Association between type of menopause and mild cognitive impairment: The REDLINC XII study.

OBJECTIVE: To evaluate the association between type of menopause (spontaneous or surgical) and mild cognitive impairment (MCI). STUDY DESIGN: This study was a cross-sectional, observational, and sub-analytical investigation conducted within gynecological consultations across nine Latin American countries. METHOD: We assessed sociodemographic, clinical, and anthropometric data, family history of dementia, and the presence of MCI using the Montreal Cognitive Assessment (MoCA) tool. RESULTS: The study involved 1185 postmenopausal women with a mean age of 55.3 years and a body mass index of 26.4 kg/m2. They had an average of 13.3 years of education, and 37 % were homemakers. Three hundred ninety-nine experienced menopause before 40, including 136 with surgical menopause (bilateral oophorectomy). Out of the 786 women who experienced menopause at 40 or more years, 110 did so due to bilateral oophorectomy. There were no differences in MoCA scores among women who experienced menopause before or after the age of 40. However, lower MoCA scores were observed in women with surgical menopause than in those with spontaneous menopause (23.8 ± 4.9 vs. 25.0 ± 4.3 points, respectively, p < 0.001). Our logistic regression model with clustering of patients within countries found a significant association between MCI and surgical menopause (OR 1.47, 95 % CI: 1.01-2.16), use (ever) of menopausal hormone therapy (OR 0.33, 95 % CI: 0.21-0.50), and having >12 years of education (OR 0.21, 95 % CI: 0.14-0.30). CONCLUSION: When comparing women who experience spontaneous menopause over the age of 40 with those who undergo it before this age, there was no observed increased risk of developing MCI, while those with surgical menopause, independent of age, are more prone to cognitive decline. Women who have ever used menopausal hormone therapy have a lower MCI risk. Further research is warranted to delve deeper into this topic.

Disparities in the diagnostic efficacy of radiomics models in predicting various degrees of cognitive impairment in patients with cerebral small vessel disease.

BACKGROUND: Aim to validate the diagnostic efficacy of radiomics models for predicting various degrees of cognitive impairment in patients with cerebral small vessel disease (CSVD). METHODS: Participants were divided into mild cognitive impairment group (mild-CSVD group) and sever cognitive impairment group (sever-CSVD group) according to Montreal Cognitive Assessment (MoCA) performance, 98 gender-age-education matched subjects served as normal controls. Radiomic features were extracted from the segmented hippocampus using PyRadiomics. The feature preprocessing involved replacing missing values with the mean, applying stratified random sampling to allocate subjects into training (80%) and testing (20%) sets, ensuring balance among the three classes (normal controls, mild-CSVD group, and sever-CSVD group). A feature selection method was applied to identify discriminative radiomic features, with the optimal texture feature chosen for developing diagnostic models. Performance was evaluated in both the training and testing sets using receiver operating characteristic (ROC) curve analysis. RESULTS: The radiomics model achieved an accuracy of 0.625, an AUC of 0.593, a sensitivity of 0.828, and a specificity of 0.316 in distinguishing mild-CSVD group from normal controls. When distinguishing mild-CSVD group from sever-CSVD group, the radiomics model reached an accuracy of 0.683, an AUC of 0.660, a sensitivity of 0.167, and a specificity of 0.897. Similarly, in distinguishing sever-CSVD group from normal controls, the radiomics model exhibited an accuracy of 0.781, an AUC of 0.818, a sensitivity of 0.538, and a specificity of 0.947. CONCLUSION: Radiomics model based on hippocampal texture had disparities in the diagnostic efficacy of radiomics models in predicting various degrees of cognitive impairment in patients with CSVD.

Effectiveness of DL-3-n-butylphthalide in the treatment of poststroke cognitive impairment and its associated predictive cytokines: a systematic review and meta-analysis.

BACKGROUND: The efficacy of DL-3-n-butylphthalide (NBP) in the treatment of post-stroke cognitive impairment (PSCI) has been reported previously. However, the course of treatment that shows curative effect and cytokines predictive of the efficacy of NBP in the treatment of PSCI have not been systematically evaluated. This study aimed to assess the efficacy, course of treatment, and cytokines that can predict the effectiveness of NBP in treating poststroke cognitive impairment PSCI. METHODS: This study has been registered with PROSPERO (registration number CRD42024518768). Randomized controlled trial (RCT) data dated by November 12, 2023 were retrieved from the PubMed, Embase, Cochrane Library, Web of Science, Wanfang, CNKI, CSTJ, and SinoMed databases using medical subject terms combined with free words. The updated Cochrane RoB-I Risk of Bias tool was utilized for literature quality evaluation. Statistical analysis were carried out using Review Manager 5.4.1 software. RESULTS: Thirty-eight original studies involving 5417 PSCI patients were analyzed. The results showed that NBP had a beneficial impact on cognitive function in PSCI patients when used alone or in combination therapy, as assessed by the Mini-mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scale. The effect sizes were significant for both monotherapy and combination therapy. Subgroup analyses based on treatment cycle indicated that NBP enhanced cognitive function in PSCI patients from 1 week after intervention: MMSE (SMD = 0.43, 95% CI [0.28, 0.58], P < 0.001), MoCA (SMD = 0.44, 95% CI [0.27, 0.61], P < 0.001). There was a cumulative enhancement in cognitive function within 6 months after NBP treatment based on the MoCA scores (SMD = 0.61, 95% CI [0.30, 0.91], P < 0.001). Furthermore, decreased levels of the cytokines Hs-CRP, TNF-α, IL-6, IL-8, Hcy, NSE, MDA, MMP-9, and Cys-C (SMD = -2.28, 95% CI [-2.97, 1.58], P < 0.001) and increased levels of BDNF, VEGF, and TIMP-1 (SMD = 2.80, 95% CI [1.66, 3.94], P < 0.001) were also predictive of treatment efficacy. CONCLUSION: NBP plays a beneficial role in improving cognitive function in PSCI patients, and their prognoses could be predicted by serum cytokine levels. However, high-quality, multicenter, multisample, and RCTs are still needed to confirm the clinical validity of NBP due to its low methodological quality.

Molecular and Functional Alterations in the Cerebral Microvasculature in an Optimized Mouse Model of Sepsis-Associated Cognitive Dysfunction.

Systemic inflammation has been implicated in the development and progression of neurodegenerative conditions such as cognitive impairment and dementia. Recent clinical studies indicate an association between sepsis, endothelial dysfunction, and cognitive decline. However, the investigations of the role and therapeutic potential of the cerebral microvasculature in sepsis-induced cognitive dysfunction have been limited by the lack of standardized experimental models for evaluating the alterations in the cerebral microvasculature and cognition induced by the systemic inflammatory response. Herein, we validated a mouse model of endotoxemia that recapitulates key pathophysiology related to sepsis-induced cognitive dysfunction, including the induction of an acute systemic hyperinflammatory response, blood-brain barrier (BBB) leakage, neurovascular inflammation, and memory impairment after recovery from the systemic inflammation. In the acute phase, we identified novel molecular (e.g., upregulation of plasmalemma vesicle-associated protein, PLVAP, a driver of endothelial permeability, and the procoagulant plasminogen activator inhibitor-1, PAI-1) and functional perturbations (i.e., albumin and small-molecule BBB leakage) in the cerebral microvasculature along with neuroinflammation. Remarkably, small-molecule BBB permeability, elevated levels of PAI-1, intra-/perivascular fibrin/fibrinogen deposition, and microglial activation persisted 1 month after recovery from sepsis. We also highlight molecular neuronal alterations of potential clinical relevance following systemic inflammation including changes in neurofilament phosphorylation and decreases in postsynaptic density protein 95 and brain-derived neurotrophic factor, suggesting diffuse axonal injury, synapse degeneration, and impaired neurotrophism. Our study serves as a standardized mouse model to support future mechanistic studies of sepsis-associated cognitive dysfunction and to identify novel endothelial therapeutic targets for this devastating condition.

Novel microglial transcriptional signatures promote social and cognitive deficits following repeated social defeat.

Chronic stress is associated with anxiety and cognitive impairment. Repeated social defeat (RSD) in mice induces anxiety-like behavior driven by microglia and the recruitment of inflammatory monocytes to the brain. Nonetheless, it is unclear how microglia communicate with other cells to modulate the physiological and behavioral responses to stress. Using single-cell (sc)RNAseq, we identify novel, to the best of our knowledge, stress-associated microglia in the hippocampus defined by RNA profiles of cytokine/chemokine signaling, cellular stress, and phagocytosis. Microglia depletion with a CSF1R antagonist (PLX5622) attenuates the stress-associated profile of leukocytes, endothelia, and astrocytes. Furthermore, RSD-induced social withdrawal and cognitive impairment are microglia-dependent, but social avoidance is microglia-independent. Furthermore, single-nuclei (sn)RNAseq shows robust responses to RSD in hippocampal neurons that are both microglia-dependent and independent. Notably, stress-induced CREB, oxytocin, and glutamatergic signaling in neurons are microglia-dependent. Collectively, these stress-associated microglia influence transcriptional profiles in the hippocampus related to social and cognitive deficits.

Gut flora reflects potential risk factors for cognitive dysfunction in patients with epilepsy.

OBJECTIVE: This cross-sectional study aims to analyze the differences in gut flora between patients with epilepsy with and without cognitive impairment and normal subjects. METHODS: One hundred patients with epilepsy who came to our hospital from 2020.12 to 2022.12 (epilepsy group) were selected, and another 100 family members of the patients were selected as the control group (control group). Patients with epilepsy were further classified by the MMSE scale into 62 patients with combined cognitive impairment (Yes group) and 38 patients without cognitive impairment (No group). Detection of gut flora in feces by 16 S rRNA high-throughput sequencing. Logistic regression was used to analyze risk factors for cognitive dysfunction in patients with epilepsy. RESULTS: There were more significant differences in the structure and composition of the gut flora between patients in the epilepsy group and the control group, but no significant differences in diversity analysis (P > 0.05). Actinobacteriota, Faecalibacterium and Collinsella were significantly lower in the Yes group than in the No group (P < 0.05), and the Alpha diversity index was numerically slightly smaller than in the No group, with the PCoA analysis demonstrating a more dispersed situation in both groups. Five metabolic pathways, including glycolysis and heterolactic fermentation, were upregulated in the Yes group. LEfSe analysis showed that five groups of bacteria, including Coriobacteriaceae and Collinsella, were selected as marker species for the presence or absence of comorbid cognitive impairment. Of these, Collinsella, Oscillospirales, and Ruminococcaceae have a greater impact on epilepsy combined with cognitive impairment. CONCLUSION: There was an imbalance in the gut flora of patients with epilepsy compared to healthy controls. The gut flora of patients with epilepsy with cognitive dysfunction differs significantly from that of patients without cognitive dysfunction. Collinsella, Oscillospirales, and Ruminococcaceae have a greater impact on epilepsy with cognitive dysfunction and can be used as an indicator for the observation of epilepsy with cognitive dysfunction.

Maternal and fetal neurocognitive outcomes in preeclampsia and eclampsia; a narrative review of current evidence.

Hypertensive disorders of pregnancy (HDP), such as preeclampsia and eclampsia, present significant risks to maternal and fetal health. While immediate complications are well-documented, emerging research highlights potential neurocognitive impacts on both mothers and their offspring. This narrative review synthesizes evidence on these neurocognitive outcomes associated with HDP, focusing on preeclampsia and eclampsia. A literature search was conducted for studies published from 2000 to February 2024. Maternal outcomes, including memory, executive function, and psychosocial well-being, were assessed across 11 studies, while fetal and neonatal neurocognitive outcomes were explored in five studies. Consistent findings indicate that preeclampsia and eclampsia are linked to impairments in maternal cognitive functions and psychosocial health. Offspring exposed to these conditions in utero also show cognitive deficits and alterations in brain connectivity. Contributing factors include placental dysfunction, altered angiokine levels, maternal stress, and socioeconomic variables. To mitigate these impacts, future research should focus on clarifying the underlying mechanisms and developing early interventions. This review emphasizes the necessity of multidisciplinary approaches to improve neurocognitive outcomes for both mothers and their children affected by preeclampsia and eclampsia.

Neuropsychology and Vascular Cognitive Impairment and Dementia.

Neuropsychology is an integral component of health care assessment for persons with vascular contributions to cognitive impairment and dementia. Since syndromes of vascular cognitive decline have multiple and varying pathophysiologies, anatomic brain locations, and levels of severity, neuropsychological assessment can be critical to clarify the cognitive manifestations of the disease, potential consequences for the patient and family, as well as the prognosis for future life planning. Cognitive profiles of vascular cognitive declines and relevant neuropsychological literature are reviewed here to provide the practicing physician with guidance for best clinical care practices.

Neuropsychological Manifestations of Multiple Sclerosis.

This review article summarizes the literature on the cognitive impairment seen amongst people with multiple sclerosis (MS) and how that impairment can impact not only their lives but also how their care needs to be managed. Recommendations regarding screening and monitoring of cognitive issues are reviewed, as well as how common comorbidities can further impact cognition. The current literature with respect to treatment options is also summarized. Finally, the article reviews the literature on some special populations living with MS.

Neuropsychological Evaluation for Oncology.

Cognitive dysfunction is common in cancers and their treatments. Factors that can contribute to cognitive dysfunction include direct and indirect effects of cancer, surgery, radiation, systemic therapy, as well as comorbidities, fatigue, and mood disturbance. Using objective, validated measures, a neuropsychological evaluation can provide information regarding patterns of cognitive function. Emphasis of cognitive domains assessed may vary depending on disease and treatment history. Cognitive interventions can minimize the effects of cancer-related cognitive dysfunction on daily life.

Cognitive Rehabilitation for Adults with a History of Traumatic Brain Injury.

Cognitive rehabilitation following traumatic brain injury (TBI) involves a targeted, individualized approach to address deficits in attention, memory, executive functions, and/or other cognitive domains. This overview highlights the importance of thorough assessment to inform cognitive rehabilitation, a multidimensional approach, and current best practices in intervention strategies. It provides exemplar compensatory strategies for each cognitive domain. In addition to broad clinical practice guidelines, it also addresses unique considerations that may be warranted in some subgroups with TBI. Finally, outcome measurement is summarized.

Chronic noise exposure induces Alzheimer's disease-like neuropathology and cognitive impairment via ferroptosis in rat hippocampus.

BACKGROUND: Chronic noise exposure poses a remarkable public health concern, drawing attention to its impacts on the brain. Ferroptosis is involved in several brain-related diseases. However, the role of ferroptosis in the effects of chronic noise on the brain remains elusive. This study aimed to investigate the effects of chronic noise exposure on the brain and elucidate the underlying mechanisms. METHODS: A chronic noise-induced cognitive impairment model in rats was constructed and validated. The pathological state and ferroptosis level of the rat hippocampus were determined using Western blotting and immunohistochemistry. Bioinformatics was employed to investigate the interrelationship between chronic noise exposure and genes. Genetic relationships were analyzed using Mendelian randomization (MR) analysis. Cytoscape was employed for the prediction of upstream molecular and drug targets. RESULTS: In vivo experiments revealed that chronic noise exposure could induce Alzheimer's disease (AD)-like neuropathological changes in rat hippocampus and cognitive impairment. Moreover, protein markers indicative of ferroptosis and levels of lipid peroxidation were quantified to elucidate underlying mechanisms. Thereafter, oxidative stress- and ferroptosis-related differentially expressed genes (DEGs) underwent functional enrichment and PPI network analyses. Additionally, 8 genes with diagnostic significance were identified. In MR analysis, retinoic acid receptor responder 2 (Rarres2) gene exhibited a negative genetic relationship with AD. CONCLUSIONS: Chronic noise exposure could induce AD-like neuropathological changes and cognitive impairment via ferroptosis. The results of MR analysis indicated that Rarres2 gene may act as a protective factor in AD. This gene may be upstream of ferroptosis and serve as a target for the prevention and treatment of chronic noise-induced cognitive impairment.

Validity and reliability of the Pain Assessment in Impaired Cognition 15 (PAIC15) observation scale in persons with aphasia.

BACKGROUND: The use of self-report pain scales in persons with aphasia can be challenging due to communication and cognitive problems, while for assessing pain self-report pain is considered the gold standard (Harrison RA, Field TS. Post stroke pain: identification, assessment, and therapy. Cerebrovasc Dis. 2015;39(3-4):190-201.). An observational scale may be used as an alternative. This study examines the validity and reliability of the observational Pain Assessment in Impaired Cognition (PAIC15) scale in persons with aphasia. METHODS: Persons with aphasia were observed during rest and transfer by two observers using the PAIC15. The PAIC15 comprises 15 items covering the three domains of facial expressions, body movements, and vocalizations. When able, the participant completed four self-report pain scales after each observation. The observations were repeated within one week. For criterion validity, correlations between the PAIC15 and self-report pain scales were calculated and for construct validity, three hypotheses were tested. Reliability was determined by assessing internal consistency, and intra- and interobserver agreement. RESULTS: PAIC15 observations were obtained for 71 persons (mean age 75.5 years) with aphasia. Fair positive correlations (rest: 0.35-0.50; transfer: 0.38-0.43) were reported between PAIC15 and almost all self-report pain scales. Results show that significantly more pain was observed in persons with aphasia during transfer than during rest. No differences were found for observed pain between persons with aphasia who use pain medication and those without, or persons who have joint diseases compared to those without. Results showed acceptable internal consistency. Intra- and interobserver agreement was high for most PAIC15 items, particularly for the domains body movements and vocalizations during rest and transfer. CONCLUSIONS: Recognition of pain in persons aphasia using the PAIC15 showed mixed yet promising results.

Cognitive Impairment in Liver Tranplant Recipients: A Cross-Sectional Study.

OBJECTIVES: The proportion of older transplant recipients has increased. Cognitive impairment is not rare after kidney transplant, but data on this issue in liver transplant recipients are scarse. MATERIALS AND METHODS: In this cross-sectional study, we evaluated all liver transplant recipients from a single center in Brazil from July 2018 to June 2020 in terms of cognitive performance to determine the prevalence of neurocognitive disorder. We compared liver transplant recipients with neurocognitive disorder with liver transplant recipients without neurocognitive disorder. We also compared those with an alcoholic cause of liver transplant with other patients. The presence of depressive symptoms was assessed. We performed correlations of clinical data with cognitive scores. RESULTS: In a sample of 100 recipients with median age of 62 years (interquartile range, 56.2-69 y), neurocognitive disorder was present in 21% of the group. Patients with cognitive impairment were older (68 y [61-72] vs 61 y [52-68]; P = .019) and had a trend to higher proportion of persistent kidney injury (33.3% vs 13.9%; P = .055) versus patients without cognitive impairment. Recipients with alcoholic cause of liver transplant exhibited worse cognitive performance in the Mini-Mental State Examination (score of 26 [23.7-28.2] vs 28 [26-29]; P = .024) and the Alzheimer Disease Assessment Scale-cognitive (score of 10.4 [8.6-14.2] vs 8 [6.3-10]; P = .008) than other patients. Weak negative correlations were shown in cognitive performance scores versus recipient age (Semantic Verbal Fluency test, r = -0.334 [P = .001]; Clock Drawing test, r = -0.209 [P = .037]; Alzheimer Disease Assessment Scale-cognitive, r = -0.323 [P = .001]). CONCLUSIONS: Neurocognitive disorder was common in liver transplant recipients, in part due to increased age. This study also suggested a role for alcoholic cause of liver transplant and persistent kidney injury in the development of cognitive impairment.

Progressive cervical cord atrophy parallels cognitive decline in Alzheimer's disease.

Alzheimer's disease (AD) is characterized by progressive episodic memory dysfunction. A prominent hallmark of AD is gradual brain atrophy. Despite extensive research on brain pathology, the understanding of spinal cord pathology in AD and its association with cognitive decline remains understudied. We analyzed serial magnetic resonance imaging (MRI) scans from the ADNI data repository to assess whether progressive cord atrophy is associated with clinical worsening. Cervical cord morphometry was measured in 45 patients and 49 cognitively normal controls (CN) at two time points over 1.5 years. Regression analysis examined associations between cord atrophy rate and cognitive worsening. Cognitive and functional activity performance declined in patients during follow-up. Compared with controls, patients showed a greater rate of decline of the anterior-posterior width of the cross-sectional cord area per month (- 0.12%, p = 0.036). Worsening in the mini-mental state examination (MMSE), clinical dementia rating (CDR), and functional assessment questionnaire (FAQ) was associated with faster rates of cord atrophy (MMSE: r = 0.320, p = 0.037; CDR: r = - 0.361, p = 0.017; FAQ: r = - 0.398, p = 0.029). Progressive cord atrophy occurs in AD patients; its rate over time being associated with cognitive and functional activity decline.

Association between surgical admissions, cognition, and neurodegeneration in older people: a population-based study from the UK Biobank.

BACKGROUND: Previous studies have shown that major surgical and medical hospital admissions are associated with cognitive decline in older people (aged 40-69 years at recruitment), which is concerning for patients and caregivers. We aimed to validate these findings in a large cohort and investigate associations with neurodegeneration using MRI. METHODS: For this population-based study, we analysed data from the UK Biobank collected from March 13, 2006, to July 16, 2023, linked to the National Health Service Hospital Episode Statistics database, excluding participants with dementia diagnoses. We constructed fully adjusted models that included age, time, sex, Lancet Commission dementia risk factors, stroke, and hospital admissions with a participant random effect. Primary outcomes were hippocampal volume and white matter hyperintensities, both of which are established markers of neurodegeneration, and exploratory analyses investigated the cortical thickness of Desikan-Killiany-Tourville atlas regions. The main cognitive outcomes were reaction time, fluid intelligence, and prospective and numeric memory. Surgeries were calculated cumulatively starting from 8 years before the baseline evaluation. FINDINGS: Of 502 412 participants in the UK Biobank study, 492 802 participants were eligible for inclusion in this study, of whom 46 706 underwent MRI. Small adverse associations with cognition were found per surgery: reaction time increased by 0·273 ms, fluid intelligence score decreased by 0·057 correct responses, prospective memory (scored as correct at first attempt) decreased (odds ratio 0·96 [95% CI 0·95 to 0·97]), and numeric memory maximum correct matches decreased by 0·025 in fully adjusted models. Surgeries were associated with smaller hippocampal volume (ß=-5·76 mm³ [-7·89 to -3·64]) and greater white matter hyperintensities volume (ß=100·02 mm³ [66·17 to 133·87]) in fully adjusted models. Surgeries were also associated with neurodegeneration of the insula and superior temporal cortex. INTERPRETATION: This population-based study corroborates that surgeries are generally safe but cumulatively are associated with cognitive decline and neurodegeneration. Perioperative brain health should be prioritised for older and vulnerable patients, particularly those who have multiple surgical procedures. FUNDING: The Australian and New Zealand College of Anaesthetists (ANZCA) Foundation and the University of Sydney.

Neuropsychiatric symptoms: Risk factor or disease marker? A study of structural imaging biomarkers of Alzheimer's disease and incident cognitive decline.

Neuropsychiatric symptoms (NPS) are risk factors for Alzheimer's disease (AD) but can also manifest secondary to AD pathology. Mild behavioral impairment (MBI) refers to later-life emergent and persistent NPS that may mark early-stage AD. To distinguish MBI from NPS that are transient or which represent psychiatric conditions (non-MBI NPS), we investigated the effect of applying MBI criteria on NPS associations with AD structural imaging biomarkers and incident cognitive decline. Data for participants (n = 1273) with normal cognition (NC) or mild cognitive impairment (MCI) in the National Alzheimer's Coordinating Center Uniform Data Set were analyzed. NPS status (MBI, non-MBI NPS) was derived from the Neuropsychiatric Inventory Questionnaire and psychiatric history. Normalized measures of bilateral hippocampal (HPC) and entorhinal cortex (EC) volume, and AD meta-region of interest (ROI) mean cortical thickness were acquired from T1-weighted magnetic resonance imaging scans. Multivariable linear and Cox regressions examined NPS associations with imaging biomarkers and incident cognitive decline, respectively. MBI was associated with lower volume and cortical thickness in all ROIs in both NC and MCI, except for EC volume in NC. Non-MBI NPS were only associated with lower HPC volume in NC. Although both of the NPS groups showed higher hazards for MCI/dementia than No NPS, MBI participants showed more rapid decline. Although both types of NPS were linked to HPC atrophy, only NPS that emerged and persisted in later-life, consistent with MBI criteria, were related to AD neurodegenerative patterns beyond the HPC. Moreover, MBI predicted faster progression to dementia than non-MBI NPS.

Exploring the impact of acetylsalicylic acid and conditioned medium obtained from mesenchymal cells, individually and in combination, on cognitive function, histological changes, and oxidant-antioxidant balance in male rats with hippocampal injury.

BACKGROUND: The hippocampus is susceptible to damage, leading to negative impacts on cognition. Conditioned medium (CM) obtained from adipose tissue-derived mesenchymal stem cells (MSCs) and acetylsalicylic acid (ASA) have shown neuroprotective effects independently. This study explored the synergistic potential of ASA and CM from adipose-derived MSCs against hippocampal injury. METHODS: Adult male Wistar rats received bilateral hippocampal ethidium bromide (EB) injections to induce hippocampal damage. Rats were treated with ASA and/or CM derived from adipose tissue MSCs every 48 h for 16 days. Behavioral tests (open field test, Morris water maze, novel object recognition, and passive avoidance), oxidative stress, Western blot analysis of brain-derived neurotrophic factor (BDNF) and cerebral dopamine neurotrophic factor (CDNF) expression, and hippocampal histological investigation were conducted. RESULTS: Administration of EB caused impairments in spatial, recognition, and passive avoidance memory, as well as heightened oxidative stress, reduced BDNF/CDNF expression, and pyramidal cell loss in the hippocampal CA1 region. Administration of ASA, CM, or a combination of both mitigated these hippocampal damages and cognitive deficits, elevated BDNF and CDNF levels, and alleviated the CA1 necrosis caused by EB. Moreover, co-administering ASA and CM resulted in greater improvements in spatial memory compared to administering ASA alone, suggesting possible synergistic interactions. CONCLUSIONS: The ability of ASA, CM obtained from adipose tissue-derived MSCs, and their combination therapy to alleviate hippocampal injuries highlights their promising therapeutic potential as a neuroprotection strategy against brain damage. Our findings provide preliminary evidence of the potential synergistic effects of ASA and CM, which warrants further investigations.

Association of obesity indicators with cognitive function among US adults aged 60 years and older: Results from NHANES.

BACKGROUND: Midlife obesity is a significant risk factor for Alzheimer's disease, but the effects of obesity on cognitive function, either detrimental or beneficial, are controversial among older individuals. This study aims to assess this associations of body mass index (BMI) or waist circumference (WC) with cognitive function among United States older individuals. METHODS: A cross-sectional research study was conducted utilizing data from the 2011 to 2014 National Health and Nutrition Examination Survey (NHANES). Initially, the study compared differences in cognitive function among the normal weight, overweight, and obese groups. Subsequently, we examined the relationships between BMI or WC and cognitive function using multivariate linear regression. Finally, structural equation models were constructed to assess the relationships among body shape, lifestyle, and cognitive function pathways. RESULTS: The study included 2254 individuals. Obese subjects had lower scores in the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) word list learning tasks (CERAD-WL) (χ2 = 7.804, p = .020) and digit symbol substitution test (χ2 = 8.869, p = .012). The regression analysis showed that WC was negatively connected with the CERAD-WL score after adjusting for confounding factors (ß = -.029, p = .045). Moreover, WC had a mediating effect on the path from lifestyle to cognition (CERAD-WL). However, there was no difference in the CERAD delayed recall score and the animal fluency test between the obese and the other groups. CONCLUSIONS: Obese older adults exhibited impaired cognitive abilities in terms of learning and working memory performance. The impact of lifestyle on cognition was mediated by obesity-related anthropometric indices. Sleep, physical activity, and diet influenced the degree of obesity, which subsequently determined cognitive function. Prioritizing weight management in elderly people is crucial for safeguarding cognitive function.