Investigation Of Cognitive Function And Magnetic Resonance Imaging Of Brain Structural And Functional Changes In Aluminum Workers

Objective:1.Investigate the cognitive function of all workers on duty in a large aluminium factory in northern China,and explore their cognitive status and abnormal detection rate.2.Establish a large cohort of aluminium exposed wokers in China,explore the influencing factors affecting the decline of cognitive function of aluminium workers through nested case-control study,and evaluate the dose-response relationship between various influencing factors and cognitive decline and whether there is interaction between the influencing factors.3.Using multimodal magnetic resonance technology,analyze the differences in brain structure and function between the MCI case group and the control group,characterize the changes in the participant's brain structure and function,and analyze aluminum,cognitive decline,and the relationship between brain structure and functional indicators.The correlation further clarifies the neuroimaging mechanism of aluminum-induced cognitive decline.The aim was to find the key brain regions concerned in the early stage and to provide new ideas for preventing and delaying brain damage induced by chronic aluminum exposure.Methods:A cross-sectional study was conducted to survey all 1741 working workers in a large aluminum plant,employed in electrolytic workshop and non-electrolytic workshop in northern China,and their baseline data,including the general population information such as gender,age,education,smoking,drinking,job resume were collected.MMSE,CDT,DS,FOM,VFT and simple response time were used to assess the cognitive function,blood samples were collected,plasma aluminum was measured by ICP-MS method,and a cohort of aluminum workers was established.The cognitive function of the workers in the electrolytic workshop and the non-electrolytic workshop was compared.The detection rate of MCI was calculated.Subsequently,the baseline investigated population was followed for 3 years,and the follow-up content included general conditions such as illness,medication,and whether there were stressful events and re-evaluation of cognitive functions,excluding new cerebrovascular diseases,brain trauma,and new family members for those with AD,a participant with a score lower than one standard deviation of the whole population was defined as a case.Using the nested case-control method,106 cases were screened,and the corresponding control was matched from the cohort at a ratio of 1:2 according to the principle of age?2 years old.Risk factors of cognitive decline caused by aluminum were analyzed with multivariate analysis,furthermore,dose-response relationship between various influencing factors with cognitive decline and the interaction between each factor.were also analyzed.Finally,the population was followed up for 2 years.Based on the population of the second part,the Montreal Cognitive Assessment Beijing Version?MoCA?scale was performed to evaluate the subject's overall cognitive function again,30 cases and 30controls were selected.Then,a brain magnetic resonance scan was performed,including3D-T1 and BOLD.Excluding unqualified imaging data,30 of the case group and 26 of the control group were included in the structural magnetic resonance data analysis,and the morphological analysis was performed using the VBM method.The characteristics of the brain structure of the case group and the control group were compared,and the independent sample t test was used to compare the differences in brain gray matter volume between the two groups with education levels,smoking,and drinking as covariates.Correlation analysis was performed between whole brain gray matter volume and MoCA scale,aluminum age,plasma Al in case group.After unqualified imaging data were excluded,27 cases and 26 controls were included in the functional magnetic resonance data analysis.The analysis was performed using the?REST?V1.8 toolkit.Regional homogeneity?ReHo?and degree centrality?DC?were used as research indicators,using independent sample t-test to compare the brain areas of the differences between the two groups.In addition,the correlation between the MoCA scale,aluminum exposure working years,and plasma Al and the above functional indicators were analyzed to find the brain areas needing attention in the early stage.Results:1.Cross-sectional study?1?General demographic characteristics:According to occupational classification of aluminum exposure,the workers were divided into electrolytic workshop group and non-electrolytic workshop group.There were significant differences in age?Z=-14.193,P<0.001?,years of education?Z=-9.996,P<0.001?and aluminum exposure workingyears?Z=-39.424,P<0.001?between the two groups?P<0.05?.Compared with the non-electrolytic workshop group,the distribution of per capita monthly income??²=24.909,P<0.001?and marital status??²=44.505,P<0.001?in the electrolytic workshop group were statistically different?P<0.05?.Smoking??²=2.857,P=0.091?and drinking??²=3.081,P=0.079?showed no significant difference in distribution?P<0.05?.?2?After adjusting age,years of education,marriage,income,smoking,and drinking,the average scores of the MMSE,CDT,DS,FOM,and VFT scales in the electrolytic workshop workers were:27.66?0.13,2.57?0.07,11.25?0.16,24.24?0.23,and 36.15?0.65.The average scores of the above scales in non-electrolytic workshop workers were:28.36?0.12,3.02?0.07,12.08?0.15,24.72?0.26,and 38.38?0.59.Comparing between the two groups,the scores of the above scales in the electrolytic workshop group were lower than those in the non-electrolytic workshop group?P<0.05?.?3?The MMSE multi-dimensional scoring results showed that the electrolytic workshop group had lower cognitive domains in orientation,computing power,language ability,and visual space ability than the non-electrolytic workshop group?P<0.05?.The qualitative analysis results after the refinement of the CDT showed that the wrong pointer position?47.5%?was the main type of error,followed by numerical position errors?8.1%?,redundant pointers?7.6%?,missing numbers?6.7%?,and numbers.Superfluous?3.9%?,missing pointers?3.1%?,and disk drawing errors?2.2%?,a small number of workers experienced direct write time?0.5%?,number inversion?0.4%?,and pointer inversion errors?0.2%?.The error rates of the four types of errors:disk drawing error,digital position error,pointer position error,and redundant pointer difference were statistically significant between the two groups.The error rate in the electrolytic workshop group was higher than that in the non-electrolytic workshop group?P<0.05?.DS order and reverse order score were compared between the two groups,and the differences were statistically significant?P<0.05?.After the refinement of the FOM scale,except that there was no difference between the two groups of repeated extraction,the total storage and total extraction scores of the electrolytic workshop group were lower than those of the non-electrolytic workshop group,and the invalid reminder was that the electrolytic workshop group was higher than the non-electrolytic workshop group There was a statistically significant difference between the two groups?P<0.05?.There was no significant difference between the two groups in the fastest response time,the slowest response time and the average response time in the simple response?P>0.05?.?4?For aluminum factory workers,the detection rates of MMSE,CDT,DS,FOM and VFT were 12%,26.6%,14.5%,14.0%and 14.9%,respectively.The abnormal rate of the electrolytic workshop group of all scales was higher than that of the non-electrolytic workshop group,and the abnormal rate was significantly different?P<0.05?.2.Nested case-control study?1?In the cohort,the plasma aluminum concentration was positively skewed,with a median of 23.02?g/L.The median plasma aluminum concentration in the electrolytic workshop group was 29.30?g/L,and in the non-electrolytic workshop group was 20.10?g/L.The difference between the two groups was statistically significant?Z=-5.989,P<0.001?.The plasma aluminum concentration of the electrolytic workshop group was higher than that of the non-electrolytic workshop group,and the plasma aluminum concentration of the non-electrolytic workshop group was higher than that of the general population.?2?General demographic data,there was no significant difference in the number of years of education between the case group and the control group?Z=-0.939,P=0.347??P>0.05?.The difference of plasma aluminum concentration was statistically significant?Z=-2.998,P=0.003?.The median plasma aluminum concentration in the case group was higher than that in the control group.The proportion of high plasma aluminum concentration?Q4?in the case group??²=15.171,P=0.002?was also significantly higher than that in the control group.There were no significant differences in the distribution of education??²=0.933,P=0.817?,per capita monthly income??²=0.000,P=1.000?,and marital status??²=0.033,P=0.856?among the two groups?P>0.05?.Compared with the control group?32.1%?,the alcohol consumption rate in the case group?41.5%?was not significantly different??²=2.757,P=0.097??P>0.05?.The distribution of smoking??²=8.591,P=0.003?was significantly different between the two groups?P<0.05?.The smoking rate in the case group?72.6%?was higher than that in the control group?55.7%?.?3?Multi-factor conditional logistic regression analysis showed that the factors affecting the cognitive function of workers in aluminum factories were:smoking and plasma aluminum levels.The risk of cognitive decline in smokers was 2.14 times that of non-smokers?OR=2.14,95%CI:1.22 to 3.78?.The risk of cognitive decline in the fourth quantile of plasma aluminum was 2.29 times higher than those in the first quantile of plasma aluminum?OR=3.29,95%CI:1.59,6.84?.There was a positive dose-response relationship between plasma aluminum concentration and the risk of cognitive decline(P_trend<0.001).?4?After adjusting for variables such as marriage,income,education,drinking,and plasma aluminum,compared with non-smokers,there was a dose-response relationship between cigarete number,smoking years,smoking pack years,smoking index,and cognitive decline.As smoking increases,the risk of cognitive decline can increase.(cigarete number:P_trend=0.009,Number of years of smoking:P_trend=0.012,Number of years of smoking pack:P_trend=0.043,Smoking index:P_trend=0.037).3.Multimodal magnetic resonance research?1?General demographic data,the average age of the case group was 46.88?5.37years and the control group was 48.56?4.31 years,the average duration of education in the case group was 11.50?1.94 years,and in the control group was 11.40?1.99 years.Age?Z=-0.123,P=0.902?,education duration?Z=-1.264,P=0.206?,smoking??²=0.278,P=0.598?and drinking??²=0.075,P=0.785?were not statistically different in the two group?P>0.05?.The average year of aluminum exposure in the case group was11.79?7.03 years,and the plasma aluminum concentration in the case group was 42.35?16.37,65.22??g/L,which was significantly higher than that in the control group.The average MoCA score of the case group was 18.83?2.44,which was significantly lower than the control group?Z=-6.681,P<0.001?.?2?Structural magnetic resonance results:The gray matter volume of right anterior gyrus,middle frontal gyrus,and left caudate nucleus were decreased in the case group compared to the control group.When the activity level of the brain region satisfied the threshold P<0.001 and k>568 voxels at the voxel level,Alphasim correction P<0.05 at the cluster level was satisfied,and there were significant differences between groups.Correlation analysis in the case group found that the relative gray matter volume of the left upper frontal gyrus and the left anterior wedge area was positively correlated with the total score of the MoCA cognitive assessment scale?r=0.763,P<0.001;r=0.381,P<0.05?,no significant effect was found in negative correlation.We did not find the correlation between the gray matter volume of the case group and the aluminum working year and plasma Al concentration.?3?Resting state functional magnetic resonance results:When the activity level of the brain region satisfied the threshold P<0.001 and k>10 voxels at the voxel level,we did not find any difference in the ReHo between the case group and the control group.In the case group,bivariate correlation analysis found that the ReHo values of the right upper marginal gyrus,left upper frontal gyrus,bilateral top parietal lobes,and right midfrontal gyrus were positively correlated with MoCA total score?r=0.443,P<0.05;r=0.649,P<0.001;r=0.664,P<0.001;r=0.460,P<0.05;r=0.491,P<0.05?;ReHo values of the right thalamus and left frontal gyrus were negatively correlated with the total MoCA score?r=-0.414,P<0.05;r=-0.504,P=0.01?.ReHo values of bilateral superior temporal gyrus,superior parietal lobe,and central posterior gyrus were positively correlated with aluminum age?r=0.735,P<0.001;r=0.720,P<0.001;r=0.614,P=0.001;r=0.680,P<0.001?.ReHo values of the left superior temporal gyrus and right hippocampus were positively correlated with plasma aluminum?r=0.418,P<0.05;r=0.630,P=0.001?.There were differences in DC values in some brain regions between the two groups?P<0.001 and k>10?.In the case group,the DC values of the left superior frontal gyrus,middle temporal gyrus,Rolandic island cap and cerebral island were significantly lower than those of the control group,and the DC values of the left anterior cingulate gyrus and Cuneus lobe were higher than those of the control group.Bivariate correlation analysis found that the DC value of the left temporal pole and left anterior cingulate gyrus was negatively correlated with the MoCA scale?r=-0.608,P=0.001;r=-0.477,P=0.016?.We did not find a significant effect of gray DC value and aluminum working age in the case group.The left posterior cingulate cortex was negatively correlated with plasma aluminum concentration?r=-0.638,P=0.001?.Conclusions:1.The cognitive function of aluminum workers in electrolytic workshops was lower than that in non-electrolytic workshop workers.It was manifested in the decline of multiple cognitive domains of orientation,computing,memory,language ability and visual space execution ability.The visual space execution ability damage was obvious and cannot be ignored.The detection rate of mild cognitive dysfunction among aluminum workers was high,especially in electrolytic workshop workers2.Plasma aluminum levels of workers in aluminum plants were higher than in the general population,and the rise in workers in electrolytic workshops was even more pronounced.Long-term aluminum exposure can cause cognitive decline in workers.Smoking was another risk factor for cognitive decline in aluminum workers.Quit smoking should be actively advocated among this group.3.Cognitive decline in brain gray matter volume and resting state functional connectivity were abnormal in aluminum workers.It is suggested that the disease may be in a state of disconnection in the early stage,which is the change of overall properties.The DC of left cingulate gyrus was abnormal,which was related to the cognitive function scale and plasma aluminum concentration,may play an important role in the decline of workers'cognitive function caused by aluminum exposure,which can be one of the future concerns.4.Magnetic resonance imaging is expected to be a powerful tool for early detection of cognitive dysfunction in aluminum workers.