Brain Imaging Study Of Cognitive Function In Late-onset Depression And Amnestic Mild Cognitive Impairment

Objective:Late-onset depression(LOD)and amnestic mild cognitive impairment(aMCI)are two common disorders characterized by cognitive impairment in the elderly.Although it is generally accepted that LOD and aMCI are two heterogeneous diseases,studies have found that they share many similar clinical manifestations and both LOD and aMCI are closely related to the development of Alzheimer’s disease(AD).However,it is not clear about the relationship between LOD and aMCI in the cognitive impairment characteristics and neurobiological mechanisms.Focusing on the strength and stability characteristics of spontaneous neural activities in the brain,this study used comprehensive neuropsychological tests and the resting state functional magnetic resonance imaging(rs-f MRI)to analyze the behavioral characteristics of cognitive impairment,abnormal changes in static(sALFF)and dynamic amplitude of low frequency fluctuations(dALFF)in LOD and aMCI and the correlation between abnormalALFF and depressive symptoms as well as the cognitive impairment,thus exploring the characteristics and neuroimaging mechanisms of cognitive impairment in LOD and aMCI,revealing the relationship between the two diseases,and providing a basis for early clinical intervention and individualized treatment.Methods:15 patients with LOD,25 patients with aMCI,and 20 healthy controls(HC)were enrolled in this study.All subjects were completed clinical symptom assessment,detailed neuropsychological tests and rs-f MRI scanning.The clinical symptoms of the two patient groups were compared with independent-samples t-test.To increase statistical power by reducing random variability,this study transformed the raw scores of the neuropsychological tests into composite Z scores and composited these tests into 6cognitive domains,including memory,information processing speed,visuospatial function,executive function,language function,and social cognitive function.The mean of Z-scores for each cognitive domain was calculated to obtain the Z score of composite cognitive function.One-way analysis of variance(ANOVA)was used for comparison of neuropsychological tests among the three groups of subjects,and post hoc tests with LSD correction were performed for the results with statistical differences(P < 0.05).DPABI was used to preprocess the rs-f MRI data.The meanALFF values of each voxel were calculated and Z-transformed to generate the sALFF map for each subject.Based on the sliding window approach,theALFF values of each voxel under every time window were calculated and Z-transformed to generate the zALFF maps for each window.dALFF is defined as the standard deviation of the zALFF values in every window.A one-way analysis of covariance(ANCOVA)with gender,age,years of education and head movement as covariates was performed for the comparison of sALFF/ dALFF among the three groups.The gaussian random field(GRF)multiple comparison correction was used,with statistical levels of P < 0.001 at voxels and P < 0.05 at clusters.The sALFF and dALFF values of brain regions with significant differences were extracted for post hoc analysis.The sliding window length was changed for validation analysis of dALFF results.Finally,Pearson correlation analysis and multiple linear stepwise regression method were performed to explore the correlation between abnormalALFF values and clinical symptoms,as well as cognitive function in LOD and aMCI.Results:1.The analysis of clinical symptoms and neuropsychological tests.For clinical symptoms,the scores of Hamilton Depression Rating Scale for Depression 24 item(HAMD-24)and Hamilton Anxiety Rating Scale(HAMA)of the LOD group were found significantly higher than the aMCI group(P < 0.05).In terms of general cognitive function,patients in the LOD and aMCI groups had significantly lower scores on the Mini-Mental State Examination(MMSE)and Montreal Cognitive Assessment(Mo CA)than the HC group(P < 0.05),with no statistical difference between the two patient groups(P > 0.05).As for the neuropsychological tests,the results of ANOVA analysis showed statistical differences among the LOD,aMCI and HC groups in all six cognitive domains(P < 0.05).The results of post hoc tests with LSD correction showed that compared to the HC group,the LOD group showed significant decreases in composite cognitive function(P < 0.001),memory(P = 0.024),information processing speed(P =0.011),visuospatial function(P < 0.001),language function(P < 0.001),and social cognitive function(P < 0.001).And in executive function,there was not significant difference between the LOD and HC groups(P = 0.164).The aMCI group showed significant decline in composite cognitive function(P < 0.001),memory(P < 0.001),information processing speed(P = 0.022),visuospatial function(P = 0.015),executive function(P = 0.021),and language function(P = 0.004),and no statistical difference was found between the aMCI and HC groups in social cognitive function(P = 0.094).The comparison of the LOD with aMCI showed that LOD had significantly lower scores in composite cognitive function(P = 0.025),visuospatial function(P = 0.032),language function(P = 0.027),and social cognitive function(P = 0.022)than the aMCI,and the two groups showed no statistical differences in memory(P = 0.320),information processing speed(P = 0.360)and executive function(P = 0.989).2.The analysis of sALFF.The results of ANCOVA analysis showed that the sALFF values in the left cuneus,left superior orbital frontal gyrus,left inferior orbital frontal gyrus,right lingual gyrus,right precuneus,right superior parietal gyrus,and right postcentral gyrus were statistically different among the three groups of subjects(P < 0.05,GRF correction).The results of post hoc tests with LSD correction showed that compared with the aMCI and HC,sALFF was significantly increased in the LOD group in the left superior orbital frontal gyrus,left inferior orbital frontal gyrus,and right postcentral gyrus(P < 0.05),while there was no significant difference between the aMCI and HC groups(P > 0.05).Compared with the LOD and HC,the aMCI group had significantly increased sALFF values in the right lingual gyrus(P < 0.05)and significantly decreased sALFF in the right precuneus(P < 0.05),while no statistical difference was found between the LOD and HC groups(P > 0.05).Both the LOD and aMCI groups exhibited abnormally increased sALFF in the right superior parietal gyrus compared with the HC group(P < 0.05),while there was no statistical difference between LOD and aMCI(P > 0.05).In addition,the sALFF values of three groups of subjects showed a trend of LOD < HC < aMCI in the left cuneus(P < 0.05).3.The analysis of dALFF.The results of ANCOVA analysis showed there were statistical differences in dALFF values of the left lingual gyrus,left middle temporal gyrus,left cuneus,left postcentral gyrus,right middle occipital gyrus,right angular gyrus,right precuneus,and right postcentral gyrus among the three groups(P < 0.05,GRF correction).The results of post hoc tests with LSD correction showed that compared with aMCI and HC,dALFF values of the LOD in the left middle temporal gyrus,bilateral postcentral gyrus,and right angular gyrus were significantly decreased(P < 0.05).And there was no significant difference in dALFF between the aMCI and HC in the above brain regions(P > 0.05).Compared with LOD and HC,dALFF values were significantly increased in the left lingual gyrus,right precuneus and right middle occipital gyrus in the group of aMCI(P < 0.05),while there was no statistical difference between the LOD and HC groups(P > 0.05).Moreover,compared with HC,LOD showed significantly decreased dALFF in the left cuneus(P < 0.05),while aMCI showed abnormally increased dALFF in the left cuneus(P < 0.05),and there were significantly differences between LOD and aMCI in the left cuneus(P < 0.05).The results of the validation analysis by varying the sliding window length were generally consistent with dALFF results described above.4.Correlation and regression analysis.(1)Pearson correlation analysis showed that in the LOD group,sALFF values in the left inferior orbital frontal gyrus were positive correlation with HAMD-24 scores(r = 0.594,P = 0.020),and sALFF values in the right postcentral gyrus were negative correlation with the scores of social cognitive function(r=-0.586,P = 0.022).(2)As for the aMCI group,the sALFF values in the left cuneus were negative correlation with the scores of memory(r =-0.408,P = 0.043),Brief Visuospatial Memory Test-immediate recall(r =-0.430,P = 0.032),and 25-min delayed recall(r =-0.535,P = 0.006).The dALFF values in the left cuneus of the aMCI group were also negative correlation with memory(r =-0.412,P = 0.041)and Brief Visuospatial Memory Test-25 min delayed recall(r =-0.479,P = 0.016).The sALFF values in the right precuneus of aMCI were positive correlation with the scores of memory(r = 0.541,P = 0.005),Hopkins Verbal Learning Test-5-min delayed recall(r =0.538,P = 0.006)and 20-min delayed recall(r = 0.543,P = 0.005),and Brief Visuospatial Memory Test-25 min delayed recall(r = 0.445,P = 0.026).In addition,sALFF values in the right lingual gyrus were negative correlation with scores of the Judgment of Line Orientation Test in the aMCI group(r =-0.477,P = 0.016).(3)Moreover,multiple linear stepwise regression analysis was performed using the memory scores of the aMCI group as the dependent variable,the sALFF and dALFF values of the left cuneus,the sALFF values of the right precuneus and general demographic information as independent variables.The results showed that age(β =-0.700,P < 0.001),education years(β = 0.261,P = 0.045)and dALFF values in the left cuneus(β =-0.606,P = 0.003)had significant effects on the memory scores of patients in the aMCI group.Conclusion:This study found that LOD and aMCI patients showed different characteristics of cognitive impairment and regional brain activities.The patients of LOD and aMCI had many common dimensions of cognitive impairment,and LOD had more severe cognitive impairment in comprehensive cognition,language and visuospatial function than aMCI.Social cognition may be a feature of cognitive impairment in LOD.Moreover,the abnormally activated brain regions in LOD patients were mainly involved in negative emotion regulation,social cognition,sentence comprehension and semantic processing,while the brain regions with abnormal activities in aMCI were mainly involved in verbal memory,visuospatial processing and encoding visuospatial memory.The abnormal neural activities in different brain regions in the LOD and aMCI may preform different patterns of cognitive impairment by damaging different neuropathological pathways and brain networks.In addition,LOD and aMCI may have similar impairment and mechanism in the information processing speed.These fingdings provide new insights into the understanding of the cognitive impairment patterns and neurophysiological mechanisms of LOD and aMCI,and future longitudinal follow-up based on an expanded sample size will help further clarify the complex relationship between the two disorders.