Cognitive Tests Research Articles

Delirium risk profiles in a population-based study of United States older adults undergoing common noncardiac surgeries.

Older adults often require surgical care and are at elevated risk of delirium. We explored delirium risk profiles across the population of U.S. older adults who underwent one of 10 common noncardiac surgeries. We analyzed Health and Retirement Study (HRS) participants linked with Medicare billing data who underwent the following 10 noncardiac surgeries from 2000 to 2018 at age 65 or more: total knee arthroplasty (TKA), total hip arthroplasty (THA), spine surgery, cholecystectomy, colorectal surgery, hernia repair (ventral, umbilical, or incisional), endarterectomy, prostatectomy, transurethral resection of the prostate (TURP), and hysterectomy. Demographic and health covariates were obtained from the HRS dataset. Latent cognitive ability was calculated from cognitive testing, proxy reports, and demographics at the preoperative HRS interview. We compared standardized differences for delirium risk factors across the 10 surgeries and qualitatively clustered them into phenotypical subgroups. We analyzed 7424 older adults (mean age 76 ± 6 years, 45% male). Endarterectomy patients presented with the highest burden of nearly all health and cognitive factors, implying higher delirium risk (e.g., stroke, 22%; depressive symptoms, 30%; high school or less education, 73%; frailty, 42%; lowest latent cognitive ability). A second "general surgery" phenotype, including cholecystectomy, colorectal, and hernia surgery patients, experienced more frailty (29%-32%) and depressive symptoms (24%-26%), with moderate comorbidity burden. A third "pain" phenotype, which included TKA, THA, and spine surgery patients, commonly reported moderate or severe pain (47%-53%) and impairment in activities of daily living (ADL, 23%-30%), but fewer comorbid medical conditions. The remaining surgery types (hysterectomy, prostatectomy, TURP) were not phenotypically grouped and generally had lower risk features for delirium. In an epidemiological cohort of US older adults, we identified clinically meaningful heterogeneity in delirium risk profiles across different surgical types, which may have implications for delirium risk stratification and delirium prevention or treatment.

Mushroom and Silymarin Supplementation to Reduce Alzheimer’s Disease Progression: A Research Protocol

As life expectancy continues to rise, the incidence of diseases like Alzheimer’s disease (AD) increases. Curative fronts remain far from satisfactory. Interestingly, the gut microbiome may modulate brain functions. Shiitake mushroom β-(1,3)/(1,6)-glucans are dietary fibres that attenuate pro-inflammatory signalling, and silymarin is a neuroprotective agent, but their effect on AD progression remains elusive. This research protocol aims to examine the effects of shiitake mushroom β-glucan and silymarin supplementation in early-stage AD to reduce progression. A literature search was conducted to formulate this protocol. The potential of this nutraceutical supplementation against AD progression will be tested within mice models. Experimental groups will be fed with mushroom β-glucans and/or silymarin supplementation. Cognitive testing will involve novel object exploration time and Y-maze tests. Furthermore, brain and intestine tissues will be analyzed ex vivo to understand the nutraceutical supplement’s effects on the gut-brain axis in AD. It is anticipated that results demonstrate a synergistic effect of mushroom β-glucans and silymarin to reduce AD progression. This proposed nutraceutical supplement shows promise in reducing AD progression for individuals with early-stage AD. It also provides the foundation for future research on accessible interventions for cognitive impairment.

Association of cognitive performance with overall, dosage, intensity, and domain physical activity in aging: NHANES 2011–2014

BackgroundThe specific relationship between PA in detailed types and cognition is still unclear due to limited evidence. Our study aimed to investigate the relationship between cognitive performance and various aspects of physical activity, including overall activity, dosage, intensity levels [moderate physical activity (MPA), vigorous PA], and different domains of activity [occupational PA (OPA), transportation PA (TPA), and leisure-time PA (LTPA)] in older adults using data from the NHANES database.MethodsThis cross-sectional analysis used data from 2 cycles of NHANES (2011–2014). PA was determined through participants' self-reports using the Global Physical Activity Questionnaire (GPAQ). Cognitive performance was evaluated by the presence of psychometric mild cognitive impairment (p-MCI), identified based on a composite measure derived from three cognitive tests including the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), the Animal Fluency test, and the Digit Symbol Substitution test (DSST). Logistic regression models were used to evaluate the association.ResultsA total of 2588 participants aged 60 years or older were included, with an average age of 69.4 years and 48% being male. In the fully adjusted model, compared to no PA, performing 300 min of PA, and MPA were associated with 44%, and 33% reductions in the prevalence of p-MCI, respectively. Additionally, engaging in 1–149 min/week [OR 0.56, 95% CI (0.33–0.92)] and ≥ 300 min/week [OR 0.66, 95% CI (0.44–0.96)] of OPA, as well as ≥ 300 min/week [OR 0.56, 95% CI (0.36–0.86)] of LTPA, were also associated with a lower prevalence of p-MCI. Additionally, engaging in a diverse range of PA had better outcomes.ConclusionsOur results suggested a positive association between higher levels of PA and enhanced cognitive performance. Different intensities and domains of PA have varying impacts on cognition. Future exploration, such as objectively measured PA and longitudinal studies were needed to validate our conclusion.

Exploring the Effect of Single-Session Transcranial Direct Current Stimulation on Attention, Verbal Fluency, and Working Memory in Patients With Alzheimer's Disease-Related Dementia.

Alzheimer's disease (AD) is a leading cause of morbidity and mortality among the elderly. Transcranial direct current stimulation (tDCS) applies low-intensity currents to the brain, resulting in short-term neurocognitive effects and long-term neuroplasticity enhancement. Limited research reported on the impact of tDCS on cognitive functions in dementia due to AD. This study aims to compare changes in verbal fluency and working memory following a single tDCS application to the left dorsolateral prefrontal cortex (DLPFC) in AD patients. Patients with mild dementia due to AD underwent cognitive assessment using the Standardized Mini-Mental Test, Clock Drawing Test, Rey Auditory Verbal Learning Test, Functional Activities Questionnaire, Informant Questionnaire on Cognitive Decline in the Elderly, and Montreal Cognitive Assessment Scale. A single-session tDCS was administered by applying anodal tDCS to the left DLPFC for a duration of 30 minutes. Verbal fluency and working memory were evaluated before and after tDCS using the WAIS-R Digit Span Test forward and backward subscales, Trail Making Test (TMT) A and B, and Verbal Fluency Test. Regarding cognitive test scores before and after tDCS application, there were statistically significant reductions in the durations of TMT-A and TMT-B. However, there were no significant differences observed for TMT B-A, VFT, DST-forward, and DST-backward performances. The findings indicate that a single anodal tDCS targeting the left DLPFC enhances attention and processing speed in AD patients but has no effect on working memory or verbal fluency.

Plasma neurofilament light chain in fibromyalgia: A case control study exploring correlation with clinical and cognitive features.

Plasma neurofilament light chain (NFL) has been measured as a biomarker of neuronal damage in various neurological disorders. Elevated tau and β-amyloid levels have been found in patients with fibromyalgia (FM). The aim of the present study was to compare plasma neurofilament levels in fibromyalgia patients with normal controls and to investigate the correlation with clinical features and cognitive tests. Plasma NFL levels were assessed in 33 FM patients and compared with 22 age-matched controls. All patients were also assessed with clinical scales examining fibromyalgia disability, sleep quality and duration, fatigue, anxiety, and depression, and a neuropsychological battery examining executive function, verbal short-term memory, and working memory, as well as attentional executive function and selective attention, interference sensitivity, and inhibition of automatic responses. NFL levels were higher in FM patients (controls 6.19± 1.92; FM 17.28± 15.94 pg/mL ANOVA p 0.002). Working memory was the most impaired cognitive function significantly correlated with high NFL scores (Pearson p 0.034). Short sleep times also correlated with higher NFL scores (Pearson p 0.02) and poorer working memory performance (Pearson p 0.02). No correlation was found with indices of disease severity and duration. Plasma NFL levels are elevated in fibromyalgia patients, suggesting neuronal damage and correlating with a slight decrease in working memory and short sleep duration. Plasma neurofilament levels are elevated in patients with fibromyalgia, regardless of disease severity and duration. Neurofilament levels are higher in patients with mild working memory impairment and sleep disorders. Subgroups of patients with primary neuronal damage phenomena could be individualized for prospective evaluation with regard to the possible development of cognitive decline and sleep disturbances, which would justify a tailored therapeutic approach.

Identifying Factors that Increase False-Positive Rates on Embedded Performance Validity Testing in ADHD Evaluations.

This study investigated why certain embedded performance validity indicators (EVIs) are prone to higher false-positive rates (FPRs) in attention-deficit/hyperactivity disorder (ADHD) evaluations. The first aim was to establish the relationship between FPRs and 15 EVIs derived from six cognitive tests when used independently and together among adults with ADHD who have valid test performance. The second aim was to determine which specific EVIs increase the FPRs in this population. Participants were 517 adult ADHD referrals with valid neurocognitive test performance as determined by multiple performance validity tests and established empirical criteria. FPRs were defined by the proportion of participants who scored below an empirically established EVI cutoff with ≥0.90 specificity. EVIs derived from two of the six tests exhibited unacceptably high FPRs (>10%) when used independently, but the total FPR decreased to 8.1% when the EVIs were aggregated. Several EVIs within a sustained attention test were associated with FPRs around 11%. EVIs that did not include demographically adjusted cutoffs, specifically for race, were associated with higher FPRs around 14%. Conversely, FPRs did not significantly differ based on whether EVIs included timed versus untimed, verbal versus nonverbal, or graphomotor versus non-graphomotor components, nor whether they had raw versus standardized cut scores. Findings suggest that practitioners should consider both the type of test from which an EVI is derived and the aggregate number of EVIs employed to minimize the FPRs in ADHD evaluations. Findings also indicate that more nuanced approaches to validity test selection and development are needed.

Rauvolfia vomitoria phenol extract relieves pentylenetetrazol-induced seizures in Swiss mice and protects some temporal lobe structures

BackgroundRauvolfia vomitoria (R. vomitoria) is a plant of economic importance due to its diverse ethnomedicinal properties, including the anticonvulsant effect. In this study, we studied the antiseizure and neuroprotective potentials of R. vomitoria extracts against pentylenetetrazol (PTZ)-induced kindling.MethodsTwenty-five adult Swiss mice (25–30 g) were assigned to five groups (n = 5): control group, PTZ treatment group, and PTZ treatment after receiving oral R. vomitoria crude extract (100 mg/kg), R. vomitoria phenol extract (50 mg/kg) or sodium valproate (15 mg/kg) every 48 h for 28 days. Seizure scores, cognitive behavioral tests including novel object test, Y-maze test, and the elevated plus maze test, as well as brain neurochemicals and histomorphology studies, were performed.ResultsCompared with the control group, the PTZ group showed comparable body weight and durations in closed and open arms (P > 0.05), but preference for familiar objects, significant (P < 0.05) spontaneous alternation, increased monoamine oxidase activity and nitric oxide level, and Nissl chromatolysis in the temporal lobe structures including the cortex, hippocampus, and amygdala. R. vomitoria phenol extract pretreatment significantly (P < 0.05) reduced seizures, prevented adverse cognitive behaviors, decreased the nitric oxide level, and reduced the temporal lobe Nissl chromatolysis compared with the R. vomitoria crude extract pretreatment group and the sodium valproate pretreatment groups.ConclusionsThus, R. vomitoria phenol extract showed promising results against seizures and potential for general brain protection, suggesting that the anticonvulsant property of R. vomitoria may be attributed to its phenol constituent. More studies are needed to delineate the mechanisms of its action.

Exploring the Relationship Between CAIDE Dementia Risk and EEG Signal Activity in a Healthy Population

Background: Accounting for dementia risk factors is essential in identifying people who would benefit most from intervention programs. The CAIDE dementia risk score is commonly applied, but its link to brain function remains unclear. This study aims to determine whether the variation in this score is associated with neurophysiological changes and cognitive measures in normative individuals. Methods: The sample comprised 38 participants aged between 54 and 79 (M = 67.05; SD = 6.02). Data were collected using paper-and-pencil tests and electroencephalogram (EEG) recordings in the resting state, channels FP1 and FP2. The EEG signals were analyzed using Power Spectral Density (PSD)-based features. Results: The CAIDE score is positively correlated with the relative power activation of the θ band and negatively correlated with the MMSE cognitive test score, and MMSE variations align with those found in distributions of EEG-extracted PSD-based features. Conclusions: The findings suggest that CAIDE scores can identify individuals without noticeable cognitive changes who already exhibit brain activity similar to that seen in people with dementia. They also contribute to the convergent validity between CAIDE and the risk of cognitive decline. This underscores the importance of early monitoring of these factors to reduce the incidence of dementia.

Sensitive written hedgehog PICture Naming and Immediate Recall (PICNIR) as a valid and brief test of semantic and short-term episodic memory for very mild cognitive impairment.

Semantic and short-term episodic memory are impaired in some brain disorders including Alzheimer's disease. Development and validation of an almost self-administered, but cognitively demanding four-minute test identifying very mild cognitive impairment (vMCI). The innovative hedgehog PICture Naming and Immediate Recall (PICNIR) consisted of two parts. The first task was to write down the names of 20 black-and-white pictures to evaluate long-term semantic memory and language. The second task involves immediate recall and writing the names of as many previously named pictures as possible in one minute. The PICNIR is assessed using the number of naming errors (NE) and correctly recalled picture names (PICR). The PICNIR and a neuropsychological battery were administered to 190 elderly individuals living independently in the community. They were divided into those with vMCI (n = 43 with Montreal Cognitive Assessment (MoCA) 24 ± 3 points) and sociodemographically matched cognitively normal (CN) individuals (n = 147 with MoCA 26 ± 3). Both subgroups had predicted mean Mini-Mental State Examination scores of 28-29 points. Compared to CN, vMCI participants made more NE (0.3 ± 0.6 versus 0.6 ± 0.9; p = 0.02) and recalled fewer PICR (8.9 ± 2.2 versus 6.8 ± 2.2; p < 0.000001). Discriminative validity was satisfactory using the area under the ROC curve (AUC): 0.76 for PICR, 0.74 for MoCA, 0.67 for MoCA-five-word recall, and 0.59 for NE. The AUCs of PICR and MoCA were comparable and larger than those of MoCA five-point recall or NE. Logical Memory scores, RAVLT scores, Digit symbol, and animal fluency correlated with PICR. The picture-based PICNIR is an ultra-brief, sensitive cognitive test valid for assessing very mild cognitive impairment. Its effectiveness should be validated for other languages and cultures.

Visualization of “Subclinical Consequence” After Successful and Uneventful Surgical Intervention for Unruptured Cerebral Aneurysms

There are many studies on post-operative cognitive function after surgical clipping (SC) and endovascular coiling (EC) for unruptured cerebral aneurysms, but few reports focusing on possible subclinical damage. The aim of the present study was to detect the subclinical damage after surgical intervention. Patients with anterior circulation aneurysms who underwent either SC (SC group) or EC (EC group) were recruited. Imaging studies and evaluation of cognitive function were performed within 1 month preoperatively and at 6 months and 2 years postoperatively. The ipsilateral/contralateral cerebral blood flow (CBF) ratio (I/C ratio) calculated from values in four regions of interest (ROIs) placed on N-isopropyl-p-[123I] iodoamphetamine (123I-IMP)-single photon emission computed tomography (SPECT) was used to detect "subclinical consequence". "Subclinical consequence" was defined as post-operative CBF reduction without abnormality in other radiological examinations and cognitive tests. There were 14 patients in the SC group (mean age, 60.6±11.7 years) and 33 patients in the EC group (mean age, 67.5±7.2 years). All cognitive assessment results showed no significant reduction through the survey period. However, I/C ratios were restored by 2 years in the EC group not but in the SC group. I/C ratios at 6 months and 2 years were significantly lower in the SC group than the EC group (P<0.01). 123IMP-SPECT revealed a statistically significant reduction in ipsilateral CBF in patients who had an uneventful clinical course and no cognitive problems. The subclinical consequence could persist for at least 2 years following SC, and was less pronounced following EC.

Sleep-spindles as a marker of attention and intelligence in dogs

The sleep spindle-generating thalamo-cortical circuitry supports attention capacity in awake humans and animals, but using sleep spindles to predict differences in attention has not been tried in either. Of the more commonly examined cognitive correlates of spindle occurrence and amplitude, post-sleep recall, and general intelligence, only post-sleep recall had been studied in dogs, rats and mice. Here, we examined a sample of companion dogs (N = 58) for whom polysomnographic recordings and several cognitive tests were performed on two occasions each, with a three-month break in-between. Five of the tests were used to extract a factor analogous to human g (general mental ability). A sixth test in the battery measured sustained attention. Both attention and g-factor scores were predicted by higher slow spindle occurrence and absolute sigma power detected in polysomnographic recordings over the central electrode. These effects persisted across measurement occasions. Higher intrinsic spindle frequency was, in turn, linked to lower g-factor scores but displayed no relationship with attention scores. The overlap in localization and direction for the effects of slow spindle density (spindles/minute) and sigma power supports that they tap into the same underlying cognition-relevant aspects of spindling. Given earlier large sample and meta-analysis validations of sigma power as a reliable predictor of cognitive performance in humans, we thus conclude that the currently handled method for quantifying spindle density in dogs indeed measures cognition-relevant spindle activity by virtue of its agreement with the sigma power alternative.

Comparison of Cognitive Functions Between Individuals With Chronic Low Back Pain With High and Low Pain Catastrophizing and Pain-free Controls: A Cross-sectional Study.

Researchers suggested that the interruptive effects of chronic pain on cognitive functions may be modulated by the level of pain catastrophizing (PC). However, in individuals with chronic low back pain (CLBP), domains of cognitive function that may be affected by the level of PC remain largely unclear. Therefore, this study aimed to compare cognitive functions between individuals with CLBP with high and low PC and pain-free controls. This cross-sectional study examined cognitive functions of 42 individuals with CLBP and 21 pain-free controls. The PC scale was used to stratify participants with CLBP into high and low PC. Participants performed 5 cognitive tests from the Cambridge Neuropsychological Test Automated Battery, namely 5-choice reaction time, rapid visual processing, spatial working memory, attention switching task, and stop signal task. The statistical analyses revealed that compared with individuals with CLBP with low PC and pain-free controls, individuals with high PC demonstrated greater values of the between errors ( P =0.01), reaction latency ( P <0.001), and stop signal reaction time variables ( P =0.004, 0.003, respectively) but lower values of probability of hit ( P =0.02, 0.01, respectively), A' ( P =0.01, <0.001, respectively), and percent correct trials variables ( P =0.002, <0.001, respectively). The results of the current study showed deficits in sustained attention, working memory, cognitive flexibility, and inhibitory control in individuals with CLBP with high PC. From a clinical perspective, therapeutic interventions targeting PC should be considered to decrease catastrophic thinking about pain in individuals with CLBP. Additional research is warranted to explore cognitive functioning as an outcome of these interventions in individuals with CLBP.

EGb761 Trials for Mild-to-Moderate Dementia—What Have We Learned in the Past 18 years?

Background: Dementia leads to cognitive decline affecting memory, thinking, and behavior. Current pharmaceutical treatments are symptomatic, with limited efficacy and significant drawbacks. Ginkgo biloba extract (EGb761) is being explored as an adjuvant therapy for dementia because of its potential neuroprotective effects. Areas of Uncertainty: Despite decades of study, EGb761 has not been incorporated into treatment guidelines for these conditions. This review evaluates research futility in EGb761 trials for dementia, analyzing efficacy and methodological challenges to inform future research directions. Data Sources: In this review, we investigate the efficacy and adverse reactions of Ginkgo biloba extract (EGb761) as a treatment for Alzheimer disease or vascular dementia. We searched the randomized controlled trials published between 2006 and 2023 on PubMed and ScienceDirect. Results: The 7 selected studies have shown that the degree of improvement in standard cognitive assessment scores [Mini-Mental State Examination (MMSE), short cognitive performance test (SKT), neuropsychiatric inventory (NPI)] was not significant enough for a substantial proportion of patients. Improvements of the SKT score with at least 3 points in the Alzheimer disease/vascular dementia groups were found only in 2 out of 7 studies, changes of less than 2 points in MMSE score were found in 2 of the studies, while an improvement of at least 4 points in NPI scores was reported in 4 out of 7 studies. We aim to understand why this extract has not reached the level of evidence to be included in guideline recommendation despite extensive research and what have we learned from systematic reviews performed since 2010? Studies included in this review have shown some improvement in outcome scores with EGb761 treatment compared with placebo, but these improvements did not reach the threshold for clinically significant enhancement in MMSE/SKT/NPI scores. Limitations such as small sample sizes, minimal score changes, predominantly placebo comparisons, and short follow-up durations make it challenging to determine the usefulness of EGb761 in dementia treatment. The changes observed and methodological constraints underscore the uncertainty surrounding the efficacy of EGb761. Conclusion: The findings do not consistently demonstrate the clinical utility of EGb761, and improved scores on cognitive and neuropsychiatric assessments may not necessarily translate into meaningful clinical outcomes for patients with dementia. Starting from the question “What have we learned in the past 18 years?”, the answer would be: not much. Consequently, the question raised is: how long should we go on with the same conclusion, continuing to spend time and financial resources to replicate these results? Research strategies should be refined to optimize decision making and advance evidence-based care for neurocognitive disorders.

Convection-enhanced delivery of [177Lu]Lu-labeled gold nanoparticles combined with anti-PD1 checkpoint immunotherapy improves the survival of immunocompetent C57BL/6J mice with orthotopic GL261 murine glioma tumors

IntroductionOur objective was to study convection enhanced delivery (CED) of 177Lu-labeled metal chelating polymer (MCP) conjugated to gold nanoparticles ([177Lu]Lu-MCP-AuNP) alone or combined with anti-PD1 immune checkpoint inhibition (ICI) for improving the survival of immunocompetent C57BL/6J mice with orthotopic GL261 murine glioma tumors. MethodsC57BL/6J mice with GL261 tumors were treated with [177Lu]Lu-MCP-AuNP (0.8 or 2.7 MBq; 4 × 1011 AuNP) alone or combined with anti-PD1 antibodies (200 μg i.p. every 2 d × 3 doses). Control mice received normal saline, non-radioactive MCP-AuNP or anti-PD1 antibodies. Kaplan-Meier median survival was estimated. T-cell infiltration into the brain was probed by flow cytometry. Toxicity was assessed by monitoring body weight and cognitive function tests [Object Location Test (OLT) and Novel Object Recognition Test (NORT)] and T2-weighted MRI of the brain, overall health and ex vivo histopathological examination of the brain. ResultsTreatment with [177Lu]Lu-MCP-AuNP (0.8 MBq) significantly increased median survival compared to MCP-AuNP (29 vs. 25 d; P = 0.007) or normal saline-treated mice (24 d; P < 0.001). Combining [177Lu]Lu-MCP-AuNP (0.8 MBq) with anti-PD1 antibodies increased median survival to 32 d (P < 0.0001 vs. normal saline). Increasing the mean amount of [177Lu]Lu-MCP-AuNP to 2.7 MBq and combining with anti-PD1 antibodies extended survival to at least 218 d in 5/9 mice. Increased CD8+ cytotoxic T-cells and decreased CD4+ helper T-cells were found in the brain vs. normal saline-treated mice. No weight loss (>20 %) was observed for treated or control mice. There was no change in cognitive function in mice treated with [177Lu]Lu-MCP-AuNP (0.8 MBq) alone or combined with anti-PD1 antibodies assessed by the OLT or NORT. T2-weighted MRI in mice treated with 2.7 MBq [177Lu]Lu-MCP-AuNP combined with anti-PD1 antibodies revealed edema, gliosis and ex vacuo dilatation of the ventricle proximal to the site of infusion. Histopathological examination of the brain revealed dilatation of the ventricle and gliosis proximal to the site of infusion but no radiation necrosis. MRI and histological analysis did not reveal tumor in the brain of these mice. Mice treated with 2.7 MBq [177Lu]Lu-MCP-AuNP combined with anti-PD1 antibodies did not demonstrate overall deleterious health effects. ConclusionsWe conclude that CED of [177Lu]Lu-MCP-AuNP combined with anti-PD1 checkpoint immunotherapy improved the survival of immunocompetent C67BL/6J mice with GL261 glioma tumors in the brain. Higher administered amounts of [177Lu]Lu-MCP-AuNP (2.7 MBq vs. 0.8 MBq) were most effective and yielded long-term survival. Advances in knowledge and implications for patient careThis study demonstrates that combining a locally-infused radiation nanomedicine, [177Lu]Lu-MCP-AuNP and anti-PD1 checkpoint immunotherapy improved the survival of mice with glioma tumors in the brain. In the future, this treatment may be useful to treat residual tumor at the surgical margins in patients with GBM to prevent local recurrence and improve survival.

Stair climbing interventions reduce postprandial hyperglycemia but not cognitive functions: findings of a randomized cross-over trial

Prolonged sitting can negatively impact postprandial glucose levels and cognitive functions. Stair climbing interventions have potential to mitigate these risks however remains unexplored. The present study aimed to explore the effects of stair climbing bouts on postprandial glucose and cognitive functions during prolonged sitting. Twenty-eight sedentary young adults (aged 20 – 30 years) underwent two intervention visits after standardized lunch for two hours: (1) STAIR: the participants climbed two flight of stairs for two minutes every 30 minutes; (2) SIT: the participants continued to sit. Blood glucose was measured using capillary finger prick method while attention function was measured using computer-based cognitive tests at baseline, end of 1st hour and 2nd hour. Significant interaction (F2, 54 = 15.96, p <0.001) was observed for conditions and time. During STAIR visit, significant changes in postprandial glucose at 1st hour (β = - 2.6 mmol/dl, p <0.001) and 2nd hour (β = 3.0 mmol/dl, p <0.001). No significant difference in the attention functions with time and conditions was observed. Stair climbing interruptions may be a promising solution to prevent high glycemic excursion occurring during prolonged sitting following postprandial sessions. However, the clinical benefits of stair climbing on attention functions remain unconvinced.

Cognitive functions among school-going children and adolescents with type 1 diabetes mellitus: Matched case-control cross-sectional study.

To investigate the cognitive performance of Saudi children and adolescents with type 1 diabetes mellitus (T1DM) compared to matched control groups. A total of 64 participants (32 T1DM patients and 32 control), matched with age, gender, ethnicity, education, and body mass index were recruited. Cognitive functions were investigated using a highly reliable and valid "Cambridge neuropsychological test automated battery". The attention switching task (AST) and choice reaction time (CRT) test were carried out to evaluate the cognitive functions. The cognitive test parameters AST mean correct latency, AST mean correct latency (congruent), AST mean correct latency (incongruent), and CRT mean correct latency were significantly delayed in the T1DM group compared to their control group (p<0.0001). Moreover, the control group did significantly better on the cognitive test parameters AST and CRT than the T1DM children and adolescents with hemoglobin A1c (HbA1C) ≥8% group (p<0.01). The findings demonstrate a delay in cognitive performance among children and adolescents with T1DM. Importantly, elevated HbA1C levels and duration of disease were associated with reduced cognitive functions. The present study findings highlight the importance of stringent glycemic management in children and adolescents with T1DM. The findings can support physicians and policymakers not only to prevent microvascular complications but also to mitigate potential cognitive deficits among children and adolescents with T1DM.

REAL AD-Validation of a realistic screening approach for early Alzheimer's disease.

Early diagnosis is crucial to treatment success. This is especially relevant for Alzheimer's disease (AD), with its protracted preclinical phase. Most health care systems do not have the resources to conduct large-scale AD screenings in middle-aged individuals in need of novel AD treatment options and early, accurate diagnosis. Recent developments in blood-based biomarkers and remote cognitive testing offer novel, cost-effective, and scalable methods to detect cognitive and biomarker changes that may indicate early AD. In research cohorts, promising results have been reported, but these modalities have not been validated in population-based settings. The validation of a realistic screening approach for early Alzheimer's disease (REAL AD) study aims to validate the diagnostic and prognostic performance of the combined use of blood-based biomarkers and remote cognitive testing as a screening approach for early AD employing an existing health care infrastructure (the Swedish Västra Götaland Region Primary Healthcare). REAL AD aims to provide a concrete, individualized diagnostic framework, which could significantly improve AD prognosis. HIGHLIGHTS: In Sweden, most Alzheimer's disease (AD) diagnoses are made in primary care, where access to AD biomarkers is almost non-existent. Most health care systems have limited resources for the screening of middle-aged adults for early evidence of AD pathology. Blood-based biomarkers and remote cognitive testing offer novel, cost-effective, and scalable methods for detecting cognitive and biomarker changes that may indicate early AD. The REAL AD study aims to validate the diagnostic and prognostic performance of blood-based biomarkers and remote cognitive testing as a screening approach for early AD in an existing primary health care infrastructure in the Västra Götaland Region in Sweden. Studies such as REAL AD will play a vital role in helping to move the field toward concrete implementation of biomarkers in AD diagnostic workup at all care levels, eventually providing more comprehensive treatments options for the large and growing AD population, and for those at risk.

The influence of alterations in the composition of intestinal microbiota on neurovascular coupling and cognitive dysfunction in individuals afflicted with CSVD

IntroductionAn expanding body of research has explored the crucial role of gut microbiota in cerebral small vessel disease (CSVD). The objective of this study is to investigate alterations in the gut microbiota structure among CSVD patients, to explore the correlation between differential taxonomic levels and the neurovascular coupling index as well as cognitive function and to elucidate the imaging and biomarkers of mild cognitive impairment (MCI) in CSVD. MethodsWe enrolled 104 patients with CSVD and 40 healthy controls (HC). Based on cognitive test scores, CSVD patients were categorized into a cognitively normal group (CSVD-NCI, n=61) and a mild cognitive impairment group (CSVD-MCI, n=43). Performing magnetic resonance imaging (MRI) scans, gut microbiota analysis, as well as clinical and neuropsychological assessments for all participants. Based on arterial spin labeling (ASL) and blood oxygen level-dependent (BOLD) imaging data, cerebral blood flow (CBF) and neural activity indices are computed. The coupling indices of CBF/mReHo, CBF/mfALFF, CBF/mALFF, and CBF/mDC are calculated to assess the whole-brain neurovascular coupling changes in patients with CSVD. ResultsSpecies annotation revealed differences in the composition at the phylum and genus levels among the HC, CSVD-NCI, and CSVD-MCI groups. Additionally, differential analysis using the Kruskal-Wallis test demonstrated specific dominant microbial communities in all three groups. The relative abundance of certain dominant microbial communities in CSVD patients exhibited correlations with neurovascular coupling and cognitive function. The combined assessment of Bacteroides genus and CBF/mDC proved effective in distinguishing between CSVD-NCI and CSVD-MCI, providing a novel non-invasive approach for the diagnosis of MCI in CSVD.

Cariprazine and Cognition in Patients with Schizophrenia and Bipolar Disorder: A Systematic Review.

Cariprazine (CAR), an antipsychotic with partial agonism at the D3 receptor and higher affinity than dopamine, has shown significant procognitive effects in preclinical animal studies. This study systematically reviews CAR's effects on cognitive measures in patients with schizophrenia and bipolar disorder. Two independent reviewers systematically searched PubMed, Web of Science, Scopus, and the Cochrane Library up to May 2024, following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Additional studies were found by hand searching the references of included studies. Eligible studies were randomized controlled trials (RCTs) in English that assessed CAR's effects on cognition in patients with schizophrenia or bipolar disorder. Quality was assessed using the Jadad scale. Out of 139 reports, 5 studies (involving 6,104 patients with schizophrenia or bipolar disorder) were included. In schizophrenia, CAR showed better cognitive outcomes (mainly indirect measures) than placebo (PBO) in both early and late stages. It also outperformed risperidone and aripiprazole in attention-related cognitive tests. In bipolar disorder, CAR improved cognition compared to PBO (also using indirect measures). Most studies found the greatest cognitive benefits with low doses of CAR (1.5-3 mg/d). CAR improved cognitive measures compared to PBO and other D2 antagonists or partial agonists in RCTs, especially in patients with greater baseline impairment. Thus, CAR may be a promising option for enhancing cognition in schizophrenic and bipolar patients; though, more trials using specific cognitive assessment tools are needed. PROSPERO CRD42023485028.

Digital detection of Alzheimer’s disease using smiles and conversations with a chatbot

In super-aged societies, dementia has become a critical issue, underscoring the urgent need for tools to assess cognitive status effectively in various sectors, including financial and business settings. Facial and speech features have been tried as cost-effective biomarkers of dementia including Alzheimer’s disease (AD). We aimed to establish an easy, automatic, and extensive screening tool for AD using a chatbot and artificial intelligence. Smile images and visual and auditory data of natural conversations with a chatbot from 99 healthy controls (HCs) and 93 individuals with AD or mild cognitive impairment due to AD (PwA) were analyzed using machine learning. A subset of 8 facial and 21 sound features successfully distinguished PwA from HCs, with a high area under the receiver operating characteristic curve of 0.94 ± 0.05. Another subset of 8 facial and 20 sound features predicted the cognitive test scores, with a mean absolute error as low as 5.78 ± 0.08. These results were superior to those obtained from face or auditory data alone or from conventional image depiction tasks. Thus, by combining spontaneous sound and facial data obtained through conversations with a chatbot, the proposed model can be put to practical use in real-life scenarios.