Risk factors and clinical features of mild cognitive impairment in patients with ischemic cerebral small vessel disease： a retrospective case series study

Dementia is associated with sleep disorders. However, the relationship between dementia and sleep arousal remains unclear. This study explored the associations among sleep parameters, arousal responses, and risk of mild cognitive impairment (MCI). Participants with the chief complaints of memory problems and sleep disorders, from the sleep center database of Taipei Medical University Shuang-Ho Hospital, were screened, and the parameters related to the Cognitive Abilities Screening Instrument, Clinical Dementia Rating, and polysomnography were determined. All examinations were conducted within 6 months and without a particular order. The participants were divided into those without cognitive impairment (Clinical Dementia Rating = 0) and those with MCI (Clinical Dementia Rating = 0.5). Mean comparison, linear regression models, and logistic regression models were employed to investigate the associations among obtained variables. This study included 31 participants without MCI and 37 with MCI (17 with amnestic MCI, 20 with multidomain MCI). Patients with MCI had significantly higher mean values of the spontaneous arousal index and spontaneous arousal index in the non-rapid eye movement stage than those without MCI. An increased risk of MCI was significantly associated with increased spontaneous arousal index and spontaneous arousal index in the non-rapid eye movement stage with various adjustments. Significant associations between the Cognitive Abilities Screening Instrument scores and the oximetry parameters and sleep disorder indexes were observed. Repetitive respiratory events with hypoxia were associated with cognitive dysfunction. Spontaneous arousal, especially in non-rapid eye movement sleep, was related to the risk of MCI. However, additional longitudinal studies are required to confirm their causality. Tsai C-Y, Hsu W-H, Lin Y-T, etal. Associations among sleep-disordered breathing, arousal response, and risk of mild cognitive impairment in a northern Taiwan population. J Clin Sleep Med. 2022;18(4): 1003-1012.

We aimed to investigate the effect of cerebral small vessel disease (SVD) on cholinergic system integrity in mild cognitive impairment (MCI) patients. Nucleus basalis of Meynert (NBM) volume and cholinergic pathways integrity was evaluated at baseline, 1-, 2-, and 4-year follow-ups in 40 cognitively unimpaired (CU) participants, 29 MCI patients without SVD, and 23 MCI patients with SVD. We compared cholinergic markers among three groups and examined their associations with SVD burden in MCI patients. We used linear mixed models to assess longitudinal changes in cholinergic markers over time among groups. Mediation analysis was employed to investigate the mediating role of cholinergic system degeneration between SVD and cognitive impairment. Increased mean diffusivity (MD) in medial and lateral pathways was observed in MCI patients with SVD compared to those without SVD and CU participants. Both MCI groups showed decreased NBM volume compared to CU participants, while there was no significant difference between the two MCI groups. Longitudinally, compared to CU participants, MCI patients with SVD displayed a more rapid change in MD in both pathways, but not in NBM volume. Furthermore, SVD burden was associated with cholinergic pathway disruption and its faster rate of change in MCI patients. However, mediation analyses showed that cholinergic pathways did not mediate significant indirect effects of SVD burden on cognitive impairment. Our findings suggest that SVD could accelerate the degeneration of cholinergic pathways in MCI patients. However, they do not provide evidence to support that SVD could contribute to cognitive impairment through cholinergic system injury.

Nutrient biomarkers and vascular risk factors in subtypes of mild cognitive impairment: a cross-sectional study.

Objective To investigate platelet α and β secretase activities and the amounts of platelet soluble fragment of APP (sAPPα) produced by α-secretase in patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Methods The neurological functions of 48 non-demented patients, 42 MCI and 40 AD patients were evaluated by neuropsychological examinations. The platelet α and β secretase activities and sAPPα production in each group were measured by fluorescence and Western blotting analysis respectively. Results The α secretase activities in non-demented, MCI and AD group were 100.0%±10.6%, 78.2%±9.4% and 61.8%±7.2% respectively. As compared with non-demented group, the α secretase activities in MCI and AD group were decreased (F=22.935, P=0.001). The α secretase activity in AD group was significantly lower than MCI group. The β secretase activities in non-demented, MCI and AD group were 100.0%±11.2%, 145.8%±12.7% and 189.8%±14.2% respectively. The β secretase activities in MCI and AD group were significantly higher than that in non-demented group (F=16.368, P=0.001). The β secretase activity in AD group was significantly decreased as compared with MCI group. The sAPPα amounts in MCI group and AD group were all decreased as compared with that in control group; the sAPPα amount in AD patients was significantly decreased as compared with that in MCI group. Conclusions The platelet α secretase activity and its production sAPPα in MCI and AD patients are decreased, while β secretase activity is increased, as compared with that in control group; the altered α and β secretase activities may participate in the pathogenesis of MCI and AD patients and may have diagnostic potential for them. Key words: Cognition disorders; Alzheimer disease; Amyloid precursor protein secretases

High Activities of BACE1 in Brains with Mild Cognitive Impairment

Background: The link between arterial stiffness and mild cognitive impairment (MCI) is receiving increasing attention, and the goal of this study was to explore the relationship among the ankle brachial index (ABI), brachial-ankle pulse wave velocity (Ba-PWV), and MCI in patients with acute lacunar infarction (ALI). Methods: A total of 103 hospitalized patients with ALI were divided into a non-MCI group (n = 41) and an MCI group (n = 62) according to their Montreal Cognitive Assessment (MoCA) scores. A binary logistic regression model was used to assess the association among ABI, Ba-PWV, and MCI after adjusting for confounding factors. Spearman correlation was utilized to analyse the correlations between ABI, Ba-PWV, and MoCA total scores and sub-scores in ALI patients. Results: Participants with cognitive impairment had significantly higher Ba-PWV and lower ABI than those with normal cognition. Correlation analysis suggested that Ba-PWV (r = −0.854, p < 0.05) and ABI (r = 0.734, p < 0.05) were correlated with MoCA total scores; of all MoCA sub-scores, visuospatial/executive function was the most strongly correlated with the vascular variables. In the binary logistic regression analysis, Ba-PWV (odds ratio [OR] = 4.507, 95% confidence interval [CI] = 2.152–9.441) and ABI (OR = 1.124, 95% CI = 1.015–1.254) were significantly associated with MCI, even after adjusting for lipoprotein (a) and systolic and diastolic blood pressure. Conclusion: The present study suggested that a higher Ba-PWV and a lower ABI were independent risk factors for MCI in patients with ALI.

ObjectiveType 2 diabetes mellitus (T2DM) has beenis known as an important risk factor for cognitive impairment. Meanwhile, the liver plays a central role in the development of T2DM and insulin resistance. The present study attempted to identify and validate marker genes for mild cognitive impairment (MCI) in patients with T2DM.MethodsIn this study, insulin resistance-related differentially expressed genes were identified from the liver tissues of individuals with T2DM and those with normal glucose tolerance using the Gene Expression Omnibus database and MCI-associated genes were identified using the GeneCards database. Next, enrichment analysis was performed with overlapping T2DM and MCI genes, followed by the identification of specific genes using the LASSO logistic regression and SVM-RFE algorithms. An important experiment involved the implementation of clinical and in vitro validation using real-time quantitative polymerase chain reaction (RT-qPCR). Finally, multiple linear regression, binary logistic regression, and receiver operating characteristic curve analyses were performed to investigate the relationship between the key gene and cognitive function in these patients.ResultThe present study identified 40 overlapping genes between MCI and T2DM, with subsequent enrichment analysis revealing their significant association with the roles of neuronal and glial projections. The marker gene complement receptor 1(CR1) was identified for both diseases using two regression algorithms. Based on RT-qPCR validation in 65 T2DM patients with MCI (MCI group) and 65 T2DM patients without MCI (NC group), a significant upregulation of CR1 mRNA in peripheral blood mononuclear cells was observed in the MCI group (P < 0.001). Furthermore, the CR1 gene level was significantly negatively associated with MoCA and MMSE scores, which reflect the overall cognitive function, and positively correlated with TMTB scores, which indicate the executive function. Finally, elevated CR1 mRNA levels were identified as an independent risk factor for MCI (OR = 1.481, P < 0.001).ConclusionThese findings suggest that CR1 is an important predictor of MCI in patients with T2DM. Thus, CR1 has potential clinical significance, which may offer new ideas and directions for the management and treatment of T2DM. The identification and clinical validation of dysregulated marker genes in both T2DM and MCI can offer valuable insights into the intrinsic association between these two conditions. The current study insights may inspire the development of novel strategies for addressing the complicated issues related to cognitive impairment associated with diabetes.

ApoE Alleles and Tau Markers in Patients with Different Levels of Cognitive Impairment

Objective To investigate the psychosocial risk factors for mild cognitive impairment (MCI) in old people. Methods A case⁃control study was conducted in MCI and normal cognition elders. One hundred and sixty ⁃ five MCI elderly patients and 508 normal cognition elders were selected. The subjects' social demography basic data (gender, age, education level), leisure activities and personal hobby (penmanship, gardening, reading, writing article, autobiography or memoirs, etc.), social activities and special experience (the Great Proletarian Cultural Revolution, serious psychic trauma), sleeping and affection, histories of chronic disease were investigated. SPSS 12.0 statistics software was used to analyse data. Univariate analysis were conducted by Chi ⁃ square test, t test, Fisher exact test, and multivariate analysis were conducted by using Logistic regression model. Results There were 165 MCI patients (MCI group) and 508 normal cognition old people (NC group) investigated. The mean age in MCI group and NC group was 77.07 ± 0.59 years old and 76.91 ± 0.58 years old, respectively. There was no significant difference in gender among two groups (P > 0.05). Univariate analysis showed that age, education level, social participation, exercises, penmanship and writing article, autobiography or memoirs had significant differences between MCI and NC group (P 0.05, for all). Multivariate analysis confirmed that age, education level, writing article, autobiography or memoirs, exercises, and social participation presented significant positive correlation with MCI (P < 0.05, for all) and ORs (95% CI) were 1.448 (1.059-1.981）, 0.513 (0.346-0.761), 0.648 (0.447-0.939), 0.570 (0.357-0.911) and 0.435 (0.205-0.922), respectively. Conclusion Age, education level, social activities, exercises and writing article, autobiography or memoirs are significantly related to senile MCI. Age is an independent risk factor for MCI, while high education level, social participation, exercises and writing article, autobiography or memoirs seem to be protective factors for MCI. Therefore, appropriate early interventions may be essential to prevent and delay the development of senile cognitive impairment. DOI：10.3969/j.issn.1672-6731.2010.02.013

Introduction: The aims of this study are to explore the factors affecting mild cognitive impairment in patients with chronic kidney disease (CKD) who are not undergoing dialysis and to construct and validate a nomogram risk prediction model. Methods: Using a convenience sampling method, 383 non-dialysis CKD patients from two tertiary hospitals in Chengdu were selected between February 2023 and August 2023 to form the modeling group. The patients were divided into a mild cognitive impairment group (n = 192) and a non-mild cognitive impairment group (n = 191), and factors such as demographics, disease data, and sleep disorders were compared between the two groups. Univariate and multivariate binary logistic regression analyses were used to identify independent influencing factors, followed by collinearity testing, and construction of the regression model. The final risk prediction model was presented through a nomogram and an online calculator, with internal validation using Bootstrap sampling. For external validation, 137 non-dialysis CKD patients from another tertiary hospital in Chengdu were selected between October 2023 and December 2023. Results: In the modeling group, 192 (50.1%) of the non-dialysis CKD patients developed mild cognitive impairment, and in the validation group, 56 (40.9%) patients developed mild cognitive impairment, totaling 248 (47.7%) of all sampled non-dialysis CKD patients. Age, educational level, Occupation status, Use of smartphone, sleep disorders, hemoglobin, and platelet count were independent factors influencing the occurrence of mild cognitive impairment in non-dialysis CKD patients (all p < 0.05). The model evaluation showed an area under the ROC curve of 0.928, 95% CI (0.902, 0.953) in the modeling group, and 0.897, 95% CI (0.844, 0.950) in the validation group. The model's Youden index was 0.707, with an optimal cutoff value of 0.494, sensitivity of 0.853, and specificity of 0.854, indicating good predictive performance; calibration curves, Hosmer-Lemeshow test, and clinical decision curves indicated good calibration and clinical benefit. Internal validation results showed a consistency index (C-index) of 0.928, 95% CI (0.902, 0.953). Conclusion: The risk prediction model developed in this study shows excellent performance, demonstrating significant predictive potential for early screening of mild cognitive impairment in non-dialysis CKD patients. The application of this model will provide a reference for healthcare professionals, helping them formulate more targeted intervention strategies to optimize patient treatment and management outcomes.

PurposeDiabetic retinopathy (DR) can increase the risk of mild cognitive impairment (MCI), which has been confirmed by previous researches. With the frequent occurrence of MCI in patients with DR, the early detection of MCI has become a research hot-spot. The aim of this study was to investigate the relationship between neuron-specific enolase (NSE) and MCI in patients with DR.Patients and MethodsA total of 124 patients with DR, including 56 MCI patients and 68 normal cognition patients, were recruited in this cross-sectional study. The demographic and clinical data of patients were collected through questionnaires. Serum NSE was measured using electrochemiluminescence immunoassay. The Minimum Mental State Examination (MMSE) scale was used to evaluate the cognitive function of the participants.ResultsCompared with the normal cognition group, serum NSE levels and HbA1c levels in the MCI group were higher, while MMSE scores and educational level were lower (P<0.05). Serum NSE levels were significantly negatively correlated with MMSE total score, attention and calculation score, and language score (P<0.05). After adjusting for confounding factors, serum NSE still increased the MCI risk in DR patients (OR:1.606, 95CI%:1.264–2.041, P<0.001). The areas under the receiver operating characteristics (ROC) curves (AUC) of the crude model and the adjusted model were 0.75 and 0.73, respectively.ConclusionA high serum NSE level is an independent risk factor for MCI in DR patients. In addition, serum NSE is expected to be a potential biomarker in DR patients with MCI.

Increased serum levels of cyclophilin a and matrix metalloproteinase-9 are associated with cognitive impairment in patients with obstructive sleep apnea

As societies age, increasing numbers of older adults undergo surgeries with anesthesia. Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) frequently occur in older surgical patients. Most of these patients already have preoperative mild cognitive impairment (MCI). However, the correlation between MCI and POD remains unclear. This study aimed to determine the incidence of POD in elderly patients with and without preexisting MCI. A prospective study enrolled patients aged 60 years and above scheduled for major surgeries between December 2017 and April 2022. Preoperative MCI was determined by a Montreal Cognitive Assessment (MoCA) score between 18 and 24. POD was diagnosed using criteria from the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). POCD was characterized by a MoCA score reduction of 2 or more points from the preoperative score. The primary outcome was the incidence of POD within the first 72h postoperatively. Secondary outcomes encompassed other postoperative complications, including POCD. The study comprised 223 elderly patients with MCI and 56 without MCI. The incidence of POD was 16.6% in the MCI group and 14.3% in the non-MCI group (P = 0.839). POCD occurred in 24.3% of MCI patients and 50% of non-MCI patients (P = 0.001). There were no significant differences in other postoperative complications between the groups. Postoperatively, the MCI group notably declined in visuospatial, attention, and orientation domains, while the non-MCI group declined in all domains except delayed recall. The incidence of POD was similar in the MCI and non-MCI groups. However, the non-MCI group demonstrated a higher incidence of POCD than the MCI group. This was identified by a reduction in postoperative MoCA scores for the visuospatial, naming, attention, language, abstraction, and orientation domains. These findings underscore the importance of postoperative cognitive assessments for both elderly patients with preexisting MCI and those with previously intact cognitive functions. This trial was retrospectively registered in the Thai Clinical Trials Registry on 15/01/2019 (registration number: TCTR20190115001).

Diabetes mellitus is a risk factor for mild cognitive impairment (MCI) and dementia. However, how the clinical characteristics of MCI patients with type 2 diabetes mellitus are linked to sarcopenia and/or its criteria remain to be elucidated. Japanese patients with type 2 diabetes mellitus were categorized into the MCI group for MoCA-J (the Japanese version of the Montreal cognitive assessment) score <26, and into the non-MCI group for MoCA-J ≥26. Sarcopenia was defined by a low skeletal mass index along with low muscle strength (handgrip strength) or low physical performance (walking speed <1.0 m/s). Univariate and multivariate-adjusted odds ratio models were used to determine the independent contributors for MoCA-J <26. Among 438 participants, 221 (50.5%) and 217 (49.5%) comprised the non-MCI and MCI groups, respectively. In the MCI group, age (61 ± 12 vs. 71 ± 10 years, p < 0.01) and duration of diabetes mellitus (14 ± 9 vs. 17 ± 9 years, p < 0.01) were higher than those in the non-MCI group. Patients in the MCI group exhibited lower hand grip strength, walking speed, and skeletal mass index, but higher prevalence of sarcopenia. Only walking speed (rather than muscle loss or muscle weakness) was found to be an independent determinant of MCI after adjusting for multiple factors, such as age, gender, body mass index (BMI), duration of diabetes mellitus, hypertension, dyslipidemia, smoking, drinking, estimated glomerular filtration rate (eGFR), HbA1c, and history of coronary heart diseases and stroke. In subgroup analysis, a group consisting of male patients aged ≥65 years, with BMI <25, showed a significant OR for walking speed. This study showed that slow walking speed is a sole determinant criterion of sarcopenia of MCI in patients with type 2 diabetes mellitus. It was suggested that walking speed is an important factor in the prediction and prevention of MCI development in patients with diabetes mellitus.

P2-180: Regional cerebral metabolic differences of mild cognitive impairment (MCI) by delayed recall impairment degree