Association Between Cerebral Small Vessel Disease And Gait Disturbance And Fall

Part 1 The association between gait disturbance and imaging features in cerebral small vessel diseaseObjective: Cerebral small vessel disease(CSVD)is composed of several diseases affecting the small arteries,arterioles,venules,and capillaries of the brain,and refers to several pathological processes and etiologies.Neuroimaging features of CSVD include recent subcortical small infarction,white matter hyperintensity(WMH),lacunes,cerebellar microbleeds(CMBs),enlarged perivascular spaces(EPVS)and brain atrophy.Gait disturbance is one of the main causes of decreased quality of life,falling and increased risk of death in the elderly.In rencent years,a large number of studies have shown a close relationship between CSVD and gait disturbance.The aim of this study was to investigate the association between the total CSVD burden or different CSVD imaging markers and gait disturbance by using gait analysis equipment for quantitative gait assessment.Methods: Outpatients were continuously included in the Department of Neurology of Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of science and technology from December 2019 to January 2022.The clinical information and data of patients were collected and recorded.All patients underwent magnetic resonance imaging scans,Instrument Timed Up and Go Test(ITUG)and 6 m walking test.CVSD burden scale(range 0–4)was used to score each CSVD imaging marker,including WMH,lacunes,CMBs and EPVS.Using SPSS software for statistical analysis,P < 0.05 was considered to be statistically significant.Results: A total of 262 patients were included in this study,with an average age of 62.0(57.0–68.0)years and 125 males(47.7%).According to the CSVD burden scale,the patients were divided into five groups with CSVD 0–4.In linear regression,after adjustment for demographics and vascular risks,the results showed that:(1)The total CSVD burden was associated with total Duration,Sit to Stand-Duration,Turns-Duration of ITUG and Turns-Turn Velocity(P < 0.05);the total CSVD burden was associated with total Duration,Lower Limb-Gait Speed and Lower Limb-Stride length(P< 0.05);(2)In the ITUG,moderate-severe WMH was associated with total Duration,Sit to Stand-Duration and Turns-Duration and Turns-Turn Velocity(P < 0.05);lacunes and CMBs were associated with total Duration and Sit to Stand-Duration and Turns-Turn Velocity(P < 0.05);moderate-severe EPVS was associated with total Duration and Sit to Stand-Duration(P < 0.05);in the 6 m walking test,moderate-severe WMH was associated with total Duration,Lower Limb-Stride length,Lumbar-Coronal Range of Motion and Lumbar-Transverse Range of Motion(P < 0.05);the lacunes were associated with total Duration Lower Limb-Gait Speed,Lower Limb-Stride length and Upper Limb-Arm Range of Motion(P < 0.05);CMBs was associated with total Duration and Lower Limb-Double Support,Lower Limb-Gait Speed and Lower Limb-Stride length(P< 0.05);moderate-severe EPVS was associated with total Duration,Lower Limb-Gait Speed and Lower Limb-Stride length(P < 0.05).Conclusion: This study showed that the total CSVD burden and different CSVD imaging markers(WMH,lacunes CMBs,EPVS)are related to lower limb gait disturbance.In addition,lacunes were related to upper limb motor disturbance,suggesting that different CSVD imaging markers may cause gait disturbance through different pathways.The total CSVD burden can better reflect the overall impact on functional impairment,therefore it may be an important marker to identify elderly individuals at risk of gait disturbance.Part 2 Cognitive function mediates the relation between white matter hyperintensity and gait in patients with cerebral small vessel diseaseObjective: Walking is not only a simple automatic motor task,but also needs the control of cognitive function.Previous studies have shown that WMH was related to gait performance and cognitive function.However,the relationship among WMH,cognitive function and gait is not clear.Therefore,the purposes of this study were: 1)to evaluate the relationship between WMH and gait in patients with CSVD;2)to assess the relationship between cognitive function and gait;3)to investigate whether cognitive function mediates the relationship between WMH and gait performance.Methods: Outpatients were continuously included in the Department of Neurology of Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of science and technology from August 2020 to December 2021.The clinical information and data of patients were collected and recorded.Total WMH,Periventricular WMH(PVWMH)and deep WMH(DWMH)were assessed by Fazekas scale,and WMH on cholinergic pathway was assessed by Cholinergic Pathways Hyperintensities Scale(CHIPS).Montreal cognitive assessment test,Clock Drawing Test,Boston Naming Test,Digital Span,Auditory Verb Learning Test,Stroop Color-Word Test,Trial Making Test and Verbal Fluency Test were used to evaluate cognitive domain and global cognitive function.Gait speed of patients were evaluated under single task walking(STW)and dual task walking(DTW)conditions.Using SPSS software for statistical analysis,P < 0.05 was considered to be statistically significant.Results: A total of 114 patients with CSVD were included in this study,with an average age of 60.0(56.0–67.0)years,61 males(53.5%),and an average CHIPS of 11.5(5.0–19.0)score;The average STW gait speed was 0.9(0.8–1.0)m/s,and the average DTW gait speed was 0.8(0.6-0.9)m/s.In linear regression,after adjustment for demographics and vascular risks,the results showed that:(1)CHIPS was associated with STW gait speed(β = –0.247,P = 0.026)and DTW gait speed(β = –0.483,P = 0.001);Total WMH was associated with STW gait speed(β= –0.235,P = 0.043)and DTW gait speed(β = –0.285,P = 0.006);PVWMH was associated with STW gait speed(β = –0.196,P = 0.014)and DTW gait speed(β = –0.393,P < 0.001);(2)Global cognitive function was related to STW gait speed(β = –0.220,P = 0.005)and DTW gait speed(β = –0.348,P = 0.005),and the execution function was related to DTW step speed(β = –0.186,P = 0.038);(3)CHIPS was associated with global cognitive function(β = –0.392,P = 0.001),executive function(β = –0.310,P = 0.007),processing speed/ attention(β = –0.291,P =0.012),language function(β = –0.368,P < 0.001);total WMH was associated with global cognitive function(β = –0.285,P = 0.015),executive function(β = –0.237,P = 0.044),and processing speed/ attention(β = –0.354,P = 0.002);PVWMH was associated with global cognitive function(β = –0.311,P = 0.003),executive function(β = –0.253,P =0.018),processing speed/attention(β = –0.274,P = 0.010),and language function(β= –0.269,P = 0.012);DWMH was associated with processing speed/attention(β = –0.284,P = 0.015).(4)Global cognition function partially mediated the relationship between total WMH/PVWMH/ CHIP and STW gait speed and DTW gait speed.Conclusion: This study suggests that WMH(total WMH,PVWMH and WMH in the cholinergic pathway)may play a key role in gait disturbance through cognitive impairment in patients with CSVD.Gait is a cognitive process to some extent and the crucial role of cognition should be considered when investigating gait disturbance in patients with CSVD.Part 3 Imaging features and the predictive value of postural sway test of fall risk associated with cerebral small vessel diseaseObjective: WMH is associated with gait disorder,balance disorder and increased falls risk in the elderly.It was reported that nearly 1/3 of the elderly over the age of 65 fall every year,which cause a serious burden on the socio-economic system.In some neurological diseases,the instrumented postural sway(ISway)test was usually used to evaluate the sensorimotor integration function in balance control,and predicted the fall risk.Therefore,the following were the purposes of this study: 1)to investigate the relationship between CSVD imaging markers and fall;2)to evaluate the correlation between WMH severity and sensorimotor integration function;and 3)to assess whether ISway can be used as a tool to predict the fall risk in patients with WMH aged ≥ 60 years.Methods: Consecutive outpatients aged ≥ 60 years in the Department of Neurology of Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of science and technology from December 2019 to February 2021 were included.Falls were ascertained prospectively for 12-months.The clinical information and data of patients were collected and recorded.Total WMH、Periventricular WMH(PVWMH)and deep WMH(DWMH)were assessed by Fazekas scale.Cognitive function was assessed by Montreal cognitive assessment test(Mo CA).And sensorimotor integration function was assessed by ISway.Seven objective parameters including Sway area,Centroid frequency,Jerk,Mean velocity,Path length,Root mean square(RMS)of sway and Range of acceleration were collected.Using SPSS software for statistical analysis,P < 0.05 was considered to be statistically significant.Results: The median age of the 150 patients with WMH was 67.0(64.0–72.0)years,45.3% were males.According to follow-up,all patients were divided into fall group(n =33)and control group(n = 117).(1)The severity of total WMH(P = 0.002),PVWMH(P = 0.001)and DWMH(P = 0.005)were related with fall,respectively;(2)Under the conditions of eyes open-firm surface(ECFIS)and eyes closed-firm surface(ECFIS),the severity of total WMH,PVWMH and DWMH were positively related with ISway parameters,including Sway area,Jerk,Mean velocity,Path length,RMS of sway and Range of acceleration,respectively(P < 0.05);(3)Under the conditions of EOFIS,ISway parameters including Sway area,Jerk,Mean velocity,Path length,RMS of sway and Range of acceleration were positively related with fall(P < 0.05);and total duration of TUG test was positively related with fall(P <0.05).(4)In ROC analysis,under the conditions of EOFIS,ISway parameters including Sway area,Jerk,Mean velocity,Path length,RMS of sway,Range of acceleration and total duration of TUG test(P < 0.05)could predict fall risk.The area under the curve of Sway area is the largest,and the optimal critical value is 0.1212 m2/ s4.Conclusion: The findings of this study suggested that the severity of total WMH,PVWMH and DWMH were related to sensorimotor integration dysfunction,which may lead to falls.In addition,under the condition of EOFIS,ISway could predict the fall risk in patients with WMH aged ≥ 60 years,and is expected to become a screening tool for early identification of fall risk in the future.