Characteristics Of Brain Structural Changes In Patients With Subjective Cognitive Decline And Amnestic Mild Cognitive Impairment And Their Correlation With Cognitive Function

Chapter 1 The characteristic of hippocampal subregion volume lesions in patients with Alzheimer's disease spectrumObjective: To explore the atrophy pattern of hippocampal subregion volume and its correlation with memory function in patients with subjective cognitive impairment(SCD),amnesia mild cognitive impairment(a MCI)and Alzheimer's disease(AD).Methods: 151 participants were recruited from the Neurology clinic,Nanjing Drum Tower Hospital,the Affiliated Hospital of Nanjing University Medical.Mini-Mental State Examination(MMSE)and Montreal Cognitive Assessment scale(Mo CA)were used to evaluate the general cognitive function and Auditory Word Learning Test(AVLT)was used to test the memory function.According to the Cognitive status and whether the subjects had memory impairment complain or not,all participants were divided into normal control group(NC,n = 43),SCD group(n = 37),a MCI group(n = 36)and AD group(n = 36).All subjects underwent 3.0 T1 MRI.The volumes of 12 subregions were calculated by Free Surfer 6.0 image analysis software,and the correlation between hippocampal subregion and memory function was analyzed by partial correlation analysis.Results: The volume of hippocampal subfields was significantly different between NC,SCD,a MCI and AD,except for the right hippocampal fissure and parasubiculum after Bonferroni multiple comparison correction.(P < 0.05).As the severity of the disease progressed,bilateral molecular layer,left hippocampal dentate gyrus and left CA4 subregion volume showed a significant downward trend.Partial correlation analysis showed that there was no significant correlation between hippocampal subfield volume and memory function in SCD group.A significant positive correlation between left hippocampal tail volume and AVLT-recognition score was observed in a MCI group(P<0.05).In AD group,bilateral subiculum,presubiculum volume,left hippocampal fissure,parasubiculum,molecular layer,dentate gyrus,CA4,hippocampal amygdala transitional area volume and right hippocampal fimbria volume were positively correlated with AVLVT-delayed recall scores(all P < 0 05).Conclusions: The overall volume of hippocampus and some of hippocampal subregion volume had changed as early as SCD stage,and with the disease course advanced,an atrophy pattern of significantly volume decreased in bilateral molecular layer,left dentate gyrus and left CA4 subregion was discovered.Early detection of the overall or subregion volume of the hippocampus is useful for the early diagnosis and monitoring the progression of Alzheimer's diseases.Chapter 2 White matter integrity and its correlation with cognitive function in patients with subjective cognitive decline and amnesia mild cognitive impairmentBackground and Objective: Subjective cognitive decline(SCD)may be a preclinical marker for Alzheimer's disease(AD),which is considered a more advanced preclinical status than amnestic mild cognitive impairment(a MCI).Our aim was to explore the change pattern of white matter microstructure and its correlation with cognitive function in patients with SCD and a MCI.Methods: A cohort of 117 subjects were enrolled at the Department of Neurology of the Affiliated Drum Tower Hospital of Nanjing University Medical School from June 2016 to June 2019 in this study.The global cognitive function was evaluated with Minimental state examination(MMSE)and Montreal Cognitive Assessment scale(Mo CA),and the memory function was evaluated with auditory verbal learning test(AVLT).According to the results of cognitive test and whether the subjects had memory complain or not,all participants were divided into three groups: 43 normal controls(NC),38 SCD,36 a MCI.All subjects were examined by 3.0T diffusion tensor magnetic resonance imaging.The diffusion parameters of 20 main white matter tracts were calculated based on the atlas-based segmentation strategy and compared among the three groups.Correlation between diffusion parameters and cognitive function was further analysed.Results: As compared to NC individuals,significantly lower fractional anisotropy(FA)values of forceps major and forceps minor were observed in both in SCD and a MCI group,as well as significantly increased mean diffusivity(MD)of bilateral anterior thalamic radiation(ATR),left corticospinal tract(CST.L),forceps minor(Fmi),left cingulum of cingulate gyrus(Cg C.L),left cingulum of hippocampus(Cg H.L),left Inferior fronto-occipital fasciculus(IFO.L).Regression model analyses suggests metrics of Fmi,Cg C.L,Cg H.L was strongly correlated with performance in general cognitive and memory functionConclusion: SCD individuals had extensive white matter microstructural damage,in a pattern like a MCI.Disrupted integrity of white matter in SCD may be a potential early biomarker for risk of future cognitive decline.Future studies should aim to characterize SCD individuals longitudinally.