Effect Of Cognitive Training And Aerobic Exercise On Neural Plasticity In Normal Aging: Behavioral And Magnetic Resonance Imaging Study

Objective: Cognitive Training and aerobic exercise are two kinds of promising approaches against cognitive aging.The present study was designed to compare the training effect between cognitive training and aerobic exercise for community-dwelling,healthy older adults,and to explore the potential neurobiomarkers predicting behavioral gains from these interventions.Methods:1.A prospective,randomized,assessor-blinded,parallel-controlled trail(Registration number: Chi CTR-TRC-13004788)was conducted.Participants were recruited from Jiangning community,Jing’an District in Shanghai.Eligibility criteria included: 65 ≤ age ≤ 75 years;educational level ≥ 1 year;independent living;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(CMMSE)over cutoff according to educational level(elementary school≥19,middle school and above≥24).2.The eligible participants were randomly assigned to three groups: cognitive training group,aerobic exercise group and control group.Assessments of cognitive function,health condition,cardiorespiratory function and brain magnetic resonance imaging(MRI)scan were performed at baseline and 12-month posttest.Assessments of cognitive function and health condition were performed at immediate posttest and 6-month posttest as well.3.A total of 24 sessions(2 sessions per week)of c ognitive training and aerobic exercise were administrated to the two intervention groups respectively over 12 weeks.The settings of cognitive training were as follows: group-based of 15-18 participants,60 minutes for each session.The cognitive training targeted on memory,reasoning,problem solving,quiz and finger exercise.The protocol of aerobic exercise was as follows:(a)All participants began by walking continuously for 10 min and proceeded to increase their walking duration in 5-min increments until a period of 45 min was achieved at week seven.For the remainder of the program,participants walked for 45 min per session.(b)Participants wore heart rate monitors(Mio Alpha)while exercising and were encouraged to stay within their target heart rate zone based on the resting and maximum heart rates achieved during the baseline maximal graded exercise test.The target heart rate zone was50–60% of the maximum heart rate reserve for weeks 1–8 and 60–75% for the remainder of the program.4.The cognitive assessments 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 color trials test(CTT).The measures of health condition included disease indices,mood status,subjective memory complaints(SMC),activities of daily living scale(ADL),healthy behaviors(HB),short form-36 health survey(SF-36),personality indicators(PI),self-efficacy scale(SES),life satisfaction index A(LSIA)and physical activity scale for the elderly(PASE).One-mile walk test and dynamic oxygen metabolism kinetics monitoring were performed to assess cardiorespiratory function.5.Brain MRI scan was performed on Siemens MAGNETOM Verio 3.0T scanner.The total scan time was 48 minutes and 18 seconds including 3D-T1-weighted structural scan,resting-state functional MRI scan,eyes-open and eyes-close task functional MRI scan,diffusion tensor imaging(DTI)scans and 2D fluid attenuated inversion recovery(FLAIR)scan.6.All data were analyzed using the SPSS version 17.0.The MRI data were preprocessed and analyzed using following software including SPM8,VBM8,Freesurfer,FSL and PANDA.According to the data distribution and research purposes,independent or paired-samples t test,chi-square test,non-parametric test,analysis of variance(ANOVA)or covariance(ANCOVA),analysis of variance of repeated measures,correlation analysis,step-wise linear regression analysis and Receiver Operating Characteristic Curve(ROC)were performed.Results:1.539 community-dwelling older adults were screening for eligibility from November 14,2013 to September 16,2014.67,68 and 67 eligible individuals were randomized to cognitive training,aerobic exercise and control group,respectively.180,158,154,150 participants completed the assessments at immediate,6-month and 12-month posttest,respectively.The dropout rate at 12-month posttest were 25.7%.2.The mean attendance was 71.8±31.3% and 60.2±39.6% of cognitive training and aerobic exercise group,respectively and no significant differences of attendance between these two groups were detected using Mann-Whitney U test(Z =-0.912,P = 0.362).3.No significant differences were found in cognitive assessments and health condition among the three groups(P > 0.05)except RBANS Language Index Score(F[2,160]=4.102,P =0.018),CWST Card B correct number(Welch’s F[2,95.63]=3.179,P =0.046),CWST Card B error number(χ2 [2]=8.586,P = 0.014),and CWST Card D repetition number(χ2 [2]=9.785,P = 0.008).4.Significant main effect of time(P < 0.001)and intervention(P=0.003,P=0.008,respectively),and time*intervention interaction(P=0.038)in RBANS Immediate Memory Index Score and score of visual reasoning test were detected using repeated measures ANOVA controlling baseline performance.The bias corrected net effect size(NES)was strongest in improvement in RBANS Delayed Memory Index Score(bias corrected NES=0.549)and visual reasoning test(bias corrected NES=0.520)for cognitive training,while the bias corrected NES was strongest in improvement in Stroop word interference time for aerobic exercise(bias corrected NES=-0.546 ~-0.361).5.Correlation analyses showed that gender,age,educational level and attendance were significantly correlated with training effects in global cognition,memory,reasoning,executive function,processing speed and task-switching.6.Partial correlation analyses showed that in the cognitive training group,the smaller D-HF/ICV(right minus left hippocampus volumes standardized by total intracranial volume)at baseline,the more gain in global cognition,visuospatial/constructional abilities and language;the larger LHF/ICV(left hippocampus volumes standardized by total intracranial volume),R-HF/ICV(right hippocampus volumes standardized by total intracranial volume)and S-HF/ICV(bilateral hippocampus volumes standardized by total intracranial volume)at baseline,the more gain in inhibition of pre-potent responses and processing speed,the smaller L-HF/ICV and S-HF/ICV at baseline,the more gain in task-switching.Partial correlation analyses also revealed that in the aerobic exercise group,the smaller R-HF/ICV at baseline,the more gain in visuospatial/constructional abilities;the larger L-HF/ICV,R-HF/ICV and S-HF/ICV at baseline,the more gain in processing speed and task-switching.7.ROC analyses showed that axial diffusivity(AD)in left inferior fronto-occipital fasciculus,AD in left posterior thalamic radiation(include optic radiata)and factional anisotropy(FA)in right posterior limb of internal capsule might be potential neurobiomarkers predicting benefit inimmediate memory,reasoning and attention at 12-month posttest after cognitive training cessation,respectively(AUC=0.703~0.734).AD and mean diffusivity(MD)in left anterior corona radiata,FA and radial diffusivity(RD)in superior corona radiata might be potential neurobiomarkers predicting benefit in inhibition of pre-potent responses at 12-month posttest after cessation of aerobic exercise(AUC=0.758~0.769).Tract-based spatial statistics(TBSS)analyses comparing subjects benefitting in inhibition of pre-potent responses at 12-month after intervention cessation showed that AD in left posterior thalamic radiation(include optic radiata),left posterior corona radiata and left superior longitudinal fasciculus was significantly lower in subjects benefitting from cognitive training than in those not benefiting,while FA in bilateral superior corona radiata and body of corpus callosum was significantly higher in subjects benefitting from aerobic exercise than in those not benefitting(Family-wise error corrected P<0.05).Conclusions:1.Cognitive training and aerobic exercise both can effectively improve cognitive function in community healthy elderly over time with well compliance and easy to administrate.2.Cognitive training and aerobic exercise have distinct training effect in different cognitive domains.Cognitive training has strongest effect in delayed memory and reasoning,while aerobic exercise has strongest effect in inhibition of pre-potent responses and last at least for one year after training cessation.3.Cognitive training has far transfer to inhibition of pre-potent responses,attention and processing speed and long-term transfer(at least one year)to attention.4.Factors related to training effect include gender,age,years of education and training attendance.5.Hippocampal volumetric indices and DTI indices in posterior thalamic radiation,corona radiata,superior longitudinal fasciculus might have different value in predicting training effect,and might be used as effective training-related neurobiomarkers in future.