OBJECTIVE: Stroke can lead to significant restructuring of brain structure and function. However, the precise changes in the coordination between brain structure and function in subcortical stroke patients remain unclear. We investigated alterations in brain structural-functional coupling (SC-FC coupling) and their impact on cognitive function in subcortical basal ganglia infarction patients.
METHODS: The study comprised 40 patients with mild stroke with basal ganglia region infarcts and 29 healthy controls (HC) who underwent multidimensional neuroimaging examination and neuropsychological testing. The subcortical stroke patients were divided into post-stroke cognitive impairment (PSCI) and stroke with no cognitive impairment (NPSCI) groups based on cognitive performance, with 22 individuals undergoing follow-up examination after three months. We investigated differences in brain structural-functional coupling across three groups, and their associations with cognitive functions.
RESULTS: Compared to both HC participants and NPSCI, PSCI exhibited significantly reduced structural-functional coupling strength in specific brain regions. After a three-month period, there was observed an increase in structural-functional coupling strength within the frontal lobe (precentral gyrus and paracentral lobule). The strength of SC-FC coupling within the precentral gyrus, precuneus, and paracentral lobule regions demonstrated a decline correlating with the deterioration of cognitive function (MoCA, memory and visual motor speed functions).
CONCLUSIONS: After subcortical basal ganglia stroke, PSCI patients demonstrated decreased SC-FC coupling in the frontal lobe region, correlating with multidimensional cognitive impairment. Three months later, there was an increase in SC-FC coupling in the frontal lobe, suggesting a compensatory mechanism during the recovery phase of cognitive impairment following stroke.

BACKGROUND: Major Depressive Disorder (MDD) affects 350 million people worldwide. Electroconvulsive therapy (ECT) is effective, yet research on cognitive assessments post-treatment is lacking. This study systematically reviews and meta-analyzes the effectiveness of cognitive assessment tools post-ECT to optimize MDD treatment.
METHODS: Following PRISMA guidelines, this review was pre-registered on PROSPERO (CRD42023470318). Searches were conducted across nine databases up to November 12, 2023. Quality assessment for Randomized Controlled Trials (RCTs) and quasi-experimental studies was performed using the Cochrane risk of bias tool, JBI critical appraisal tools, and the Jadad scale. Meta-analyses for short-term and long-term cognitive function involved 24 and 18 tools, respectively.
RESULTS: Thirty studies (20 RCTs and 10 quasi-experimental) involving 2462 MDD patients were evaluated. Results indicated no significant differences in overall short-term and long-term cognitive functions post-ECT. Short-term analysis showed impairments in memory, learning, and verbal abilities but improvements in attention and processing speed. Long-term analysis revealed enhancements in memory, learning, verbal, and visuospatial abilities compared to baseline. Based on GRADE classification, we recommend 11 tools for assessing acute cognitive function and 10 tools for chronic cognitive impairment. These tools demonstrated high reliability and validity, supporting their clinical use.
CONCLUSIONS: These findings provide critical evidence for future ECT clinical guidelines in managing MDD. The recommended tools can aid clinicians in adjusting ECT regimens, identifying early cognitive changes, and improving therapeutic outcomes in MDD treatment.

BACKGROUND: The Chinese formula Guben-Jiannao Ye (GBJNY) formula has a long history of usage in traditional Chinese medicine (TCM) for the treatment of learning and memory disorders as well as senile insomnia. This formulation is derived from Sun Simiao\'s five tonic pills. Furthermore, modern pharmacological investigations have revealed its ability to improve cognitive impairment and ameliorate sleep-wake circadian rhythm disorders. However, the precise mechanism underlying its efficacy remains elusive.
OBJECTIVE: The current research explored the modulatory effects and possible mechanisms of GBJNY in circadian rhythm sleep-wake disorders and cognitive dysfunction in Alzheimer\'s disease using transcriptome sequencing and experimental validation.
METHODS: The LC-MS/MS tandem technology was utilized to qualitatively discern the active components present in GBJNY. The APP/PS1 mice received continuous treatment with GBJNY or Melatonin for 3 months. The learning and memory abilities of mice were assessed utilizing the Morris water maze (MWM) test, while sleep changes were studied utilizing the electroencephalogram (EEG) and electromyogram (EMG). Concurrently, mice\'s hippocampus clock gene rhythmicity was investigated. Subsequently, we employed HE staining, Golgi staining, and immunofluorescence to observe GBJNY\'s impact on synaptic damage and neuronal loss. We performed high-throughput sequencing to analyze the mRNA expression profiles of mice, aiming to identify differentially expressed genes (DEGs). Subsequently, we conducted GO and KEGG enrichment analyses to explore associated signaling pathways. Furthermore, we evaluated the expression levels of proteins involved in the PI3K/AKT/mTOR pathway and Aβ deposition in the hippocampus of mice. Through this comprehensive approach, we sought to elucidate and validate the potential mechanisms of action of GBJNY in APP/PS1 mice.
RESULTS: Results showed 216 DEGs. Following this, we conducted GO enrichment and KEGG pathway analyses to delve deeper into the distinctions and fundamental functions of the mRNA target genes. The enrichment analysis underscored the prominence of the PI3K/Akt/mTOR signaling pathway as the most pivotal among them. Through in vivo experiments, it was further demonstrated that the administration of GBJNY enhanced memory and learning capacities in APP/PS1 mice. Additionally, GBJNY treatment resulted in alterations in the sleep-wake circadian rhythm, characterized by reduced wakefulness and an increase in non-rapid eye movement (NREM) sleep. Moreover, alterations in the peak expression of Per1, Per2, Clock, Cry1, Cry2, and Bmal1 mRNA were noted in the hippocampus of treated mice. Particularly noteworthy were the observed reductions in amyloid-beta (Aβ) deposition within the hippocampus, improvements in neuronal synaptic integrity, and upregulation of mTOR, Akt, and PI3K protein expression in the hippocampal region. These findings underscore the critical involvement of the PI3K/Akt/mTOR signaling pathway in mitigating disturbances in sleep-wake circadian rhythms.
CONCLUSIONS: GBJNY enhanced the cognitive performance of APP/PS1 mice and altered clock gene expression patterns, alleviating sleep-wake circadian rhythm disruptions. The fundamental mechanism appears to be linked to the PI3K/Akt/mTOR pathway regulation, offering a foundation for potential clinical applications.

Air pollution has become a major global threat to human health. Urbanization and industrialization over the past few decades have increased the air pollution. Plausible connections have been made between air pollutants and dementia. This study used machine learning algorithms (k-nearest neighbors, random forest, gradient-boosted decision trees, eXtreme gradient boosting, and CatBoost) to investigate the association between cognitive impairment and air pollution. Data from the Taiwan Biobank and 75 air-pollution-monitoring stations in Taiwan were analyzed to determine individual levels of exposure to air pollutants. The pollutants examined were particulate matter with a diameter of ≤ 2.5 μm (PM2.5), nitrogen dioxide, nitric oxide, carbon monoxide, and ozone. The results revealed that the most strongly correlated with cognitive impairment were ozone, PM2.5, and carbon monoxide levels with adjustment of educational level, age, and household income. The model based on these factors achieved accuracy as high as 0.97 for detecting cognitive impairment, indicating a positive association between air pollutions and cognitive impairment.

BACKGROUND: Cognitive impairment (CI) is common in older adults, especially those with renal dysfunction. We aimed to investigate the complex relationships among renal function, nutritional status, and CI in older people free from late chronic kidney disease (CKD) and severe CI.
METHODS: A study of older people (≥60 years old) with an estimated glomerular filtration rate (eGFR) of >30 mL/min/1.73 m2 and Montreal Cognitive Assessment (MoCA) scores of >10 (n = 237) was conducted at Beijing Tongren Hospital. Their eGFR was determined using the CKD-EPI-cr-Cysc equation. Cognitive function was evaluated with the MoCA. We tested the relationship between eGFR and MoCA scores using Spearman correlation analysis and multivariate logistic regression analysis. We then conducted a mediation analysis to figure out the mediating roles of nutritional indicators (Mini Nutritional Assessment-Short Form (MNA-SF) scores, albumin (ALB), and haemoglobin (HGB)) between the eGFR and MoCA scores.
RESULTS: The incidence of CI was 48.5% (115/237) in older people. Spearman correlation analysis revealed that the better the kidney function, the better the cognitive function (R = 0.297, P < 0.001). Multivariate logistic regression analysis revealed that eGFR decrease per 15 mL/min/1.73 m2 (OR: 1.415, 95% confidence interval: 1.055-1.896, P = 0.020) was related to CI after adjusting for age and sex. However, the eGFR was not associated with cognitive decline after adjusting for nutritional indicators, behavioural risk factors, other biomarkers, and chronic conditions, suggesting that eGFR is not independently associated with CI. Mediation analysis revealed that the MNA-SF scores (a*b = 0.006 (0.0002-0.012)) and HGB (a*b = 0.008 (0.001-0.017)) were mediating factors between the eGFR and MoCA scores.
CONCLUSIONS: A decline in renal function can directly lead to CI and can also exacerbate cognitive deficits through intermediary factors such as MNA-SF scores and HGB. Therefore, correcting anaemia and improving nutritional status are significantly important for enhancing cognitive function in older patients, especially those with renal dysfunction.

BACKGROUND: In recent years, several studies have suggested that obesity may play an important role in cognitive impairment. Individuals with cognitive impairment often also exhibit depressive symptoms. This study aimed to explore the association between obesity and cognitive impairment and to elucidate the mediating role of depressive symptoms in this association.
METHODS: Older participants in the U.S. were examined in this cross-sectional study (n = 2391). The WWI was computed as follows: WWI = waist circumference/square root of body weight. The Consortium for Alzheimer\'s Disease Word Learning (CERAD-WL), the Animal Fluency Test (AFT), and the Digit Symbol Substitution Test (DSST) were used to evaluate cognitive function. Depression symptoms were evaluated with the Patient Health Questionnaire 9 (PHQ-9). Subgroup analysis and multiple logistic regression analysis were utilized to investigate the relationships between the WWI and depressive symptoms and cognitive decline. Threshold effects were computed using a two-segment linear regression model. To ascertain whether depression mediates the relationship between the WWI and cognitive impairment, mediation analysis was also employed.
RESULTS: A total of 2391 participants were included, 33.29 % of whom had cognitive impairment. There was a significant correlation between the WWI and depressive symptoms and cognitive function (P < 0.05). With increasing WWI quartiles, the prevalence of cognitive impairment increased (Q1: 27.09 %, Q2: 33.00 %, Q3: 31.44 %, Q4: 41.64 %). It was highly likely that the WWI and cognitive impairment were positively correlated (OR = 1.34, 95 % CI = 1.13, 1.59), and this link was steady across all subgroups (P for trend >0.05). A nonlinear curve with an inflection point of 10.71 connected the WWI and cognitive deterioration. A significant correlation was found between the WWI and cognitive impairment on the left side of the inflection point (OR = 3.58, 95 % CI = 1.57, 8.15). With a 5.4 % mediation rate, mediation analysis revealed that depressive symptoms mediated the relationship between cognitive impairment and the WWI.
CONCLUSIONS: There was a positive association between the WWI and the incidence of cognitive impairment in older Americans. Among other factors, depressive symptoms slightly mediated the association between the WWI and cognitive impairment. However, large-scale prospective studies are still needed to analyse the interactions between the three factors in depth.

BACKGROUND: Cognitive impairments are common in patients with AUD and worsen the prognosis of addiction management. There are no clear guidelines for screening cognitive impairments in hospitalized patients with AUD.
METHODS: Fifty-seven patients with an AUD history who were admitted to an acute hospital and assessed by the addiction care team were included. Those patients were screened for cognitive impairments using the Montreal Cognitive Assessment (MoCA) test. We collected clinical information regarding addiction history, comorbidities, and current treatments. Chi-square tests, t-tests, and Mann-Whitney tests were performed to determine factors associated with a pathological MoCA score (<26).
RESULTS: A pathological MoCA score was positively associated with spatial-temporal disorientation, difficulty in recalling addiction history, patient underreporting of AUD and a date of last alcohol consumption lower than 11 days ago, and negatively associated with a reason for hospitalization due to alcohol-related health issues. No medication was associated with cognitive impairments.
CONCLUSIONS: Clinical elements from assessment by the addiction care team allow for relevant indication for screening cognitive impairments.

This study examined the separate and combined associations of cognitive impairment and body pain with functional and mobility disabilities (FMDs) among older women and men in India. Multivariable linear regression models were applied using data from the Longitudinal Aging Study in India (2017-18) comprising 31,464 adults aged 60+. Older adults with cognitive impairment and pain reported higher levels of FMDs than peers without any pain and cognitive impairment. The likelihood of FMDs was significantly greater among older Indians enduring both cognitive impairment and pain (p < 0.05). Moreover, the association between cognitive impairment and functional disability was noticeably stronger in older women, particularly those with frequent pain, while the link between cognitive impairment and mobility disability was more pronounced in men with pain. Integrated cognitive rehabilitation and pain management programs, along with guided physical therapy, gender-specific support groups, and community-based health promotion activities, should be considered to reduce FMDs in older Indians.

UNASSIGNED: Few studies have directly compared the cognitive characteristics of patients with mild autonomous cortisol secretion (MACS) and Cushing\'s syndrome (CS). The effect of surgical or conservative treatment on cognitive function in patients with MACS is still unclear.
UNASSIGNED: To compare the differences in cognitive function between patients with MACS and CS and evaluate the effect of surgery or conservative treatment on cognitive function.
UNASSIGNED: We prospectively recruited 59 patients with nonfunctional adrenal adenoma (NFA), 36 patients with MACS, and 20 patients with adrenal CS who completed the global cognition and cognitive subdomains assessments. Seventeen MACS patients were re-evaluated for cognitive function after a 12-month follow-up period; of these, eleven underwent laparoscopic adrenalectomy and six received conservative treatment.
UNASSIGNED: Patients with MACS and CS performed worse in the global cognition and multiple cognitive domains than those with NFA (all P<0.05). No statistical difference was found in cognitive functions between patients with MACS and CS. Logistic regression analysis showed that patients with MACS (odds ratio [OR]=3.738, 95% confidence intervals [CI]: 1.329-10.515, P=0.012) and CS (OR=6.026, 95% CI: 1.411-25.730, P=0.015) were associated with an increased risk of immediate memory impairment. Visuospatial/constructional, immediate and delayed memory scores of MACS patients were significantly improved at 12 months compared with pre-operation in the surgical treatment group (all P<0.05), whereas there was no improvement in the conservative treatment group.
UNASSIGNED: Patients with MACS have comparable cognitive impairment as patients with CS. Cognitive function was partially improved in patients with MACS after adrenalectomy. The current data support the inclusion of cognitive function assessment in the clinical management of patients with MACS.

BACKGROUND: Temporal lobe epilepsy (TLE) is associated with abnormal dynamic functional connectivity patterns, but the dynamic changes in brain activity at each time point remain unclear, as does the potential molecular mechanisms associated with the dynamic temporal characteristics of TLE.
METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) was acquired for 84 TLE patients and 35 healthy controls (HCs). The data was then used to conduct HMM analysis on rs-fMRI data from TLE patients and an HC group in order to explore the intricate temporal dynamics of brain activity in TLE patients with cognitive impairment (TLE-CI). Additionally, we aim to examine the gene expression profiles associated with the dynamic modular characteristics in TLE patients using the Allen Human Brain Atlas (AHBA) database.
RESULTS: Five HMM states were identified in this study. Compared with HCs, TLE and TLE-CI patients exhibited distinct changes in dynamics, including fractional occupancy, lifetimes, mean dwell time and switch rate. Furthermore, transition probability across HMM states were significantly different between TLE and TLE-CI patients (p < 0.05). The temporal reconfiguration of states in TLE and TLE-CI patients was associated with several brain networks (including the high-order default mode network (DMN), subcortical network (SCN), and cerebellum network (CN). Furthermore, a total of 1580 genes were revealed to be significantly associated with dynamic brain states of TLE, mainly enriched in neuronal signaling and synaptic function.
CONCLUSIONS: This study provides new insights into characterizing dynamic neural activity in TLE. The brain network dynamics defined by HMM analysis may deepen our understanding of the neurobiological underpinnings of TLE and TLE-CI, indicating a linkage between neural configuration and gene expression in TLE.