Fazekas scale magnetic resonance imaging assessment in Alzheimer's disease and primary age-related tauopathy.

BACKGROUND: Brain vascular pathology is an important comorbidity in Alzheimer's disease (AD), with white matter damage independently predicting cognitive impairment. However, it is still unknown how vascular pathology differentially impacts primary age-related tauopathy (PART) compared to AD. Therefore, our objectives were to compare the brain microangiopathic burden in patients with PART and AD, evaluated by MRI, while assessing its relation with neuropathological findings, patterns of brain atrophy and degree of clinical impairment. METHODS: Clinical information, brain MRI (T1 and T2-FLAIR) and neuropathological data were obtained from the National Alzheimer's Coordinating Centre ongoing study, with a total sample of 167 patients identified, that were divided according to the presence of neuritic plaques in Consortium to Establish a Registry for Alzheimer's disease (CERAD) 0 to 3. Microangiopathic burden and brain atrophy were evaluated by two certified neuroradiologists, using, respectively, the Fazekas score and previously validated visual rating scales to assess brain regional atrophy. RESULTS: Significant correlations were found between the Fazekas score and atrophy in the fronto-insular and medial temporal regions on both groups, with PART showing overall stronger positive correlations than in AD, especially in the fronto-insular region. For this specific cohort, no significant correlations were found between the Fazekas score and the degree of clinical impairment. CONCLUSION: Our results show that PART presents different pathological consequences at the brain microvascular level compared with AD and further supports PART as an independent pathological entity from AD.

Late-Life Blood Pressure and Cerebral Amyloid Angiopathy: Findings from the U.S. National Alzheimer's Coordinating Center Uniform Dataset.

High blood pressure (BP) and cerebral amyloid angiopathy (CAA) are two common risk factors for intracranial hemorrhage, potentially leading to cognitive impairment. Less is known about the relationship between BP and CAA, the examination of which was the objective of this study. We analyzed data from 2510 participants in the National Alzheimer's Coordinating Center (NACC) who had information on longitudinal BP measurements before death and on CAA from autopsy. Using the average of four systolic BPs (SBPs) prior to death, SBP was categorized into three groups: <120 mmHg (n = 435), 120-139 mmHg (n = 1335), and ≥140 mmHg (n = 740). CAA was diagnosed using immunohistochemistry in 1580 participants and categorized as mild (n = 759), moderate (n = 529), or severe (n = 292). When adjusted for age at death, sex, APOE genotype, Braak, CERAD, antihypertensive medication use, and microinfarcts, the odds ratios (95% CIs) for CAA associated with SBPs of 120-139 and ≥140 mmHg were 0.91 (0.74-1.12) and 1.00 (0.80-1.26), respectively. Findings from predictor effect plots show no variation in the probability of CAA between the three SBP categories. Microbleeds had no association with CAA, but among those with SBP ≥ 130 mmHg, the proportion of those with microbleeds was numerically greater in those with more severe CAA (p for trend, 0.084). In conclusion, we found no evidence of an association between SBP and CAA. Future studies need to develop non-invasive laboratory tests to diagnose CAA and prospectively examine this association and its implication on the pathophysiology and outcome of Alzheimer's disease.

Exploring the Association Between Visual Field Testing and CERAD Neuropsychological Battery in Idiopathic Normal Pressure Hydrocephalus Patients.

Background: Association between visual field test indices and The Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Battery (CERAD-NB) is unknown. Idiopathic normal pressure hydrocephalus (iNPH) patients provide a unique set of patient data for analysis. Objective: To assess the reliability of visual field testing using the CERAD-NB in patients with iNPH and to investigate the association between visual field test results and cognitive function. Methods: 62 probable iNPH patients were subjected to comprehensive ophthalmological examination, ophthalmological optical coherence tomography imaging studies, visual field testing, and CERAD-NB. Based on visual field indices, the patients were divided into two groups: unreliable (n = 19) and reliable (n = 43). Independent T-test analysis was performed to examine the relationship between visual field test results and cognitive function. Pearson Chi-square test was used for non-continuous variables. Results: The unreliable group performed worse in CERAD-NB subtests compared to the reliable group. Statistically significant differences were observed in nine out of ten subtests, with only Clock Drawing showing no statistical significance. Pairwise comparison of the groups showed no statistical significance between amyloid-ß (Aß) biopsy, hyperphosphorylated tau biopsy, apolipoprotein E allele or the ophthalmological status of the patient. But there was a statistically significant difference in cerebrospinal fluid Aß42 and age between the groups. Conclusions: Patients with unreliable visual field tests performed worse on CERAD-NB subtests. CERAD-NB subtests do not provide a specific cut-off value to refrain patients from visual field testing. Should patients with unreliable visual field tests be screened for cognitive impairment?

go4cognition: Evaluation of a Newly Developed Multicomponent Intervention in Mild Cognitive Impairment.

Background: 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. Objective: 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. Methods: 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. Results: 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. Conclusions: 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.

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.

Delayed primacy recall performance predicts post mortem Alzheimer's disease pathology from unimpaired ante mortem cognitive baseline.

We propose a novel method to assess delayed primacy in the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) memory test. We then examine whether this measure predicts post mortem Alzheimer's disease (AD) neuropathology in individuals who were clinically unimpaired at baseline. A total of 1096 individuals were selected from the Rush Alzheimer's Disease Center database registry. All participants were clinically unimpaired at baseline, and had subsequently undergone brain autopsy. Average age at baseline was 78.8 (6.92). A Bayesian regression analysis was carried out with global pathology as an outcome; demographic, clinical, and apolipoprotein E (APOE) data as covariates; and cognitive predictors, including delayed primacy. Global AD pathology was best predicted by delayed primacy. Secondary analyses showed that delayed primacy was mostly associated with neuritic plaques, whereas total delayed recall was associated with neurofibrillary tangles. Sex differential associations were observed. We conclude that CERAD-derived delayed primacy is a useful metric for early detection and diagnosis of AD in unimpaired individuals. Highlights: We propose a novel method to analyse serial position in the CERAD memory test.We analyse data from 1096 individuals who were cognitively unimpaired at baseline.Delayed primacy predicts post mortem pathology better than traditional metrics.

miR-129-5p as a biomarker for pathology and cognitive decline in Alzheimer's disease.

BACKGROUND: Alzheimer's dementia (AD) pathogenesis involves complex mechanisms, including microRNA (miRNA) dysregulation. Integrative network and machine learning analysis of miRNA can provide insights into AD pathology and prognostic/diagnostic biomarkers. METHODS: We performed co-expression network analysis to identify network modules associated with AD, its neuropathology markers, and cognition using brain tissue miRNA profiles from the Religious Orders Study and Rush Memory and Aging Project (ROS/MAP) (N = 702) as a discovery dataset. We performed association analysis of hub miRNAs with AD, its neuropathology markers, and cognition. After selecting target genes of the hub miRNAs, we performed association analysis of the hub miRNAs with their target genes and then performed pathway-based enrichment analysis. For replication, we performed a consensus miRNA co-expression network analysis using the ROS/MAP dataset and an independent dataset (N = 16) from the Gene Expression Omnibus (GEO). Furthermore, we performed a machine learning approach to assess the performance of hub miRNAs for AD classification. RESULTS: Network analysis identified a glucose metabolism pathway-enriched module (M3) as significantly associated with AD and cognition. Five hub miRNAs (miR-129-5p, miR-433, miR-1260, miR-200a, and miR-221) of M3 had significant associations with AD clinical and/or pathologic traits, with miR129-5p by far the strongest across all phenotypes. Gene-set enrichment analysis of target genes associated with their corresponding hub miRNAs identified significantly enriched biological pathways including ErbB, AMPK, MAPK, and mTOR signaling pathways. Consensus network analysis identified two AD-associated consensus network modules and two hub miRNAs (miR-129-5p and miR-221). Machine learning analysis showed that the AD classification performance (area under the curve (AUC) = 0.807) of age, sex, and APOE ε4 carrier status was significantly improved by 6.3% with inclusion of five AD-associated hub miRNAs. CONCLUSIONS: Integrative network and machine learning analysis identified miRNA signatures, especially miR-129-5p, as associated with AD, its neuropathology markers, and cognition, enhancing our understanding of AD pathogenesis and leading to better performance of AD classification as potential diagnostic/prognostic biomarkers.

Personality predictors of dementia diagnosis and neuropathological burden: An individual participant data meta-analysis.

INTRODUCTION: The extent to which the Big Five personality traits and subjective well-being (SWB) are discriminatory predictors of clinical manifestation of dementia versus dementia-related neuropathology is unclear. METHODS: Using data from eight independent studies (Ntotal = 44,531; Ndementia = 1703; baseline Mage = 49 to 81 years, 26 to 61% female; Mfollow-up range = 3.53 to 21.00 years), Bayesian multilevel models tested whether personality traits and SWB differentially predicted neuropsychological and neuropathological characteristics of dementia. RESULTS: Synthesized and individual study results indicate that high neuroticism and negative affect and low conscientiousness, extraversion, and positive affect were associated with increased risk of long-term dementia diagnosis. There were no consistent associations with neuropathology. DISCUSSION: This multistudy project provides robust, conceptually replicated and extended evidence that psychosocial factors are strong predictors of dementia diagnosis but not consistently associated with neuropathology at autopsy. HIGHLIGHTS: N(+), C(-), E(-), PA(-), and NA(+) were associated with incident diagnosis. Results were consistent despite self-report versus clinical diagnosis of dementia. Psychological factors were not associated with neuropathology at autopsy. Individuals with higher conscientiousness and no diagnosis had less neuropathology. High C individuals may withstand neuropathology for longer before death.

The positive effect of spermidine in older adults suffering from dementia after 1 year.

BACKGROUND: A positive effect of the effect of a 3-month oral spermidine intake on memory performance has already been demonstrated. The continuation of this study aimed to examine whether there could be observed an improvement in memory performance after one year. METHOD: 45 residents of the nursing home "Gepflegt Wohnen" in Hart bei Graz, Styria, Austria, were given a daily dose of 3.3 mg spermidine in their diet for one year. RESULTS: The comparison of the MMSE test results at baseline and after one year demonstrated a significant (p < 0.001) difference. The mean improvement is 5 points. CONCLUSION: The new results confirm the already proven positive effect of oral spermidine intake on memory performance.

miR-129-5p as a biomarker for pathology and cognitive decline in Alzheimer's disease.

Background: Alzheimer's dementia (AD) pathogenesis involves complex mechanisms, including microRNA (miRNA) dysregulation. Integrative network and machine learning analysis of miRNA can provide insights into AD pathology and prognostic/diagnostic biomarkers. Methods: We performed co-expression network analysis to identify network modules associated with AD, its neuropathology markers, and cognition using brain tissue miRNA profiles from the Religious Orders Study and Rush Memory and Aging Project (ROS/MAP) (N = 702) as a discovery dataset. We performed association analysis of hub miRNAs with AD, its neuropathology markers, and cognition. After selecting target genes of the hub miRNAs, we performed association analysis of the hub miRNAs with their target genes and then performed pathway-based enrichment analysis. For replication, we performed a consensus miRNA co-expression network analysis using the ROS/MAP dataset and an independent dataset (N = 16) from the Gene Expression Omnibus (GEO). Furthermore, we performed a machine learning approach to assess the performance of hub miRNAs for AD classification. Results: Network analysis identified a glucose metabolism pathway-enriched module (M3) as significantly associated with AD and cognition. Five hub miRNAs (miR-129-5p, miR-433, miR-1260, miR-200a, and miR-221) of M3 had significant associations with AD clinical and/or pathologic traits, with miR129-5p by far the strongest across all phenotypes. Gene-set enrichment analysis of target genes associated with their corresponding hub miRNAs identified significantly enriched biological pathways including ErbB, AMPK, MAPK, and mTOR signaling pathways. Consensus network analysis identified two AD-associated consensus network modules, and two hub miRNAs (miR-129-5p and miR-221). Machine learning analysis showed that the AD classification performance (area under the curve (AUC) = 0.807) of age, sex, and apoE ε4 carrier status was significantly improved by 6.3% with inclusion of five AD-associated hub miRNAs. Conclusions: Integrative network and machine learning analysis identified miRNA signatures, especially miR-129-5p, as associated with AD, its neuropathology markers, and cognition, enhancing our understanding of AD pathogenesis and leading to better performance of AD classification as potential diagnostic/prognostic biomarkers.

Association between serum globulin and cognitive impairment in older American adults.

Background and aims: Cognitive impairment is on the rise around the world, with profound economic and social consequences. Serum globulin, a marker of liver function, may also play a role in cognitive function. Unfortunately, no consistent conclusion exists regarding the association between serum globulin and cognitive function. Methods: Data from the 2011 to 2014 National Health and Nutrition Examination Survey were used to assess the association between serum globulin and cognitive impairment. Cognitive function was assessed by three tests: Consortium to Establish a Registry for Alzheimer's Disease (CERAD), Animal Fluency (AF), and Digit Symbol Substitution Test (DSST). Furthermore, the breakthrough point of cognitive impairment correlated with CERAD < 5, AF < 14, and DSST < 34. A weighted multiple logistics regression model was used to verify the association between serum globulin and cognitive impairment. Generalized additive models (GAMs) and a smooth curve fit (penalty spline method) were used to determine a non-linear relationship between serum globulin and cognitive impairment. Finally, subgroup analysis and interaction tests were conducted to further verify the association between serum globulin and cognitive impairment. Results: Data from 2,768 participants aged ≥60 (in accordance with the study design) were collected for the final analysis. Data suggested that serum globulin levels were associated with an elevated cognitive impairment based on the AF [full adjustment, OR = 1.05, 95% CI: 1.01-1.08] and DSST [full adjustment, OR = 1.06, 95% CI: 1.02-1.10] tests. Eventually, the GAM and smooth curve fit model was conducted to confirm that the association between serum globulin and cognitive impairment was non-linear. Moreover, the inflection point was 27 g/L serum globulin based on the CERAD test and 35 g/L serum globulin based on the AF test. Finally, the interaction term between serum globulin and cognitive impairment based on the AF test indicated no significant interactions among all variables (all p for interaction >0.05). Conclusion: The association between serum globulin levels and cognitive impairment is non-linear. A threshold effect exists between serum globulin and cognitive impairment. Large-scale prospective clinical trials are needed to validate our findings.

Investigating the relationship between allocentric spatial working memory and biomarker status in preclinical and prodromal Alzheimer's disease.

The 4 Mountain Test (4MT) is a test of allocentric spatial working memory and has been proposed as an earlier marker of predementia Alzheimer's disease (AD) than episodic verbal memory. We here compare the 4MT to the CERAD word list memory recall in both cognitively normal (CN) and mild cognitive impairment (MCI) cases with or without cerebrospinal fluid markers (CSF) of Alzheimer's disease pathology. Linear regression was used to assess the influence of CSF determined Aß-plaque (Aß-/+) or neurofibrillary tau tangles (Tau-/+) on 4MT and CERAD recall performance. Analyses were performed in the full sample and the CN and MCI sub-samples. Pearson correlations were calculated to examine the relationship between 4MT and tests of psychomotor speed, verbal memory, cognitive flexibility, verbal fluency, and visuo-spatial perception. Analyses showed no significant differences in 4MT scores between Aß-/Aß+, nor Tau-/Tau + participants, irrespective of cognitive status. In contrast, CERAD recall scores were lower in both Aß+ compared to Aß- (p<.01), and Tau + compared to Tau- participants (p<.01) in the full sample analyses. There were no significant differences in CERAD recall performance between Aß- vs. Aß+ and Tau- vs. to Tau + in the in CN/MCI sub-samples. 4MT scores were significantly correlated with tests of psychomotor speed, cognitive flexibility, and visuo-spatial perception in the full sample analyses. In conclusion, the CERAD recall outperformed the 4MT as a cognitive marker of CSF determined AD pathology. This suggests that allocentric working memory, as measured by the 4MT, may not be used as an early marker of predementia AD.

Delayed primacy recall performance predicts post mortem Alzheimer's disease pathology from unimpaired ante mortem cognitive baseline.

INTRODUCTION: We propose a novel method to assess delayed primacy in the CERAD memory test. We then examine whether this measure predicts post mortem Alzheimer's disease (AD) neuropathology in individuals who were clinically unimpaired at baseline. METHODS: A total of 1096 individuals were selected from the Rush Alzheimer's Disease Center database registry. All participants were clinically unimpaired at baseline, and had subsequently undergone brain autopsy. Average age at baseline was 78.8 (6.92). A Bayesian regression analysis was carried out with global pathology as outcome; demographic, clinical and APOE data as covariates; and cognitive predictors, including delayed primacy. RESULTS: Global AD pathology was best predicted by delayed primacy. Secondary analyses showed that delayed primacy was mostly associated with neuritic plaques, whereas total delayed recall was associated with neurofibrillary tangles. DISCUSSION: We conclude that CERAD-derived delayed primacy is a useful metric for early detection and diagnosis of AD in unimpaired individuals.

Correlation analysis between subtest scores of CERAD-K and a newly developed tablet computer-based digital cognitive test (Inbrain CST).

Introduction: The prevalence of Alzheimer's disease (AD) and other dementias is increasing; therefore, identifying individuals at risk for dementia is crucial. Traditional neuropsychological assessments are expensive and time-consuming; however, computerized cognitive testing is becoming popular in clinical and research settings, particularly during the COVID-19 pandemic. This study aimed to investigate the correlation between the computerized cognitive test, Inbrain cognitive screening test (CST), and the traditional neuropsychological battery, the consortium to establish a registry for Alzheimer's disease assessment packet (CERAD-K). Methods: We enrolled 166 participants from five districts in Republic of Korea, including cognitively unimpaired individuals and those with mild cognitive impairment (MCI) diagnosed by experienced neurologists. We used the Inbrain CST and CERAD-K to evaluate the cognitive function of the participants, and the scores of each subtest of the Inbrain CST and CERAD-K were compared. Results: A significant correlation was found between the Inbrain CST and CERAD-K subtests. Furthermore, multivariate analysis revealed a significant correlation between the Inbrain CST and the CERAD-K test pairs after adjusting for age, educational level, and sex. Discussion: In conclusion, this study demonstrates that the Inbrain CST is a reliable tool for detecting cognitive impairment in cognitively unimpaired individuals and patients with MCI, because it has a high correlation and agreement with CERAD-K. Therefore, the Inbrain CST can be a useful, time-efficient, and cost-effective computer-based cognitive test for individuals at risk for cognitive impairment.

Association between selenium intake and cognitive function among older adults in the US: National Health and Nutrition Examination Surveys 2011-2014.

Cognitive decline occurs commonly as people age. Despite the complexity of cellular mechanisms, oxidative stress is a critical contributor to age-associated cognitive impairment. Selenium plays an important role in antioxidant defense systems. The purpose of the present study was to assess the correlation between selenium intake and cognitive function among older adults. The participants were individuals ≥65 years old (n=1681) who participated in the 2011-2014 National Health and Nutrition Examination Survey (NHANES), a country-wide cross-sectional survey. Dietary selenium intake and adequacy were evaluated with 2 d of 24-h recalls and the estimated average requirement (EAR) cut-point method, respectively. Cognitive function was assessed with the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) score, which was significantly higher when selenium intake was adequate. After adjusting for energy intake, the association was no longer significant. Inadequate intake of selenium is rare in the US and dependent on caloric intake in older adults.

CERAD (Consortium to Establish a Registry for Alzheimer's Disease) Neuropsychology Assessment Battery: 35 Years and Counting.

BACKGROUND: In 1986, the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) was mandated to develop a brief neuropsychological assessment battery (CERAD-NAB) for AD, for uniform neuropsychological assessment, and information aggregation. Initially used across the National Institutes of Aging-funded Alzheimer's Disease Research Centers, it has become widely adopted wherever information is desired on cognitive status and change therein, particularly in older populations. OBJECTIVE: Our purpose is to provide information on the multiple uses of the CERAD-NAB since its inception, and possible further developments. METHODS: Since searching on "CERAD neuropsychological assessment battery" or similar terms missed important information, "CERAD" alone was entered into PubMed and SCOPUS, and CERAD-NAB use identified from the resulting studies. Use was sorted into major categories, e.g., psychometric information, norms, dementia/differential dementia diagnosis, epidemiology, intervention evaluation, genetics, etc., also translations, country of use, and alternative data gathering approaches. RESULTS: CERAD-NAB is available in ∼20 languages. In addition to its initial purpose assessing AD severity, CERAD-NAB can identify mild cognitive impairment, facilitate differential dementia diagnosis, determine cognitive effects of naturally occurring and experimental interventions (e.g., air pollution, selenium in soil, exercise), has helped to clarify cognition/brain physiology-neuroanatomy, and assess cognitive status in dementia-risk conditions. Surveys of primary and tertiary care patients, and of population-based samples in multiple countries have provided information on prevalent and incident dementia, and cross-sectional and longitudinal norms for ages 35-100 years. CONCLUSION: CERAD-NAB has fulfilled its original mandate, while its uses have expanded, keeping up with advances in the area of dementia.

Linear and Nonlinear Effect of Years of Schooling, Sex, and Age on the CERAD-MX and Complementary Tasks in a Mexican Sample: A Cross-Sectional Study.

OBJECTIVE: Since evidence of adults' cognition decline is based on standardized testing, we developed regression-based continuous norms by linear regression (LR) and nonlinear quantile regression (NQR) with years of schooling (YoS), age, and sex as covariates on the Mexican adaptation of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD-MX) and complementary tasks. METHODS: 392 healthy, Spanish-speaking Mexican adults (50.25% women) aged 18-59 completed the 15 CERAD-MX cognitive tasks and complementary tasks. We used raw scores and examined YoS-related effects considering sex and age as covariates. For the NQR, we used calibrated scores for sex and age. While LR represents one line across the performance, NQR differentiated several nonlinear performance bands by quantiles. RESULTS: LR showed positive relationships between YoS and cognitive performance with a funnel variance pattern. Therefore, this relationship is better represented with NQR than LR. A small, but significant, negative effect of age was found for this age range (18-59 years). The band with fewer years of schooling (1-6) showed greater variability in the cognitive measures than those with more years of schooling (16-22). CONCLUSION: This study shows that NQR is useful for accurately positioning participants' performance relative to their peers. NQR accounts more than LR for the inconsistent variability of cognitive performance as a function of YoS by identifying the variability according to YoS (low, medium, high). Thus, NQR represents an appropriate way to construct norms for the cognitive performance of adults.

Associations between urinary caffeine and caffeine metabolites and cognitive function in older adults.

BACKGROUND: The effects of caffeine on cognitive impairment have not been conclusively determined. This study aimed to objectively assess the correlation between the urinary caffeine and caffeine metabolites and cognitive decline in older adults. METHODS: Data on urinary caffeine and caffeine metabolites and the cognitive performance of participants aged 60 years and older were extracted from the National Health and Nutrition Examination Surveys 2011-2014. Binary logistic regression and restricted cubic splines (RCS) analyses were used to evaluate the association between urinary caffeine and caffeine metabolites and cognitive performance. RESULTS: Eight hundred twenty-seven individuals were enrolled in this cross-sectional study. We observed that 1-methylxanthine, 3-methylxanthine, 7-methylxanthine, 1,3-dimethylxanthine, 1,7-dimethylxanthine, and 3,7-dimethylxanthine levels were significantly and inversely associated with cognitive decline. The RCS results suggested an approximately linear dose-response relationship between the aforementioned metabolites and cognitive performance. Moreover, the effects of urinary caffeine and caffeine metabolites on cognitive function assessed using the AFT were more evident in men. CONCLUSIONS: Our study suggested that urinary caffeine and caffeine metabolite levels were associated with a reduced risk of cognitive impairment in a linear manner, especially in men.

The CERAD Word List Memory Test: Normative Data Based on a Norwegian Population-Based Sample of Healthy Older Adults 70 Years and Above. The HUNT Study.

BACKGROUND: The CERAD Word List Memory Test (WLMT) is widely used in the assessment of older adults with suspected dementia. Although normative data of the WLMT exist in many different regions of the world, normative data based on large population-based cohorts from the Scandinavian countries are lacking. OBJECTIVE: To develop normative data for the WLMT based on a large population-based Norwegian sample of healthy older adults aged 70 years and above, stratified by age, gender, and education. METHODS: A total of 6,356 older adults from two population-based studies in Norway, HUNT4 70 + and HUNT4 Trondheim 70+, were administered the WLMT. Only persons with normal cognitive function were included. We excluded persons with a diagnosis of mild cognitive impairment (MCI) and dementia, and persons with a history of stroke and/or depression. This resulted in 3,951 persons aged between 70 and 90 years, of whom 56.2% were females. Regression-based normative data were developed for this sample. RESULTS: Age, gender, and education were significant predictors of performance on the WLMT list-learning subtests and the delayed recall subtest, i.e., participants of younger age, female sex, and higher education level attained higher scores compared to participants of older age, male sex, and lower level of education. CONCLUSION: Regression-based normative data from the WMLT, stratified by age, gender, and education from a large population-based Norwegian sample of cognitively healthy older adults aged 70 to 90 years are presented. An online norm calculator is available to facilitate scoring of the subtests (in percentiles and z-scores).

Handgrip strength is associated with learning and verbal fluency in older men without dementia: insights from the NHANES.

Low handgrip strength, a hallmark measure of whole-body strength, has been linked with greater odds of cognitive decline and dementia; however, conflicting findings, which could be due to population characteristics and choice of tools, such for the assessment of handgrip strength and cognitive function domains, also exist. Therefore, we examined the relationship of handgrip strength with a comprehensive list of tests to assess domains of cognitive function using a representative sample of US older men and women without neurodegenerative disorders such as dementia. We analyzed cross-sectional data from the US National Health and Nutrition Examination Survey (NHANES) between 2011 and 2014, with a study cohort of 777 older adults (380 men and 397 women) above 60 years of age. Handgrip strength was assessed using a handgrip dynamometer, while cognitive function was assessed through the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word List Learning Test (WLLT), Word List Recall Test (WLRT), Intrusion Word Count Test (WLLT-IC and WLRT-IC), the Animal Fluency Test (AFT), and the Digit Symbol Substitution Test (DSST). Sex-stratified multiple linear regression analyses were performed upon covariate adjustment for age, ethnicity, socio-economic status, education, medical history, body mass index, physical activity, energy, protein, and alcohol intake. Maximal handgrip strength was positively associated with cognitive function scores, including CERAD WLLT (P = 0.009, R2 = 0.146) and AFT (P = 0.022, R2 = 0.024) in older men, but not in women (CERAD WLLT: P = 0.253, AFT: P = 0.370). No significant associations with CERAD WLLRT (men: P = 0.057, women: P = 0.976), WLLT-IC (men: P = 0.671, women: P = 0.869), WLLRT-IC (men: P = 0.111, women: P = 0.861), and DSST (men: P = 0.108, women: P = 0.091) were observed. Dose-response curves exhibited a prominent linear relationship between all significant associations after covariate adjustment, with no indication of a plateau in these relationships. In conclusion, higher handgrip strength was independently associated with better learning ability for novel verbal information and verbal fluency in US men over the age of 60 and without dementia. Longitudinal studies are required to confirm whether muscle strength independently predicts cognitive function changes in older adults in a sex-specific manner, and whether this connection is affirmed to the possibility of reverse causation due to declines in physical activity levels in the preclinical phase of dementia.