| BackgroundChinese population aging trend is more and more obvious.According to the data of National Bureau of Statistics in 2018,there are about 170 million people over 65 years old in China,accounting for 11.9% of the total population.Under the assumption of medium or low mortality,the number of people aged 65 and above will rise to 3.37-4 million in 2050,accounting for 23.9%-26.9%of the total population.At present and in the near future,China will face important social,public health and clinical medical problems caused by population aging.For example,the number of patients with Alzheimer’s disease and mild cognitive impairment has reached 5.9 million(5.1%)and 23.9 million(20.8%)respectively,The decline of cognitive function associated with aging and the increase of dementia cases will be a major public health challenge in China.Manganese(Mn)is an important trace element for human health.It is the component and activator of RNA polymerase,superoxide dismutase(SOD)and other enzymes.However,high concentration of manganese intake will lead to manganese poisoning and cause harm to human health.Excessive manganese can damage cognitive function,affect neurobehavioral function in the early stage,and further develop into Parkinson’s disease.Mild cognitive impairment(MCI)is a transitional state between normal aging and early Alzheimer’s disease(AD).It is considered to be a preclinical syndrome of AD.It is suggested that MCI may be related to high level manganese exposure.High concentration of manganese exposure will affect the hippocampal formation and affect the homeostasis of copper,which will lead to degeneration of nerve cells and increase the risk of cognitive impairment.Therefore,exploring the relationship between manganese and cognitive function of the elderly is of great significance for improving the quality of life of the elderly and realizing healthy aging.ObjectiveObjective to explore the relationship between different blood manganese exposure levels and cognitive impairment in longevity areas of China,and the sensitivity between manganese exposure levels and cognitive impairment in different ages(65～79,80～89,90～99 and over 100 years old).Objective to explore the mediating effect of oxidative stress or lipid metabolism on cognitive impairment induced by manganese.MethodsBased on the cross-sectional survey data of 8 longevity areas in Chinese Longitudinal Health Longevity Survey(CLHLS)from 2017 to 2018,a total of 2423 elderly people aged 65 and above were included in this study.The data collection includes three parts:questionnaire survey to collect the general demographic characteristics of the respondents,such as age,gender,education level,marital status,body measurement to collect height,weight,blood pressure,waist circumference,blood biochemical test to collect SOD,malondialdehyde(MDA),triglyceride(TG)and plasma cholesterol(CHO).The mini mental state examination(MMSE)was used to evaluate the cognitive function of the elderly.Two ways were adopted.One was to judge whether the cognitive function was impaired based on the MMSE score of the international general cognitive function scale.The total score was 30.The cognitive function was impaired if the MMSE score was less than 24,and normal if the MMSE score was more than 24;The other is divided according to the level of education,the uneducated group≤19 points,the group with 1-6 years of education≤22 points,the group with more than 6 years of education≤26 points,otherwise it is defined as normal cognition.Fasting venous blood was collected and the blood manganese level was detected by inductively coupled plasma mass spectrometry(ICP-MS).According to the quartile of blood manganese exposure level of the elderly,they were divided into four groups,which were Q1 group(<8.69μg/L),Q2 group(8.69～10.71μg/L),Q3 group(10.71～13.39μg/L)and Q4 group(≥13.39μg/L)。EpiData was used to input data,and SAS 9.4 software was used for data cleaning and statistical analysis.Wilcoxon rank sum test was used to compare the differences of blood manganese levels between different genders and subjects with different cognitive scores;Kruskal-Wallis H test was used to compare the differences of blood manganese levels in different age groups.Chi square test(for categorical variables)was used to compare the differences of general demographic characteristics,lifestyle and prevalence of chronic diseases between normal cognitive function group and cognitive impairment group.The dummy variables were set,and all subjects were grouped according to the quartile of blood manganese exposure level.The lowest quartile array(Q1)was used as the reference group.The odds ratio(or)and 95%confidence intervals(CI)of the high score group(Q2,Q3 and Q4)relative to the lowest quartile array were calculated.Multiple logistic regression model was used to adjust different confounding factors to explore the relationship between blood manganese exposure and cognitive impairment.The model 1 of multivariate logistic regression model is single factor analysis,and it is not included in covariate;Model 2 further adjusted the age based on Model 1;Model 3 further adjusted the factors of gender,urban and rural,education,marital status,smoking,drinking,eating nuts,ADL disability,hypertension,diabetes,stroke or cardiovascular disease and central obesity.Finally,the relationship between manganese exposure and cognitive impairment was studied in different age groups by using multivariate logistic regression model 1,model 2 and model 3.The correlation coefficient of Mn exposure,SOD,MDA,TG and CHO was analyzed by SAS 9.4 software.The mediating effects of SOD,MDA,TG and CHO were analyzed by using process 3.2 by Andrew F.Hayes plug-in to test the mediating effects of SOD,MDA,TG and CHO.The difference was statistically significant with P<0.05 by bilateral test.Results1.Basic information of the subjects:a total of 2423 elderly people aged 65 and above,of which the average age of the subjects was 84.5±11.4.There were 911,620,523 and 369 elderly people aged 11.4 years,65～79 years,80～89 years,90～99 years and 100 years and above,accounting for 37.60%,25.59%,21.58%and 15.23%respectively.There are 1155 males,accounting for 47.67%,and 1268 females,accounting for 52.33%.The proportion of the elderly without education was 52.99%,the smoking rate was 17.41%,the drinking rate was 17.39%,and the ADL disability rate was 17.95%;36.4%of the elderly suffered from hypertension;5.06%of the elderly had diabetes;7.01%of the elderly suffered from stroke or cardiovascular disease;36.36%of the elderly suffered from central obesity.2.Blood manganese level:the geometric mean of blood manganese level in male and female was 10.03μg/L and 11.06μg/L.The geometric mean of blood manganese levels in 65～79 years old,80～89 years old,90～99 years old and 100 years old and above were 10.25μg/L,10.51μg/L,10.60μg/L and 11.36μg/L.The difference was statistically significant.3.Cognitive function:in 2423 subjects,the average score of MMSE was 23.9,of which the female was 21.8,lower than the male 26.2.The average MMSE scores of the elderly aged 65～79,80～89,90～99,100 and above were 28.4,25.7,20,8 and 14.3 respectively.A total of 673 cases of cognitive impairment occurred in the elderly,the prevalence rate was 27.78%,of which 73.11% was female,higher than 26.89% in male.4.Relationship between blood manganese exposure level and cognitive function:according to MMSE score<24,the prevalence of cognitive impairment in group Q1,Q2,Q3 and Q4 was 21.9%(132/603),27.2%(165/607),31.8%(193/607)and 30.2%(183/606),respectively,with significant difference(P<0.05).After adjusting for confounding factors in multivariate logistic regression model,compared with group Q1,the risk of cognitive impairment increased in group Q3,with or(95%CI)of 1.46(1.04～2.05);Compared with group the risk of cognitive impairment increased in group Q,and Q4,with or(95%CI)of 3.61(1.22～10.69)and 3.10(1.06～9.05),respectively;Compared with group Q1,the risk of cognitive impairment was increased in group Q3,with or(95%CI)of 2.41(1.06～5.48).5.The mediating effect of oxidative stress or lipid metabolism on cognitive impairment caused by manganese:there was no significant difference in SOD and MDA between blood manganese exposure level and cognitive function;TG was a partial mediating effect between blood manganese exposure and cognitive function,and the mediating effect accounted for 2.5%of the total effect;The absolute value of the ratio of indirect effect to direct effect was |ab/c ’|=6.9%;ConclusionThis study is the first exploration on the relationship between blood manganese exposure level and cognitive impairment of the elderly aged 65 and above in eight longevity areas of China.In longevity areas of China,there are differences in blood manganese exposure level among different genders and ages.The blood manganese exposure level of women is higher than that of men,and that of the elderly is higher than that of the young.After adjusting for potential confounding factors,there was a correlation between blood manganese exposure and cognitive impairment.Among them,65～79 years old and 100 years old and above are more susceptible to high blood manganese,which may increase the risk of cognitive impairment.TG may mediate the relationship between blood manganese exposure and cognitive function.The results of this study suggest that blood manganese exposure may increase the risk of cognitive impairment in the elderly in China,but further validation of prospective cohort studies is needed. |
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