The Effect Of APOE Risk Gene And Gender Difference On Brain Structural Basis Related Spatial Navigation Ability

Part 1 Gender Differences on the Correlation between Spatial Navigation ability and Hippocampal subfields' volumePurpose:Spatial navigation skill,which is an essential living ability that encompasses a number of complex cognitive and perceptual processes,is correlated with hippocampal volumetry changes.Influence of gender difference on spatial navigation have been widely reported by previous researches.However,the role of brain structural changes in such influence remain unclear.The aim of this study is to investigate the influence of gender differences on healthy young adults' spatial navigation abilities,and to investigate the correlation of such influence with the volumetry changes of hippocampal and hippocampal subfields.Materials and methods:Through the volunteer recruitment process,63 normal young volunteers?male:33,age:24.0± 1.27;female:30,age:23.9 ± 1.95?were included in this study.All participants underwent the spatial navigation test and head magnetic resonance examination.The spatial navigation tests,which include a battery of mixed navigation test,allocentric navigation test,egocentric navigation test and delayed navigation test,were performed using a PC version of Hidden Goal Task?HGT?,which is a human virtual analogue of the Morris Water Maze.A three-dimensional turbo fast echo?3D-TFE?T1 weighted imaging sequence was performed for structural imaging acquisition.The volume of the bilateral hippocampus were obtained by FreeSurfer?5.3.0?software,which further segmented the hippocampus into following subfields:CA1,CA2₃,CA4_DG,subiculum,presubiculum,hippocampal fissure,and the undividable remaining part of hippocampal tail?labeled as hippocampus?.All subjects were divided into two groups by gender.Two-sample t-test were used to examine the differences of demography and spatial navigation abilities between the groups.Pearson's Correlation Test and partial correlation test were performed to investigate the correlation between the spatial navigation ability and the hippocampal volumetry changes.Results:Mixed spatial navigation ability decreased in male subjects in comparison with that of female participants?male:28.69 ± 16.59;female;22.33 ± 6.27;p=0.047?.No significant differences of allocentric and egocentric navigation were found between the groups.Changes of spatial navigation performances were found to be correlated with right presubiculum?r=0.313,p=0.013?and subiculum?r=0.262,p=0.040?volumetric changes.Conclusions:Gender differences might influence the performances of general spatial navigation in healthy young adults.Such differences of spatial navigation skills were correlated with volumetric changes in right presubiculum and subiculum.This study suggestted that different hippocampal subfields play different roles in spatial navigation tasks,indicating a structural foundation for further understanding of the spatial navigation processing abilityPart 2 The Correlation between Spatial Navigation Ability and Fiber Characteristics in APOE Risk Gene CarriersPurpose:APOE s4 allele was considered to be a major risk gene for Alzheimer's disease?AD?.Impairment of spatial navigation and damages of fibers integrity were also widely reported in elderly and AD patients.However,the correlation between fibers damages and spatial navigation impairment in APOE ?4 carriers remain unclear.The aim of this study is to determine the correlation between spatial navigation ability and fiber characteristics of APOE s4 carriers in normal young adults.Materials and methods:Sixty volunteers,which were recruited through the volunteer recruitment process and underwent the spatial navigation test and MRI examination as previously described,were included for genotype detection using their peripheral blood.The fractional anisotropy?FA?and mean diffusivity?MD?coefficient of 100 nodes on the 20 fiber bundles were analyzed by Automating Fiber-tract Quantification?AFQ?.All subjects were divided into three groups according their APOE genotype.One-way ANOVA and Spearman's Correlation Test were performed to analyze the differences and correlations of spatial navigation skills and diffusion tensor values of 20 fiber bundles between the groups,respectively.Results:No significance differences of mixed navigation?p=0.627?,egocentric navigation?p=0.768?and allocentric navigation?p = 0.491?were found among the three APOE allele??2/?3,?3/?3,?4/?3?groups.Lower FA values in bilateral thalamic radiation?left:t=2.839,p=0.007;right:t=4.174,p=0.000?and callosum forceps?genu:t=2.487,p=0.016,splenium:t=3.425,0.001?were found in the APOE ?3/?3 group in compared with APOE ?2/?3 group.The APOE ?4/?3 group has lower FA value than APOE ?2/?3 group in callosum forceps?splenium:t=2.350,p=0.039?.The APOE ?4/?3 group obtained higher MD value in the right arcuate?t=-2.958,p=0.018?,left superior longitudinal fasciculus?t=-2.737,p=0.025?and callosum forceps?splenium:t=-3.208,p=0.008?than the APOE ?2/?3 group.The APOE ?3/s3 subjects were found to possessed higher MD values in right cingulum cingulate?t=-3.211,p=0.002?than their APOE ?2/?3 counterparts,whereas the APOE ?3/?3 group obtained lower MD values in the left inferior frontal-occipital fasciculus?t=2.656,p=0.011?and right thalamic radiation?t=2.738,p=0.009?than the APOE ?2/?3 subjects.In further correlation analysis,the MD value of right cingulum cingulate was found to be positively correlated with the mixed spatial navigation ability?r = 0.829,p = 0.042?in the APOE?2/?3 group.Conclusion:No significant differences of spatial navigation ability were found between the APOE ?4 carriers and non-?4 carriers young adults.However,the fiber integrity of APOE ?4 carriers was found to be compromised.Furthermore,correlations between general spatial navigation ability and fiber integrity were found among the APOE ?2 carriers,which indicated that the APOE ?4 gene could be one of the risk factors for spatial navigation impairment.