Clinical Study About Chemotherapy Related Cognitive Impairment On Neuroimaging And Efficacy Of Acupuncture Therapy In Breast Cancer Patients

Background: Chemotherapy-related cognitive impairment(CRCI)is one of the common side effects of chemotherapy.The main clinical features are declining on memory,attention,executive function,and visual spatial ability.Cancer patients have created the term "chemotherapy brain" or "chemotherapy fog" to refer to these changes,and that chemotherapy is a direct cause of disease.Several studies have verified the existence of CRCI by neuropsychological testing.In addition,the mechanism of CRCI has also been studied more and more,and the neural structure or pathway affected by chemotherapy remains unclear.Magnetic resonance imaging(MRI)has minimal invasiveness,and high-quality images can be obtained to reveal the structure of the brain,which can help reveal the changes of related central nervous imaging.However,imaging studies on CRCI are still limited,and the conclusions are different,so more brain imaging studies are needed.In addition,although various studies on genetics,biology,and neuroimaging can help us elucidate the mechanism of CRCI and identify high-risk groups of cognitive impairment,we still do not have standard recommended treatments.There are few published research treatments to address the problem of cancer survivors.Findingeffective treatments for CRCI and identifying relevant mechanisms will enable us to better understand the development of the disease and improve the quality of life of patients.Part1:A Prospective Study about Chemotherapy Related Cognitive Impairment Based On multivoxel Magnetic Resonance Spectroscopy and Diffusion Tensor Imaging in Patients with Breast CancerObjective: The purpose of our study is to prospectively analyze the specific characteristics of chemotherapy-related cognitive impairment(CRCI)in breast cancer,analyze the absolute concentration and structural changes of metabolites in different brain regions by multimodal neuroimaging technology,and explore the correlation between them,so as to provide neuroimaging diagnostic basis for CRCI.Methods: Breast cancer patients with chemotherapy treatment group(Ctx+,N=25)and control group without treatment(Ctx-,N=25)were recruited.Neuropsychological tests,multivoxel magnetic resonance spectroscopy(MRS),and diffusion tensor imaging(DTI)were performed before and after chemotherapy.Neuropsychological tests were assessed using functional assessment of cancer treatment cognition test(FACT-Cog,version 3),auditory-verbal learning test(AVLT),verbal fluency test(VFT),symbol digit modality test(SDMT),clock drawing test(CDT),and trail-making test part B(TMT-B).Regions of interest(ROls)in magnetic resonance scan include bilateral posterior cingulate gyrus(PCG),bilateral dorsal thalamus(DT),bilateral lenticular nucleus(LN),bilateral posterior horn of thelateral ventricle paratrigonal white matter(PWM).In MRS,the absolute concentrations ofN-acetylaspartate(NAA),myo-inositol(MI),choline-containing compounds(Cho),total creatine(tCr),glutamine + glutamate(Glx)were quantified using LC Model and SAGE software.In DTI,we used fractional anisotropy(FA)and mean diffusivity(MD)to reflect the integrity of white matter.Paired t test was used to calculate the scores of neuropsychological tests,absolute concentrations of metabolites,and FA,MD values.To assess interaction of time and group,we used a repeated-measures ANOVA in the scores of neuropsychological tests.Finally,in the chemotherapy group,the correlations between the change of neuropsychological test scores,absolute concentrations of metabolites,and FA,MD values were analyzed.Results: In Ctx+ patients,the scores of FACT-Cog,PCI,QOL,PCA,AVLT-recognition and CDT were lower than that before chemotherapy(P <0.05).Repeated-measures ANOVA showed that the scores of FACT-Cog,PCI,QOL,PCA,AVLT recognition and CDT had significant group-by-time interaction,and the effect of chemotherapy factor had statistical significance.In MRS,Ctx+ patients had significantly lower NAA values in bilateral PCG,DT respectively.The concentrations of t Cr were observed to decline in the bilateral PCG and RDT respectively.Glx values decreased in RDT.Cho values decreased significantly in bilateral DT.In DTI,the Ctx+ patients had lower FA values in bilateral PCG compared with that before chemotherapy.These changes were not found in the control group.Among imaging metrics and cognitive scores,positive correlations were observed between change in AVLT-recognition scores and change in NAA values in bilateral PCG(LPCG: r= 0.470,P <0.01;RPCG: r= 0.500,P <0.01).Positive correlations were also found between change in AVLT-recognition and change in FA values in the bilateral PCG(LPCG:r=0.513,P <0.01;RPCG: r=0.563,P <0.01).The control group showed no statistical difference in any measures over the same period.Conclusions: This prospective study combines MRS and DTI to study chemotherapy-related cognitive impairment in breast cancer,supporting the existence of “chemotherapy brain”.Chemotherapy can lead to a decrease in memory function,accompanied by changes in brain metabolite concentration and white matter integrity in part of brain.This study also showed the potential applications of MRS and DTI in assessing chemotherapy-related cognitive impairment.Part2:Efficacy of Acupuncture Therapy for Chemotherapy-Related Cognitive Impairment in Breast Cancer PatientsObjective: Chemotherapy can cause side effects in patients such as chemotherapy-related cognitive impairment(CRCI).In this prospective study,the efficacy of traditional Chinese medicine acupuncture therapy in relieving CRCI and its impact on serum brain-derived neurotrophic factor(BDNF)are evaluated.Methods: Eighty patients with breast cancer were randomly divided into a treatment group and a control group with 40 patients in each group.The treatment group was treated at the following acupuncture points: Baihui(DU20),Sishencong(EX-HN1),Shenting(DU24),Zusanli(ST36),Taixi(K13),Dazhong(K14),and Juegu(GB39).Before and after treatment,cognitive function was assessed using the functional assessment of cancer treatment cognition test(FACT-Cog,version 3),the auditory-verbal learning test(AVLT),the verbal fluency test(VFT),the symbol digitmodality test(SDMT),the clock drawing test(CDT),and the trail-making test part B(TMT-B).Blood serum levels of BDNF were measured before and after treatment.In addition,to assess interaction of time and group,we used a repeated-measures ANOVA in the scores of cognitive function tests.Correlations between change in BDNF levels and cognitive function were also analyzed.Results: CRCI was ameliorated in the acupuncture treatment group,with scores on FACT-Cog,PCI,QOL,OTH,PCA,AVLT-recognition and CDT assessments all significantly increased(P < 0.05 in all cases).Repeated-measures ANOVA showed that the scores of FACT-Cog,PCI,PCA,AVLT recognition and CDT had significant group-by-time interaction,and the effect of acupuncture factor had statistical significance.In addition,serum BDNF levels after acupuncture treatment were significantly higher than before treatment(t = 3.242,P < 0.01).Moreover,the level of BDNF was positively correlated with the total score of FACT-Cog,AVLT-recognition and CDT(r = 0.694,0.628,and 0.532,respectively;all P < 0.05).The control group showed no statistical difference in any measures over the same period.Conclusions: Acupuncture therapy is effective in the treatment of CRCI in breast cancer patients through a mechanism that may be related to an increase of BDNF.