Standardized Cognitive Tests Research Articles

Single and joint exposure of Pb, Cd, Hg, Se, Cu, and Zn were associated with cognitive function of older adults

Background: Impaired cognitive function following exposure to heavy metals has emerged as a significant global health concern. Nevertheless, the impact of combined exposure to multiple heavy metals on cognitive impairment remains unclear. Objective: This study aimed to explore the association between multiple heavy metals exposure and cognitive function to provide theoretical evidence to guide prevention strategies. Methods: The blood levels of lead (Pb), cadmium (Cd), mercury (Hg), selenium (Se), copper (Cu) and zinc (Zn) and the results of the cognitive function tests were extracted from 811 elderly Americans who completed the NHANES between 2011 and 2014. Quantile regression (QR), restricted cubic splines (RCS), and Bayesian kernel machine regression (BKMR) were used to explore the individual and joint association between heavy metals exposure and performance in 4 standardized cognitive tests; Item Response Theory (IRT), Delayed Recall Test (DRT), Animal Fluency Test (AFT) and Digit Symbol Substitution Test (DSST). Results: A negative association was noted between Cd levels and IRT (p = 0.048, 95%CI: -2.7, -0.1). Se concentrations ranging between 2.197 µg/L (95%CI: 0.004, 0.15) to 2.29 µg/L (95%CI: 2.56, 7.64) (log10Se) was postively associated with DSST (p = 0.001 ). Cu was negatively associated with DSST (p = 0.049, 95%CI: -37.75, -0.09), while Zn was positively associated with IRT (p = 0.022, 95%CI: 0.55, 11.73). Exposure to the 6 heavy metals combined showed a positive linear association with IRT, DRT, and a negative linear association with DSST. An interaction between Cd and the other heavy metals (excepted for Pb). Conclusion: Exposure to Pb, Cd, Hg, Se, Cu, and Zn was associated with cognitive function. Joint exposure to the 6 heavy metals showed a positive linear association with IRT, DRT, contrarily, a negative linear association with DSST.

Relationship of subjective and objective cognition with post-stroke mood differs between early and long-term stroke

Objective: Depression and anxiety affects approximately 1 in 3 stroke survivors. Performance on standardized objective cognitive tests and self-reported subjective cognitive symptoms are associated with concurrent depression and anxiety, but longitudinal data on whether and how objective and subjective cognition relate to emotional outcomes are lacking. Method: N = 99 stroke survivors (M age = 68.9, SD = 13.1; Median NIH Stroke Severity = 5) completed measures of depression and anxiety (Hospital Anxiety and Depression Scale; HADS), objective cognition (Oxford Cognitive Screen) and subjective cognitive symptoms (Cognitive Failures Questionnaire) at 6-months, 4.5, and 5.5 years post-stroke. The contribution of objective and subjective cognition to depression and anxiety was determined via mixed-effects models. Results: We found no evidence that age, stroke severity, years of education, and participant sex related to changes in HADS-Depression or HADS-Anxiety scores (Marginal R 2=0.03 and 0.05, respectively). Objective cognitive impairments at 6-months and increases in subjective cognitive symptoms at 5.5 years significantly related to increased HADS-Depression scores (Marginal R 2=0.22). Only increases in subjective cognitive symptoms at 5.5 years significantly related to increased HADS-Anxiety scores (Marginal R 2=0.20). When conducting models in reverse, HADS-Depression and HADS-Anxiety scores did not reciprocally explain changes in subjective cognitive symptoms. Conclusions: Objective cognitive abilities are more strongly associated with depression at 6-months post-stroke, while subjective cognitive symptoms are more relevant to both long-term post-stroke depression and anxiety. There may be a unique unidirectional influence of subjective cognitive symptoms to post-stroke depression and anxiety.

Neuropsychological Correlates of Clinical Progression in Subjective Cognitive Decline.

Subjective cognitive decline (SCD) refers to self-reported cognitive decline in individuals with normal performance on standardized cognitive tests. Understanding the factors predicting progression from SCD to mild cognitive impairment (MCI) is crucial, as approximately 14% of SCD cases progress to dementia and about 27% develop MCI over four years. This study aims to identify neuropsychological predictors of progression from SCD to MCI, focusing on cognitive domains assessed through neuropsychological tests. This retrospective study at Seoul National University Bundang Hospital analyzed a cohort of 107 patients diagnosed with SCD through comprehensive assessment. Patients underwent annual neuropsychological testing, including the Digit Span Test, Boston Naming Test, Rey Complex Figure Test, Seoul Verbal Learning Test, and Stroop Test. Annually, these patients underwent neuropsychological tests over a 5-year period; 24 progressed to MCI per NIA-AA criteria. Key predictors of MCI progression included age, ischemic heart disease, and scores from the forward digit span, delayed recall, and Boston naming tests. Lower scores in delayed recall and Boston naming tests significantly correlated with a higher risk of MCI (p < 0.001). These findings suggest a need for targeted management of memory and language functions to monitor disease progression effectively.

Psychometric and adherence considerations for high-frequency, smartphone-based cognitive screening protocols in older adults.

The psychometric rigor of unsupervised, smartphone-based assessments and factors that impact remote protocol engagement is critical to evaluate prior to the use of such methods in clinical contexts. We evaluated the validity of a high-frequency, smartphone-based cognitive assessment protocol, including examining convergence and divergence with standard cognitive tests, and investigating factors that may impact adherence and performance (i.e., time of day and anticipated receipt of feedback vs. no feedback). Cognitively unimpaired participants (N = 120, Mage = 68.8, 68.3% female, 87% White, Meducation = 16.5 years) completed 8 consecutive days of the Mobile Monitoring of Cognitive Change (M2C2), a mobile app-based testing platform, with brief morning, afternoon, and evening sessions. Tasks included measures of working memory, processing speed, and episodic memory. Traditional neuropsychological assessments included measures from the Preclinical Alzheimer's Cognitive Composite battery. Findings showed overall high compliance (89.3%) across M2C2 sessions. Average compliance by time of day ranged from 90.2% for morning sessions, to 77.9% for afternoon sessions, and 84.4% for evening sessions. There was evidence of faster reaction time and among participants who expected to receive performance feedback. We observed excellent convergent and divergent validity in our comparison of M2C2 tasks and traditional neuropsychological assessments. This study supports the validity and reliability of self-administered, high-frequency cognitive assessment via smartphones in older adults. Insights into factors affecting adherence, performance, and protocol implementation are discussed.

Abstract P344: APOe Genotype Modifies the Association Between Long-Term Blood Pressure Variability and Cognitive Decline/Dementia in Older Adults

We previously reported an increased risk of cognitive decline and dementia with high visit-to-visit long-term blood pressure variability (BPV) in the ASPREE randomized trial of low-dose aspirin, conducted in 19,114 community-dwelling older adults in Australia and the USA who were initially free of significant cognitive impairment and diagnosed dementia at enrollment. Upon completion of the randomized trial phase, ASPREE participants were invited into the ASPREE-eXTension (ASPREE-XT) observational study. In this analysis, we re-examined the risks of cognitive decline and dementia using extended follow-up from ASPREE-XT, and including recently available APOe genotype as an additional covariate. Long-term BPV was estimated in each participant using standard deviation (SD) of the means of three within-visit systolic BPs obtained with a validated automated oscillometric BP monitor from the baseline and first two annual ASPREE visits. During ASPREE and continued into ASPREE-XT, participants underwent annual/biennial standardized cognitive testing (4-test battery). Incident cognitive decline was defined as &gt;1.5 SD decline from baseline score on any cognitive test; incident dementia was a pre-specified secondary endpoint of ASPREE/ASPREE-XT and adjudicated by expert panel using DSM-IV criteria and clinical records. Participants reaching cognitive decline or dementia endpoints during the BPV estimation period were excluded from the analysis. Multivariable Cox proportional hazards regression showed the highest SD tertile of BPV, compared to the lowest SD tertile, remained associated with highest risk of cognitive decline (HR=1.16, 95% CI=1.04-1.30) and dementia (HR=1.27 (95% CI=1.02-1.59) in men, and cognitive decline (HR=1.12, 95% CI=1.01-1.24) in women (see accompanying Table), over a median follow-up of 5.8 years (for cognitive decline) and 6.5 years (for dementia). When APOe genotype was included as an additional covariate in an available subset of the cohort (81%), the presence of APOe4 allele partially attenuated the associations in both sexes, although cognitive decline remained significant in men. Our findings suggest the relationship between high long-term BPV and cognitive decline and dementia is stronger in men than women, but also modified by underlying APOe genotype.

MED13L-related disorder characterized by severe motor speech impairment.

MED13L-related disorder is associated with intellectual disability, motor delay, and speech deficits. Previous studies have focused on broad clinical descriptions of individuals, but limited information regarding specific speech diagnoses and results of direct testing has been published to date. We conducted deep phenotyping to characterize the speech, language, motor, cognitive, and adaptive phenotypes of individuals with MED13L-related disorder. In this cross-sectional study, we administered standardized articulation, language, motor, and cognitive testing to 17 children and adolescents (mean age 9y 9m; SD 4y 5m; range 4y 2m to 19y 7m). In-person testing was supplemented with broad developmental, medical, and behavioral information collected virtually from a cohort of 67 individuals. All individuals who completed in-person articulation testing met diagnostic criteria for speech apraxia, dysarthria, or both. Language impairment was present in all of the in-person cohort and almost all (97%) of the virtual cohort. Those who were able to complete motor testing demonstrated significant deficits in visual motor integration (mean 57.08, SD 9.26). Full scale IQs fell in the borderline to intellectual disability range, consistent with reported cognitive impairment in 97% of the virtual cohort. Notable medical features included hypotonia (83%), vision problems (72%), recurrent otitis media (58%), gastrointestinal problems (57%), and seizures (31%). MED13L-related disorder is characterized by a high rate of motor speech disorders that occur in the context of globally impaired motor, language, and cognitive skills. Children would benefit from intensive, individualized speech therapy and the early adoption of augmentative communication strategies.

Advancing Alzheimer's Research With Zebrafish Models: Current Insights, Addressing Challenges, and Charting Future Courses.

Alzheimer's disease (AD) is a neurological condition that progressively impairs cognitive function and results in memory loss.Despite substantial research efforts, little is known about the specific processes driving AD, and there are few proven therapies. Because of their physiological and genetic resemblance to humans, zebrafish (Danio rerio) have become an important model organism for furthering research on AD.This abstract discusses the difficulties faced, looks at the insights currently garnered from zebrafish models, and suggests future research options. AD knowledge has greatly benefited from the use of zebrafish models. Transgenic zebrafish that express human AD-associated genes, such as tau and amyloid precursor protein (APP), display tau neurofibrillary tangles (NFTs) and amyloid-beta (Aβ) plaques, two of the disease's main clinical characteristics. These models have clarified the roles of oxidative stress, inflammation, and calcium homeostasis in the course of AD and allowed for the purpose of high-throughput screening of potential therapeutic agents.Understanding the growth and deterioration of neurons has been greatly aided by real-time zebrafish imaging. Fully using zebrafish models in AD research requires addressing a number of issues. The dissimilarities in zebrafish anatomy and physiology from humans, the difficulty of developing models that replicate progressive and late-onset AD (LOAD), and the requirement for standardized procedures to evaluate alterations in zebrafish cognition and behavior are a few issues.Furthermore, variations in the genetic makeup of zebrafish strains might affect the results of experiments. Future directions include developing standardized behavioral assays and cognitive tests, working together to create extensive databases of zebrafish genetic and phenotypic data, and using genetic engineering techniques like CRISPR/Cas9 to create more complex zebrafish models. Combining zebrafish models with other model species helps expedite the conversion of research results into therapeutic applications and offers a more thorough knowledge of AD.To sum up, zebrafish models have made a substantial contribution to Alzheimer's research by offering insightful information on the causes of the illness and possible therapies. By tackling present issues and formulating a planned future path, we can improve the use of zebrafish to decipher the mysteries of Alzheimer's and help create successful treatments.

Providing a brief corrective statement does not improve test performance in patients invalidating testing: A multisite, single-blind randomized controlled trial

Objective: Performance below the actual abilities of the examinee can be measured using performance validity tests (PVTs). PVT failure negatively impacts the quality of the neuropsychological assessment. In our study, we addressed this issue by providing a brief corrective statement regarding invalidity to improve test-taking behavior. Methods: This study is a multisite single-blind randomized controlled trial in a consecutive sample of clinically referred adult patients (N = 196) in a general hospital setting. Patients who failed a PVT (n = 71) were randomly allocated to a corrective statement approach (CS; n = 39), in which a brief verbal corrective statement was given by the technician, or received no corrective statement upon indications of invalid performance (NO-CS; n = 32). Both groups (CS and NO-CS) were provided with the same subsequently repeated and newly administered tests. Results: There were no group (CS vs. NO-CS) differences on both the repeated and single-administered PVTs and standard cognitive tests. Furthermore, invalid performing participants benefited significantly less from the repeated test administration compared to the valid performing group. Conclusions: Our study found that a brief corrective within-session statement, to address PVT failure and improve test-taking behavior, did not improve consequent test performance. These results suggest limited value of a brief verbal corrective statement to influence performance below best of capabilities. It highlights the need for more research to identify more effective approaches that can enhance patients test-taking behavior. Ultimately, such efforts are critical in ensuring accurate diagnosis and effective treatment recommendations for patients.

Alignment of Consumers' Expected Brain Benefits from Food and Supplements with Measurable Cognitive Performance Tests.

Consumers often cite cognitive improvements as reasons for making dietary changes or using dietary supplements, a motivation that if leveraged could greatly enhance public health. However, rarely is it considered whether standardized cognitive tests that are used in nutrition research are aligned to outcomes of interest to the consumer. This knowledge gap presents a challenge to the scientific substantiation of nutrition-based cognitive health benefits. Here we combined focus group transcript review using reflexive thematic analysis and a multidisciplinary expert panel exercise to evaluate the applicability of cognitive performance tools/tasks for substantiating the specific cognitive benefits articulated by consumers with the objectives to (1) understand how consumers comprehend the potential benefits of nutrition for brain health, and (2) determine the alignment between consumers desired brain benefits and validated tests and tools. We derived a 'Consumer Taxonomy of Cognitive and Affective Health in Nutrition Research' which describes the cognitive and affective structure from the consumers perspective. Experts agreed that validated tests exist for some consumer benefits including focused attention, sustained attention, episodic memory, energy levels, and anxiety. Prospective memory, flow, and presence represented novel benefits that require the development and validation of new tests and tools. Closing the gap between science and consumers and fostering co-creative approaches to nutrition research are critical to the development of products and dietary recommendations that support realizable cognitive benefits that benefit public health.

Lévy Flight Model of Gaze Trajectories to Assist in ADHD Diagnoses.

The precise mathematical description of gaze patterns remains a topic of ongoing debate, impacting the practical analysis of eye-tracking data. In this context, we present evidence supporting the appropriateness of a Lévy flight description for eye-gaze trajectories, emphasizing its beneficial scale-invariant properties. Our study focuses on utilizing these properties to aid in diagnosing Attention-Deficit and Hyperactivity Disorder (ADHD) in children, in conjunction with standard cognitive tests. Using this method, we found that the distribution of the characteristic exponent of Lévy flights statistically is different in children with ADHD. Furthermore, we observed that these children deviate from a strategy that is considered optimal for searching processes, in contrast to non-ADHD children. We focused on the case where both eye-tracking data and data from a cognitive test are present and show that the study of gaze patterns in children with ADHD can help in identifying this condition. Since eye-tracking data can be gathered during cognitive tests without needing extra time-consuming specific tasks, we argue that it is in a prime position to provide assistance in the arduous task of diagnosing ADHD.

Plasma galectin-9 relates to cognitive performance and inflammation among adolescents with vertically acquired HIV.

Adolescents with perinatally acquired HIV (AWH) are at an increased risk of poor cognitive development yet the underlying mechanisms remain unclear. Circulating galectin-9 (Gal-9) has been associated with increased inflammation and multimorbidity in adults with HIV despite antiretroviral therapy (ART); however, the relationship between Gal-9 in AWH and cognition remain unexplored. A cross-sectional study of two independent age-matched cohorts from India [AWH on ART ( n = 15), ART-naive ( n = 15), and adolescents without HIV (AWOH; n = 10)] and Myanmar [AWH on ART ( n = 54) and AWOH ( n = 22)] were studied. Adolescents from Myanmar underwent standardized cognitive tests. Plasma Gal-9 and soluble mediators were measured by immunoassays and cellular immune markers by flow cytometry. We used Mann-Whitney U tests to determine group-wise differences, Spearman's correlation for associations and machine learning to identify a classifier of cognitive status (impaired vs. unimpaired) built from clinical (age, sex, HIV status) and immunological markers. Gal-9 levels were elevated in ART-treated AWH compared with AWOH in both cohorts (all P < 0.05). Higher Gal-9 in AWH correlated with increased levels of inflammatory mediators (sCD14, TNFα, MCP-1, IP-10, IL-10) and activated CD8 + T cells (all P < 0.05). Irrespective of HIV status, higher Gal-9 levels correlated with lower cognitive test scores in multiple domains [verbal learning, visuospatial learning, memory, motor skills (all P < 0.05)]. ML classification identified Gal-9, CTLA-4, HVEM, and TIM-3 as significant predictors of cognitive deficits in adolescents [mean area under the curve (AUC) = 0.837]. Our results highlight a potential role of Gal-9 as a biomarker of inflammation and cognitive health among adolescents with perinatally acquired HIV.

Relationships between cortisol levels across early childhood and processing speed at age 4.5 years in children born very preterm

ABSTRACT Children born very low gestational age (VLGA, 29–32 weeks gestational age [GA]) display slower processing speed and altered hypothalamic pituitary adrenal (HPA) axis function, with greater effects in those born extremely low gestational age (ELGA; 24–28 weeks GA). We investigated trajectories of HPA axis activity as indexed by cortisol output and patterns across cognitive assessment at ages 1.5, 3 and 4.5 years, comparing children born ELGA and VLGA and associations with 4.5-year processing speed. In a prospective longitudinal cohort study, infants born very preterm (<33 weeks gestation) returned for developmental assessment at ages 1.5, 3, and 4.5 years. At each age, children completed standardized cognitive testing and saliva samples collected before (Pretest), during (During) and after (End) challenging cognitive tasks were assayed for cortisol. For the total group (n = 188), cortisol area under the curve with respect to ground (AUCg) decreased, while cortisol reactivity to challenge (Pre-test to During) increased from 1.5 to 3 years, remaining stable to 4.5 years. This longitudinal pattern was related to higher Processing Speed (WPPSI-IV) scores at 4.5 years. Children born ELGA displayed higher AUCg than VLGA, particularly at age 3, driven by higher Pre-test cortisol levels. Overall, relative to those born VLGA, children born ELGA displayed greater cortisol responsivity to cognitive challenge. A higher setpoint of cortisol levels at age 3-years in children born ELGA may reflect altered HPA axis regulation more broadly and may contribute to difficulties with information processing in this population, critical for academic and social success.

Increased intraindividual variability in reaction time performance is associated with emerging cognitive decline in cognitively unimpaired adults.

To investigate whether intraindividual variability (IIV) in reaction time (RT) over monthly administered cognitive tasks is increased in cognitively unimpaired older adults who are at risk for cognitive decline, and whether this is independent of mean RT performance. N = 109 cognitively unimpaired individuals (age 77.4 ± 5.0, 61.5% female, Mini-Mental State Examination 29.1 ± 1.3) from the Harvard Aging Brain Study completed the self-administered Computerized Cognitive Composite (C3) monthly at home for up to 1 year (12.7 ± 3.2 C3 assessments). Baseline C3 assessment coincided with routine in-clinic visits, including amyloid and tau positron emission tomography imaging and standardized cognitive testing, with cognitive testing repeated annually (1.6 ± 1.2 years follow-up). The C3 includes two simple RT tasks and two complex RT tasks. IIV estimates were derived by computing intraindividual standard deviations on residual RT scores after regressing out age and session order effects. Cross-sectional associations of IIV with cognition (global cognition, memory, executive functions [EF], processing speed) and amyloid and tau burden were examined using linear regression analyses correcting for demographics and mean RT. The association between IIV and cognitive decline was assessed using linear mixed models correcting for demographic factors, mean RT, and amyloid burden. After adjusting for mean RT, increased IIV on complex RT tasks was independently associated with worse EF performance (β = -0.10, 95% CI [-.16, -0.03], p = .004), greater inferior-temporal tau deposition (β = 0.18, 95% CI [0.02, 0.34], p = .024), and faster cognitive decline in those with elevated amyloid (β = -0.62, 95% CI [-1.18, -0.06], p = .033). Increased variability in monthly RT may reflect subtle EF deficits and provide unique information about short-term cognitive decline in preclinical Alzheimer's disease. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Evaluation of a non-auditory neurocognitive test battery in hearing-impaired according to age.

Due to the demographic shift, the number of older people suffering from hearing loss and from cognitive impairment increases. Both are closely related and hard to differentiate as most standard cognitive test batteries are auditory-based and hearing-impaired individuals perform worse also in non-auditory test batteries. Therefore, reference data for hearing-impaired are mandatory. The computer-based battery ALAcog assesses multiple cognitive domains, such as attention, (delayed) memory, working memory, inhibition, processing speed, mental flexibility and verbal fluency. A data set of 201 bilaterally hearing-impaired subjects aged ≥ 50 (mean 66.6 (SD 9.07)) was analysed. The LMS method, estimated curves for the 10th, 25th, 50th, 75th and 90th percentile were calculated, and classified according to age, starting from the age of 50. Cognitive function shows a decline in all subtests as people age, except for verbal fluency, which remains almost stable over age. The greatest declines were seen in recall and delayed recall and in mental flexibility. Age and hearing ability did not correlate (p = 0.68). However, as people age, inter-subject variability of cognitive test results increases. This was especially the case for inhibition. Cognitive function was not correlated with hearing ability (each p ≥ 0.13). The present results make an approach to establish reference data for a comprehensive non-auditory test battery in a large sample of elderly hearing-impaired people which can be used as a simple tool to better contextualise cognitive performance beyond mean and median scores.

SARS-CoV-2's brain impact: revealing cortical and cerebellar differences via cluster analysis in COVID-19 recovered patients.

COVID-19 is a disease known for its neurological involvement. SARS-CoV-2 infection triggers neuroinflammation, which could significantly contribute to the development of long-term neurological symptoms and structural alterations in the gray matter. However, the existence of a consistent pattern of cerebral atrophy remains uncertain. Our study aimed to identify patterns of brain involvement in recovered COVID-19 patients and explore potential relationships with clinical variables during hospitalization. In this study, we included 39 recovered patients and 39 controls from a pre-pandemic database to ensure their non-exposure to the virus. We obtained clinical data of the patients during hospitalization, and 3months later; in addition we obtained T1-weighted magnetic resonance images and performed standard screening cognitive tests. We identified two groups of recovered patients based on a cluster analysis of the significant cortical thickness differences between patients and controls. Group 1 displayed significant cortical thickness differences in specific cerebral regions, while Group 2 exhibited significant differences in the cerebellum, though neither group showed cognitive deterioration at the group level. Notably, Group 1 showed a tendency of higher D-dimer values during hospitalization compared to Group 2, prior to p-value correction. This data-driven division into two groups based on the brain structural differences, and the possible link to D-dimer values may provide insights into the underlying mechanisms of SARS-COV-2 neurological disruption and its impact on the brain during and after recovery from the disease.

Is Education Level a Modulation Factor of Cognitive Abilities in Older Individuals?

Purpose: Similar to bilingualism, musical abilities, socio-economic status, and physical activities; education level also plays a contributing factor to cognitive reserve in an individual. Literature suggests that educational level and years of schooling enhance cognitive development and also show a correlation with better Intelligence Quotient. It is important to consider the level of education and its relationship with cognitive abilities particularly assessed on standardized cognitive tests which were not considered in earlier research.Methods: The present study recruited 25 native Kannada speakers aged 50 to 70 years and divided them into two groups based on level of education (lower education and higher education group). All the participants were assessed on Cognitive Linguistic Assessment Protocol (CLAP)-Kannada (Kamath &amp; Prema, 2001). The performance scores were tabulated and analyzed across all the domains of the test.Results: Descriptive statistics highlighted that the higher education group had greater overall scores and also across the domains compared to their counterparts. Inferential statistics utilizing the Mann-Whitney U test found a significant difference between the two groups on overall performance and also across the domains with high effect size. Both groups performed poorly in the organization domain, attributed to task demands that need a greater level of processing skills.Conclusions: The current study highlights that higher education levels influence better cognitive function and that this effect persists with age as compared to the lower education levels group indicating higher educational levels can help an individual to resist the effects of the aging process on cognitive function decline.

Early Detection of Amyloid-Related Changes in Memory among Cognitively Unimpaired Older Adults with Daily Digital Testing.

This study was undertaken to determine whether assessing learning over days reveals Alzheimer disease (AD) biomarker-related declines in memory consolidation that are otherwise undetectable with single time point assessments. Thirty-six (21.9%) cognitively unimpaired older adults (aged 60-91 years) were classified with elevated β-amyloid (Aβ+) and 128 (78%) were Aβ- using positron emission tomography with 11C Pittsburgh compound B. Participants completed the multiday Boston Remote Assessment for Neurocognitive Health (BRANCH) for 12 min/day on personal devices (ie, smartphones, laptops), which captures the trajectory of daily learning of the same content on 3 repeated tests (Digit Signs, Groceries-Prices, Face-Name). Learning is computed as a composite of accuracy across all 3 measures. Participants also completed standard in-clinic cognitive tests as part of the Preclinical Alzheimer's Cognitive Composite (PACC-5), with 123 participants undergoing PACC-5 follow-up after 1.07 (standard deviation = 0.25) years. At the cross-section, there were no statistically significant differences in performance between Aβ+/- participants on any standard in-clinic cognitive tests (eg, PACC-5) or on day 1 of multiday BRANCH. Aβ+ participants exhibited diminished 7-day learning curves on multiday BRANCH after 4 days of testing relative to Aβ- participants (Cohen d = 0.49, 95% confidence interval = 0.10-0.87). Diminished learning curves were associated with greater annual PACC-5 decline (r = 0.54, p < 0.001). Very early Aβ-related memory declines can be revealed by assessing learning over days, suggesting that failures in memory consolidation predate other conventional amnestic deficits in AD. Repeated digital memory assessments, increasingly feasible and uniquely able to assess memory consolidation over short time periods, have the potential to be transformative for detecting the earliest cognitive changes in preclinical AD. ANN NEUROL 2024;95:507-517.

Augmented reality versus standard tests to assess cognition and function in early Alzheimer’s disease

Augmented reality (AR) apps, in which the virtual and real world are combined, can recreate instrumental activities of daily living (IADL) and are therefore promising to measure cognition needed for IADL in early Alzheimer’s disease (AD) both in the clinic and in the home settings. The primary aim of this study was to distinguish and classify healthy controls (HC) from participants with AD pathology in an early AD stage using an AR app. The secondary aims were to test the association of the app with clinical cognitive and functional tests and investigate the feasibility of at-home testing using AR. We furthermore investigated the test-retest reliability and potential learning effects of the task. The digital score from the AR app could significantly distinguish HC from preclinical AD (preAD) and prodromal AD (proAD), and preAD from proAD, both with in-clinic and at-home tests. For the classification of the proAD group, the digital score (AUCclinic_visit = 0.84 [0.75–0.93], AUCat_home = 0.77 [0.61–0.93]) was as good as the cognitive score (AUC = 0.85 [0.78–0.93]), while for classifying the preAD group, the digital score (AUCclinic_visit = 0.66 [0.53–0.78], AUCat_home = 0.76 [0.61–0.91]) was superior to the cognitive score (AUC = 0.55 [0.42–0.68]). In-clinic and at-home tests moderately correlated (rho = 0.57, p < 0.001). The digital score was associated with the clinical cognitive score (rho = 0.56, p < 0.001). No learning effects were found. Here we report the AR app distinguishes HC from otherwise healthy Aβ-positive individuals, both in the outpatient setting and at home, which is currently not possible with standard cognitive tests.

Environmental exposure to metallic pollution impairs honey bee brain development and cognition

Laboratory studies show detrimental effects of metallic pollutants on invertebrate behaviour and cognition, even at low levels. Here we report a field study on Western honey bees exposed to metal and metalloid pollution through dusts, food and water at a historic mining site. We analysed more than 1000 bees from five apiaries along a gradient of contamination within 11 km of a former gold mine in Southern France. Bees collected close to the mine exhibited olfactory learning performances lower by 36% and heads smaller by 4%. Three-dimensional scans of bee brains showed that the olfactory centres of insects sampled close to the mine were also 4% smaller, indicating neurodevelopmental issues. Our study raises serious concerns about the health of honey bee populations in areas polluted with potentially harmful elements, particularly with arsenic, and illustrates how standard cognitive tests can be used for risk assessment.

Plasma glucose does not influence performance on standard cognitive screening tests in a mixed memory clinic cohort

AbstractBackgroundIt has been shown under experimental conditions that cognitive performance, especially working memory, is impaired in type I and type II diabetes during hyperglycemic and hypoglycemic conditions, perhaps due to altered cerebral glucose metabolism. It is not known if patients with neurodegenerative diseases, who also exhibit pathological cerebral glucose metabolism, are affected in a similar manner by their intrinsic plasma glucose levels. We aimed to test if performance on two standard cognitive screening tests is influenced by intrinsic plasma glucose levels in a memory clinic cohort.MethodIn this retrospective study, we included patients from the Copenhagen Memory Clinic Cohort (CMCC) with an available Mini Mental‐State Examination (MMSE) test score and a plasma glucose measurement performed in conjunction with cognitive testing. Patients were included from the inception of the cohort in 2008 till September 2021. We built linear regression models with MMSE and Addenbrooke’s Cognitive Examination (ACE) test scores as the outcome and plasma glucose as the explaining variable and adjusted models for age, sex and diabetes (plasma glucose measurement &gt; 11.1 mmol/L). We explored non‐linear relationships by adding squared terms to the models and by fitting cubic spline regression models.ResultIn total, 2714 patients had an available MMSE score and a plasma glucose measurement. Patients had a mean age of 71.6 years [range 19‐99] and a baseline plasma glucose level of 5.8 mmol/L [range 2.7‐28.1]. A total of 581 of patients had a plasma glucose level outside normal range (&lt;4.2 or &gt;6.3 mmol/L). A total of 31.2% of the cohort studied had a diagnosis of Alzheimer’s disease (AD). MMSE and ACE total scores were not influenced by plasma glucose in a linear nor in a non‐linear fashion, when we adjusted for age, sex and diabetes. Sub‐group analyses in patients with AD and in patients with cerebrovascular disease showed similar results.ConclusionPlasma glucose levels inside normal range were not shown to influence performance on routinely applied cognitive tests and do not need be taken into consideration when interpreting test results from memory clinic patients.