Cognitive Test Results Research Articles

High altitude modulates concussion incidence, severity, and recovery in young athletes

ABSTRACT Background High altitude may affect concussion, but prior studies are limited . We tested whether high altitude affects sport-related concussion (SRC) incidence, severity, and recovery. Methods Twenty-five thousand eight hundred fifteen baseline and post-injury Immediate Post-Concussion Assessment and Cognitive Testing results were compiled from Florida and Colorado, low (27 m or 62 m) and high (1,640 m or 1,991 m) altitude locations, respectively. Incidence, severity, and recovery of injury were compared between altitudes. Results High altitude was associated with increased suspected concussion incidence (adjusted OR, 2.04 [95% CI, 1.86 to 2.24];P < .0001). However, high altitude was associated with lower concussion severity measured by Severity Index (SI) (adjusted OR, 0.42 [95% CI, 0.37 to 0.49];P < .0001). High altitude was associated with decreased recovery from post-concussive symptoms in the migraine (β, −2.72 [95% CI, −3.31 to −2.13]; P < .0001), cognitive (β, −1.88 [95% CI, −2.40 to −1.36]; P < .0001), and sleep symptom clusters (β, −0.30 [95% CI, −0.52 to −0.08]; P = .007). Athletes with initial SI≥8 showed prolonged neurocognitive dysfunction at high altitude (HR, 1.38 [95% CI, 1.06 to 1.81]; P = .02). Conclusions High altitude was associated with increased suspected concussions and prolonged recovery but less severe initial injury.

The assessment of cognitive function in the German National Cohort (NAKO) – Associations of demographics and psychiatric symptoms with cognitive test performance

Objectives To describe the cognitive test battery of the German National Cohort (NAKO), a population-based mega cohort of 205,000 randomly selected participants, and to examine associations with demographic variables and selected psychiatric and neurological conditions. Methods Initial data from 96,401 participants providing data on the cognitive performance measured by a brief cognitive test battery (12-word list recall task, semantic fluency, Stroop test, digit span backwards) was examined. Test results were summarised in cognitive domain scores using exploratory and confirmatory factor analyses. Associations with sociodemographic and psychiatric factors were analysed using linear regression and generalised additive models. Results Cognitive test results were best represented by two domain scores reflecting memory and executive functions. Lower cognitive functions were associated with increasing age and male sex. Higher education and absence of childhood trauma were associated with better cognitive function. Moderate to severe levels of anxiety and depression, and a history of stroke, were related to lower cognitive function with a stronger effect on executive function as compared to memory. Some associations with cognition differed by German language proficiency. Conclusions The NAKO cognitive test battery and the derived cognitive domain scores for memory and executive function are sensitive measures of cognition.

Improved post-injury cognitive test results: examining invalid baseline ImPACT testing

ABSTRACT Objective Evidence suggests that Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) validity thresholds may not be adequately sensitive to baseline performances that are not representative of an athlete’s full, uninjured cognitive abilities. The true prevalence of this occurrence is unknown. This study used improvement on post-injury testing (i.e., better performance after the athlete has been removed from play due to suspected concussion than at baseline) to assess the frequency of unrepresentative baseline ImPACT assessments. Method Post-injury ImPACT assessments by NCAA athletes with preceding baseline performance that was considered valid using traditional indices were included. Published reliable change indices (RCI) identified acute post-injury composite scores that improved from baseline. Results Of 155 post-injury assessments, 68 (43.9%) exhibited reliable improvement from baseline on at least 1 composite score, even after excluding persons with invalid protocols. Conclusions Prevalence of ImPACT unrepresentative baseline ImPACT performances may be higher than previously estimated, and many individuals may not be detected by current validity indices. Further research is needed to refine assessment and promote player safety.

Personality predictors of cognitive dispersion: A coordinated analysis of data from seven international studies of older adults.

Dispersion in cognitive test performance within a single testing session is proposed as an early marker of poor brain health. Existing research, however, has not investigated factors that may explain individual differences in cognitive dispersion. We investigate the extent to which the Big Five personality traits are associated with cognitive dispersion in older adulthood. To promote transparency and reliability, we applied preregistration and conceptual replication via coordinated analysis. Drawing data from seven longitudinal studies of aging (Ntotal = 33,581; Mage range = 56.4-71.2), cognitive dispersion scores were derived from cognitive test results. Independent linear regression models were fit in each study to examine personality traits as predictors of dispersion scores, adjusting for mean cognitive performance and sociodemographics (age, sex, education). Results from individual studies were synthesized using random effects meta-analyses. Synthesized results revealed that openness was positively associated with cognitive dispersion, 0.028, 95% CI [0.003, 0.054]. There was minimal evidence for associations between cognitive dispersion and the other personality traits in independent analyses or meta-analyses. Mean cognitive scores were negatively associated with cognitive dispersion across the majority of studies, while sociodemographic variables were not consistently associated with cognitive dispersion. Higher levels of openness were associated with greater cognitive dispersion across seven independent samples, indicating that individuals higher in openness had more dispersion across cognitive tests. Further research is needed to investigate mechanisms that may help to explain the link between openness and cognitive dispersion, as well as to identify additional individual factors, beyond personality traits, that may be associated with cognitive dispersion. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Identifying Mild Cognitive Impairment by Using Human–Robot Interactions

Background: Mild cognitive impairment (MCI), which is common in older adults, is a risk factor for dementia. Rapidly growing health care demand associated with global population aging has spurred the development of new digital tools for the assessment of cognitive performance in older adults. Objective: To overcome methodological drawbacks of previous studies (e.g., use of potentially imprecise screening tools that fail to include patients with MCI), this study investigated the feasibility of assessing multiple cognitive functions in older adults with and without MCI by using a social robot. Methods: This study included 33 older adults with or without MCI and 33 healthy young adults. We examined the utility of five robotic cognitive tests focused on language, episodic memory, prospective memory, and aspects of executive function to classify age-associated cognitive changes versus MCI. Standardized neuropsychological tests were collected to validate robotic test performance. Results: The assessment was well received by all participants. Robotic tests assessing delayed episodic memory, prospective memory, and aspects of executive function were optimal for differentiating between older adults with and without MCI, whereas the global cognitive test (i.e., Mini-Mental State Examination) failed to capture such subtle cognitive differences among older adults. Furthermore, robot-administered tests demonstrated sound ability to predict the results of standardized cognitive tests, even after adjustment for demographic variables and global cognitive status. Conclusion: Overall, our results suggest the human–robot interaction approach is feasible for MCI identification. Incorporating additional cognitive test measures might improve the stability and reliability of such robot-assisted MCI diagnoses.

Discrepancy Between Cognitive Test and Brain Imaging Results in Alzheimer's Disease Associated with Diabetes.

Although a large number of studies have been performed on the association between Alzheimer's disease (AD) and type 2 diabetes mellitus (DM), the underlying pathophysiology of AD associated with DM has not been fully elucidated to date. We compared cognitive functions and brain imaging findings between AD patients with and without DM to characterize the association between cognition and imaging findings in AD patients with DM. Cognitive functions and brain imaging findings, including medial temporal lobe atrophy analyzed by magnetic resonance imaging, and hypoperfusion in the parietal, posterior cingulate, and frontal regions analyzed by single-photon emission computed tomography were compared between 126 AD patients without DM ([AD-DM]) and 51 AD patients with DM ([AD+DM]). Factors associated with cognitive-imaging associations, including education, occupation, leisure activity, comorbidity, frailty, and other demographics, were analyzed. The [AD+DM] group showed significantly more severe cognitive dysfunction than the [ADDM] group, despite a similar degree of brain imaging abnormalities. Among the factors associated with cognitive-imaging associations, the level of leisure activity was significantly lower in the [AD+DM] group than in the [AD-DM] group, but no significant differences in other factors were observed between the 2 groups. The cognitive-imaging discrepancy observed in AD patients with DM may be associated with their low cognitive reserve, possibly caused by their low amount of leisure activities. Our findings suggest that lifestyle interventions, including physical, cognitive, and social activities, may reduce cognitive decline in AD patients with DM.

Desain Didaktis Pada Pelajaran al-Qur’an Hadist berdasarkan Analisis Hypothetical Learning Trajectory (HTL) terhadap Learning Obstacle Siswa Kelas XI

This study based on the results of teachers discussions with preliminary data in the form of students’ cognitive test results and class observations. Cognitive tests of students were carried out aiming to see the problems that students often faced in learning Al-Qur’an Hadith. Problem that arise include; 1) students have difficulty memorizing verses and hadith, 2) difficult to master the interpretation and interpretation of the arguments provided in learning, 3) and it is difficult to practice the law of reading (tajwid). This is because learning Al-Qur’an Hadith is theoretical in nature so it necessary to prepare a learning design that is able to facilitate students learning and understanding the concept of Al-Qur’an Hadith. The learning design is based on a hypothetical learning trajectory (HTL) analysis of students cognitive abilities. This research is a descriptive analysis with a participant of 30 students of class XI. The result of study provide information for further research in the development of a didactical design that is hypthesized to improve students understanding in learning the Al-Qur’an and Hadith

발달장애 아동의 운동능력 평가 및 시스템 : 특허출원 10-2021-0165242

Purpose: The present invention has a technical purpose to provide a method and system for evaluating the motor ability of children with developmental disabilities based on their cognitive test and sociality test results.<BR> Method: This invention relates to a technique for evaluating comprehensive motor ability by performing cognitive function test and social function test in children with developmental disabilities, but evaluating an appropriate level of motor performance in consideration of their developmental state.<BR> Results: This invention evaluates exercise performance in children whit developmental disabilities through the following steps, and then using the indoor exercise test equipment in the service server: 1) In Step 1, provide a cognitive test screen to an indoor test terminal to execute a cognitive test on children with developmental disabilities, and generate cognitive test result information based on the response information, 2) in Step 2, provide a sociality test screen from the service server to the corresponding indoor test terminal to run a sociality test for them, and generate sociality test result information based on the response information, and 3) in Step 3, determine the indoor exercise test level based on the cognitive test and sociality test results in the service server.<BR> Conclusion: This exercise evaluation system will be used as an important indicator for the development of effective convergence exercise programs to promote social and cognitive functions of children with developmental disabilities, along with their health improvement.

Validation of UK Biobank data for mental health outcomes: A pilot study using secondary care electronic health records

UK Biobank (UKB) is widely employed to investigate mental health disorders and related exposures; however, its applicability and relevance in a clinical setting and the assumptions required have not been sufficiently and systematically investigated. Here, we present the first validation study using secondary care mental health data with linkage to UKB from Oxford - Clinical Record Interactive Search (CRIS) focusing on comparison of demographic information, diagnostic outcome, medication record and cognitive test results, with missing data and the implied bias from both resources depicted.We applied a natural language processing model to extract information embedded in unstructured text from clinical notes and attachments. Using a contingency table we compared the demographic information recorded in UKB and CRIS. We calculated the positive predictive value (PPV, proportion of true positives cases detected) for mental health diagnosis and relevant medication.Amongst the cohort of 854 subjects, PPVs for any mental health diagnosis for dementia, depression, bipolar disorder and schizophrenia were 41.6%, and were 59.5%, 12.5%, 50.0% and 52.6%, respectively. Self-reported medication records in UKB had general PPV of 47.0%, with the prevalence of frequently prescribed medicines to each typical mental health disorder considerably different from the information provided by CRIS.UKB is highly multimodal, but with limited follow-up records, whereas CRIS offers a longitudinal high-resolution clinical picture with more than ten years of observations. The linkage of both datasets will reduce the self-report bias and synergistically augment diverse modalities into a unified resource to facilitate more robust research in mental health.

The Relationship between Cognitive Performance and Quality of Life in Elite Athletes after Spinal Cord Injury.

Background: The present investigation was designed to determine cognitive performance and quality of life (QoL) in a group of elite athletes who sustained spinal cord injury (SCI). Methods: nine participants suffering a SCI participated in the study. Different cognitive functions were evaluated through the following tests: COWAT, Digit Span, Stroop color–word and QoL through the WHOQoL-BREF scale. Results: Generally, participants positively assessed their overall quality of life and health status. Although the tests conducted indicate reduced cognitive function among the athletes, it did not affect the reduction in QoL. Single correlations between the results of cognitive tests and QoL could be treated as coincidental. Conclusions: Despite the observed decline in selected cognitive functions, the participants positively assessed their quality of life and physical health.Reduced cognitive functioning could be influenced by the impact of sleep-disordered breathing, pain, depressive disorders and medication. This indicates the need for an individualized approach to define the patient’s deficits, needs and best care. Further studies with a larger group of participants are needed.

Sufficiently Elevated Core Body Temperature May Be Necessary to Maintain Cerebral Blood Flow Response throughout the Morning

In comparison to a carbohydrate-rich breakfast, a nutritionally balanced breakfast reportedly leads to a higher core body temperature because of diet-induced thermogenesis (DIT) and also results in higher task performance. This study aimed to examine the relationships among the core body temperature, blood glucose level, cerebral blood flow, and cognitive performance when the core body temperature is raised to a similar extent as in DIT in the morning. This crossover study included 18 male participants who performed four sets of cognitive tests in the morning with four different foot baths and glucose intake conditions. In elevated body temperature (EBT) conditions, the core body temperature was increased by a foot bath at 42˚C or 39˚C, while in low body temperature (LBT) conditions, it was maintained at 35˚C by a foot bath; the participants received no glucose or two intakes of 20-g glucose for each thermal condition. In addition to the core body temperature measurement, the cerebral blood flow in the dorsolateral prefrontal cortex (DLPFC) was measured using near-infrared spectroscopy. Three blood collections were performed to measure the changes in blood glucose levels. The results revealed that in the EBT conditions, the core body temperature remained 0.3˚C - 0.5˚C higher than that at wake-up time, while the glucose intake conditions increased blood glucose levels which remained higher than those during fasting. No significant between-treatment difference was observed in the results of cognitive tests. However, the blood flow in the DLPFC increased during the second test period in the EBT/glucose and LBT/glucose conditions, whereas during the fourth test period, it increased solely in the EBT/glucose condition. Thus, in addition to the blood glucose level, an elevated core body temperature within the physiological range may be needed for long-term maintenance of the cerebral blood flow response.

Personality traits as risk factors for the development of cognitive impairment and affective symptoms in patients with COVID-19

To identify possible associations between premorbid personality traits and cognitive impairment and affective symptoms in patients who have recovered from COVID-19. The study included 30 people with the so-called post-COVID syndrome. The diagnosis of COVID-19 was previously confirmed by laboratory tests in each patient. The control group included 15 healthy individuals. The Hospital Anxiety and Depression Scale was used to assess depression and anxiety. Cognitive function was assessed using the Verbal Fluency Test (VF), the Montreal Cognitive Scale (MOCA), and the Wisconsin Card Sorting Test (WCST). The Munich Personality Test (MRT) and the Toronto Alexithymia Scale (TAS-26) were used to assess premorbid personality characteristics. Multiple stepwise regression analysis was used as the main statistical method to identify the relationship between premorbid personality constructs and cognitive test results and affective and anxiety symptoms. The presence of frustration tolerance in the personality structure reduced the number of incorrect answers (beta coefficient -0.811) in WCST and decreased the delay in responses with positive reinforcement (-0.630), and also reduced the level of depression (-0.465). Extraversion decreased the MOCA test score (-0.675) and increased the percentage of perseverative incorrect answers on the WCST test (0.573). The constructs of adherence to social norms and propensity to isolate lowered the final MOCA score (beta coefficients are -0.725 and -0.527, respectively). The esoteric tendencies construct decreased the latency of positive and negative reinforcement responses in WCST (-0.441 and -0.528, respectively). The severity of alexithymia was positively correlated with depression (beta 0.577), while neuroticism was positively correlated with anxiety (0.737). Low levels of frustration tolerance and esoteric tendencies have negative effects on cognition in COVID-19 survivors, while high levels of these constructs are protective against cognitive decline and depression.

Development and evaluation of serious games for diagnosis and cognitive improvement of patients with mild cognitive impairment: A study protocol

IntroductionEarly diagnosis of cognitive impairment and improving cognitive function of patients with mild cognitive impairment (MCI) are of particular importance for preventing Alzheimer's disease (AD). Health-oriented serious games (SGs) could be innovative tools for evaluating and improving cognitive status. In this study, a SG will be developed to evaluate and improve cognitive status of patients with MCI based on different cognitive aspects of mini-mental state examination (MMSE) and Addenbrooke's cognitive examination-revised version (ACE-R). Furthermore, the SG will be validated and assessed in diagnosing and improving the cognitive status of patients with MCI. Material and methodsThis qualitative and quantitative study includes four steps. In the first step, the literature is reviewed systematically. In the second step, game stories and scenarios are designed for the proposed game series based on the results of step 1 in collaboration with the clinical experts. Then, a game will be designed for the different cognitive aspects of MMSE and ACE-R. The third step includes the technical design and development of the game and usability evaluation. 60 participants in two healthy or patient (who are at the MCI stage) groups will be selected using convenience and purposive sampling methods based on inclusion and exclusion criteria. In the fourth step, evaluation of the serious game for patients with MCI is performed. We will conduct correlation analysis to evaluate the degree of coordination between the game and the cognitive test results. Moreover, we will evaluate the effect of the game on improving cognitive status through a before-after study. ResultsThe correlation between the game and MMSE/ACE-R results will be calculated. Furthermore, the MMSE/ACE-R mean difference before and after playing the game will be examined. The results of machine learning algorithms and indicators such as sensitivity and specificity to evaluate the effectiveness of the game in disease diagnosis will also be reported. ConclusionMedical staff who intend to use SGs for diagnosing MCI can choose the game based on the results of correlation between different games and aspects of psychological tests. Moreover, examining the impact of each game on the cognitive status could help therapists choose games that could improve the cognitive status of people with MCI. The results could also be useful for technical designers who intend to design suitable games for the patients with MCI.

Evaluation of the cognitive performance under hot-humid environments using heart rate variability

The human cognitive performance under hot and humid exposure is a critical issue for people working under hot and humid environments, for the considerations of both their health and safety. In order to find an indicator of the cognitive performance, the electrocardiogram (ECG) data were recorded continuously for 2.5 hours with portable Holter, when participants were exposed to 4 hot-humid environmental conditions and conducting different cognitive tests. The ECG data then were analysed to obtain the HRV indices that were used to establish a relationship with the cognitive test results. Temporal index pNN50 of HRV time domain indices was selected as a biomarker of the cognitive performance in this study. Results showed that the pNN50 responded significantly to the air temperature, while the influences of the cognitive tasks and the exposure time were found to be less significant. Meanwhile, the mean accuracy of the cognitive tasks was found to be positively related to the changes of mean pNN50, but a negatively related relationship between the mean reaction time and the mean pNN50 was observed. Furthermore, a positive relationship between the relative cognitive performance and the pNN50 was obtained, which meant that higher pNN50 responded to the higher cognitive performance. The potential reason could be ascribed to the changes in temperature-related allocation of the mental resources. And the low cognitive performance could be attributed to the rise of the mental fatigue due to the high sympathetic activities that corresponded to the low pNN50. The results revealed that the pNN50 could act as a biomarker of the cognitive performance under hot-humid exposure. The findings gave some implications to the real-time evaluation of the working performance and health of the people working under hot-humid environments.

Показатели человеческого капитала в исследованиях экономического роста: обзор

Quantity and quality of human capital are important components of economic growth. However, assessing the relationship between human capital and growth is complicated both by the multidimensional nature of human capital itself, and by the fact that many of its characteri­stics are difficult to observe and to measure. Economic growth studies use various measures for different aspects of human capital - such as education, experience and health of workers. Choice of a particular measure depends largely on the objectives of the research, available data and established approaches; its motives and implications are often less visible, though.In this paper, I discuss human capital measures that are used in macroeconomic studies. The main ones include quantitative and qualitative characteristics of education, returns to education, cognitive skills test results, work experience and health of workers. Choice of a measure is reflected in differences in estimates of human capital impact on economic growth, ranging from the complete absence of any influence to the fairly high role of human capital as a factor of economic growth. This paper discusses the strengths and weaknes­ses and the peculiarities of the respective measures. Specific research results obtained using various approaches to human capital measurement are presented for illustrative purposes.

A Coordinated Analysis Examining the Association Between Personality Traits and Cognitive Dispersion

Cognitive dispersion is the degree of within-person variation in performance across cognitive tasks at the same testing occasion. Existing literature indicates that cognitive dispersion may be an early marker of poor brain health, dementia and mortality. Limited research, however, has examined individual differences in cognitive dispersion. Although personality traits are associated with individual differences in cognitive functioning, no research has examined personality and cognitive dispersion. In this project, we execute a pre-registered, coordinated analysis of seven diverse, international longitudinal studies of aging (Ntotal=33,581; mean age range=56.4-71.2) to investigate the extent to which the Big Five personality traits are associated with cognitive dispersion. For methodological approach, see /osf.io/wrnjq/. Cognitive dispersion scores were derived from cognitive test results, and independent linear regression models were fit independently in each study to examine personality traits as predictors of dispersion scores, adjusting for mean cognitive performance and socio-demographics (age, sex, education). Results from individual studies were synthesized using random-effects meta-analyses. Results revealed minimal evidence for associations between cognitive dispersion and personality traits in independent analyses or in meta-analyses. Based on the meta-analytic estimates, only higher levels of openness were associated with greater cognitive dispersion. Mean cognitive scores were negatively associated with cognitive dispersion across the majority of studies, indicating that individuals with higher mean performance had less dispersed cognitive scores. Our study contributes to the replicability and transparency efforts characteristic of open science by pre-registering our study and drawing on the collaborative network of the Integrative Analysis of Longitudinal Studies of Aging and Dementia (IALSA).

Factors that influence the emotional impact of memory problems in older adults: A qualitative descriptive study.

Associations among psychological health and memory concerns in older adults are well-established, but much of this research is quantitative. This study examined how memory problems influence emotional well-being in older adults without dementia, and whether this differs by cognitive status and current depressive or anxiety symptoms. A qualitative descriptive design was used to examine our research questions. Community-dwelling older adults without dementia (n=49, Mage =74.5[10.1], 63% women) completed a cognitive assessment, questionnaires and two semi-structured interviews. Content analysis was used to code and categorise the transcribed interview data, then identify themes within and across participant groups. Five themes described the influence of memory problems on emotional well-being: Evoking Emotions, Fearing Future, Undermining Self, Normalising Problems and Adjusting Thinking. Memory problems' impact on emotional well-being varied by current anxiety symptoms, characteristics of the problem and personal experience with dementia. The emotional impact of memory problems tended to differ by affective symptoms, not cognitive status. Older adults who report memory concerns without objective evidence of impairment may be at risk for negative impacts to mental health and well-being. Cognitive screening guidelines should consider best practices for responding to memory concerns when cognitive testing results are normal.

Lower cognitive resilience against brain atrophy in cognitively unimpaired elderly is partly explained by Alzheimer's disease pathology

AbstractBackgroundCognitive resilience refers to processes involved in coping with effects of brain pathology on cognition. Factors contributing to cognitive resilience against brain atrophy are unclear, as there have been few longitudinal studies investigating this. Therefore we aimed to identify factors explaining the discrepancy between brain atrophy and longitudinal cognitive decline. One proposed method of investigating cognitive resilience is a residual approach, which suggests using the variance in cognition not explained by a specified predictor as a measure of resilience.MethodCognitively unimpaired subjects (n=406) from The Swedish BioFINDER Study with magnetic resonance imaging (MRI) and cognitive test results from at least two time points were included. Using FreeSurfer, global cortical thickness was calculated. A cognitive composite score was calculated from Mini Mental State Examination, Alzheimer´s Disease Assessment Scale – Cognitive Subscale delayed word recall, Trail Making Test B, and Animal fluency. For each subject, the beta coefficients for change in cortical thickness and change in cognition over time were calculated. Linear regression was performed between the two beta coefficients, and the residuals were used as a measure of cognitive resilience. Associations were calculated between this resilience measure and baseline demographics, biomarkers of amyloid (cerebrospinal fluid (CSF) β‐amyloid (Aβ) 42/40 ratio), tau (CSF phosphorylated tau (p‐tau)), and vascular (MRI white matter lesion (WML) volume) pathology as well as neurodegeneration (CSF neurofilament light (NfL)). For dichotomous variables (sex and pathologic Aβ42/40 ratio) independent samples t‐tests, and for continuous variables (all other variables) Pearson correlations, were performed.ResultIn univariate models, lower age at baseline, female sex, higher cortical thickness and better cognitive results at baseline were associated with higher cognitive resilience against cortical atrophy, while education was not. Further, pathological Aβ42/40 ratio and higher levels of p‐tau, NfL, and WMLs at baseline were negatively associated with cognitive resilience in univariate analyses. In a multivariable linear regression model, lower baseline cortical thickness, a pathological Aβ42/40 ratio, and higher NfL were significantly associated with worse cognitive resilience (Figure 1, Table 1).ConclusionMarkers of Alzheimer´s disease pathology and neurodegeneration are associated with worse than expected cognitive decline at a given rate of brain atrophy.

Selective affinity of extravasated brain-reactive IgG autoantibodies for pyramidal neurons is linked to brain amyloid beta deposition, neuronal dysfunction, and cognitive decline.

Amyloid beta plaques (APs) containing amyloid beta peptides (Aβ), blood-brain barrier (BBB) breakdown, and progressive cognitive decline are hallmarks of Alzheimer's disease (AD) pathology. Pathophysiological changes that initiate and perpetuate these hallmarks remain unresolved. We hypothesize that chronic extravasation of immunoglobulin Gs (IgGs) and Aβ via chronically impaired BBB promotes their interaction with pyramidal neurons (PNs). This interaction impairs PN function, consequentially initiates and perpetuates these AD-associated hallmarks. We tested our hypothesis associating neurocognitive decline with BBB breakdown in humans and a mouse model. In humans, antemortem neurocognitive status and postmortem BBB breakdown in their Brodmann area 39/40 were analyzed [AD, mild cognitive impairment (MCI), and no cognitive impairment (NCI) subjects, n=15]. Additionally, we tested the association between chronic BBB compromise, Aβ injection, and long-term memory in CD1 mice (10 months, male, n=33) with Pertussis toxin (PT) injection-induced BBB breach. This mouse-model comprised three injection groups: Saline only, PT+Saline, and PT+Aβ42. We used the immunohistochemistry technique and image-analysis software to track and quantify the fate of blood-borne Aβ42 in mouse brain by injecting synthetic, fluorescent-tagged monomeric Aβ42 (F-Aβ42). We used Lashley's III Maze and Water Maze to evaluate the impact of BBB breach and Aβ42 injection on animals' long-term memory. Brodmann areas 39/40 of AD subjects showed a greater incidence and extent of BBB breach than MCI and NCI subjects. Cognitive test results demonstrating reduced cognitive function for Brodmann areas 39/40 correlated with the extent of BBB breach. Likewise, PT+Aβ42 mice exhibited increased BBB permeability and selectively heightened immunoreactivity between PNs and extravasated IgGs compared to other groups. Since these IgGs target "self" epitopes in the brain parenchyma, we refer to this subset of IgGs as brain-reactive autoantibodies (BrAbs). Additionally, in PT+Aβ42 mice, we observed intraneuronal accumulations of F-Aβ42 in cortical and hippocampal PNs and significant impairment in long-term memory. In AD pathogenesis, BBB compromise induces chronic extravasation of BrAbs and Aβ, an event that serves as a mechanistic link that initiates and perpetuates Aβ deposition in PNs. Deposition of Aβ may perturb PN function and lead to progressive cognitive decline.

The association of serum immunoglobulins with cognition and dementia: The Rotterdam Study

AbstractBackgroundChronic neuro‐inflammation has emerged in recent years as important pathological process underlying dementia, including Alzheimer’s disease. Most studies so far have investigated the innate immune system, but the role of the adaptive immune system remains largely unknown. We investigated the association of serum immunoglobulins (IgA, IgG, IgM) as markers of the adaptive immune system with cognitive function and risk of dementia.MethodThis study was embedded in the Rotterdam Study, an ongoing prospective population based cohort study, and included participants with baseline measurements (between 1997 and 2009) of serum immunoglobulins and informed consent for follow‐up. We performed Cox proportional hazard regression analyses to obtain hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between serum immunoglobulins and risk of dementia until 2016 (longitudinal). We performed linear regression analyses to quantify the cross‐sectional association between serum immunoglobulins and cognition summarized into global cognition as well as separate cognitive test scores. Effect estimates are adjusted for age, sex, lifestyle and cardiovascular factors.ResultWe have included 8,768 participants with a mean age of 64 years and of whom 57% are female. Due to non‐proportional hazards, the follow‐up time was divided into two strata (≤10 and &gt;10 years). We found that IgM was associated with a lower risk of dementia after ten years in women (HR: 0.71; 95% CI: 0.58‐0.86). When restricting analyses to participants with immunoglobulin levels within the reference range and excluding users of immunomodulating medication, we found that IgM was associated with a lower risk of dementia after 10 years in the entire population (HR: 0.78; 95% CI: 0.62‐0.97). We furthermore found that higher IgG levels were associated with lower scores of global cognition, Stroop I, and Stroop II (betas ranging from ‐0.01 to ‐0.02; p‐value &lt;0.002 for all).ConclusionHigher IgM levels are associated with a decreased risk of dementia in women and in all participants with reference range immunoglobulin levels. Higher IgG levels are associated with worse cognitive test outcomes. Our results suggest a protective effect of the adaptive immune system on dementia onset, but possibly a reversed effect on cognitive function.