Normal Cognitive Function Research Articles

Frequency, sociodemographic, and neuropsychological features of patients with subjective cognitive decline diagnosed using different neuropsychological criteria

BackgroundSubjective Cognitive Decline (SCD) is recognized as a risk stage for future cognitive impairment and dementia. The criteria for SCD include normal performance on neuropsychological testing; however, there is a lack of consensus regarding standard score cut-offs for neuropsychological tests to define cognitive impairment and to differentiate between SCD and Mild Cognitive Impairment (MCI). This study aimed to assess the frequency of SCD diagnosis using various neuropsychological definitions of cognitive normality and to characterize the sociodemographic and neuropsychological features of SCD patients diagnosed under these criteria.MethodsThe Cognitive Complaints Cohort (CCC) participants were diagnosed following Subjective Cognitive Decline Initiative (SCD-I) criteria. Normal cognitive performance was defined by the absence of Mild Cognitive Impairment (MCI) according to the five sets of MCI neuropsychologically based criteria defined by Jak and Bondi. Descriptive statistics were used to analyze sociodemographic, clinical, and neuropsychological data. A bootstrap methodology was employed to estimate the mean and 95% confidence intervals (CI) for specific parameters of interest, namely the SMC scale (subjective memory complaints scale), Mini-Mental State Examination (MMSE), Blessed Dementia Rating Scale – first part (BDRS first part), and Geriatric Depression Scale (GDS).ResultsAmong the 1268 subjects included, the prevalence of SCD diagnosis exhibited substantial variation across SCD-I criteria using different neuropsychological definitions of cognitive normality (ranging from 16.4 to 81.3%). When using the most conservative criteria to define cognitive impairment (2 tests within a cognitive domain > 1.5 SD below age-adjusted means), the resulting Conservative SCD group had poorer global cognitive function (MMSE: mean 27.15, 95% CI 27.00-27.31), whereas when using the most liberal criteria to define cognitive impairment (only one test > 1 SD below age-adjusted means) the resulting Liberal SCD group had superior performance in daily-life functioning (BDRS first part: mean 0.30, 95% CI 0.23–0.38). However, subjective cognitive complaints and neuropsychiatric symptoms did not significantly differ among SCD diagnostic groups.ConclusionsThe utilization of diagnostic criteria using distinct neuropsychological definitions of cognitive normality significantly impacts the frequency of SCD diagnosis and characterizes different patient populations. Consequently, it is essential to specify the criterion when diagnosing a SCD patient and to understand the risks and benefits of using different criteria to define cognitive impairment.

To Study the Iodine Concentration of Mothers’ Consumed Salt, Water, and Staple Food in the Neonatal Screening Program of Rural and Urban Vidarbha Region

ABSTRACT Background: This study aimed to examine the iodine concentration in the food items consumed by mothers participating in neonatal screening programs in both areas of the Vidarbha region. A developing fetus relies on a consistent supply of iodine for proper brain and body development. During pregnancy, only the mother can provide the necessary iodine levels. If the mother is iodine-deficient, the child will also lack this essential nutrient. Severe deficiency in the mother can lead to significant stunting of the child’s brain and body, potentially preventing normal walking, talking, or cognitive function. Even if the mother’s deficiency is mild, the child can still be adversely affected, even if they appear healthy at first glance. The detrimental effects on brain development may manifest later in life as poor academic performance and difficulties in managing daily tasks. Material and Method: The present cross-sectional research will be performed in collaboration with the Departments of Biochemistry, Obstetrics and Gynecology, Community Medicine, and Pediatrics at Jawaharlal Nehru Medical College Sawangi (Meghe) Wardha, along with Datta Meghe Institute of Medical Science (Deemed University) in Maharashtra, India. Mothers who gave birth agreed to participate by providing written consent for the study. Results: The average iodine concentrations are quite similar across all sources, though hand pumps show slightly more variability. Different staple foods contain varying levels of iodine, with some foods (like pulses) exhibiting a lot of variation, while others (like rice and potatoes) are more consistent in their iodine content. Conclusion: The current study is a hospital-based investigation aimed at screening neonates for congenital hypothyroidism (CH) and does not reflect the broader population. To identify CH, screening of neonates will be conducted within the study area, providing a representative view of the condition. The clinical and pathological effects of CH are subtle and often remain unnoticed. Our findings suggest that the prevalence of iodine reflects dietary quality, educational background, and socioeconomic status, all of which can influence growth and development. There are various factors contributing to CH and inadequate fetal growth beyond low iodine levels, which can disrupt thyroid function. The study indicates that iodine levels are indicative of dietary quality as well as educational and social statuses, potentially impacting growth and development through both dietary deficiencies and other factors.

Beyond chronological age: exploring how different future time perspective influences the health tourism intention

BackgroundThe burgeoning field of health tourism has garnered significant attention due to its integration of health and leisure, reflecting a growing consumer demand for wellness-oriented travel experiences. Based on the socioemotional selectivity theory, this study examines the relationship between future time perspective, health awareness, involvement, and health tourism intention. It aims to understand how different dimensions of future time perspective influence the intention to engage in health tourism, beyond the traditional chronological age.MethodsA cross-sectional survey was conducted among individuals aged 16 years and above with normal cognitive function. Data was collected through online questionnaires distributed on popular Chinese social media platforms, WeChat and QQ. A total of 536 valid questionnaires were returned, with a validity rate of 91.47%. The study employed the structural equation modeling (SEM) to test the proposed hypotheses.ResultsThe effect of different dimensions of future time perspective on health tourism intention differed. Limited future time perspective (LFTP) positively influenced health tourism intention, while open-ended future time perspective (OFTP) did not have a significant effect on health tourism intention. Involvement and health awareness not only directly influence health tourism intention, but also mediate the relationship between future time perspective (OFTP and LFTP) and health tourism intention respectively. Moreover, there is a significant difference in the effect of LFTP on healthy tourism intention between different age groups.ConclusionsThe findings highlight the importance of considering subjective time perspectives in understanding health tourism intention. Health tourism companies should focus on strategies that enhance health awareness and consumer involvement to capitalize on the positive effects of health tourism intention. Additionally, the study suggests that marketing efforts should be tailored to address the specific needs and goals of individuals with different future time perspectives, thereby optimizing the appeal of health tourism products. Future research should explore these relationships across diverse populations and contexts to further refine the understanding of health tourism decision-making.

Connectome-based predictive modelling of ageing, overall cognitive functioning and memory performance.

Resting-state functional magnetic resonance imaging (rs-fMRI) and brain functional connectome (we use 'brain connectome' hereafter for simplicity) have advanced our understanding of the ageing brain and age-related changes in cognitive function. Previous studies have investigated the association among brain connectome and age, global cognition, and memory function separately. However, very few have predicted age, overall cognitive functioning and memory performance in a single study to better understand their complex relationship. In this cross-sectional study, we applied an exploratory, data-driven method to investigate the brain connectome markers that could predict ageing, overall cognitive functioning assessed as intelligence quotient (IQ, measured by Wechsler Memory Scale) and memory performance assessed as memory quotient (MQ, measured by Wechsler Memory Scale) in a carefully designed, multicentre, normal ageing cohort (n = 313). Our results showed that brain connectome could predict ageing and IQ, but the association with MQ was weak. We found that the connectivity with orbital frontal cortex was associated with both ageing and IQ. Mediation analysis further showed that the brain connectome mediated the relationship between age and overall cognitive functioning, suggesting a protective brain connectomic mechanism for maintaining normal cognitive functions during healthy ageing. This work may shed light on the potential neural correlates of healthy ageing, overall cognitive functioning and memory performance.

Association of time in range with cognitive impairment in middle-aged type 2 diabetic patients

ObjectiveThis study investigated the association of Time In Range (TIR) obtained from Blood Glucose Monitoring (BGM) with Cognitive Impairment (CI) inpatients with middle-aged Type 2 Diabetes Mellitus (T2DM) and further explored whether a TIR goal for T2DM in adults with > 70% possess a protective effect on cognitive function.Research design and methodsA total of 274 inpatients with T2DM aged 40–64 years, who underwent seven-point BGM ( pre meals and 120 min post meals and at bedtime) were recruited in this cross-sectional study. TIR was defined as the percentage of blood glucose within the target range of 3.9-10.0mmol/L. Subjects were divided into Normal Cognitive Function (NCF) (n = 160) and CI (n = 114) groups according to the results of the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE). The association of TIR and other glycemic metrics, calculated from seven-point BGM data, with cognitive dysfunction was analyzed.ResultsThe prevalence of CI was 41.6% in patients with middle-aged T2DM (median age 58 years). TIR was lower in CI group than in NCF group (28.6% vs. 42.9%, P = 0.004). The prevalence of CI decreased with ascending tertiles of TIR (p for trend < 0.05). Binary logistic regression analysis showed a significant association between TIR and CI (odds ratio [OR] = 0.84, p < 0.001) after adjusting for confounders (age, education, marital status, age at Diabetes Mellitus (DM) onset, cerebrovascular disease). Further adjustment of Standard Deviation (SD)(OR = 0.84, p = 0.001) or Coefficient of Variation (CV)(OR = 0.83, p < 0.001), TIR was still associated with CI. While a TIR goal of > 70% probably possessed independent protective effect on cognitive function (OR = 0.25, p = 0.001) after controlling for confounders above.ConclusionsTIR obtained from BGM was related to CI in middle-aged T2DM individuals and a TIR goal of > 70% probably possessed a protective effect on cognitive function for middle-aged T2DM .

Disgust-specific impairment of facial emotion recognition in Parkinson's disease patients with mild cognitive impairment.

This study investigated the association between cognitive function and facial emotion recognition (FER) in patients with Parkinson's disease (PD) and mild cognitive impairment (PD-MCI). We enrolled 126 participants from Taiwan, including 63 patients with idiopathic PD and 63 matched healthy controls. The PD group was divided into two groups: those with normal cognitive function (PD-NC) and those with MCI (PD-MCI). Participants underwent a modality emotion recognition test and comprehensive cognitive assessment. Our findings reveal that patients with PD-MCI exhibit significantly impaired FER, especially in recognizing "disgust," compared with patients with PD-NC and healthy adults (P = .001). This deficit correlates with executive function, attention, memory, and visuospatial abilities. Attention mediates the relationship between executive function and "disgust" FER. The findings highlight how patients with PD-MCI are specifically challenged when recognizing "disgust" and suggest that cognitive training focusing on cognitive flexibility and attention may improve their FER abilities. This study contributes to our understanding of the nuanced relationship between cognitive dysfunction and FER in patients with PD-MCI, emphasizing the need for targeted interventions.

Socioeconomic inequalities linked to the transitioning to neurocognitive disorders and mortality

Research on socioeconomic position (SEP) and mild neurocognitive impairment, considered a transient state between normal cognitive function and dementia is limited. The purpose of this study was to determine the role of SEP in transitioning between different cognitive states and mortality risk. Using nationally representative English data and utilising a multistate model association between SEP and the risk of transitioning from no cognitive impairment (NOCI) to Cognitive impairment no dementia (CIND), dementia and death were investigated. The potential reverse transition from CIND to NOCI was also explored. The probabilities of transitioning between cognitive states and time spent in each state differed significantly between those with lower and higher levels of SEP. Higher wealth was associated with a reverse transition from CIND to NOCI [HR = 1.56, CI (1.42,1.72)]. Socioeconomic advantage might protect against the progression to the early stages of neurocognitive disorders (CIND) and facilitate the potential reversion from mild cognitive impairment to a healthy cognitive state in later life. Lower levels of education affect the risk of mortality after the onset of dementia.

Association between sleep quality and cognitive impairment in older adults hypertensive patients in China: a case-control study.

Previous studies have found that poor sleep quality promotes the occurrence of cognitive impairment (CI), but this relationship has been rarely reported in older adults hypertensive patients. The purpose of this study was to investigate the relationship between sleep quality and CI in older adults hypertensive patients and the mediating effect of sleep quality between physical activity (PA) and CI. A total of 2072 older adults hypertensive patients were included in this case-control study. Five hundred and eighteen older adults hypertensive patients with CI were matched 1:3 by age and sex to 1,554 older adults hypertensive patients with normal cognitive function. The International Physical Activity Questionnaire-Long Form, Pittsburgh Sleep Quality Index, and Mini-Mental State Examination were used to evaluate PA intensity, sleep quality, and cognitive function in older adults hypertensive patients. Multivariate logistic regression and the mediation package in R Language were used to analyze the relationship between sleep quality and CI and the mediating effect of sleep quality between PA intensity and CI in older adults hypertensive patients. After adjusting for all confounding factors, sleep quality was positively correlated with CI in older adults hypertensive patients (OR = 2.565, 95%CI: 1.958-3.360, p < 0.001), and this relationship also existed in the older adults hypertensive patients with education levels of primary school and below and junior high school and above (OR = 2.468, 95%CI: 1.754-3.473, p < 0.001; OR = 2.385, 95%CI: 1.367-4.161, p = 0.002). In addition, sleep quality mediated part of the mediating effect between PA intensity and CI in older adults hypertensive patients (Za*Zb: - 17.19339; 95%CI: -0.37312, -0.04194). Poor sleep quality was associated with the occurrence of CI in older adults hypertensive patients, and this relationship also existed in older adults hypertensive patients with education levels of primary school and below and junior high school and above.

Cognitive function in older adults with stroke: A latent profile analysis

BackgroundPost-stroke cognitive impairment (PSCI) is one of the major complications after a stroke. Therefore, it is necessary to identify different categories of cognitive function in older adults with stroke and to explore factors associated with different levels of cognitive function in older adults after stroke. MethodsA cross-sectional survey was conducted using convenience sampling to collect data from 1076 older adults with stroke from 5 hospitals in Lanzhou City, Gansu Province, China, from June 2022 to August 2023. Latent Profile Analysis (LPA) was used to identify cognitive function subgroups among older adults with stroke, and multinomial logistic regression was used to analyze the related factors. Results1076 older adults with stroke were identified and classified as class-1: cognitive impairment, class-2: mild cognitive impairment, class-3: normal cognitive function. Age, gender, education level, hemorrhagic stroke, cerebrovascular disease are associated with different levels of cognitive function in older adults after stroke. ConclusionsThese findings highlight the heterogeneity of cognitive function in older adults with stroke. Our research could assist healthcare professionals in China to identify older adults with a high risk of cognitive impairment and to develop individualized interventions based on their characteristics.

Curved multiplanar reformatting allows the accurate histological delineation of hippocampal subfields.

Hippocampal subfields perform specific roles in normal cognitive functioning and have distinct vulnerabilities in neurological disorders. However, measurement of subfields with MRI is technically difficult in the head and tail of the hippocampus. Recent studies have utilized curved multiplanar reconstruction (CMPR) to improve subfield visualization in the head and tail, but this method has not yet been applied to histological data. We utilized BigBrain data, an open-source database of serially sectioned histological data for our analyses. The left hippocampus was segmented according to histological criteria by two raters in order to evaluate intra- and inter-rater reliability of histology-based segmentation throughout the long axis. Segmentation according to our previous protocol for the hippocampal body was then compared to these histological measurements to evaluate for histological validity. Agreement between segmentations was evaluated using Dice similarity coefficients (DSCs). Intra-rater reliability (DSCs) of histological segmentation was excellent for all subfields: CA1 (0.8599), CA2 (0.7586), CA3/CA4/DG (0.8907), SLM (0.9123), subiculum (0.8149). Similarly, inter-rater reliability analysis demonstrated excellent agreement (DSCs) for all subfield locations: CA1 (0.8203), CA2 (0.7253), CA3/CA4/DG (0.8439), SLM (0.8700), subiculum (0.7794). Finally, histological accuracy (DSCs) for our previous protocol was excellent for all subfields: CA1 (0.8821), CA2 (0.8810), CA3/CA4/DG (0.9802), SLM (0.9879), subiculum (0.8774). When subfields in the hippocampus head, body, and tail were analyzed independently, DSCs also showed excellent agreement. CMPR allows reliable subfield segmentation based on histological criteria throughout the hippocampal head, body, and tail. Our previous protocol for the hippocampal body can be applied to provide histologically valid subfield measurements throughout the entire hippocampal long axis.

Proteomic analysis of APOEε4 carriers implicates lipid metabolism, complement and lymphocyte signaling in cognitive resilience

BackgroundApolipoprotein E (APOE) ε4 allele is the strongest genetic risk factor for late onset Alzheimer’s disease (AD). This case-cohort study used targeted plasma biomarkers and large-scale proteomics to examine the biological mechanisms that allow some APOEε4 carriers to maintain normal cognitive functioning in older adulthood.MethodsAPOEε4 carriers and APOEε3 homozygotes enrolled in the Women’s Health Initiative Memory Study (WHIMS) from 1996 to 1999 were classified as resilient if they remained cognitively unimpaired beyond age 80, and as non-resilient if they developed cognitive impairment before or at age 80. AD pathology (Aß42/40) and neurodegeneration (NfL, tau) biomarkers, as well as 1007 proteins (Olink) were quantified in blood collected at study enrollment (on average 14 years prior) when participants were cognitively normal. We identified plasma proteins that distinguished between resilient and non-resilient APOEε4 carriers, examined whether these associations generalized to APOEε3 homozygotes, and replicated these findings in the UK Biobank.ResultsA total of 1610 participants were included (baseline age: 71.3 [3.8 SD] years; all White; 42% APOEε4 carriers). Compared to resilient APOEε4 carriers, non-resilient APOEε4 carriers had lower Aß42/40/tau ratio and greater NfL at baseline. Proteomic analyses identified four proteins differentially expressed between resilient and non-resilient APOEε4 carriers at an FDR-corrected P < 0.05. While one of the candidate proteins, a marker of neuronal injury (NfL), also distinguished resilient from non-resilient APOEε3 homozygotes, the other three proteins, known to be involved in lipid metabolism (ANGPTL4) and immune signaling (PTX3, NCR1), only predicted resilient vs. non-resilient status among APOEε4 carriers (protein*genotype interaction-P < 0.05). Three of these four proteins also predicted 14-year dementia risk among APOEε4 carriers in the UK Biobank validation sample (N = 9420). While the candidate proteins showed little to no association with targeted biomarkers of AD pathology, protein network and enrichment analyses suggested that natural killer (NK) cell and T lymphocyte signaling (via PKC-θ) distinguished resilient from non-resilient APOEε4 carriers.ConclusionsWe identified and replicated a plasma proteomic signature associated with cognitive resilience among APOEε4 carriers. These proteins implicate specific immune processes in the preservation of cognitive status despite elevated genetic risk for AD. Future studies in diverse cohorts will be needed to assess the generalizability of these results.

Safety and Efficacy of Trospium Chloride and Solifenacin in Stroke-Induced Neurogenic Lower Urinary Tract Dysfunction: A Randomized Controlled Trial.

Neurogenic dysfunction of the lower urinary tract is one of the challenging diseases with high burdens in urology. Our study aims to evaluate the efficacy of a 4-week treatment with Solifenacin and Trospium chloride and assess their safety and impact on quality of life. Following the selection of 206 stroke patients from two centers who met specific eligibility criteria, including a clinical diagnosis of stroke, normal cognitive function, and the presence of lower urinary tract symptoms (LUTS), participants were randomly assigned to receive oral Solifenacin, Trospium chloride, or a placebo. Under the supervision of the Ethics Committee, the baseline characteristics, compliance with medication, and outcomes were monitored, gathered, and analyzed. The majority of participants were male, with a mean age of 67.3, and most had ischemic stroke. The groups had no significant difference in urinary symptoms after stroke. All of the symptoms in the study groups, according to the NBSS questionnaire, were decreased following treatment compared to the baseline (p < 0.05). After treatment, ICIQ-OAB, and ICIQ-LUTS-QOL total scores and bothersome scores decreased significantly compared to baseline (p < 0.001). When compared to the placebo, both Trospium chloride and Solifenacin alleviated symptoms according to the NBSS questionnaire and ICIQ-LUTS-QOL, total ICIQ-OAB, and the total score of ICIQ-OAB-Bothersome. However, the total LUTS-QOL-Bothersome score did not change in the active treatment groups compared to the placebo. While comparing the two drugs, these values were similar except for the total score of LUTS-QOL-Bothersome, ICIQ-OAB, and ICIQ-OAB-Bothersome in favor of the Solifenacin group. Moreover, Solifenacin had fewer side effects compared to Trospium chloride or placebo. The study analyzed 206 stroke patients in two international centers and found both drug arms effective in treating overactive bladder. However, inconsistencies were found in efficacy and safety, necessitating further studies with larger populations. This triple-blind, multicenter, randomized controlled trial was done on 206 stroke patients after getting Ethical Committee approval and registering the project on IRCT (IRCT20160606028304N2).

Towers of Kuwait Arabic Neurocognitive Assessment: A novel executive and visuospatial functions assessment tool added to the CERAD neuropsychological battery-Arabic version (CERAD-ArNB)

Assessment of executive and visuospatial neurocognitive domains is lacking in the Omani population, especially for elderly individuals with low educational levels. Therefore, the Towers of Kuwait-Arabic Neurocognitive Assessment (ToK-ArNA) was developed using similar psychometric features of Tower of London (ToL) test, and the unique architecture of Towers of Kuwait, with the potential to overcome the limitation of ToL color perception difficulties that might be encountered in subjects with hereditary or acquired color vision disorders. We enrolled 120 older Arabic-speaking Omanis from January 2022 to November 2022 and all participants underwent screening to ensure normal cognitive function before performing the ToL and ToK-ArNA tests. Validity, reliability, and non-parametric statistical tests were used for data analysis. A total of 85 participants, 51 men (60%) and 34 women (40%) met the inclusion criteria and completed the testing. Statistical analyses confirmed the validity and reliability of ToK-ArNA compared to ToL, with comparable total Time and Accuracy scores and more preference towered the ToK-ArNA among the participants. Despite the study limitations, these results indicate that the ToK-ArNA is a reliable and applicable executive and visuospatial function assessment tool and further studies are warranted to establish its validity in patients with various neurocognitive disorders

Essential Oils and Mindfulness Exercises in Influencing Gene Expression Involved in Mild Cognitive Impairment (MCI): A Systematic Review

Mild Cognitive Impairment (MCI) represents a transitional stage between normal cognitive function and dementia, affecting memory and other cognitive abilities. This systematic review explores the impact of essential oils and mindfulness exercises on gene expression involved in MCI. Despite the prevalence of pharmacological treatments, they offer limited prevention of MCI progression to dementia. Non-pharmacological interventions, such as mindfulness exercises, have demonstrated cognitive benefits, albeit with moderate efficacy. Essential oils, used in aromatherapy, show promise in supporting cognitive improvement through their impact on amyloid-beta and cholinesterase pathways. This review synthesizes findings from multiple studies between 2017 and 2024, highlighting that combining essential oils and mindfulness exercises may offer enhanced therapeutic outcomes for individuals with MCI. Further research is needed to establish the efficacy of this integrative approach, which could slow the progression of MCI and improve patients' quality of life.

Association between plasma osteopontin level and mild cognitive impairment in patients with type 2 diabetes mellitus

Objective: To analyze the influencing factors of type 2 diabetes mellitus (T2DM) patients with mild cognitive impairment (MCI), and to explore the association between plasma osteopontin (OPN) levels and MCI. Methods: A retrospective analysis was conducted on the clinical data of 254 patients with T2DM admitted to Zhongda Hospital Affiliated to Southeast University from October 2021 to May 2023. The patients were divided into MCI group (n=106) and normal cognitive function control group (n=148) according to whether they had MCI. Clinical data were collected, cognitive function was assessed using neurological scales and plasma OPN levels were measured by enzyme linked immunosorbent assay. A multivariate logistic regression model was applied to analyze the influencing factors of MCI in T2DM patients. Interaction terms between gender, age, body mass index (BMI), and OPN were established to verify their significance levels. Receiver operating characteristic (ROC) curves were plotted to evaluate the predictive value of OPN for MCI in T2DM patients. The mediation model of OPN-FPG-montreal cognitive assessment(MoCA) was constructed with fasting plasma glucose (FPG) as the mediating variable to test the mediating effect, and the mediating effect percentage was calculated. Results: A total of 254 patients were included, including 162 males and 92 females, with an average age of (61.5±7.5) years old. Compared with the control group, the patients in MCI group were older[63.0(59.0, 69.0) years vs 60.0(54.2, 66.8) years], had a greater proportion of females [(43.4%(46/106) vs 31.1%(46/148)], shorter years of education[12(9, 12) years vs 12(9,15) years], longer duration of diabetes[15.0(8.0, 20.0) years vs 10.0(5.0, 15.0) years], and higher levels of FPG[7.78(6.07, 10.23) mmol/L vs 6.86(5.36, 8.59) mmol/L], insulin resistance index[2.93(2.47, 3.98) vs 2.79(2.27, 3.25)], glycated hemoglobin (HbA1c) [9.24%(7.89%, 10.96%) vs 7.97%(7.00%, 9.45%)], total cholesterol(TC)[(4.51±1.17) mmol/L vs (4.19±0.99) mmol/L], and OPN [11.30(8.68, 12.84) ng/ml vs 9.69(7.82, 11.74) ng/ml] (all P<0.05). The scores of various neuropsychological tests in MCI patients were lower than those in control group with normal cognitive function (all P<0.05). Spearman correlation analysis showed that age(r=-0.212), duration of diabetes mellitus(r=-0.156), duration of hypertension(r=-0.132), FPG(r=-0.207), insulin resistance index(r=-0.171), HbA1c(r=-0.271), OPN(r=-0.238), and total cholesterol (r=-0.125) were negatively correlated with MoCA scores, whereas years of education(r=0.285) were positively correlated with MoCA scores(all P<0.05). Multifactorial logistic regression analysis showed that age, years of education, duration of diabetes mellitus, HbA1c, TC and OPN levels were the influencing factors of T2DM patients with MCI, and the risk of MCI increased by 15% for every 1 ng/ml increase in OPN (OR=1.15, 95%CI: 1.021-1.295, P=0.021), and the relationship was not affected by age, gender and BMI(The interaction effects are all P>0.05). The area under the curve (AUC) of the working curve of subjects with OPN predicting combined MCI in patients with T2DM was 0.612 (95%CI: 0.541-0.682), and the AUC was 0.702 (95%CI: 0.638-0.767) after the combination of HbA1c and OPN. The results of the mediated effect model showed that FPG partially mediated the correlation between OPN and MoCA in T2DM patients, and the mediated effect accounted for 11.34% of the total effect. Conclusions: Plasma OPN level is associated with MCI in patients with T2DM,and the higher the OPN level, the higher the risk of T2DM patients developing MCI.

The Association Between Cognitive Function and Oral Health in Home Dwellers and Nursing Home Residents: The HUNT Study.

To evaluate the relationships of cognitive function and care dependency with oral health in a Norwegian older adult population. This cross-sectional study included 2623 participants aged 70 and older from the fourth wave of the Trøndelag health study (HUNT4 70+) and the city of Trondheim (Trondheim 70+). Neurocognitive disorders (NCDs) were diagnosed by clinical experts according to the DSM-5 framework. Care dependency referred to nursing home residency. Oral health was assessed by using the Revised Oral Assessment Guide-Jönköping (ROAG-J). Individuals were considered as 'having oral problem' if the score was two or three in at least one of the nine ROAG-J items. Poisson regression was used to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs). The prevalence of having oral problems was 19% higher in participants with NCDs than those with normal cognitive function after adjusting for potential confounders (PR 1.19, 95% CI: 1.09-1.29). Further analysis showed a higher prevalence of having oral problems for home dwellers with NCDs (PR 1.23, 95% CI: 1.13-1.33) and nursing home residents (PR 1.32, 95% CI: 1.20-1.45) compared to home dwellers with normal cognitive function. NCDs were associated with an increased prevalence of oral problems in this Norwegian older adult population. The study suggests the need for increasing oral care for home dwellers with NCDs and nursing home residents.

Ictal and interictal epileptic networks of 34 patients with Hypothalamic Hamartoma on scalp electroencephalography.

To investigate ictal and interictal cortical involvement in epilepsy associated with hypothalamic hamartoma. We conducted a retrospective study of 34 patients with epilepsy and hypothalamic hamartoma, using data from long-term video-EEG-monitoring. We analyzed onset and propagation of ictal and interictal scalp EEG and visualized the resulting networks of cortical involvement. According to clinical and EEG criteria we grouped patients in: (1) focal disease, (2) focal advanced disease, (3) extended disease. We compared networks between these groups and different seizure types. Eight patients underwent several video-EEGs, and we analyzed all to investigate epilepsy progression. Epileptic activity mainly involved frontal and temporal cortex regions. Involvement of frontal regions was more common in advanced stages of the disease, and strong fronto-temporal connections were observed in the ictal networks of patients in intermediate stages (25.0% (left) and 35.7% (right) of seizures with EEG correlate). Occurrence and timing of EEG-correlate significantly depended on the seizure type (Chi-2-test, p<<0.001). In patients with several EEGs, seizure activity increased by +0.67 seizures/day/month (mean). There were significant differences between patients with normal and impaired cognitive function, with the latter showing pronounced ictal involvement of fronto-temporal cortex areas (p<0.001). Overall, in epilepsy due to hypothalamic hamartoma, cortical involvement focuses on frontal and temporal regions and varies systematically with the stage of the disease, different seizure types and presence of impaired cognitive function. We propose that these data may help improve our general understanding of epileptogenesis and potentially provide insights for the surgical therapy of hypothalamic hamartomas.

Machine learning models for diagnosing Alzheimer's disease using brain cortical complexity.

This study aimed to develop and validate machine learning models (MLMs) to diagnose Alzheimer's disease (AD) using cortical complexity indicated by fractal dimension (FD). A total of 296 participants with normal cognitive (NC) function and 182 with AD from the AD Neuroimaging Initiative database were randomly divided into training and internal validation cohorts. Then, FDs, demographic characteristics, baseline global cognitive function scales [Montreal Cognitive Assessment (MoCA), Functional Activities Questionnaire (FAQ), Global Deterioration Scale (GDS), Neuropsychiatric Inventory (NPI)], phospho-tau (p-tau 181), amyloidβ-42/40, apolipoprotein E (APOE) and polygenic hazard score (PHS) were collected to establish multiple MLMs. Receiver operating characteristic curves were used to evaluate model performance. Participants from our institution (n = 66; 33 with NC and 33 with AD) served as external validation cohorts to validate the MLMs. Decision curve analysis was used to estimate the models' clinical values. The FDs from 30 out of 69 regions showed significant alteration. All MLMs were conducted based on the 30 significantly different FDs. The FD model had good accuracy in predicting AD in three cohorts [area under the receiver operating characteristic (ROC) curve (AUC) = 0.842, 0.808, and 0.803]. There were no statistically significant differences in AUC values between the FD model and the other combined models in the training and internal validation cohorts except MoCA + FD and FAQ + FD models. Among MLMs, the MoCA + FD model showed the best predictive efficiency in three cohorts (AUC = 0.951, 0.931, and 0.955) and had the highest clinical net benefit. The FD model showed favorable diagnostic performance for AD. Among MLMs, the MoCA + FD model can predict AD with the highest efficiency and could be used as a non-invasive diagnostic method.

Perinatal Reduction of Genetically Aberrant Neurons from Human Cerebral Cortex.

Since human neurons are postmitotic and long-lived, the regulation of their genomic content is crucial. Normal neuronal function is uniquely dependent on gene dosage, with diverse genome copy number alterations (CNA) associated with neurodevelopmental and neuropsychiatric conditions 1-3 . In this study, we evaluated the landscape of CNA arising in normal human brains, focusing on prenatal and perinatal ages. We surveyed ∼5,897 CNA in >1,200 single neurons from human postmortem brain of individuals without a neurological diagnosis, ranging in age from gestational week (GW) 14 to 90 years old. Using Tn5-based single-cell whole-genome amplification (scWGA) and informatic advances to validate CNAs in single neurons, we determined that a striking proportion of neurons (up to 45%) in human prenatal cortex showed aberrant genomes, characterized by large-scale CNAs in multiple chromosomes, which reduces significantly during the perinatal period (p<0.1). Furthermore, we identified micronuclei in the developing cortex, reflecting genetic instability reminiscent of that described in early embryonic development 4-6 . The scale of CNA appeared to alter the trajectory of neuronal elimination, as subchromosomal CNAs were more slowly eliminated, over the course of a lifetime. CNAs were depleted for dosage-sensitive genes and genes involved in neurodevelopmental disorders (p<.05), and thus represent genomic quality control mechanisms that eliminate selectively those neurons with CNA involving critical genes. Perinatal elimination of defective neuronal genomes may in turn reflect a developmental landmark essential for normal cognitive function.

Crucial role of Snf7-3 in synaptic function and cognitive behavior revealed by conventional and conditional knockout mouse models

Snf7-3 is a crucial component of the endosomal sorting complexes required for transport (ESCRT) pathway, playing a vital role in endolysosomal functions. To elucidate the role of Snf7-3 in vivo, we developed conventional-like and conditional Snf7-3 knockout (KO) mouse models using a “Knockout-first” strategy. Conventional-like Snf7-3 KO mice showed significantly reduced Snf7-3 mRNA expression, and older mice (25–40 weeks) exhibited impaired social recognition and increased miniature excitatory postsynaptic currents (mEPSCs). Similarly, conditional KO mice aged 8–24 weeks, with Snf7-3 specifically deleted in forebrain excitatory neurons, displayed impaired object location memory and elevated mEPSC frequency. Consistently, Snf7-3 knockdown in cultured mouse hippocampal neurons led to increased densities of pre- and postsynaptic puncta, supporting the observed increase in mEPSC frequency. In addition, enhanced dendritic complexity was observed in the medial prefrontal cortex of these mice, indicating early synaptic disturbances. Our findings underscore the critical role of Snf7-3 in maintaining normal cognitive functions and social behaviors. The observed synaptic and behavioral deficits in both conventional-like and conditional KO mice highlight the importance of Snf7-3 in specific neuronal populations, suggesting that early synaptic changes could precede more pronounced cognitive impairments.