-12.176,P=0.006).Conclusion Unhealthy lifestyle is associated with an increased risk of cognitive decline in cognitively normal people aged 40 years and older.