Consortium To Establish A Registry For Alzheimer's Disease Research Articles

Handgrip strength is associated with cognitive function in older patients with stage 3-5 chronic kidney disease: results from the NHANES

In this study, we aimed to investigate the association between handgrip strength (HGS) and cognitive performance in stage 3-5 chronic kidney disease (CKD) patients aged ≥ 60 years. This cross-sectional study analyzed data from National Health and Nutrition Examination Survey (NHANES) database 2011–2014. Three tests were used to assess the cognitive performance, including consortium to establish a registry for Alzheimer’s disease (CERAD), animal fluency test (AFT), and digit symbol substitution test (DSST). The multivariate linear regression analyses adjusting for confounding factors were utilized to evaluate the association of HGS with cognitive performance. A total of 678 older stage 3-5 CKD patients were included in this study. After adjusting for multiple factors, a higher HGS was positively associated with a higher CERAD-delayed recall and DSST score. In addition, our analysis indicated that HGS probably correlated with better performance of immediate learning ability in male, while working memory, sustained attention, and processing speed in female. HGS may be an important indicator for cognitive deficits in stage 3-5 CKD patients, especially for learning ability and executive function. Further research to explore the sex-specific and domain-specific and possible mechanisms are required.

Go4cognition: Evaluation of a Newly Developed Multicomponent Intervention in Mild Cognitive Impairment.

Cognitive training and physical exercise show positive effects on cognitive decline in subjects with mild cognitive impairment (MCI). Multimodal interventions for MCI patients, combining physical and cognitive training in a social context seem to slow down cognitive decline. Based on a previous study, a new mobile gamification tool (go4cognition; https://www.ontaris.de/go4cognition) has been developed to train cognitive and physical functions simultaneously in a group setting. It involves tasks targeting various cognitive functions (short-term memory, working memory, executive functions). The computer-based setup allows for individual performance analysis. This study evaluated the effects of this tool. 30 participants with MCI, as defined by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) cut-off-score, aged between 66 and 89 years, trained for one hour two days a week for twelve weeks. Additionally, standard neuropsychological assessment of memory and attention was carried out before and after the intervention. The go4cognition device is highly effective in improving various cognitive functions. A significant improvement in the CERAD total score resulting in re-classification of 70% of former MCI patients into non-MCI patients was found. Additionally, an improvement of verbal fluency, verbal memory, spatial memory, and attention was observed. Furthermore, the CERAD total score was significantly correlated with performance in the go4cognition tool. The results of the intervention support the idea of the effectiveness of a combined cognitive and motor intervention by incorporating neuropsychological paradigms in a group setting and suggest a close relation between combined cognitive and physical exercise and cognitive performance.

Non-linear relationship of serum albumin-to-globulin ratio and cognitive function in American older people: a cross-sectional national health and nutrition examination survey 2011-2014 (NHANES) study.

Inflammation and liver function are associated with cognitive decline and dementia. Little is known about the serum albumin-to-globulin ratio on cognitive function. The objective of this study was to investigate the association between albumin-to-globulin ratio and cognitive function among the American older people. The public data available on the US National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014 was used for this cross-sectional study. Participants aged ≥60 years completed the cognitive function assessments, including word learning and recall modules from the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), the animal fluency (AF) test, and the digit symbol substitution test (DSST). A composite cognition score was calculated to evaluate global cognition. The univariate and multivariate linear regression analysis, curve fitting, a threshold effect, along with a subgroup analysis and interaction tests were conducted. Serum albumin-to-globulin ratio (per 0.1 unit) was positively associated DSST score (β = 0.36, 95% CI: 0.21, 0.51), AF score (β = 0.1, 95% CI: 0.04, 0.16) and global cognition score (β = 0.05, 95% CI: 0.02, 0.07), after being fully adjusted, while albumin-to-globulin ratio was not related to CERAD score (β = 0.05, 95% CI: -0.02, 0.12). A non-linear was observed in the dose-response relationship between albumin-to-globulin ratio and global cognition (P for non-linearity < 0.001). The subgroup analysis was overall stable, yet the interaction test was significant for age on global cognition (P for interaction = 0.036). The findings of this cross-sectional study suggested a positive and non-linear association between albumin-to-globulin ratio and cognitive function in the American older people. Maintaining albumin-to-globulin ratio with an appropriate range may be one of the therapeutic strategies to limit the progression of cognitive decline for the older people.

Chronic kidney disease and cognitive performance: NHANES 2011–2014

PurposePrevious studies suggest an association between chronic kidney disease (CKD) and cognitive impairment. The purpose of this study was to explore the association between the diverse stages of CKD and the cognitive performance of elderly American adults.MethodsData from the National Health and Nutrition Examination Survey (NHANES) 2011–2014 were used. Multivariate adjusted logistic regression, subgroup analysis, and the restricted cubic spline model were used to assess the associations of CKD stage and estimated glomerular filtration rate (eGFR) with cognitive performance. The measures used to evaluate cognitive function included the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) test, the Animal Fluency test, and the Digit Symbol Substitution test (DSST).ResultsThis study included 2234 participants aged ≥ 60 years. According to the fully adjusted model, stages 3–5 CKD were significantly associated with the CERAD test score (OR = 0.70, 95% CI [0.51, 0.97], p = 0.033), the Animal Fluency test score (OR = 0.64, 95% CI [0.48, 0.85], p = 0.005), and the DSST score (OR = 0.60, 95% CI [0.41, 0.88], p = 0.013). In addition, the incidence of poor cognitive function increased with decreasing eGFR, especially for individuals with low and moderate eGFRs. Both the DSST score (p nonlinearity < 0.0001) and the Animal Fluency test score (p nonlinearity = 0.0001) had nonlinear dose–response relationships with the eGFR. However, a linear relationship was shown between the eGFR and CERAD test score (p nonlinearity = 0.073).ConclusionsCKD, especially stages3–5 CKD, was significantly associated with poor cognitive performance in terms of executive function, learning, processing speed, concentration, and working memory ability. All adults with CKD should be screened for cognitive impairment.

Association Between Composite Dietary Antioxidant Index and Cognitive Function Among Aging Americans from NHANES 2011-2014.

Antioxidant diets are considered to be protective factors for cognitive function. However, comprehensive measures of antioxidant diets are lacking. To examine the association between the Composite Dietary Antioxidant Index (CDAI) and cognitive function in the elderly. This cross-sectional study included a total of 2,456 participants (≥60 years old) from NHANES 2011-2014. Calculation of CDAI based on 6 minerals and vitamins (manganese, selenium, zinc, vitamins A, C, and E). Cognitive function was measured by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word Learning sub-test, Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST). We also created a composite cognitive z-score to represent global cognition. The statistical analyses we used included multiple linear regression analyses, subgroup analyses, curve-fitting analyses, and threshold effects analyses. After controlling for demographic characteristics, lifestyle factors, and disease history, multivariate linear regression analyses showed that increased CDAI was positively associated with scores on global cognitive function and each cognitive domain (p < 0.05), with subgroup analyses suggesting that this association was more pronounced in stroke patients (p for interaction < 0.05). Curve-fitting analyses and threshold effect analyses showed saturation effects between CDAI and CREAD Test, AFT, and composite Z-score, and an inverted U-shaped relationship with DSST, with inflection points of -1.89, 0.79, 1.13, and 1.77, respectively. Our findings support that higher levels of CDAI are correlated with significantly elevated cognitive function. Maintaining CDAI in an appropriate range may contribute to cognitive health in elderly.

Association between Life's Essential 8 and cognitive function: insights from NHANES 2011-2014.

Life's Essential 8 (LE8) is prompted by the American Heart Association (AHA) to assess cardiovascular health. The association between LE8 and cognitive function in America is unknown. Our study was to investigate the association of LE8 with cognitive function in general adults. A total of 2,301 participants were enrolled in the National Health and Nutrition Examination Surveys (NHANES). LE8 scores (range 0-100) were obtained from measurements based on American Heart Association definitions, divided into health behavior and health factor scores. Cognitive function was assessed by three tests including the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), Animal fluency test (AFT), and Digit Symbol Substitution test (DSST). The multivariable linear regression analysis explored the associations between LE8 and cognitive function. Smooth curve fitting was explored using restricted cubic splines. The inflection point was determined by the two-piecewise linear regression. In the multivariable linear regression model with full adjustment for confounding variables, AFT scores were 1.2 points higher in participants with LE8 scores >80 than in those with LE8 scores <50 (high LE8 score group: β = 1.20, 95% CI 0.37, 2.03), and 3.32 points higher in DSST (high LE8 score group: β = 3.32, 95% CI 1.24, 5.39). Although high LE8 scores show a Negative association with high CERAD, we found a significant association between higher LE8 scores and higher CERAD when LE8 scores were higher than 82.5 (β = 0.21 95%CI 0.04, 0.39, p-value = 0.0179). Our study highlighted a positive association between Life's Essential 8 and cognitive function in older adults.

Association between dietary inflammatory index and cognitive impairment among American elderly: a cross-sectional study.

It has been shown that inflammation may be associated with cognitive impairment (CI). Diet modulates inflammation. However, there is currently a scarcity of epidemiological studies exploring the connection between the inflammatory potential of diet and CI. The objective was to investigate the correlation between the dietary inflammatory index (DII) and cognitive impairment in older adults in the United States. The present investigation utilized a cross-sectional dataset obtained from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014. Dietary intake data was used to calculate DII scores, which were then used to categorize participants into quartiles. Participants' cognitive function was assessed using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST). Individuals who scored in the lowest quartile on any of these tests were classified as exhibiting low cognitive performance. The association between DII and cognitive impairment was investigated by multivariate logistic regression, smooth curve fitting, and subgroup analysis. A total of 947 older adults were enrolled in the study. Following the adjustment of confounding variables, DII scores exhibited a significant and positive correlation with low cognitive performance, as measured by AFT (OR 1.15, 95% CI 1.02-1.28, p = 0.02) and the DSST (OR 1.38, 95% CI 1.13-1.68, p = 0.004). Compared with the lowest quartile of DII, the highest weighted odds ratio of cognitive impairment based on AFT was observed in the fourth quartile group (OR 1.89, 95% CI 1.05-3.38, p = 0.03). Similarly, a comparable pattern was evident in DSST (OR 4.30, 95% CI 1.85-9.98, p = 0.003). Additionally, the smooth curve fitting results showed a nonlinear relationship between DII and cognitive decline evaluated by DSST (p for nonlinearity = 0.016). No interaction effects between cognitive impairment and age or gender were observed in relation to all cognitive test scores. This research reveals a positive link between diet with higher inflammatory potential and cognitive decline among elderly individuals in America. However, additional studies on dietary interventions are necessary to explore the cause-and-effect relationship.

Utility of learning ratio scores from the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) Word List Memory Test in distinguishing patterns of cognitive decline in veterans referred for neuropsychological evaluation

Background: The Learning Ratio (LR) is a novel learning score that has shown improved utility over other learning metrics in detecting Alzheimer’s disease (AD) across multiple memory tasks. However, its utility on the Consortium to Establish a Registry for Alzheimer’s Disease Word List Memory Test (CERAD WLMT), a widely used list learning measure sensitive to decline in neurodegenerative disease, is unknown. The goal of the current study was to determine the utility of LR on the CERAD WLMT in differentiating between diagnostic (MiNCD vs MaNCD) and etiologic groups (VaD vs AD) in a veteran sample. Methods: Raw learning slope (RLS) and LR scores were examined in 168 veterans diagnosed with major neurocognitive disorder (MaNCD), mild neurocognitive disorder (MiNCD), or normal aging following neuropsychological evaluation. Patients with MaNCD were further classified by suspected etiology (i.e. microvascular disease vs AD). Results: Whereas RLS scores were not significantly different between MiNCD and MaNCD, LR scores were significantly different between all diagnostic groups (p’s < .05). Those with AD had lower LR scores and RLS scores compared to those with VaD (p’s < .05). LR classification accuracy was acceptable for MiNCD (AUC = .76), excellent for MaNCD (AUC = .86) and VaD (AUC = .81), and outstanding for AD (AUC = .91). Optimal cutoff scores for WLMT LR were derived from Youden’s index. Conclusion: Results support the use of LR scores over RLS when interpreting the CERAD WLMT and highlight the clinical utility of LR in differentiating between diagnostic groups and identifying suspected etiology.

Development and validation of a cognitive dysfunction risk prediction model for the abdominal obesity population.

This study was aimed to develop a nomogram that can accurately predict the likelihood of cognitive dysfunction in individuals with abdominal obesity by utilizing various predictor factors. A total of 1490 cases of abdominal obesity were randomly selected from the National Health and Nutrition Examination Survey (NHANES) database for the years 2011-2014. The diagnostic criteria for abdominal obesity were as follows: waist size ≥ 102 cm for men and waist size ≥ 88 cm for women, and cognitive function was assessed by Consortium to Establish a Registry for Alzheimer's Disease (CERAD), Word Learning subtest, Delayed Word Recall Test, Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST). The cases were divided into two sets: a training set consisting of 1043 cases (70%) and a validation set consisting of 447 cases (30%). To create the model nomogram, multifactor logistic regression models were constructed based on the selected predictors identified through LASSO regression analysis. The model's performance was assessed using several metrics, including the consistency index (C-index), the area under the receiver operating characteristic (ROC) curve (AUC), calibration curves, and decision curve analysis (DCA) to assess the clinical benefit of the model. The multivariate logistic regression analysis revealed that age, sex, education level, 24-hour total fat intake, red blood cell folate concentration, depression, and moderate work activity were significant predictors of cognitive dysfunction in individuals with abdominal obesity (p < 0.05). These predictors were incorporated into the nomogram. The C-indices for the training and validation sets were 0.814 (95% CI: 0.875-0.842) and 0.805 (95% CI: 0.758-0.851), respectively. The corresponding AUC values were 0.814 (95% CI: 0.875-0.842) and 0.795 (95% CI: 0.753-0.847). The calibration curves demonstrated a satisfactory level of agreement between the nomogram model and the observed data. The DCA indicated that early intervention for at-risk populations would provide a net benefit, as indicated by the line graph. Age, sex, education level, 24-hour total fat intake, red blood cell folate concentration, depression, and moderate work activity were identified as predictive factors for cognitive dysfunction in individuals with abdominal obesity. In conclusion, the nomogram model developed in this study can effectively predict the clinical risk of cognitive dysfunction in individuals with abdominal obesity.

Association of PM2.5 Exposure and Alzheimer Disease Pathology in Brain Bank Donors-Effect Modification by APOE Genotype.

Fine particulate matter (PM2.5) exposure has been found to be associated with Alzheimer disease (AD) and is hypothesized to cause inflammation and oxidative stress in the brain, contributing to neuropathology. The APOE gene, a major genetic risk factor of AD, has been hypothesized to modify the association between PM2.5 and AD. However, little prior research exists to support these hypotheses. This study investigates the association between traffic-related PM2.5 and AD hallmark pathology, including effect modification by APOE genotype, in an autopsy cohort. A cross-sectional study was conducted using brain tissue donors enrolled in the Emory Goizueta AD Research Center who died before 2020 (n = 224). Donors were assessed for AD pathology including the Braak stage, Consortium to Establish a Registry for AD (CERAD) score, and combined AD neuropathologic change (ABC) score. Traffic-related PM2.5 concentrations were modeled for the metro-Atlanta area during 2002-2019 with a spatial resolution of 200-250 m. One-year, 3-year, and 5-year average PM2.5 concentrations before death were matched to participants' home address. We assessed the association between traffic-related PM2.5 and AD hallmark pathology and effect modification by APOE genotype, using adjusted ordinal logistic regression models. Among the 224 participants, the mean age of death was 76 years, and 57% had at least 1 APOE ε4 copy. Traffic-related PM2.5 was significantly associated with the CERAD score for the 1-year exposure window (odds ratio [OR] 1.92; 95% CI 1.12-3.30) and the 3-year exposure window (OR 1.87; 95% CI 1.01-3.17). PM2.5 was also associated with higher Braak stage and ABC score albeit nonsignificantly. The strongest associations between PM2.5 and neuropathology markers were among those without APOE ε4 alleles (e.g., for the CERAD score and 1-year exposure window, OR 2.31; 95% CI 1.36-3.94), though interaction between PM2.5 and APOE genotype was not statistically significant. Our study found traffic-related PM2.5 exposure was associated with the CERAD score in an autopsy cohort, contributing to epidemiologic evidence that PM2.5 affects β-amyloid deposition in the brain. This association was particularly strong among donors without APOE ε4 alleles. Future studies should further investigate the biological mechanisms behind this association.

Association between dietary vitamin B1 intake and cognitive function among older adults: a cross-sectional study

BackgroundThis study aims to investigate the relationship between vitamin B1 intake and cognitive function in older adults.MethodsThis cross-sectional observational study utilized data from the National Health and Nutrition Examination Survey (NHANES) 2011–2014. A total of 2422 participants were included in the analysis, with dietary vitamin B1 intake being determined by averaging two 24-h dietary recalls. Cognitive function was assessed using three cognitive function tests: the Digit Symbol Substitution Test (DSST) for processing speed, the Animal Fluency Test (AFT) for executive function, a Consortium to Establish a Registry for Alzheimer's disease (CERAD) subtest for memory. Test-specific and global cognition z score was created. Multivariate linear regression models were used to explore the association between vitamin B1 and cognitive function.Results2422 participants, aged 60 years and older, were included from NHANES across two survey cycles (2011–2014). Higher vitamin B1 intake was associated with higher DSST, AFT scores (P < 0.001) as well as the global cognition z score (P = 0.008).In the fully adjusted model, as compared to the lowest quartile (Q1), the highest quartile (Q4) of vitamin B1 intake was related to higher DSST score (β = 2.23, 95% CI 0.79 ~ 3.67) and global cognition z sore (β = 0.09, 95% CI 0.02 ~ 0.16). The association between dietary vitamin B1 intake and cognitive function scores in US adults is linear. There was no detected significant statistical interaction between these variables.ConclusionsIncreased dietary intake of vitamin B1 was associated with better cognitive function in individuals aged over 60.

Increased serum methylmalonic acid levels were associated with the presence of cognitive dysfunction in older chronic kidney disease patients with albuminuria

BackgroundThis study aimed to evaluate the correlation between serum methylmalonic acid (MMA) levels and cognition function in patients with chronic kidney disease (CKD).MethodsIn this cross-sectional study, we included 537 CKD individuals aged ≥ 60-year-old with albuminuria from the National Health and Nutrition Examination Survey (NHANES) 2011–2014. Four cognitive tests including the Digit Symbol Substitution Test (DSST), the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) Delayed Recall and Word Learning tests, and the Animal Fluency test (AF) were performed. Associations between MMA and cognition scores were assessed with linear regression models.ResultsMMA level was negatively associated with residual renal function and nutrition status. After multivariate adjustment, elevated serum MMA levels were independently correlated with decline of cognition in CKD patients with albuminuria.ConclusionOur study showed that higher serum MMA levels were independently associated with the presence of cognition dysfunction in CKD patients. The exact pathogenesis of MMA and cognition needs further research.

Mild Cognitive Impairment detection based on EEG and HRV data

Brain volume decrease is usually connected to neurodegeneration and aging. In this environment, an important percentage of elderly persons suffer from mild cognitive impairment (MCI), a kind of dementia that can lead to Alzheimer's disease (AD). Since the symptoms of cognitive impairment are scarcely discernible, developing a safe and effective method for early MCI detection has emerged as an important challenge. According to this regard, numerous cognitive training tests can be targeted to help aging people retain a good quality of life, especially in the case of fragility disorders. A Consortium to Establish a Registry for Alzheimer's Disease (CERAD) task was initially created to detect the early stages of AD. This task specifically targets various tests related to specific cognitive domains. However, it has since developed into a popular diagnostic tool for many kinds of dementia, such as MCI. Several low-cost equipment, such as electroencephalography (EEG) and heart rate variability (HRV), may be useful for predicting MCI. On the other side, various machine learning (ML) models can be employed to extract/analyze relevant features from biomedical and physiological signals, especially in the context of anomaly detection and classification. To this regard, we developed a new method based on ML models to categorize MCI and healthy control (HC) patients during the CERAD task using EEG and HRV multimodal data. Our dataset includes 15 subjects who were randomly assigned to training and testing groups of 7 HC and 8 MCI, respectively. Our raw EEG and HRV data are analyzed to extract time, frequency, and non-linear features. A scaling step is employed to reduce the significant disparity between features. For the classification task, five ML models are evaluated, including support vector machine (SVM), k-nearest neighbors (KNN), decision tree (DT), random forest (RF), and gradient boosting (GB). To enhance accuracy, a hybrid ML model with a voting system is developed, combining the top ML models with the highest accuracy rates. A comparison step is performed between the use of ML and hybrid ML models. The experimental findings demonstrated the efficacy of our proposed technique, which included a hybrid ML model. An average accuracy of 93.86%, a sensitivity of 93.87%, and a specificity of 93.53% are achieved. The obtained results allow one to conclude that the first CERAD test plays a prominent role as a novel biomarker with an ultra-short duration for early MCI identification through the combination of EEG and HRV signals.

Association Between Urinary Glyphosate Exposure and Cognitive Impairment in Older Adults from NHANES 2013-2014.

Glyphosate is the most commonly used herbicide with potential neurotoxicity. However, limited epidemical evidence is found in the relationship between glyphosate and cognitive impairment, especially in the cognitive-disrupting sensitive elderly populations. This study aimed to examine the association of urinary glyphosate exposure with cognitive impairment in the United State (US) older adults. Cognitive impairment was determined by the following four tests: the Consortium to Establish a Registry for Alzheimer's disease (CERAD) Immediate Recall test (IR), the CERAD Delayed Recall tests (DR), the Animal Fluency (AF) test and the Digit Substitution test (DSST). Survey weighted logistic regression and restricted cubic splines were applied to evaluate and visualize the association between glyphosate and cognitive impairment. A total of 465 elderly adults were identified in the National Health and Nutrition Examination Survey (NHANES) 2013-2014 cycle, and among them, 83.87% individuals had detectable urinary levels of glyphosate (0.628 ng/mL in average). After adjusting for the potential covariates, glyphosate was significantly linked to increased DR and AF impairment, and the corresponding ORs were 1.52 (1.01 to 2.30, p = 0.049) and 1.69 (1.11 to 2.59, p = 0.019), respectively. No significant association was identified between glyphosate and IR or DSST impairment. The RCS plot further confirmed the linear and positive relationships between glyphosate and DR and AF impairment. These findings suggested that exposure to glyphosate might be associated with declined cognitive function in the elderly, and it might be prudent to evaluate cognitive outcomes for aged individuals with glyphosate exposures.

Association between 2,4-dichlorophenoxyacetic acid and cognitive impairment in older adults: a cross-sectional study from NHANES 2001-2002 and 2011-2014.

2,4-Dichlorophenoxyacetic acid (2,4-D) is reported to be the most widely used herbicide in home and garden environments, rendering it commonly encountered in daily life. Despite being ubiquitous, there is a scarcity of studies that have comprehensively assessed the relationship between 2,4-D exposure and cognition using multiple models. To explore the association between 2,4-D exposure and cognition among older American people. This was a cross-sectional study that included 3 cycles of data from the National Health and Nutrition Examination Survey. Generalized linear models (GLMs), restricted cubic spline (RCS) regression, and generalized additive models (GAMs) were used to assess the relationship between exposure to 2,4-D and cognitive performance by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) word learning sub-test, Digit Symbol Substitution Test (DSST), and Animal Fluency Test (AFT). A total of 1364 older U.S. adults (60+ years) were included in the study. The GLMs revealed a negative association between median high levels(0.315-0.566μg/L) of 2,4-D and cognitive impairment on the DSST and AFT, with multivariate-adjusted ORs of 0.403 (95% CI: 0.208-0.781, P = 0.009) and 0.396 (95% CI: 0.159-0.986, P = 0.047); the RCS regression and GAMs revealed a "U" shaped curve, the left part of which is consistent with the result of the GLMs. There is a U-shaped relationship between human urinary 2,4-D concentrations andcognitive impairmentin older U.S. adults, especially in males, so controlling 2,4-D exposurewithin an appropriate range is particularly important for cognitive function.

Effect of dietary protein intake on cognitive function in the elderly with chronic kidney disease: analysis of the National Health and Nutrition Examination Survey 2011–2014

Background Cognitive dysfunction is prevalent among the elderly diagnosed with chronic kidney disease (CKD). Low protein diets are used for retarding the progression of CKD in clinical practice. Nonetheless, the impact of dietary protein consumption on cognitive function in this population remains uncertain. Methods We recruited 2306 participants (≥60 years) from 2011 to 2014 National Health and Nutrition Examination Survey (NHANES). 24-h dietary recall questionnaire was utilized to evaluate protein intake. Cognitive function was measured using the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST). Participants’ characteristics were analyzed, and the interaction between protein consumption and CKD on cognitive impairment were analyzed using a logistic regression model. Results We divided participants into three groups based on CKD stages: no CKD, CKD stage G1 to G2 (19%), and CKD stage G3 to G5 (18%). The average protein intake was 0.97 g/(kg·d). In the higher protein intake group, CKD stages G1 to G2 elevated the risk of immediate memory impairment (OR: 2.441, 95% Cl: 1.161–5.132 for protein consumption in 1.0-1.2g/(kg·d); OR: 2.225, 95% Cl: 1.015–4.876 for protein consumption in >1.2 g/(kg·d)). However, no similar resuts were observed in the lower protein intake group. In addition, the interaction between CKD status and protein intake on immediate memory was statistically significant (p = .041). Conclusion A higher probability of cognitive impairment in the elderly with early-stage CKD may be linked to higher protein intake. Low protein diets may be a potential strategy to release cognitive impairment in the elderly with early-stage CKD.

Anticholinergic deprescribing interventions for reducing risk of cognitive decline or dementia in older adults with and without prior cognitive impairment.

Anticholinergics are medications that block the action of acetylcholine in the central or peripheral nervous system. Medications with anticholinergic properties are commonly prescribed to older adults. The cumulative anticholinergic effect of all the medications a person takes is referred to as the anticholinergic burden. A high anticholinergic burden may cause cognitive impairment in people who are otherwise cognitively healthy, or cause further cognitive decline in people with pre-existing cognitive problems. Reducing anticholinergic burden through deprescribing interventions may help to prevent onset of cognitive impairment or slow the rate of cognitive decline. Primary objective • To assess the efficacy and safety of anticholinergic medication reduction interventions for improving cognitive outcomes in cognitively healthy older adults and older adults with pre-existing cognitive issues. Secondary Objectives • To compare the effectiveness of different types of reduction interventions (e.g. pharmacist-led versus general practitioner-led, educational versus audit and feedback) for reducing overall anticholinergic burden. • To establish optimal duration of anticholinergic reduction interventions, sustainability, and lessons learnt for upscaling • To compare results according to differing anticholinergic scales used in medication reduction intervention trials • To assess the efficacy of anticholinergic medication reduction interventions for improving other clinical outcomes, including mortality, quality of life, clinical global impression, physical function, institutionalisation, falls, cardiovascular diseases, and neurobehavioral outcomes. We searched CENTRAL on 22 December 2022, and we searched MEDLINE, Embase, and three other databases from inception to 1 November 2022. We included randomised controlled trials (RCTs) of interventions that aimed to reduce anticholinergic burden in older people and that investigated cognitive outcomes. Two review authors independently assessed studies for inclusion, extracted data, and assessed the risk of bias of included studies. The data were not suitable for meta-analysis, so we summarised them narratively. We used GRADE methods to rate our confidence in the review results. We included three trials with a total of 299 participants. All three trials were conducted in a cognitively mixed population (some cognitively healthy participants, some participants with dementia). Outcomes were assessed after one to three months. One trial reported significantly improved performance on the Digit Symbol Substitution Test (DSST) in the intervention group (treatment difference 0.70, 95% confidence interval (CI) 0.11 to 1.30), although there was no difference between the groups in the proportion of participants with reduced anticholinergic burden. Two trials successfully reduced anticholinergic burden in the intervention group. Of these, one reported no significant difference between the intervention versus control in terms of their effect on cognitive performance measured by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) immediate recall (mean between-group difference 0.54, 95% CI -0.91 to 2.05), CERAD delayed recall (mean between-group difference -0.23, 95% CI-0.85 to 0.38), CERAD recognition (mean between-group difference 0.77, 95% CI -0.39 to 1.94), and Mini-Mental State Examination (mean between-group difference 0.39, 95% CI -0.96 to 1.75). The other trial reported a significant correlation between anticholinergic burden and a test of working memory after the intervention (which suggested reducing the burden improved performance), but reported no effect on multiple other cognitive measures. In GRADE terms, the results were of very low certainty. There were no reported between-group differences for any other clinical outcome we investigated. It was not possible to investigate differences according to type of reduction intervention or type of anticholinergic scale, to measure the sustainability of interventions, or to establish lessons learnt for upscaling. No trials investigated safety outcomes. There is insufficient evidence to reach any conclusions on the effects of anticholinergic burden reduction interventions on cognitive outcomes in older adults with or without prior cognitive impairment. The evidence from RCTs was of very low certainty so cannot support or refute the hypothesis that actively reducing or stopping prescription of medications with anticholinergic properties can improve cognitive outcomes in older people. There is no evidence from RCTs that anticholinergic burden reduction interventions improve other clinical outcomes such as mortality, quality of life, clinical global impression, physical function, institutionalisation, falls, cardiovascular diseases, or neurobehavioral outcomes. Larger RCTs investigating long-term outcomes are needed. Future RCTs should also investigate potential benefits of anticholinergic reduction interventions in cognitively healthy populations and cognitively impaired populations separately.

Identifying change on the CERAD Word List with standardized regression‐based scores

AbstractBackgroundList learning and memory tests are frequently used to evaluate older adults for Mild Cognitive Impairment and Alzheimer’s disease. One such test, the Word List subtest of the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD), has been widely‐used in clinical trials track such disorders. However, data is lacking on the amount of change that is needed to accurately identify decline.MethodParticipants included 897 older adults (age in years: M = 81.1, SD = 8.1, range 55‐100; 67% women; education in years: M = 14.8, SD = 2.8, range = 7‐24) who were cognitively intact at two annual visits in a longitudinal observational study from the Uniform Data Set of the National Alzheimer’s Coordinating Center. Each participant completed the Word List subtest at two visits, which were approximately 1 year apart (interval in years: M = 1.3, SD = 1.0). Multiple linear regression predicted Time 2 scores from Time 1 scores and simple demographic variables (age, sex, education). The predicted Time 2 scores were compared to observed Time 2 scores to preliminarily validate this change data.ResultFor three primary scores from the Word List subtest (Acquisition Total Correct, Delay Recall Total Correct, Recognition Total Correct), the Time 2 scores were significantly predicted from the other variables, with R2s ranging from 0.16 – 0.41 (p‐values&lt;0.001). When these predicted Time 2 scores were compared to observed Time 2 scores, there were no significant differences (p‐values≧0.19), indicating preliminary support for these prediction scores.ConclusionThe current prediction equations appear to allow clinicians and researchers to accurately track change on the Word List subtest of the CERAD by comparing their patients/participants to the current sample of robustly intact older adults. Consistent with past work in this area, Time 1 cognitive scores were the best predictors of Time 2 cognitive scores, although demographic variables added to that prediction. Future work should consider if additional variables can improve the prediction equations. Future work should also validate these equations in independent samples to examine their clinical utility.

The effect of short Aβ(1‐38) peptides on cognitive decline and conversion to AD dementia: longitudinal data using the DELCODE cohort

AbstractBackgroundThe current research consensus is that long Aβ(1‐42) peptides are neurotoxic pathological hallmarks of AD. Interestingly, short Aβ peptides, such as Aβ(1‐38), appear to be less neurotoxic and may counteract AD neuropathology. However, research on Aβ(1‐38) is scarce and their effect on AD pathophysiology in humans in vivo remains unclear. Here, we investigate whether higher relative concentrations of Aβ(1‐38) levels in the cerebrospinal fluid (CSF), compared to Aβ(1‐42) alone, with phospho Tau (pTau) or with both, protect against cognitive decline and risk of conversion to AD dementia.MethodParticipants with subjective cognitive decline (n = 56), mild cognitive impairment (n = 60) and AD dementia (n = 61) from the DELCODE study with a likely pathological Aβ42/P‐tau ratio of &gt; 9.68 at baseline were included. Cognitive performance was assessed annually for five years with the Mini‐Mental State Examination (MMSE) and the Preclinical Alzheimer Cognitive Composite (i.e., PACC5), which was derived from the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). Conversion to AD dementia was assessed with the Clinical Dementia Rating (CDR) and NINCDS‐ARDA criteria. CSF was collected at baseline. Data was analysed using statistical model fitting procedures for linear mixed models, i.e., Likelihood Ratio (LR) testing. Additionally, we controlled for baseline diagnostic status and the relative effect of Aβ(1‐42) and pTau.ResultHigher Aβ(1‐38) baseline levels were associated with better follow‐up performance on the PACC5 in all three groups across the AD continuum (p &lt; .001). For the MMSE, only the MCI group showed significantly better follow‐up performance (p = .003), and a trend was found in the other groups (SCD: p = .090, AD p = .099). Furthermore, higher Aβ(1‐38) baseline levels decreased risk of conversion to AD dementia within three years by 88% (p = .003) in the SCD and MCI groups.ConclusionAcross the AD spectrum, higher Aβ(1‐38) levels protect against cognitive decline and reduce the risk of conversion to AD dementia. This could inform individual risk prediction in memory clinic patients.

The neural nitric oxide synthase is associated with cognitive decline and Alzheimer’s disease pathology

AbstractBackgroundAlthough Alzheimer’s disease (AD) etiology is partially explained by the deposition of aggregated forms of β‐amyloid proteins and neurofibrillary tangles in the brain, the process that triggers the deposition of these proteins is still unknown. The neural (nNOS), endothelial (eNOS), and inducible nitric oxide synthases (iNOS) may play an important role in AD pathophysiology according to previous studies in animals. However, studies on humans are scarce. Therefore, we aimed to quantify the expression of NOS enzymes in the hippocampus of individuals with AD compared to individuals without the disease and investigate the association of NOS expression with cognition and AD‐related pathology.MethodWe evaluated the nNOS, eNOS, and iNOS expressions using immunohistochemistry in the cornu ammonis (CA) and the dentate gyrus (DG) from hippocampi from subjects with pure AD and sex‐matched controls. Cognitive abilities were evaluated using the Clinical Dementia Rating (CDR) and AD pathology using Braak staging for neurofibrillary tangles and the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) for neuritic plaque. We used linear regression to examine the association of NOS with cognition and AD pathology.ResultsSociodemographic and clinical variables were similar between the control and AD groups (Table 1). In individuals with AD, nNOS was overexpressed in the CA (β = 23.62, IC95% = 5.13;42.10, p = 0.01) and DG (β = 16.76, IC95% = 0.35;3.18, p = 0.01), while eNOS and iNOS were increased only in the CA (β = 0.93, IC95% = 0.02;1.84, p = 0.04; β = 0.19, IC95% = 0.09;0.90, p = 0.01, respectively) (Figure 1). Larger nNOS levels in the CA and DG were associated with worse cognitive abilities, higher Braak and CERAD scores (Table 2).ConclusionThe nNOS, eNOS, and iNOS were increased in the hippocampi of subjects with AD. However, only nNOS overexpression was associated with cognitive impairment and AD‐related pathology.