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Objective:To investigate the relationship between brain derived neurotrophic factor (BDNF) gene polymorphism and the change of grey matter volume (GMV) and fractional amplitude of low-frequency fluctuation (fALFF) in cerebral small vessel disease (CSVD) patients with subcortical ischemic depression (SID).Methods:Eighty-seven CSVD patients in the First Affiliated Hospital of Anhui Medical University were enrolled from July 2017 to November 2020 and divided into CSVD-SID group [Geriatric Depression Scale (GDS) score>10] and CSVD-non - depression group (CSVD-ND group, GDS score≤10) according to GDS. Both GMV and fALFF were calculated based on structural and functional magnetic resonance imaging data, and the interactions between SID diagnosis and BDNF gene on brain function and structure alteration were explored.Results:GMV was significantly increased in the posterior default network (pDMN; such as posterior cingulate gyrus/precuneus and middle temporal gyrus) in the CSVD-SID group compared with the CSVD-ND group. On GMV property, significant interactions between BDNF gene and SID were found in the cuneus ( F=25.50, P<0.001), precuneus lobe ( F=13.61, P<0.001) and cerebellum ( F=17.23, P<0.001). In the aspect of fALFF, the brain functional activity in the superior frontal gyrus was significantly increased in the CSVD-SID group compared with that in the CSVD-ND group (0.363±0.648 vs -0.427±0.514,cluster size=48 voxels, t=5.63, P<0.001). But there was no significant interaction between diagnosis and BDNF genotype on brain function. Conclusions:Both the GMV and fALFF were increased in CSVD-SID, mainly located in the pDMN and frontal lobe. Significant interaction was found between CSVD-SID and BDNF genotype on GMV.
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Objective:To investigate the impact of altering brain gray matter volume (GMV) on cognition and gait disorder in patients with amnestic mild cognitive impairment (aMCI).Methods:Thirty-six patients with aMCI, who admitted to the First Affiliated Hospital of Anhui Medical University from July 2018 to August 2020, were collected, and 33 normal controls (NC) matched with age, sex and education level were included in the same period. The neuropsychological assessment was done in all the subjects using Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment scale (MoCA), Cambridge Cognitive Examination-Chinese version (CAMCOG-C), Geriatric Depression Scale (GDS) and Activities of Daily Living scale (ADL). The timed up and go test (TUG), dual task of timed up and go test (D-TUG) and Berg Balance Scale (BBS) were used in the subjects for assessment. The parameters such as stride length, gait speed, gait frequency were collected by intelligent device for energy expenditure and activity. All the subjects received 3.0 T magnetic resonance imaging scan to obtain high-resolution T 1 structural images. Voxel-based morphometry (VBM) was used to compare the difference of GMV between aMCI patients and NC. Partial correlation analysis was performed among altering GMV in the regions of interest (ROI), cognitive score and gait parameters, respectively. Linear regression analysis was used between whole brain GMV and gait parameters. Results:The scores of MMSE, MoCA, CAMCOG-C and the subitems of CAMCOG-C in aMCI group were significantly lower than those in NC group ( P<0.05). In aMCI patients, both the test time of TUG and D-TUG increased, gait speed slowed down, stride length shortened, and stride frequency and BBS score decreased ( P<0.05).VBM analysis showed that the whole brain GMV in aMCI patients was obviously lower than that of NC. In the aMCI group, GMV in ROI1 (right hippocampus, right parahippocampal gyrus, right amygdala and right fusiform gyrus), ROI2 (right middle temporal gyrus), ROI3 (right angular gyrus), ROI4 (right occipital lobe), ROI5 (bilateral orbital frontal lobe), ROI6 (left middle frontal gyrus and rectus gyrus), ROI7 (left fusiform gyrus and left parahippocampal gyrus) was significantly decreased compared with the NC group [Gaussian random field (GRF) correction, two-tailed test, voxel level P<0.001, cluster level P<0.05). In the aMCI group, GMV in ROI1 was positively correlated with orientation ( r=0.437, P=0.012), memory ( r=0.360, P=0.043), execution ( r=0.414, P=0.019), and negatively correlated with ADL score ( r=-0.529, P=0.002). GMV in ROI2 was negatively correlated with ADL score ( r=-0.400, P=0.023). GMV in ROI4 and in ROI5 was positively correlated with the calculation ( r=0.370, P=0.037) and execution ( r=0.360, P=0.043), respectively. GMV in ROI6 was positively correlated with MMSE score ( r=0.357, P=0.045), CAMCOG-C total score ( r=0.503, P=0.003) and calculation ( r=0.395, P=0.025), and negatively correlated with ADL score ( r=-0.387, P=0.028). GMV in ROI5 was positively correlated with gait speed ( r=0.391, P=0.027). In the aMCI group, CAMCOG-C total score was negatively correlated with D-TUG results ( r=-0.387, P=0.035), executive function was negatively correlated with TUG results ( r=-0.450, P=0.013) and D-TUG results ( r=-0.553, P=0.002), and positively correlated with gait speed ( r=0.379, P=0.039). Attention was positively correlated with gait speed ( r=0.590, P=0.001), and computing was positively correlated with gait speed ( r=0.371, P=0.044). The linear regression of whole brain GMV and gait parameters showed negative correlation between the GMV of left occipital lobe and TUG results in the aMCI group. The GMV of bilateral prefrontal cortex, right occipital lobe and surrounding cortex was positively correlated with gait speed (GRF correction, two-tailed test, voxel level P<0.001, cluster level P<0.05). Conclusions:Patients with aMCI presented with gray matter atrophy, cognition impairment, and gait disorders. The cognition impairment was closely related to the atrophy of medial temporal lobe. Gait disorders were not only associated with cognition impairment but also with gray matter volume in the prefrontal lobe, occipital lobe and its surrounding cortex, and anterior central gyrus.
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Objective:To analyze the changes of total gray matter volume in patients with subcortical vascular cognitive impairment (SVCI) and their correlation with cognitive impairment.Methods:Data of fifty patients with subcortical ischemic vascular disease (SIVD) who admitted to the outpatient department or ward of the Department of Neurology, the First Affiliated Hospital of Anhui Medical University from November 2017 to March 2019, were collected for the study, including 23 patients with SVCI and 27 patients with subcortical ischemic vascular disease without cognitive impairment (SIVD-NCI). All subjects were assessed using the Minimal Mental State Examination (MMSE), the Montreal Cognitive Assessment scale (MoCA), the Cambridge Cognitive Assessment scale for the elderly-Chinese version (CAMCOG-C), the Stroop test, the Geriatric Depression Scale, and the Activity of Daily Living scale (ADL). All subjects underwent 3.0 T magnetic resonance imaging scans to obtain T 1WI, T 2WI, fluid attenuated inversion recovery (FLAIR) images and 3D-T 1 structural image data. Voxel-based morphometry (VBM) was used to analyze and compare the differences in gray matter volume between SVCI group and SIVD-NCI group. Results:Compared with the SIVD-NCI group, the MMSE score (22.00 (20.00, 24.00) vs 28.00 (27.00, 29.00), Z=-6.073, P<0.001), MoCA score (15.00 (13.00,19.00) vs 24.00 (23.00, 26.00), Z=-5.233, P<0.001), total score of CAMCOG-C (67.65±13.35 vs 88.41±10.98, t=-6.032, P<0.001) and the directional (8.00 (5.00, 9.00) vs 10.00 (9.00, 10.00), Z=-4.133, P<0.001), language (24.00 (21.00, 26.00) vs 27.00 (24.00, 28.00), Z=-3.171, P=0.002), memory (11.00 (9.00, 15.00) vs 19.00 (17.00, 21.00), Z=-4.648, P<0.001), attention (4.00 (2.00, 6.00) vs 7.00 (6.00, 7.00), Z=-3.929, P<0.001), executive (8.00 (6.00, 10.00) vs 11.00 (9.00, 12.00), Z=-3.696, P<0.001), calculation (2.00 (2.00, 2.00) vs 2.00 (2.00, 2.00), Z=-2.528, P=0.011), thinking (6.00 (3.00, 6.00) vs 6.00 (6.00, 8.00), Z=-4.029, P<0.001), perception (6.00 (6.00, 7.00) vs 8.00 (7.00, 9.00), Z=-4.221, P<0.001) in the SVCI group were obviously decreased. ADL score (21.00 (20.00, 26.00) vs 20.00 (20.00, 20.00), Z=-2.634, P=0.008) and Stroop test score (28.61±4.53 vs 20.04±6.07, t=5.704, P<0.001) were significantly higher in the SVCI group than in the SIVD-NCI group. The total gray matter volume ((556.86±49.19) mm 3vs (618.13±51.73) mm 3, t=-3.572, P=0.001) and white matter volume ((479.35±48.17) mm 3vs (507.22±43.84) mm 3, t=-2.141, P=0.037) in the SVCI group were smaller than that in the SIVD-NCI group. VBM analysis showed that the SVCI group had significantly smaller gray matter volume in the left inferior temporal gyrus ( t=5.17, P<0.001, family wise error (FWE) correction), right middle temporal gyrus ( t=4.99, P<0.001, FWE correction), right orbital superior frontal gyrus ( t=5.02, P<0.001, FWE correction), left middle occipital gyrus ( t=5.67, P<0.001, FWE correction), right middle occipital gyrus ( t=5.77, P<0.001, FWE correction). MoCA score was positively correlated with the volume of gray matter in the left inferior temporal gyrus of patients with SIVD ( r=0.292, P<0.05), language function score was positively correlated with the volume of gray matter in the left inferior temporal gyrus ( r=0.322, P<0.05), and Stroop test score was negatively correlated with gray matter volume in the left inferior temporal gyrus ( r=-0.329, P<0.05). Conclusion:Gray matter atrophy exists in multiple brain regions in patients with SVCI, and these atrophic brain regions are associated with cognitive impairment of SIVD.
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Objective To investigate the characteristics of cognitive impairment in critical patients, and to explore the role of early cognitive intervention training in improving cognitive impairment in critical patients. Methods A prospective cohort study was conducted. 133 patients in conscious and normal intelligence admitted to intensive care unit (ICU) of Hefei Second People's Hospital from January 2015 to June 2018 were enrolled. The patients were divided into control group (n = 66) and cognitive intervention group (n = 67) according to random number table based on chronological number for entry into the study. Cognitive function was assessed by Montreal cognitive assessment scale (MoCA scale) within 24 hours after ICU admission. The patients in the cognitive intervention group received a series of scientifically designed cognitive training sessions (playing electronic musical keyboard, learning simple Spanish, clock-drawing, psychological intervention) for 2 months, and follow-up was completed if the patient was discharged from ICU. While the patients in the control group did not undertake any cognitive training. After 2 months, the cognitive function of patients in both groups were assessed with MoCA scale. Subgroup analysis was conducted according to different age groups (20-40 years old, 41-60 years old, 61-80 years old) to explore the effect of cognitive intervention training in different age groups. According to the subjective evaluation of the patient's ability to live 2 months after cognitive intervention by the patient or his relatives, receiver operating characteristic (ROC) curve was plotted to evaluate the predictive value of the total score of MoCA for patients' ability to live after cognitive intervention. Results 133 critical patients were enrolled in the final analysis. There was no significant difference in gender, age, education, complications, ICU hospitalization, sedative or analgesic drug usage between the two groups, indicating that the data of the two groups were balanced and comparable. No significant difference in MoCA scale total score or sub-item cognitive domain score within 24 hours of ICU admission was found between the two groups. After 2 months of intervention, the incidence of cognitive impairment in the cognitive intervention group was significantly lower than that in the control group [38.8% (26/67) vs. 60.6% (40/66), χ2 = 6.321, P = 0.015]. The total score of MoCA scale and four sub-item cognitive domain scores including visual space and execution power, protection of memory, attention execution, and orientation in the cognitive intervention group were significant higher than those in the control group (MoCA scale total score: 26.73±1.92 vs. 24.95±2.26, visual space and executive power score: 4.39±0.70 vs. 3.95±0.88, protection of memory score: 8.91±1.03 vs. 8.24±1.37, attention execution score: 5.21±0.77 vs. 4.79±1.00, orientation score: 5.67±0.53 vs. 5.44±0.68, all P < 0.05), but no significant difference was found in verbal skills score (2.55±0.56 vs. 2.53±0.56, P > 0.05). Subgroup analysis showed that the total MoCA scale score of the younger sample (20-40 years old, n = 20) was recovered by 2.10±1.55 in the cognitive intervention group after 2 months of cognitive intervention, which was significantly higher than that in the control group (n = 21; 0.24±2.76, P < 0.05). In the middle-aged and the older population [aged 41-60 years old (n = 20) and 61-80 years old (n = 27)], the total MoCA scale scores were recovered slightly after cognitive intervention as compared with those in the younger sample (0.43±1.47, -1.91±2.20 vs. 2.10±1.55, both P < 0.05), which were significantly lower than those in the control group [aged 41-60 years old (n = 21) and 61-80 years old (n = 24), -0.78±1.38, -4.41±2.17,both P < 0.01]. It was suggested that cognitive intervention training played an active role in the recovery of cognitive function in young critical patients. It was shown by ROC curve analysis that the area under ROC curve (AUC) of MoCA scale total score for predicting daily life ability after cognitive intervention was 0.732 with 95% confidence interval (95%CI) of 0.646-0.819. When the best cut-off value was 24.5, the sensitivity was 89.3%, the specificity was 60.2%, the positive predictive value was 85.7%, and the negative predictive value was 80.8%. Conclusions Early cognitive intervention could efficiently abate the deterioration of cognitive function in critical patients in ICU and had significant effects on the visual space and executive power, protection of memory, attention execution and orientation. Cognitive intervention exerted significantly positive effects on the recovery of cognitive function in the younger sample population (aged 20-40 years old).
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Objective To explore the correlation between apolipoprotein E (ApoE) gene polymorphism and urine Alzheimer-associated neuronal thread protein (AD7c-NTP) level in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI).Methods The cognitive function of 30 AD patients (AD group),30 MCI patients (MCI group) and 30 normal controls (NC group) was evaluated by neuropsychological batteries like MMSE,the Cambridge Cognitive Examination-Chinese Version (CAMCOG-C),etc.ELISA was used to test the urine level of AD7c-NTP.The genotypes of ApoE were analyzed by the high-resolution melting assay in blood samples.Results Compared with the NC group (0.59 (0.40,0.66) ng/ml),the urine level of AD7c-NTP in the AD group (1.03(0.80,1.41) ng/ml) and the MCI group (0.69(0.53,0.91) ng/ml) was increased (Z =33.727,P ＜0.01).The urine level of AD7c-NTP in the AD group was higher than that in the MCI group (Z =8.232,P ＜ 0.05).The level of AD7c-NTP in urine was negatively correlated with MMSE and CAMCOG-C scores (rMMSE =-0.604,P ＜ 0.01;rCAMCOG-C =-0.486,P ＜ 0.01).According to receiver operating characteristic curve,the optimal cutoff point of AD7c-NTP in urine for diagnosis of patients including AD and MCI was 0.70 ng/ml,with sensitivity of 71.7％ and specificity of 83.3％,and area under the curve of 0.82 (95％ CI 0.73-0.90,P ＜0.05).There were four genotypes comprising ε2/3,ε3/3,ε3/4 and ε4/4 for ApoE gene.The frequencies of ε4 carriers were 46.7％ (14/30),23.3％ (7/30) and 23.3％ (7/30) in the AD,MCI and NC groups,respectively.There was a notable increase in urine AD7c-NTP and a significant decrease in CAMCOG-C scores in MCI patients who harbored the ApoE ε4 allele (ZAD7c-NTP =4.857,P ＜ 0.05;ZCAMCOG-C =4.284,P ＜0.05).Conclusions The urine level of AD7c-NTP was significantly increased in AD and MCI patients,the higher the level of AD7c-NTP,the more serious the cognitive impairment.The ε4 carriers exhibited higher urine level of AD7c-NTP,but worse cognitive function compared to ε4 non-carriers in the MCI group.
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Objective To explore the ascendency of the teaching mode of problem-based learning seminar (PBL-seminar) in comparison to the traditional mode of 1ecture-based learning (LBL) in Neurology teaching.Methods 100 students were recruited from the department of clinical medicine of Anhui Medical University,and they were divided randomly into observation group and control group (50 students in each group).Teaching modes of PBL-seminar and LBL were employed for teaching in observation group and control group respectively.Teaching effects were evaluated through questionnaire,theory test and clinical skill measurement.Learning interest and enthusiasm,self-study and development ability,and problem-analyzing and solving ability,team cooperation ability,communication skills and theory test scores were compared between the two groups.Results The learning interest and enthusiasm,self-study and development ability,and problem-analyzing and solving ability,team cooperation ability,communication skills and theory test scores in the observation group were significantly better than those in the control group(x2=27.47,18.88,21.42,32.19,all P<0.01).The theoretical examinations and clinical practice skills between the two groups had statistically significant differences (t=5.94,P<0.05;t=9.13,P<0.01).Conclusion PBL-seminar teaching mode is superior to the traditional mode.
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Objective To explore the levels of serum alkaline phosphatase ( ALP) as well as its impact on the cognitive impairment in patients with subcortical ischemic vascular disease ( SIVD).Methods One hundred and fifty-eight SIVD patients were divided into two subgroups which included 86 patients with mild cognitive impairment ( SVMCI ) and 72 patients with vascular dementia ( SVaD ) according to the severity of cognitive impairment.Sixty-seven old people with normal cognitive function were selected as control qruop.Multiple lacunar infarction ( LI) or leukoaraiosis ( LA) was detected according to their MRI scan appearances and graded LA according to the severity.Serum ALP was measured by an enzymatic method as well as the Mini-Mental State Examination ( MMSE) and the Cambridge Cognitive Examination-Chinese Version (CAMCOG-C) were used in assessments.Serum ALP was divided into 3 groups and the occurrence rate of LI , LA and cognitive impairment were compared with each other.The levels of ALP were compared in different cognitive impairment and Logistic regression was used to explore the relation between ALP and cognitive impairment.Results Both SVaD and SVMCI groups (17.00 (13.00, 20.00), 59.50 (49.00, 68.75);25.00 (25.00, 26.00), 82.50 (76.75, 89.00)) showed significantly lower scores in MMSE and CAMCOG-C than control group (28.00 (28.00, 29.00), 93.00 (89.00, 96.00); Z=187.337, P=0.000; Z=150.480, P=0.000).A positive relationship between the elevated ALP level and the severity of cognitive impairment was found after adjusting for sex , age and other confunding factors ((68.60 ±15.52), (78.76 ±13.39), (86.75 ±18.85) U/L, F=22.587, P=0.000).The occurrence rate of LI, LA and SVaD among the three groups were significantly different (χ2 =8.008, P=0.018;χ2 =17.998, P=0.000;χ2 =12.255, P=0.002).The ALP level was negatively correlated with MMSE and CAMCOG-C scores ( r=-0.350, P=0.000; r=-0.286, P=0.000 ).Logistic regression analysis revealed the relation between ALP and cognitive impairment was positive when we controlled all the vascular risk factors.However , the relation had gone when futher adjusting for the grade of LA.Conclusions The level of ALP is significantly higher in SIVD patients and positively relates with cognitive impairment especially in those whose grade of LA is severe.