Association between structural-functional coupling changes image and cognitive function in patients with cerebral small vessel disease

Wang Xin; Wang Wei; Wu Xiaosan; Tian Yanghua; Zhang Jun

doi:10.3969/j.issn.1672-5921.2025.01.004

Abstract：Objective To analyze the whole-brain structural-functional coupling imaging characteristics of patients with cerebral small vessel disease(CSVD)based on multiparametric functional and structural MRI,and to explore their correlation with cognitive function.Methods A prospective,consecutive study enrolled 60 CSVD patients from the Department of Neurology,the Second Affiliated Hospital of Anhui Medical University,between May 2021 and December 2023,and 47 controls matched for age,sex,education level,and handedness recruited from the community during the same period.Baseline data,including demographic information(age,sex,education),cognitive function,and imaging data,were collected for both groups.All participants underwent standardized neuropsychological assessments in a quiet environment.Emotional function was assessed using the patient health questionnaire-9(PHQ-9).Global cognitive function was screened using the Montreal cognitive assessment scale(MoCA)and Alzheimer's disease 8-item questionnaire(AD-8).Executive function was evaluated using the trail making test-B(TMT-B),the TMT time difference(TMT-B time minus TMT-A time),and the verbal fluency test(VFT).Attention and processing speed were assessed using TMT-A and the digit span test(DS).Memory function was evaluated using the Chinese auditory verbal learning test(AVLT),including learning,immediate recall,and delayed recall.Multimodal brain functional and structural MRI images were acquired for all participants.Fractional amplitude of low-frequency fluctuations(fALFF)and gray matter volume(GMV)were calculated using the DPABI software.A structure-function coupling index was computed by integrating the fALFF and GMV values of corresponding voxels.Structural-function coupling changes in CSVD patients and controls were assessed,and the correlations between fALFF,GMV,fALFF/GMV and cognitive function were explored.Results(1)Compared to the control group,CSVD patients showed significant lower scores in MoCA score(21.5[20.0,24.0]vs.24.3[23.0,26.0],Z=-4.094),higher PHQ-9 score(5.4±5.0vs.2.1±2.2,t=4.150),less VFT(15.5±3.8 vs.17.2±4.3,t=-3.258),increased TMT-B time([164.4±72.7]s vs.[123.6±45.7]s,t=3.307),TMT-A time([83.8±34.3]s vs.[62.9±22.7]s,t=3.704),and less DS forward span(6.3[5.0,8.0]vs.7.4[6.0,8.0],Z=-3.679),DS backward span(3.7±1.2 vs.4.5±1.4,t=-3.119),AVLT-learning(7.0±1.8 vs.8.7±1.9,t=-4.523),A VLT-immediate recall(7.2[6.0,9.0]vs.9.6[7.2,11.8],Z=-4.105),AVLT-delayed recall(6.9±3.1 vs.9.6±3.0,t=-4.310;all P＜0.01).No significant differences were observed in age,education,sex,AD-8 score,or TMT time difference(all P＞0.05).(2)CSVD patients showed decreased fALFF values in the right anterior cingulate gyrus(1.00±0.06 vs.1.07±0.06,t=-4.66)and increased fALFF values in the left superior parietal lobule(1.14±0.07 vs.1.07±0.07,t=5.68)and the right postcentral gyrus(1.08±0.05 vs.1.01±0.05,t=5.22;both P＜0.01).CSVD patients had increased GMV in the bilateral caudate nucleus(right:[0.27±0.06]mm3 vs.[0.21±0.04]mm3,t=6.12,left:[0.27±0.05]mm3 vs.[0.22±0.04]mm3,t=6.67;both P＜0.01)but decreased fALFF/GMV in the bilateral caudate nucleus(left:6.27±0.97 vs.7.75±1.70,t=-7.33;right:3.12±0.97 vs.4.18±0.95,t=-5.96)and the right globus pallidus(14.11±4.14 vs.19.99±4.03,t=-6.36;all P＜0.01).(3)Right anterior cingulate gyrus fALFF positively correlated with DS backward scores(R=0.348,P=0.013).Left superior parietal lobule fALFF negatively correlated with PHQ-9 scores(R=-0.308,P=0.029)and TMT time difference(R=-0.360,P=0.012).Right postcentral gyrus fALFF negatively correlated with TMT-A time(R=-0.419,P=0.003).Right caudate nucleus GMV positively correlated with TMT time difference(R=0.293,P=0.042),while left caudate nucleus GMV negatively correlated with AD-8 score(R=-0.284,P=0.043).fALFF/GMV in the right caudate nucleus(R=0.288,P=0.046)and right globus pallidus(R=0.290,P=0.045)positively correlated with VFT.After multiple comparison corrections,only the negative correlation between right postcentral gyrus fALFF and TMT-A time remained significant(P(alse discovery rate adjusted=0.024).Conclusions CSVD patients exhibit significant structure-function decoupling values in bilateral caudate nucleus and right globus pallidus are reduced,and this reduction is associated with a decline in verbal fluency.The results of this study still need to be further validated in larger sample size studies.