Index Of Cognitive Function Research Articles

Investigating heterogeneity of cognitive and functional decline using Subtype and Stage Inference machine learning

AbstractBackgroundAlzheimer’s disease (AD) is a heterogeneous disease with different clinical phenotypes and pathophysiological subtypes. Identifying cognitive/functional subtypes in AD could elucidate the diverse clinical progression patterns. The Cognitive Function Index (CFI), a 15‐item questionnaire completed by participants and study partners, captures aspects of cognitive and functional decline. We investigated participant heterogeneity using the CFI and compared differences between subtypes based on participant or study partner reports.MethodsParticipants were 4486 cognitively unimpaired older adults from the Anti‐Amyloid Treatment in Asymptomatic Alzheimer’s (A4) Study. All participants and study partners completed the CFI. Participants had baseline demographics, neuropsychological test scores, and amyloid PET measures available. The Staging and Subtype Inference (SuStaIn) algorithm was independently applied to participant (PT) and study partner (SP) CFI reports to identify subtypes. Differences between subtypes were assessed using Analysis for Variance (ANOVA) with post hoc analysis.ResultsTable 1 summarizes participant characteristics. Analysis of PT and SP CFI responses independently identified three subtypes with distinct progression patterns. Notably, 35.2% and 57.5% of participants showed no progression based on PT and SP reports, respectively. All subtypes, except SP‐2, had CFI items related to difficulties with recall, needing written reminders, and misplacing items as the first items of suspected decline (Figure 1). Clusters PT‐1 (66.5%) and SP‐1 (45.8%) were the subtypes with most frequent progression pattern (Figure 1). Subtypes PT‐2 and SP‐2 had the highest scores on Digit Symbol Substitution test, walked the most, and for SP‐2 lowest Geriatric Depression Scores (p<0.05 for all; Figure 3). Subtypes PT‐3 and SP‐3 scored lowest on the participant Activities of Daily Living (ADL; p<0.05). Additionally, PT‐3 scored lowest on the Study Partner ADL.ConclusionWe identified distinct subtypes from both participant and study partner CFI reports. Post hoc analysis indicated consistency within subtypes identified from the two sources of information. Subjective reports on cognitive decline could serve as a valuable tool for classifying participants into different risk groups.

The relationship of subjective cognitive decline (SCD) and the Stages of Objective Memory Impairment (SOMI) system in preclinical AD

AbstractBackgroundSelf‐awareness of declining cognition in the absence of objective cognitive impairment is called subjective cognitive decline (SCD). Herein, we examine the association of SCD measured by the Cognitive Function Index (CFI; Amariglio, et al. 2015) with the Stages of Objective Memory Impairment (SOMI) system (Grober, et al. 2018) that classifies cognitively normal individuals into one of five stages based on the Free and Cued Selective Reminding Test (FCSRT; Grober & Buschke, 1987) and that maps onto the presence of AD pathology (Grober, et al. 2022 & Petersen, et al. 2023). In early SOMI stages (SOMI‐1, 2) there is increasing retrieval difficulty; in later stages (SOMI‐3/4) storage deficits emerge.MethodsWe used baseline data from 4109 neuropsychologically normal, older adults from the Anti‐Amyloid Anti‐Amyloid Treatment in Asymptomatic Alzheimer’s (A4) Study. All participants had amyloid PET measures and completed the FCSRT used for determing SOMI classification. Additionally, all participants and study partners completed the CFI. An adjusted CFI score was used that excluded three items that assess functional rather than cognitive ability. CFI positivity was defined by cutoffs, 7.8 and 6.5 for participant and partner versions respectfully, representing one standard deviation above the mean. Analysis of Variance (ANOVA) with post hoc analysis was used to assess differences of CFI scores between SOMI stages.ResultsWe found fewer A+ participants were SOMI‐0 compared to A‐ participants (34.1% vs. 42.7%, p<0.001, Figure 1). Additionally, more A+ participants were SOMI‐3/4 compared to A‐ participants (15.4% vs. 10.3%, p<0.001). Among A+ participants, memory impairment (SOMI‐2/3/4) was more prevalent among those with self‐perceived SCD (34.9%) than those without SCD (29.5%, p = 0.016). Similarly, among A+ participants, prevalence of memory impairment was higher among those with partner‐perceived SCD (40%) than those without (28%, p<0.001). Post hoc results found higher SOMI stages were associated with higher partner and study partner CFI scores except between SOMI‐2 and SOMI‐3/4 (p<0.05 for all, Figure 2).ConclusionsMemory impairment was found to be more prevalent among A+ participants with self‐ and partner‐rated SCD. SCD increases with increasing memory impairment.

Trimethylamine‐N‐Oxide regulates cognitive function in Alzheimer’s Disease patients and mice model through brain‐gut‐microbiota axis

AbstractBackgroundThe regulatory role of Trimethylamine‐N‐oxide (TMAO) for cognition from the perspective of microbiota‐gut‐brain (MGB) axis in AD remains unclear.MethodIn clinical cohort study for effects of 24‐week computerized cognitive training (CCT), registered on clinicaltrials.gov (NCT06094452), plasma TMAO levels were quantified using ELISA in MCI (n=39) and mild AD patients (n=35). Correlation analyses were conducted to assess the relationship between changes in TMAO levels and cognitive function (ADAS‐cog score) and gut microbiota indices. In animal model experiments, C57/BL6 aged mice and APP/PS1 transgenic mice were administrated by water feeding with 1.2% TMAO for 16 weeks and 1.0% of its inhibitor 3,3‐Dimethyl‐1‐butanol (DMB) for 8 weeks. TMAO levels in plasma and cerebrospinal fluid (CSF) were measured by ELISA. Cerebral blood flow (CBF) activation was detected by a laser speckle imaging system. Cognitive behavior was evaluated using Morris Water Maze test. The expressions of BBB function proteins (ZO‐1, Occludin, and PDGFRβ,) and neuroinflammatory markers (HMGB1 and IL‐1β) were detected by western blotting. The deposition of β‐amyloid (Aβ) plaques and neuronal survival in hippocampus were visualized by histochemical and Nissl staining.ResultTMAO was significantly increased in plasma of AD patients. After CCT intervention, TMAO was significantly decreased in the CCT group, and this decrease was positively correlated with ADAS‐cog (r=0.549), and negatively correlated with Shannon evenness (r= ‐0.372). TMAO changes were also negatively correlated with the relative abundance change of Roseburia (r=‐0.443), Lachnospiraceae_UCG‐004 (r=‐0.392), and Lactobacillus (r=0.480), while positively correlated with Ruminococcus_torgues (r=0.443), Fusobacterium (r=0.484) and Herbasporillum (r=0.365). In animal models, TMAO was increased in the plasma and CSF of APP/PS1 mice. After supplemented with 1.2% TMAO, the cognitive performances of C57 and APP/PS1 mice were significantly impaired. The activation amplitude of CBF was decreased, and the expression of BBB function proteins (ZO‐1, Occludin, and PDGFRβ) were significantly decreased. The expressions of neuroinflammation marker HMGB1 and IL‐1β were significantly increased; the accumulation of Aβplaques was increased with decreased neuronal survival. Circulating level of TMAO was decreased after DMB intervention, which showed cognitive protection effects.ConclusionTMAO may be a novel biomarker that regulates cognition of AD through MGB axis.

Association between self-reported weight loss and new long-term care insurance certifications: A 9-year Japanese older adult cohort study.

This cohort study aimed to assess weight loss associated with new long-term care insurance (LTCI) certifications over a 9-year period, accounting for the competing risk of death. We analyzed data from 3749 Japanese individuals aged ≥65 years in Kami Town, Hyogo Prefecture, Japan. Weight loss was assessed using the Kihon Checklist during the baseline survey. Data regarding LTCI certifications were collected until March 2022. Cox proportional hazards models were used to calculate adjusted hazard ratios (HRs) of 9-year LTCI certification because of weight loss, adjusted for confounding factors. To exclude the effect of competing risks, Fine-Gray regression was used to estimate subdistribution HRs. Subgroup analyses were carried out after the examination of potential interactions between subjective cognitive function, body mass index categories and weight loss. The incidence rate of new LTCI certifications was 5.16 per 100 person-years overall - broken down into 7.02 for those with weight loss and 4.97 for those without. The adjusted HR for weight loss to new LTCI certifications was 1.35 (95% CI 1.15-1.59). Considering mortality as a competing risk, the adjusted subdistribution HR was 1.37 (95% CI 1.16-1.61). Conversely, no interaction was observed between weight loss and subjective cognitive function or body mass index categories. Excluding the effect of mortality, weight loss was identified as a risk factor for new LTCI certifications. However, no interaction was observed between weight loss and subjective cognitive function or body mass index categories. Geriatr Gerontol Int 2024; 24: 1320-1327.

Can early gut microbiota screening reduce the incidence of cognitive impairment? A Mendelian randomization study.

Background: Gastrointestinal symptoms are now detected early in the clinical course of many dementia patients, and studies of the microbiome-gut-brain axis have confirmed bidirectional interactions between the gut and the brain. However, the causal relationship between gut microbiota and cognitive impairment has not been fully established. Therefore, this study conducted a bidirectional Mendelian randomization study to elucidate the potential causal relationship of gut microbiota to cognitive impairment. Objective: Using Mendelian randomization to identify gut flora with a genetic causal effect on the development of cognitive impairment. Methods: This study utilized publicly available genome-wide association study summary data to perform MR analysis, with gut microbiota as the exposure and various cognitive function indicators as well as scores for Alzheimer's disease as outcomes. This study selected single nucleotide polymorphisms as instrumental variables based on p-values, F-statistics, and r2. Bidirectional Mendelian randomization was conducted using methods such as inverse variance weighted, MR-Egger, simple mode, and weighted mode to assess the causal relationship. Concurrently, this study carried out Cochran's Q test, MR-Egger intercept test, and leave-one-out analysis to identify potential heterogeneity and horizontal pleiotropy. Results: This study identified a total of 31 gut microbes that have a causal relationship with cognitive impairment, which include 1 phylum, 4 classes, 3 orders, 2 families, and 21 genera. Conclusions: This study unveiled specific gut microbiota associated with cognitive impairment, offering new insights and approaches for the prevention and treatment of cognitive impairment through gut microbiota such as Bifidobacterium and Ruminococcus gnavus group.

Contingent negative variation for assessment of neurological deficits in children with hypothyroidism

Objectives: Hypothyroidism is one of the most common endocrine disorders. Its effect on the central nervous system is more pronounced, especially in the pediatric age group. Despite receiving adequate thyroid hormone replacement therapy, several patients continue to suffer from neurological impairments including cognitive dysfunction. Contingent negative variation (CNV) is an event-related potential (ERP) that is considered as an indicator of cognitive function. In this study, CNV was recorded in children with hypothyroidism. To the best of our knowledge to date, there have been no studies of CNV in hypothyroidism. Materials and Methods: This prospective study included 52 children between 8 and 15 years of age who were newly diagnosed with hypothyroidism. Diagnosis of hypothyroidism was based on laboratory thyroid function tests. CNV ERP was recorded in the enrolled children at the time of diagnosis, 1-month, and 6-month follow-up. Initial CNV (iCNV) and late CNV (lCNV) amplitudes and latencies were recorded each time. Results: Although the amplitudes of iCNV and lCNV appeared to increase during follow-ups, the changes were not statistically significant (P > 0.05). Similarly, there appeared to be a modest reduction in latencies of iCNV or lCNV during follow-up; however, these changes were not statistically significant either. Conclusion: Our study did not show any significant changes in neurophysiological parameters. This may be attributed to a shorter time period of follow-up of six months and a smaller sample size. There is a possibility that CNV parameters may show more pronounced changes after a prolonged duration of treatment.

Evaluation of the efficiency of the hepatoprotector glucuronate in toxic hepatitis of various etiology

The objective was to study the effectiveness of the use of hepatoprotector glucuronate at the early stage of intensive therapy of toxic hepatitis of various etiologies.Materials and methods. We studied 120 patients with toxic hepatitis who were treated at the Republican research center for emergency medicine in 2022–2023. The study was carried out in two groups of patients. Group I – 60 patients admitted in 2023, who, in addition to traditional therapy, received a complex hepatoprotector glucuronate (Jetepar®)*. Group II (comparison group) – 60 patients who applied in 2022 and received only traditional therapy. Biochemical blood parameters were studied upon admission and over time on day 5. The severity of intellectual impairment was assessed using cognitive scales and the Reitan test on days 2 and 5 from the start of treatment.Results. Upon admission, both groups showed signs of toxic liver damage. In dynamics by the 5th day in patients of group I, there was a decrease in ALT by 63.7%, AST by 66.4%, alkaline phosphatase by 54.2% from the initial values, which was 3.9 and 2.6, 2. 1 lower than in the comparison group. The level of free ammonia in patients of group I on the 5th day decreased by 52%, and lactate by 57% from the initial level, almost to the physiological norm, while in the comparison group (II) only by 24.8% and 38.1%, which was 2.2 and 1.5 times worse than in the main group. Screening of the level of intelligence using two cognitive scales and the Reitan test showed that in patients in the comparison group, cognitive function indicators on the 5th day were 1.4, 1.5 and 1.2 times lower than in the main group.Conclusion. The use of the hepatoprotector glucuronate improves liver parameters and cognitive functions in patients with toxic hepatitis.

Contextuality of cognitive control deficits in alcohol dependence — pro et contra

Cognitive impairment, including cognitive control, mediates the negative social consequences of alcohol-related behavior, but few studies have examined these processes in the Russian speaking population using modern and standardized assessment methods. Thus, the aim of the study was to examine the features of cognitive control (inhibition of automatic response) and the general level of cognitive functioning in a Russianspeaking sample of alcohol-dependent individuals (AD) using quantitative assessment methods. Materials and Methods. 111 individuals diagnosed with alcohol dependence (F10.30) and 27 healthy participants were examined by using the Brief Assessment of Cognitive Functioning in Affective Disorders Battery (BAC-A) and additional tests of cognitive control (Stroop test with incongruent stimuli, Stroop test with alcohol-associated stimuli). The statistical methods were U-Mann-Whitney test, Spearman correlation coefficient, two-stage least squares regression. Results. In the AD group the indices of cognitive functioning were significantly lower in all parameters except for the subtests of verbal memory and digit sequence (p<0,05). The model of the relationship between the parameters of general cognitive functioning and cognitive control reveals that the index of incongruence to alcohol-related stimuli was a significant predictor of sampe affiliation. Discussion. The obtained results may indicate the presence of impairments of speed of mental processes, planning , verbal fluency and response inhibition function in the group of individuals with AD. In the studied group, the automatic response inhibition function mediates the general cognitive functioning only within the relevant contextual stimuli.

Uncovering the relationship between trace element exposure, cognitive function, and dietary inflammation index in elderly americans from the National Health and Nutrition Examination Survey 2011–2014

BackgroundThe consequences of trace element exposure on cognitive function in elderly adults have been recognized as primarily attributed to the inflammatory response. It is noteworthy that diet can either exacerbate or reduce the inflammatory response. Despite this, there have been limited studies about the effects of diet on the relationship between trace element exposure and cognitive function.MethodsA cross-sectional study utilized data from the 2011–2014 NHANES survey to explore the association between trace element exposure and cognitive function in elderly adults. The study enrolled 1726 participants, and generalized linear regression model (GLM), Bayesian kernel machine regression model (BKMR), weighted quantile sum regression (WQS), and quantile g-computation regression analysis (Qg-comp) were conducted to assess the impact of five trace elements (lead, cadmium, mercury, manganese, and selenium) in blood on cognitive function under the anti-inflammatory and pro-inflammatory diet.ResultsThe GLM analysis showed a positive correlation between selenium (Se) and both the instant recall test (IRT) and digit symbol substitution test (DSST) (β = 2.06, 95% CI: 0.70 ~ 3.41; and β = 6.41, 95% CI: 2.35 ~ 10.46, respectively). In contrast, cadmium (Cd) was negatively associated with DSST (β = -1.17, 95% CI: -2.13~ -0.22), and lead (Pb) was negatively associated with IRT (β = -0.47, 95% CI: -0.82~ -0.11). For the animal fluency test (AFT), the highest quartile of manganese (Mn) was negatively associated with the lowest quartile (β = -0.72, 95% CI: -1.34~-0.10), while mercury (Hg) showed no significant associations with cognitive function tests. Subgroup analysis revealed the effects of Cd on IRT and DSST and Se on DSST under the pro-inflammatory diet. Furthermore, The BKMR analysis showed an inverted U-shaped curve with the negative impact of trace element mixtures and DSST and a linearly negative trend with IRT in the pro-inflammatory diet. Among them, Cd was emphasized as the most potent risk factor, and Se was the most vital protective factor for IRT and DSST in WQS and Qg-comp analysis.ConclusionsThe study suggests that a high-quality diet might alleviate the adverse effects of Cd on IRT and DSST. High Se levels were also associated with better IRT and DSST scores in the pro-inflammatory diet. These findings provide valuable insights into the connection between diet, trace element exposure, and cognitive function in elderly adults.

Audio-biofeedback versus the scale method for improving partial weight-bearing adherence in healthy older adults: a randomised trial.

To investigate how audio-biofeedback during the instruction of partial weight-bearing affected adherence, compared to traditional methods, in older adults; and to investigate the influence of individual characteristics. The primary outcome measure of this randomised controlled trial was the amount of load, measured as the ground reaction force, on the partial weight-bearing leg. The secondary outcome was the influence of individual characteristics on the amount of load. Included were healthy volunteers 60 years of age or older without gait impairment. Participants were randomly allocated to one of two groups; blinding was not possible. Partial weight-bearing of 20 kg was trained using crutches with audio-biofeedback (intervention group) or a bathroom scale (control group). The degree of weight-bearing was measured during six activities with sensor insoles. A mean load between 15 and 25 kg was defined as adherent. There was no statistically significant difference in weight-bearing between the groups for all activities measured. For the sit-stand-sit activity, weight-bearing was within the adherence range of 15-25 kg (audio-biofeedback: 21.7 ± 16.6 kg; scale: 22.6 ± 13 kg). For standing, loading was below the lower threshold (10 ± 7 vs. 10 ± 10 kg). Weight-bearing was above the upper threshold for both groups for: walking (26 ± 11 vs. 34 ± 16), step-up (29 ± 18 vs. 34 ± 20 kg) and step-down (28 ± 15 vs. 35 ± 19 kg). Lower level of cognitive function, older age, and higher body mass index were correlated with overloading. Audio-biofeedback delivered no statistically significant benefit over the scale method. Lower cognitive function, older age and higher body mass index were associated with overloading. Not applicable due not being a clinical trial and due to the cross-sectional design (one measurement point, no health intervention, no change in health of a person).

Individual differences in attention and working memory modulate the process of tone merging: evidence from Macau Cantonese

Cognitive functions, including attention and working memory, have been recognized to be associated with tone processing. However, it remains unclear how these cognitive functions might modulate the process of tone merging. In Macau Cantonese, three pairs of tones are currently undergoing or have completed merging, exhibiting different rates and ranges of merging within the speech community, providing a valuable opportunity to investigate this issue. Through a perception task, a production task, and a series of cognitive function tasks, we examined differences in cognitive performances among individuals distinguishing different tone pairs and explored the correlations between various indices of tone processing and cognitive functions. The results revealed that the completed merging of the T2–T5 pair showed no significant correlation with cognitive functions in perception and production. The T3–T6 pair, with an intermediate merging speed, exhibited a significant positive correlation between cognitive functions and both their perception and production. In contrast, the T4–T6 pair, characterized by a slower merging speed, showed a correlation only in the perception modality. Our findings suggested that cognitive functions affect tones at different stages of the merging process, influencing their perception and production in distinct ways. The results provide a novel perspective on the origin of tonal variation and the relationship between perception and production.

An Atlas on Multitudinous Risk Factors Associated with Incident Hypertension: Comprehensive Exposome-Wide Association and Wide-angled Genetic Analyses.

Despite numerous risk factors being associated with hypertension, the breadth of research remains constrained, with a notable absence of systematic, data-driven exploration into established and novel factors across a broad spectrum of exposures. This study aims to construct an atlas on known and emerging factors for hypertension through comprehensive epidemiological and genetic analyses. We conducted exposome-wide association studies (ExWAS) via Cox regression models on two equally sized datasets for discovery and replication in UK Biobank, a large prospective cohort study. A maximum of 10,806 exposome variables were included in ExWAS and were grouped into 13 categories: genomics, sociodemographic, lifestyle, physical measure, biomarkers, medical history, imaging markers, sex-specific factors, psychosocial factors, cognitive function indicators, local environment, family history, and early life factors. The credibility of epidemiological associations was assessed through meta-analyses. The genetic underpinnings were explored through linkage-disequilibrium score regression (LDSC), quantifying global genetic correlation. Two-sample Mendelian randomization (MR) studies were conducted to investigate the causal effects of each exposure on hypertension, with co-analyses undertaken to identify associations supported by both epidemiological and genetic evidence. This study included 214,957 UK Biobank participants, hypertension-free at baseline. In our ExWAS analyses, 964 significant exposome variables were replicated. In meta-analyses, 462 were backed by convincing and highly suggestive evidence. Among 10,765 exposures in LDSC, 1923 had global genetic correlations with hypertension. The MR analyses yielded robust evidence for a causal relationship with 125 phenotypes, probable evidence for 270 phenotypes, and suggestive evidence for 718 phenotypes. Co-analyses identified 146 associations supported by strong epidemiological and genetic evidence. These primarily encompassed traits like anthropometry, lung function, lipids, and factors such as urate and walking pace. This coverage further extended from well-studied factors (like BMI and physical activity) to less explored exposures (including high light scatter reticulocyte count and age at first live). All study results are compiled in a webserver for user-friendly exploration of exposure-hypertension associations. This study provides an atlas on established and novel risk factors for hypertension, underpinned by epidemiological and causal evidence. Our findings present a multiple perspective to prioritize hypertension prevention strategies, encompassing modifiable risk factors like television watching time and walking pace. The study also emphasized the roles of urate in hypertension pathogenesis. Consequently, our study may serve as a critical guide for hypertension prevention and bear significant clinical implications.

Associations Between Self and Study Partner Report of Cognitive Decline With Regional Tau in a Multicohort Study.

Self-reported cognitive decline is an early behavioral manifestation of Alzheimer disease (AD) at the preclinical stage, often believed to precede concerns reported by a study partner. Previous work shows cross-sectional associations with β-amyloid (Aβ) status and self-reported and study partner-reported cognitive decline, but less is known about their associations with tau deposition, particularly among those with preclinical AD. This cross-sectional study included participants from the Anti-Amyloid Treatment in Asymptomatic AD/Longitudinal Evaluation of Amyloid Risk and Neurodegeneration studies (N = 444) and the Harvard Aging Brain Study and affiliated studies (N = 231), which resulted in a cognitively unimpaired (CU) sample of individuals with both nonelevated (Aβ-) and elevated Aβ (Aβ+). All participants and study partners completed the Cognitive Function Index (CFI). Two regional tau composites were derived by averaging flortaucipir PET uptake in the medial temporal lobe (MTL) and neocortex (NEO). Global Aβ PET was measured in Centiloids (CLs) with Aβ+ >26 CL. We conducted multiple linear regression analyses to test associations between tau PET and CFI, covarying for amyloid, age, sex, education, and cohort. We also controlled for objective cognitive performance, measured using the Preclinical Alzheimer Cognitive Composite (PACC). Across 675 CU participants (age = 72.3 ± 6.6 years, female = 59%, Aβ+ = 60%), greater tau was associated with greater self-CFI (MTL: β = 0.28 [0.12, 0.44], p < 0.001, and NEO: β = 0.26 [0.09, 0.42], p = 0.002) and study partner CFI (MTL: β = 0.28 [0.14, 0.41], p < 0.001, and NEO: β = 0.31 [0.17, 0.44], p < 0.001). Significant associations between both CFI measures and MTL/NEO tau PET were driven by Aβ+. Continuous Aβ showed an independent effect on CFI in addition to MTL and NEO tau for both self-CFI and study partner CFI. Self-CFI (β = 0.01 [0.001, 0.02], p = 0.03), study partner CFI (β = 0.01 [0.003, 0.02], p = 0.01), and the PACC (β = -0.02 [-0.03, -0.01], p < 0.001) were independently associated with MTL tau, but for NEO tau, PACC (β = -0.02 [-0.03, -0.01], p < 0.001) and study partner report (β = 0.01 [0.004, 0.02], p = 0.002) were associated, but not self-CFI (β = 0.01 [-0.001, 0.02], p = 0.10). Both self-report and study partner report showed associations with tau in addition to Aβ. Additionally, self-report and study partner report were associated with tau above and beyond performance on a neuropsychological composite. Stratification analyses by Aβ status indicate that associations between self-reported and study partner-reported cognitive concerns with regional tau are driven by those at the preclinical stage of AD, suggesting that both are useful to collect on the early AD continuum.

Fruit ripening retardant Daminozide induces cognitive impairment, cell specific neurotoxicity, and genotoxicity in Drosophila melanogaster

BackgroundWe explored neurotoxic and genotoxic effects of Daminozide, a fruit ripening retardant, on the brain of Drosophila melanogaster, based on our previous finding of DNA fragmentation in larval brain cell in the flies experimentally exposed to this chemicals. MethodsAdult flies were subjected to two distinct concentrations of daminozide (200 mg/L and 400 mg/L) mixed in culture medium, followed by an examination of specific behaviors such as courtship conditioning and aversive phototaxis, which serve as indicators of cognitive functions. We investigated brain histology and histochemistry to assess the overall toxicity of daminozide, focusing on neuron type-specific effects. Additionally, we conducted studies on gene expression specific to neuronal function. Statistical comparisons were then made between the exposed and control flies across all tested attributes. ResultsThe outcome of behavioral assays suggested deleterious effects of Daminozide on learning, short term and long term memory function. Histological examination of brain sections revealed cellular degeneration, within Kenyon cell neuropiles in Daminozide-exposed flies. Neurone specific Immuno-histochemistry study revealed significant reduction of dopaminergic and glutaminergic neurones with discernible reduction in cellular counts, alteration in cell and nuclear morphology among daminozide exposed flies. Gene expression analyses demonstrated upregulation of rutabaga (rut), hb9 and down regulation of PKa- C1, CrebB, Ace and nAchRbeta-1 in exposed flies which suggest dysregulation of gene functions involved in motor neuron activity, learning, and memory. ConclusionTaken together, our findings suggests that Daminozide induces multifaceted harmful impacts on the neural terrain of Drosophila melanogaster, posing a threat to its cognitive abilities.

Effects of Baduanjin exercise on cognitive frailty, oxidative stress, and chronic inflammation in older adults with cognitive frailty: a randomized controlled trial.

Oxidative stress and chronic inflammation play an important role in the pathogenesis process of cognitive frailty (CF). Regular Baduanjin exercise could improve cognitive frailty in older adults, but it is unclear whether the effect of Baduanjin exercise on improving CF is mediated by modulating circulating oxidative stress and inflammatory process. A total of 102 community-dwelling older adults with CF were recruited and randomly allocated into a 24-week Baduanjin exercise training group or no specific exercise intervention control group at an equal rate. Cognitive function and physical frailty index were assessed using the Montreal Cognitive Assessment (MoCA) and the Edmonton Frail Scale (EFS), as well as the oxidative stress and inflammatory cytokines were measured at baseline and after intervention. After 24 weeks of intervention, the increased MoCA score (2.51 ± 0.32 points, p < 0.001) and the decreased EFS scores (1.94 ± 0.20 points, p = 0.012) in the Baduanjin group were significantly higher than those in the control group. Serum antioxidant SOD levels were increased by 10.03 ± 4.73 U/mL (p < 0.001), and the prooxidative MDA and 8-iso-PGF2α levels were decreased by -1.08 ± 0.80 nmol/mL (p = 0.030) and -86.61 ± 15.03 ng/L (p < 0.001) in the Baduanjin training group; while inflammatory cytokines IFN-γ, IL-2 and IL-4 levels were increased (1.08 ± 0.33 pg./mL, p = 0.034, 2.74 ± 0.75 pg./mL, p = 0.04 and 1.48 ± 0.35 pg./mL, p = 0.042). In addition, a mediation effect that Baduanjin training improved cognitive ability mediated by an increase of circulating IFN-γ and IL-2 levels were observed in this study. Regular Baduanjin exercise training could improve the cognitive frailty of the community-dwelling older adults with CF, and modulate oxidative stress and inflammatory processes by reducing circulating pro-oxidative MDA and 8-iso-PGF2α levels and increasing anti-oxidative SOD levels, as well as impacting inflammatory cytokines IFN-γ, IL-2, and IL-4 levels. Nevertheless, the mechanism of Baduanjin exercise mediating oxidative stress and inflammatory processes should be cautious to be explained. http://www.chictr.org.cn/index.aspx, ChiCTR1800020341.

The Benefits of Acute Exercise for Children's Cognition Are Associated with Trait Anxiety.

Children's anxiety is associated with decreased cognitive performance. One well-established behavioral intervention to transiently improve cognitive performance in children is acute aerobic exercise (AAE). Thus far, however, it is unclear whether the benefits of AAE on cognition vary based on individual differences in children's anxiety level. Therefore, we investigated whether trait anxiety levels mediate the effects of AAE on cognitive outcomes in preadolescent children. Ninety-five preadolescent children (9 to 11 yr, 41 females) underwent two experimental interventions in a random, crossover, and counterbalanced design: an exercise protocol (20 min of walking at 65% to 75% of HRpeak) and a nonexercise control (seated rest). Behavioral indices of cognitive performance (accuracy, reaction times, response time (RT) variability) were assessed before and after each intervention using a modified flanker task. The effects of each intervention on cognitive performance were calculated as pre- to postintervention differences (effect scores). These scores were first correlated with children's personal characteristics: anxiety (STAIC), sex, age, body mass index, intelligence quotient, and aerobic fitness. Significant correlations guided subsequent hierarchical regression models, which specifically tested for associations between the effects scores and anxiety levels while controlling for remaining relevant covariates. Regression analysis revealed that anxiety was a significant predictor of the effects that AAE and rest had on cognitive performance. Specifically, higher anxiety scores were associated with greater exercise-induced cognitive benefits (increased accuracy, decreased RT variability; all P < 0.05) and greater rest-induced cognitive impairments (decreased accuracy, increased RT variability; all P < 0.01). These findings suggest that children reporting higher trait anxiety might experience greater cognitive benefits from a single bout of AAE.

Habitual consumption of anthocyanin is associated with improvements in mood and cognitive performance in older people with memory complaints

The role of flavonoids on cognitive performance in older adults has been intensively studied, with the subclass of anthocyanins showing promising outcomes(1). However, there is conflicting evidence in the case of individuals at high risk of developing dementia, namely those with mild cognitive impairment (MCI). A recent study has suggested that cognitive scores in people with MCI were higher in those who had higher anthocyanin intake (&gt;10 mg)(2). Baseline data from 65 participants of an ongoing clinical trial that had an MIS (Memory Index Score) score ≤ 13 with self-reported subjective memory complaints, (mean age 69.1y ± 6.2) were used to investigate the relationship between dietary anthocyanin intake and indices of mood and cognitive performance. Repeated 24-hour dietary intake was recorded through Intake24 (a computer-based program) for three days (2Xweekday and 1Xweekend day) and anthocyanin intake was quantified using the PhenolExplorer food composition database. The primary outcome of interest was the Buschke and Grober Free and Cued Selective Reminding Test-Immediate Recall (FCSRT+IR) (assesses auditory anterograde memory functioning), while other cognitive functions assessed included: Spot the Word-2 (assessing premorbid estimate); Oral Symbol Digit Test (speed of processing); List Sorting (working memory); Trail Making Test A &amp; B (speed of processing/executive function); and Verbal Fluency (language/semantic memory). Subjective memory complaints were assessed using the Memory Assessment Clinic-Q (MAC-Q) and mood was assessed using the Geriatric Depression Scale (GDS). Independent t-tests were used to compare differences in cognitive tasks and mood scores between high (&gt;10 mg/d) and low consumers of anthocyanins (&lt;10 mg/d). There was a trend for high anthocyanin consumers (n = 35, median = 44.87 (10.01, 177.83)) to score better on FCSRT-Delayed Free Recall scores (16.57 ± 3.74) compared to lower consumers (n = 30, median = 0.01 (0, 9.51)), (15.97 ± 0.18) with a mean difference (SE) of −1.06 (0.58) (p = 0.06) suggesting recall of 1.06 more words after a 20-30 minute delay. Higher consumers had a lower GDS score (1.77 ± 3.73) compared to lower consumers (3.73 ± 1.77), p = 0.01. Spot the word test scores (assesses premorbid verbal abilities using a robust lexical decision task) were higher for high anthocyanin consumers (53.06 ± 4.38) compared to lower consumers (50.40 ± 4.38), mean difference (SE) = −2.66 (1.10), p = 0.01, meaning participants with higher intake of dietary anthocyanin were able to point at 2.7 more real words than low consumers. Dietary consumption of anthocyanin in older adults with MIS is associated with beneficial effects on depressive scores and the ability to retrieve words. Further research is warranted to identify optimal dosage for recommended intake. This cross-sectional study used baseline data from a randomised controlled trial registered with the Australian New Zealand Clinical Trials Registry (ANZCTR):12622000065796.

Influence of Early Childhood Education Programmes on Child Development Metrics: A Systematic Review and Meta-analysis of Randomised Controlled Trials

Abstract Background: Early childhood experiences have a significant influence on children’s cognitive, social, emotional and physical development, making them crucial for their overall development. It has been suggested that early childhood education (ECE) is an essential intervention to improve certain developmental parameters. Although research on the advantages of ECE on social and cognitive domains is already available, more research is needed to determine how ECE affects certain developmental outcomes such as motor function, linguistic ability, emotional reactivity, cognitive function and body mass index (BMI) Z-scores. This systematic review and meta-analysis aim to evaluate the impact of ECE on various child development outcomes. Materials and Methods: Following PRISMA guidelines, we performed an exhaustive search across PubMed, Scopus, Web of Science and Cochrane Library databases to identify randomised controlled trials (RCTs) that assess the effectiveness of ECE on child development outcomes. Six RCTs were ultimately included in our analysis. Data extraction and quality assessment were conducted meticulously, with the ROB2 tool utilised to ascertain the risk of bias in the studies. Results: Our meta-analysis integrated data from 1595 participants across the included studies. The results revealed a significant improvement in motor function, with a pooled mean difference (MD) of 1.47 (95% confidence interval [CI]: 0.29–2.65, P = 0.01), and language ability, with a pooled MD of 1.27 (95% CI: 0.03–2.52, P = 0.04). Emotional reactivity also showed significant enhancement, with a pooled MD of 0.19 (95% CI: 0.06–0.32, P = 0.004). Cognitive function improvements were significant, with a pooled MD of 2.58 (95% CI: 1.0–4.16, P = 0.001). However, changes in BMI Z-scores were not statistically significant, with a pooled MD of − 0.01 (95% CI: −0.19–0.17, P = 0.91). Conclusion: The systematic review and meta-analysis demonstrate that ECE significantly benefits motor function, language ability, emotional reactivity and cognitive function in children, with no discernible impact on BMI Z-scores. These findings confirm the value of ECE in supporting early developmental milestones, underscoring the need for integrating high-quality ECE programmes into early childhood policy and practice.

Longitudinal relationship between grip strength and cognitive function in a European population older than 50 years: A cross-lagged panel model

ObjectivesThe aim of this study was to investigate the dynamic longitudinal relationship between grip strength and cognitive function. Methods6175 participants aged ≥50 years were included in the study using three waves of follow-up data from the Survey of Health, Ageing, and Retirement in Europe in 2015 (T1), 2017 (T2) and 2019 (T3). Cognitive function was assessed using numeracy, verbal fluency, immediate recall, delayed recall and total. The cross-lagged panel model was used for analysis. ResultsThere was a correlation between grip strength and cognitive function. Standardized path coefficient from numeracy T1 to grip strength T2 was 0.017 (p = 0.003), and from numeracy T2 to grip strength T3 was 0.014 (p = 0.012). Standardized path coefficient from grip strength T1 to numeracy T2 was 0.096 (p < 0.001), and from grip strength T2 to numeracy T3 was 0.113 (p < 0.001). Other indicators of cognitive function had similar relationships with grip strength. ConclusionsThe study found a statistically significant longitudinal and bidirectional relationship between grip strength and cognitive function in a sample of people aged ≥50 years from several European countries.

Cognitive rehabilitation program in patients with multiple sclerosis: A pilot study

IntroductionIn recent years, there has been an increase of studies dedicated to cognitive rehabilitation in patients with multiple sclerosis (MS); however, few of these analyze the impact on such variables as cognitive reserve. The study aims to explore the effects of a cognitive rehabilitation program comprising a combination of cognitive and physical exercises, as well as group sessions to improve cognitive performance, emotional state, and cognitive reserve index. MethodFifty patients with MS were subdivided into 2 groups: the control group, which performed aerobic exercise (n=25), and the experimental group (n=25), which participated in the integrated cognitive rehabilitation program (ICRP). All participants were evaluated 3 times (baseline, post-treatment, and long-term) with the Brief Repeatable Battery of Neuropsychological Tests, Cognitive Reserve Scale, Beck Depression Inventory, and a scale evaluating trait and state anxiety. ResultsCompared with the control group, patients in the experimental group showed improvements in cognitive function, with significant changes in measures of information processing speed, attention, memory, cognitive reserve index, and long-term mood. ConclusionsThe ICRP was effective in improving cognitive and emotional function in MS, and increased the cognitive reserve index.