Brain Structural Characteristics Of Alzheimer's Disease And Its Correlation With TCM Syndromes

Objectives:Explore the cortical atrophy and white matter lesions of Alzheimer’s Disease(AD)and their correlation with olfactory disorders and TCM syndromes.Methods:A case-control study was used to collect AD,Mild Cognitive Impairment(MCI)and Normal Cognitive(NC)subjects who attended Dongzhimen Hospital of Beijing University from September 2018 to March 2021.Then match the three groups of subjects at a ratio of 1:1:1 according to age and gender.Study 1 included 48 people(16 people in each group)who underwent structural Magnetic Resonance Imaging(sMRI)examinations.FreeSurfer 6.0 was used to extract sMRI parameters,including subcortical volume,cortical volume,and cortical thickness.Study 2 included 36 people(12 people in each group)who underwent Diffusion Tensor Imaging(DTI)and used PANDA 1.3.1 to extract DTI parameters.DTI parameters were mainly used to show the degree of white matter barrier damage,axon degeneration,and demyelinating.Sniffin’ Sticks 12 olfactory scores and TCM syndrome scores were collected,an Excel database was established,SPSS 26.0 was used for statistical analysis,and the differences in sMRI parameters and DTI parameters of the Region of Interest(ROI)between the three groups were compared.Analyze the correlation of sMRI parameters and DTI parameters with olfactory score and TCM syndrome score by correlation test.Results:1.A quantitative study of brain atrophy in AD:(1)The comparison between ROI volume and cortical thickness showed:The left hippocampus volume of AD(V=2806.219±804.428 mm3)was significantly smaller than that of NC(V=3758.762±533.644 mm3)(P=0.001).The volume of the right hippocampus of AD(V=2956.163±677.293 mm3)was significantly smaller than that of NC(V=3895.113±664.343 mm3)(P=0.002).The volume of the left amygdala of AD(V=1043.756±343.151 mm3)was significantly smaller than that of NC(V=1446.669±200.654 mm3)(P=0.002).The volume of the right amygdala of AD(V=1141.719±325.303 mm3)was significantly smaller than that of NC(V=1510.531±179.758 mm3)(P=0.001).The volume of the left accumbens of AD(V=299.488±109.179 mm3)was significantly smaller than that of NC(V=418.475±99.488mm3)(P=0.004).The volume of the right accumbens of AD(V=382.625±84.674mm3)was significantly smaller than that of NC(V=477.694±64.938 mm3)(P=0.001).The thickness of the left olfactory cortex of AD(D=2.539±0.644 mm)was significantly smaller than that of NC(D=3.371±0.373 mm)(P=0.000).The thickness of the right olfactory cortex of AD[D=2.411(2.697,3.221)mm]was significantly smaller than that of NC[D=3.482(3,799,4.023)mm](P=0.000).The thickness of the left parahippocampal gyrus of AD(D=2.029±0.442 mm)is smaller than that of NC(D=2.421±0.277 mm)(p=0.023).The thickness of the right parahippocampal gyrus of AD(D=2.023±0.336 mm)was significantly smaller than that of NC(D=2.391±0.211 mm)(P“0.003).The volume of the left parahippocampal gyrus of AD(V=1432.560±319.429 mm3)is smaller than that of NC(V=1818.750±360.918 mm3)(P=0.012).The volume of the right parahippocampal gyrus of AD(V=1353.310±234.101 mm3)was significantly smaller than that of NC(V=1686.190±258.886mm3)(P=0.003).The volume of the left olfactory cortex of AD[V=1203.50(882.75,1619.50)mm3]was significantly smaller than that of NC[V=1920.00(1549.25,2116.75)mm3](P=0.003).The volume of the right olfactory cortex of AD(V=1181.560±385.955 mm3)was significantly smaller than that of NC(V=1741.940±308.221mm3)(P=0.000).The thickness of the left olfactory cortex of MCI(D=2.903±0.532 mm)is smaller than that of NC(D=3.371±0.373 mm)(P=0.041).The thickness of the right olfactory cortex of MCI[D=3.007(3.454,3.521)mm]is minor than NC[D=3.482(3.799,4.023)mm](P=0.014).The volume of the left olfactory cortex of MCI[V=1670.000(1015.000,1882.000)mm3]is smaller than that of NC[V=1920.000(1549.250,2116.750)mm3](P=0.045).(2)Correlation between thickness and volume of the cortex and olfactory score:Sniffin’Sticks 12 olfactory score is positive correlate with the thickness of the left olfactory cortex(r=0.462,P=0.004),the thickness of the right olfactory cortex(r=0.439,P=0.007),and the volume of the left olfactory cortex(r=0.485,P=0.002).(3)Correlation between cortical volume and TCM syndromes:There is a negative correlation between marrow reduction syndrome and left temporal pole volume(r=-0.368,P=0.010),right lower middle frontal gyrus volume(r=-0.351,P=0.014).The kidney deficiency syndrome was negatively correlated with the volume of the left frontal pole(r=-0.356,P=0.013).2.Quantification study of white matter microstructure lesions in AD:(1)Comparison of DTI parameters between groups:The damage of the white matter barrier of the left hippocampus of AD[MD(Mean Diffusion)=0.00104842±0.000144335]is more serious than that of NC(MD=0.00091775±0.000091303)(P=0.020).The damage of the white matter barrier of the right hippocampus of AD[MD=0.0009435(0.00090425,0.00109225)]is more severe than that of NC[MD=0.0008365(0.00080450,0.00089275)](P=0.002).The left hippocampus demyelinating lesions of AD[DR(Radial Diffusion)=0.00133550±0.000143498]are more serious than that of NC(DR=0.00121433±0.000106171)(P=0.043).The right hippocampus demyelinating lesions of AD[DR=0.00127450(0.00119550,0.00141300)]are more serious than that of NC[DR=0.00111875(0.00115550,0.00116850)](P=0.006).The left hippocampus axon degeneration of AD[DA(Axial Diffusion)=0.00090450±0.000147751]is more serious than that of NC(DA=0.00076933±0.000087468)(P=0.016).The axon degeneration in the right hippocampus of AD[DA=0.00078650(0.00075125,0.00092975)]is more serious than that of NC[DA=0.00062900(0.00068350,0.00076225)](P=0.012).(2)Correlation between demyelinating lesions and olfactory score:Sniffin’ Sticks 12 olfactory score was negatively correlated with the degree of demyelination of the left hook bundle(r=-0.470,P=0.005).(3)Correlation between white matter lesions and TCM syndrome scores:The syndrome of marrow reduction is negatively correlated with the integrity of the right medial colliculus system white matter barrier(r=-0.353,P=0.035).Kidney deficiency syndrome is positively correlated with the degree of white matter barrier damage of the corpus callosum spleen(r=0.345,P=0.040),the right medial colliculus system(r=0.343,P=0.041).The degree of demyelinating lesions on the the corpus callosum spleen(r=0.366,P=0.028),the left posterior radiated crown(r=0.364,P=0.029)and right fornix/terminal stria(r=0.355,P=0.034)are positively correlated with Kidney deficiency.Conclusion:The atrophy of the bilateral olfactory cortex has already appeared in the MCI stage.With the decline of cognitive function in AD patients,axon lesions and demyelination changes in the hippocampus on both sides.The decreased sense of smell in AD patients is related to bilateral olfactory cortex atrophy and white matter lesions in the olfactory pathway.Kidney deficiency and marrow reduction are common symptoms of AD cortical atrophy and white matter lesions.