| PART ONEObjective:To explore the effect of cognitive training on plasticity of aging brain structure and functional connectivity.Methods:A control and assessor-blind cognitive training?CogTr?was conducted in 60healthy elderly selected from three randomized groups?multi-domain CogTr group,single-domain CogTr group and control group?.The participants were recruited from three communities in Shanghai.Eligibility criteria included:65?age?75 years;educational level?1 year;able to live independently;score of the Chinese version of the Mini-Mental State Examination equal 19 or above.Two intervention groups were given cognitive training with different content respectively.Cognitive capacity assessment and magnetic resonance imaging?MRI?were tested before training beginning and at one year after training ending.Twenty-four sessions of CogTr were administrated to the two intervention groups over a three-month period.All CogTr took place in small group settings with an average class size of 15 individuals,with a frequency of twice a week.Each session lasted 60 minutes.The total times was twenty four.The assessment included the Repeatable Battery for the Assessment of Neuropsychological Status?RBANS,Form A?,the Color Word Stroop test?CWST?,the visual reasoning test and the trail making test?TMT?.MRI scan was performed on Siemens 3.0T Trio scanner.The total scan time was about 45 minutes including T1-weighted image scanning,resting-state functional MRI scanning,eye-open and eyes-close task functional MRI scanning and diffusion tensor imaging?DTI?scans.All data were analyzed using the SPSS version 17.0.The MRI data were preprocessed and analyzed using“SPM8”,”DPARSFA”and“Freesurfer”software.According to the data distribution and research purposes,descriptive statistical analysis,ANOVA,paired-samples T test,analysis of covariance and Pearson correlation analysis were used for statistics.Results:Sixty people completed the pre-intervention assessment of cognitive function and MRI scanning including 22 participants of multi-domain CogTr group,21 participants of single-domain CogTr group and 17 participants of the control group.One year after the intervention,50 people completed the cognitive assessments and MRI scanning with 10 participants withdrawal.At baseline and one year after training,the demographic data of the three groups showed no significant difference?P>0.05?.At one year after training,analysis of covariance was used to compare the benefit of cognitive function among the three groups,controlling the cognitive function of the three groups at baseline as a covariate.The results showed that the among the difference of delayed memory score among the three groups was statistically significant?P=0.04?.Pairwise comparisons showed that the delayed memory score of multi-domain CogTr group was significantly higher than that of control group?P=0.04?and single-domain group?P=0.02?.Other items scores of cognitive assessment among the three groups showed no significant difference,but pairwise comparisons showed that RBANS and language scores of multi-domain CogTr group were significantly higher than that of control group?P=0.05,P=0.06?.At one year after training,the brain regions where the gray matter density changed significantly were left middle frontal gyrus,left middle temporal gyrus,left precentral gyrus and right parietal lobe?single voxel P-value less than 0.005,cluster size>40?.The comparisons between groups and within group showed that gray matter density in the control group in prior brain regions decreased at one year after training than baseline?P<0.05?.The gray matter density of left middle frontal gyrus,right parietal lobe and left precentral gyrus in the multi-domain CogTr group increased compared to the baseline,different statistically significantly with control group?P=0.00;P=0.009;P=0.053?;The gray matter density of left middle temporal gyrus increased and that of right parietal lobe in the single-domain CogTr group didn't change when compared with baseline,different statistically significantly with control group?P=0.000;P=0.026?;The gray matter density of left middle frontal gyrus and left precentral gyrus increased in the multi-domain CogTr group while that of right parietal lobe in the single-domain CogTr group decreased when compared with baseline,the difference was statistically significantly?P=0.000;P=0.005?.The gray matter density of left middle temporal increased in the single-domain CogTr group and decreased in the multi-domain CogTr group,the difference was statistically significantly?P=0.007?.At one year after training,the mean rate of decrease of the time-domain entropy was not changed in the multi-domain CogTr group?t=-0.77,P=0.224?and single-domain CogTr?t=0.81,P=0.787?.The mean rate of increase of the functional entropy was significantly reduced in both the multi-domain CogTr?t=1.77,P=0.047?and the single-domain CogTr group(t=3.67,P=9.51×10-4).And we found that in Multi-domain training group,there was one link which can pass Bonferroni correction(P=7.2×10-6<0.05/4005).It was the link from Amygdala?Right hemisphere?to Middle Orbitofrontal Cortex?Right hemisphere?.The regional time-domain entropy of the hippocampus had a significantly positive correlation with delayed memory,in the single-domain CogTr group(r=0.76,P=2.56×10-4).Conclusions:Multi-domain CogTr can significantly improve cognitive function in healthy elderly,better than single-domain CogTr.Multi-domain CogTr and single-domain CogTr can induce changes of gray matter density,decrease aging-related decreasing trend of brain gray matter density.The brain regions effected by multi-domain CogTr are more extensive than by single-domain CogTr.There is overlap of the brain regions effected by two types of CogTr that is right parietal lobe.Cognitive training can change functional connectivity of aging brain,especially multi-domain cognitive training can significantly improve the functional connectivity between right amygdala and right orbitofrontal cortex.PART TWOObjective:To explore the difference of the effect of cognitive training and aerobic exercise on cognition aging and the influence factors.Methods:A randomized control designed and assessor-blind cognitive training?Cog Tr?was conducted in healthy elderly recruited from several communities in Shanghai.Eligibility criteria included: 65 ? age ? 75 years;educational level ? 1 year;able to live independently;absence of significant hearing,vision,or communication difficulties;absence of severe physical diseases or psychotic disorders;the score of the Chinese version of the Mini-Mental State Examination equal 19 or above.The participants were randomly assigned to three groups: cognitive training group,aerobic exercise group and control group.Cognitive capacity assessment,cardiorespiratory function assessment and MRI were tested before training beginning.Cognitive training and aerobic exercise were administrated to the two intervention groups respectively.Follow-up assessments and MRI scanning were conducted immediately after intervention,at a half year and one year after intervention ending.Twenty-four sessions of cognitive training and aerobic exercise were administrated to the two intervention groups over a three-month period.Cognitive training took place in small group settings with an average class size of 16-17 individuals.Cognitive training and aerobic exercise occurred with a frequency of twice a week.Each session lasted 60 minutes.The total times was twenty four.The assessment included the Repeatable Battery for the Assessment of Neuropsychological Status?RBANS,Form A and Form B?,the Color Word Stroop test?CWST?,the visual reasoning test and the trail making test?TMT?.One-mile-walk cardiorespiratory function assessment.MRI scan was performed on Siemens Verio 3.0T scanner.The total scan time was about 48 minutes including T1-weighted image scanning,resting-state functional MRI scanning,eye-open and eyes-close task functional MRI scanning and diffusion tensor imaging scans?DTI?.All data were analyzed using the SPSS version 17.0.The MRI data were preprocessed and analyzed using “Freesurfer” software.According to the data distribution and research purposes,descriptive statistical analysis,ANOVA,paired-samples T test,analysis of covariance and Pearson correlation analysis et al.were used for statistics.Results:Forty nine participants finished assessment at baseline,while 42 finished after training.The follow-up rate was 77.8%.Immediate after training,there were 10 participants withdrawal including 3 of cognitive training group,4 of aerobic exercise group and 7 of control group.The difference of withdraw rate among three groups was not statistically significant?x2 = 2.51,P = 0.29?.At the time immediate after training,all the scores of cognition assessment items of the three groups were not different significantly?P > 0.05?except for the score of TMT line two.Pairwise comparisons showed the delayed memory score of the cognitive training group was higher significantly than that of control group?P = 0.08?,the reason score higher than aerobic exercise group?P = 0.08?.While aerobic exercise group compared with control group,none of the cognition assessment items was significantly different?P > 0.05?.Multiple regression analysis showed that years of education and left hippocampal volume index could explain 10.9% and 4.4% of the variation of attention respectively;years of education and right hippocampal volume index has could explain 11.9% and 9.7% of the variation of delayed memory variability respectively;the word interference time of female was shorter than female,sex can explain 12% of variation of word interference time.The correlation analysis of hippocampus formation and training effect showed that there was significant negative correlation between the hippocampal volume asymmetry index and the improvement of delayed memory score and RBANS score?r =-0.80,P < 0.01;r =-0.56,P < 0.05?.Conclusions:Cognitive training can improve cognitive function in healthy elderly particularly delayed memory ability,while the role of aerobic exercise on cognitive function is not obvious in a short period.Cognitive function-related factors include gender,age,years of education and hippocampal volume.The right hippocampus volume index correlates positively with delayed memory.The left hippocampal volume index correlates positively with attention.There is negative correlation between the cognitive benefits of aerobic exercise and hippocampal volume asymmetry index.Hippocampal volume asymmetry index may be used as biological indicators of cognition benefit from aerobic exercise. |
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