Predictors Of Cognitive Performance Research Articles

The prevalence and clinical correlation factors of cognitive impairment in patients with major depressive disorder hospitalized during the acute phase.

This study aimed to investigate the prevalence of cognitive impairment among patients with major depressive disorder (MDD) hospitalized during the acute phase and to analyze the in-depth association between this cognitive impairment and clinical correlation factors. In this cross-sectional study, we recruited 126 patients aged between 18 and 65 years who were diagnosed with MDD. All these patients were inpatients from the Department of Psychiatry at the Second People's Hospital of Hunan Province. We employed a series of assessment tools, including the Pittsburgh Sleep Quality Index (PSQI), the 16-item Dysfunctional Beliefs and Attitudes about Sleep Scale (DBAS-16), the Pre-sleep Arousal Scale (PSAS), the Morningness-Eveningness Questionnaire (MEQ), the Hamilton Anxiety Rating Scale (HAMA), and the 17-item Hamilton Depression Rating Scale (HAMD-17). The patients were divided into a cognitive impairment group and a non-cognitive impairment group based on their scores on the Montreal Cognitive Assessment Scale (MoCA). Through Spearman's correlation analysis, we explored the correlation between the total MoCA score and the score of each factor. Additionally, we utilized binary logistic regression analysis to investigate the relationship between cognitive impairment and clinically relevant factors in MDD patients hospitalized during the acute phase and plotted ROC curves to evaluate their clinical efficacy. In this study, we found that the prevalence of cognitive impairment among MDD patients hospitalized during the acute phase was as high as 63.49%. Through statistical analysis, we observed significant differences between the cognitive impairment group and the non-cognitive impairment group in terms of age, place of residence, education level, and HAMD-17 scores. In the Spearman correlation analysis, we noted the following trends: visuospatial and executive abilities were negatively correlated with the HAMD-17 score (P < 0.05); naming ability was positively correlated with the PSAS score but negatively correlated with the MEQ score (P < 0.05); memory was also negatively correlated with the MEQ score (P < 0.05); attention was negatively correlated with the HAMA score; and abstract cognitive ability was negatively correlated with the MEQ score (P < 0.05). Through binary logistic regression analysis, we further revealed the relationship between cognitive impairment and factors such as living in a rural area (OR = 2.7, 95% CI = 1.083-6.731, P < 0.05), increased age (OR = 1.049, 95% CI = 1.013-1.087, P < 0.01), and the HAMD-17 score (OR = 1.10295, 95% CI = 1.031-11.79, P < 0.01). Additionally, ROC curve analysis demonstrated a significant correlation between the HAMD-17 score and the prediction of cognitive function in MDD patients hospitalized during the acute phase (P < 0.001). Specifically, the AUC for the HAMD-17 score was 0.73, with an optimal cut-off value of 19.5, sensitivity of 70.0%, and specificity of 63.0%. Furthermore, the AUC for age was 0.71, with an optimal cut-off value of 33.5, sensitivity of 59.0%, and specificity of 80.0%. This study indicates that MDD patients hospitalized during the acute phase have a higher prevalence of cognitive impairment. This phenomenon reflects a significant correlation between clinical factors such as age, sleep-related characteristics, and the severity of depression with cognitive impairment. Therefore, regular assessment of cognitive function in MDD patients and early intervention may be crucial for the treatment and prognosis of the disease.

Immune Response and Cognitive Impairment in Post-COVID Syndrome: A Systematic Review

BackgroundAltered immune response and cognitive difficulties have been demonstrated in studies of post-COVID syndrome, including differences in immune status and cognitive functioning in the months following infection. This review aimed to examine immune status and cognitive differences in post-COVID syndrome 12 or more weeks after COVID-19 infection. A further aim of this review was to explore a link between immune response and the cognitive deficits observed in this group. MethodsA systematic review was carried out using PubMed, PsychInfo, EMBASE, and Web of Science electronic databases of observational studies 12+ weeks after COVID-19 infection, with assessment of immune status and cognitive function in post-COVID syndrome samples. This review protocol was recorded on PROSPERO with registration number CRD42022366920. ResultsFollowing eligibility screening, 11 studies met inclusion criteria and were selected for our review. Six of eight studies that examined between-group differences in specific domains suggested impaired cognition in the post-COVID syndrome population, with the domain of executive function particularly affected. Of 11 studies with immune data, 7 studies reported increased markers of inflammation in the post-COVID syndrome group, when compared with an age- and sex-matched “healthy control” sample, or population norms. Finally, when immune function and cognition are examined together, 6 studies presented results indicating a significant association between elevated immune response and cognitive function in post-COVID syndrome. ConclusionThis review highlights the frequency of cognitive difficulties months after COVID-19 infection and explores heightened immune response as a predictor of this change. Six studies suggest that immune status is a predictor of cognitive function, examining a marker of immune function and objective cognitive performance at 12 or more weeks following infection. Future studies of cognitive function in post-COVID syndrome are needed to explore this relationship and underlying mechanisms leading to changes in cognitive performance.

The role of family health, socio-economic status, and heritability of neurodevelopmental disorders in the severity of cognitive dysfunctions in school-age children with ADHD

Introduction and objective: Little is known about the association between socioeconomic status, alcohol and tobacco use, and specific cognitive functions, like attention, working memory or executive functions in attention-deficit/hyperactivity disorder. We aimed to determine if socioeconomic adversity and unhealthy family behaviours are predictors of cognitive functions in children with attention-deficit/hyperactivity disorder. Materials and methods: We tested 176 Polish children with attention-deficit/hyperactivity disorder aged 10–13 using the PU1 Battery of Cognitive Functions, while the children’s parents completed a questionnaire on socioeconomic status and alcohol and tobacco use at home during their child’s life stages. We applied cluster analysis of family types and moderation analysis that tested the heritability of neurodevelopmental disorders in family interactions. Results: We identified three family types that raise children with attention-deficit/hyperactivity disorder: 1) families with higher socioeconomic status, lower level of unhealthy family behaviours, and average levels of children’s cognitive functioning, 2) families with low socioeconomic status, high level of unhealthy family behaviours, and average levels of children’s cognitive functioning, and 3) families with average socioeconomic status, low level of unhealthy family behaviours and low level of children’s cognitive functioning. We found no statistically significant associations between family predictors, the moderator variable, and cognitive functions in children with attention-deficit/hyperactivity disorder. Conclusions: The results of our study contrast with the large amount of evidence that shows a link between cognitive dysfunctions in children with attention-deficit/hyperactivity disorder and socioeconomic status and alcohol and tobacco use.

Optimizing Detection and Prediction of Cognitive Function in Multiple Sclerosis With Ambulatory Cognitive Tests: Protocol for the Longitudinal Observational CogDetect-MS Study.

Cognitive dysfunction is a common problem in multiple sclerosis (MS). Progress toward understanding and treating cognitive dysfunction is thwarted by the limitations of traditional cognitive tests, which demonstrate poor sensitivity and ecological validity. Ambulatory methods of assessing cognitive function in the lived environment may improve the detection of subtle changes in cognitive function and the identification of predictors of cognitive changes and downstream effects of cognitive change on other functional domains. This paper describes the study design and protocol for the Optimizing Detection and Prediction of Cognitive Function in Multiple Sclerosis (CogDetect-MS) study, a 2-year longitudinal observational study designed to examine short- and long-term changes in cognition, predictors of cognitive change, and effects of cognitive change on social and physical function in MS. Participants-ambulatory adults with medically documented MS-are assessed over the course of 2 years on an annual basis (3 assessments: T1, T2, and T3). A comprehensive survey battery, in-laboratory cognitive and physical performance tests, and 14 days of ambulatory data collection are completed at each annual assessment. The 14-day ambulatory data collection includes continuous wrist-worn accelerometry (to measure daytime activity and sleep); ecological momentary assessments (real-time self-report) of somatic symptoms, mood, and contextual factors; and 2 brief, validated cognitive tests, administered by smartphone app 4 times per day. Our aim was to recruit 250 participants. To ensure standard test protocol administration, all examiners passed a rigorous examiner certification process. Planned analyses include (1) nonparametric 2-tailed t tests to compare in-person to ambulatory cognitive test scores; (2) mixed effects models to examine cognitive changes over time; (3) mixed effects multilevel models to evaluate whether ambulatory measures of physical activity, sleep, fatigue, pain, mood, and stress predict changes in objective or subjective measures of cognitive functioning; and (4) mixed effects multilevel models to examine whether ambulatory measures of cognitive functioning predict social and physical functioning over short (within-day) and long (over years) time frames. The study was funded in August 2021 and approved by the University of Michigan Medical Institutional Review Board on January 27, 2022. A total of 274 adults with MS (first participant enrolled on May 12, 2022) have been recruited and provided T1 data. Follow-up data collection will continue through March 2026. Results from the CogDetect-MS study will shed new light on the temporal dynamics of cognitive function, somatic and mood symptoms, sleep, physical activity, and physical and social function. These insights have the potential to improve our understanding of changes in cognitive function in MS and enable us to generate new interventions to maintain or improve cognitive function in those with MS. ClinicalTrials.gov NCT05252195; https://clinicaltrials.gov/study/NCT05252195. DERR1-10.2196/59876.

Associations between circadian alignment and cognitive functioning in a nationally representative sample of older adults

Proper alignment of activity-rest and light–dark patterns allows for healthy bodily functions to occur at optimal times of the day. Disruptions to this alignment may cause poor sleep as well as physical, mental, and cognitive problems. The purpose of this cross-sectional study was to determine if poorer circadian alignment was associated with decreased cognitive functioning among older (> 60 years) participants in the National Health and Nutrition Examination Survey. We utilized actigraphy-based rest-activity and dark-light measurements to calculate phasor magnitude (strength of circadian alignment coupling) and phasor angle (phase difference between activity-rest and light–dark cycles). Multiple linear regression models were used to determine associations of phasor magnitude and angle with performance in various cognitive tests, including Digit Symbol Substitution Test score (DSSS), CERAD Savings Percentage (CSP), and Animal Fluency Test (AFT) score. The results showed that a lower phasor magnitude (which indicates decreased strength of alignment coupling between rest-activity and dark–light cycles) was significantly associated with decreased DSSS (indicating slower processing speed and poorer working memory) when controlling for many important sociodemographic factors. However, this association became non-significant when accounting for sleep duration and total physical activity. Phasor angle did not have a significant association with any of the cognitive scores. Overall, we provided evidence indicating that circadian alignment may be a predictor of cognitive performance. Future studies should investigate whether improving circadian alignment may improve cognitive function and prevent cognitive decline.

Effective Factors in Cognitive Functions of Patients with Temporal Lobe Epilepsy

Background: Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy and increases the risk of cognitive impairment, negatively impacting the quality of life of affected individuals. Objectives: This study aimed to investigate cognitive function in patients with low socioeconomic status affected by TLE and identify factors influencing such function. Methods: This case-control study, conducted between July 2021 and August 2022, compared the cognitive function of 40 patients affected by TLE to 92 healthy controls. The Montreal cognitive assessment (MoCA) was used for neurocognitive evaluation. Data analysis was performed using SPSS 25.0 for Windows. Results: The mean age of the patient group was 33.35 years, compared to 35.37 years in the control group. Moreover, 70% of patients affected by TLE displayed cognitive impairment and demonstrated lower performance in cognitive functions than the control group (P &lt; 0.05). Significant correlations were identified between overall MoCA scores and several factors, including seizure frequency, educational level, polytherapy, disease duration, and self-esteem scores (P &lt; 0.05). Multivariate analysis revealed that seizure control and higher educational level were statistically significant predictors of overall MoCA scores in patients affected by TLE. Conclusions: In low-income patients affected by TLE, seizure control and a higher educational level emerged as predictors of cognitive performance. These findings underscore the importance of identifying and managing comorbidities and the need for tailored cognitive rehabilitation programs for this population.

Development and validation of a brain fog scale for coeliac disease.

Brain fog is a subjective cognitive impairment commonly reported in coeliac disease. A standardised tool to define and assess it is an important unmet need. To develop a patient-informed tool to assess brain fog in coeliac disease to support clinical care, research and drug development. A pilot online study defined patient descriptors of brain fog. A second study evaluated the factor structure and performance of the scale across two-time points ('Now' and in the 'Past week'). One month later, participants were invited to repeat the study with two online cognitive processing tests, the Stroop task and the trail making test. Among adults with treated coeliac disease, 37 (91.9% F) participated in the pilot study and 510 (88.8% F) in the second study of whom 99 repeated the study 1 month later with 51 completing cognitive testing. The most common brain fog descriptors were 'difficulty focusing', 'difficulty thinking' and 'difficulty finding the right words and communicating'. The 12-item scale reflects 'cognitive impairment' and 'somatic and affective experience' and demonstrates strong psychometric properties. It tracked with patients report of brain fog being present or absent across two-time points. It did not significantly correlate with the cognitive tests. The brain fog assessment and severity scale is the first patient-informed clinical outcomes assessment tool measuring brain fog in coeliac disease. It is brief and validated for two time-based formats. Further research coupling it with biomarker discovery is needed to confirm its validity as a predictor of cognitive performance.

Predictors of Cognitive Functions After Stroke Assessed Using the Wechsler Adult Intelligence Scale: A Retrospective Study.

The mechanism(s) of cognitive impairment remains complex, making it difficult to confirm the factors influencing poststroke cognitive impairment (PSCI). This study quantitatively investigated the degree of influence and interactions of clinical indicators of PSCI. Information from 270 patients with PSCI and their Wechsler Adult Intelligence Scale (WAIS-RC) scores, totaling 18 indicators, were retrospectively collected. Correlations between the indicators and WAIS scores were calculated. Multiple linear regression model(MLR), genetic algorithm modified Back-Propagation neural network(GA-BP), logistic regression model (LR), XGBoost model (XGB), and structural equation model were used to analyze the degree of influence of factors on the WAIS and their mediating effects. Seven indicators were significantly correlated with the WAIS scores: education, lesion side, aphasia, frontal lobe, temporal lobe, diffuse lesions, and disease course. The MLR showed significant effect of education, lesion side, aphasia, diffuse lesions, and frontal lobe on the WAIS. The GA-BP included five factors: education, aphasia, frontal lobe, temporal lobe, and diffuse lesions. LR predicted that the lesion side contributed more to mild cognitive impairment, while education, lesion side, aphasia, and course of the disease contributed more to severe cognitive impairment. XGB showed that education, side of the lesion, aphasia, and diffuse lesions contributed the most to PSCI. Aphasia plays a significant mediating role in patients with severe PSCI. Education, lesion side, aphasia, frontal lobe, and diffuse lesions significantly affected PSCI. Aphasia is a mediating variable between clinical information and the WAIS in patients with severe PSCI.

THE DUAL IMPACT OF EDUCATION AND OCCUPATION ON COGNITIVE FUNCTIONING IN OLDER MEXICAN ADULTS

Abstract Our research investigates the relationships among educational attainment, occupational mental demands, and cognitive functioning in Mexican adults aged 50 and older. We expand on prior studies demonstrating education’s link to cognitive function by examining how the complexity of one’s primary occupation also influences cognitive health. We hypothesize that cognitively demanding work, irrespective of education level, correlates positively with enhanced cognitive performance. Furthermore, we propose an additive effect, wherein high occupational mental demands amplify cognitive functioning beyond education’s influence. Our study uses data from 12,939 participants in the 2012 Mexican Health and Aging Study (MHAS) linked to an occupational database (Occupational Information Network O*NET). Employing generalized linear models to predict a summary cognition score, the findings unveil compelling insights. Both mental processes (β=0.17) and cognitive abilities (β=0.16) required in participants’ main occupations demonstrate positive correlations with cognitive scores (p&amp;lt;.01). Education emerges as a predictor of cognitive performance and had a stronger relationship with cognitive functioning compared to occupational mental demands (β=0.79, p&amp;lt;.01), highlighting the long-lasting effects of education in cognition emphasizing its role in shaping cognitive abilities throughout life. Adjusting for demographic and health factors reaffirms these associations. Moreover, our research introduces an innovative approach by creating an additive score for education and occupational mental demands. Our results reveal that the combined impact of education and mental demands is associated with higher cognitive scores (β=0.97, p&amp;lt;.01). In conclusion, our study presents a novel perspective by demonstrating that a combination of education and occupational mental demands may yield amplified cognitive benefits.

Potentially Cognitive Stimulating Activities and cognitive performance in middle‐age and older adults

AbstractBackgroundLow education attainment is rampant in low‐ and middle‐income countries (LMICs). Considering that education is a protective factor against dementia, engagement in activities promoting learning might be an alternative to the impact of classical schooling. Therefore, we aim to verify if potentially cognitive stimulating activities (PCSAs) could be an alternative to enhance and maintain cognitive performance in middle‐aged and older adults with diverse educational attainment.MethodWe analyzed baseline data from 7,568 participants of the Brazilian Longitudinal Study of Aging (ELSI‐Brazil). We evaluated engagement in PCSAs through questions about currently attending the Open University for older adults program or attending free courses (foreign language, data processing or computer sciences, sewing/tailoring, cooking, or arts). A global cognition regression‐based norms z‐score was computed using episodic memory and fluency tests scores. We performed three linear regression models to verify the association between engagement in PCSAs with cognition. The first unadjusted model with only the PCSAs as a predictor of cognitive performance. The second model was adjusted for sociodemographic characteristics (age, sex/gender, education, and race), and the third model was additionally adjusted for variables related to memory self‐ratings (current performance and perceived decline for the past two years), general health perception, depressive symptoms, and chronic diseases.ResultParticipants had a mean age of 61.5 (±8.98) years, a mean of 6.3 (±4.73) years of schooling, 53.5% of females and 54.9% of Black/Brown (Table 1). Engagement in PCSAs was a predictor of better cognitive performance in model 1 (β = 0.10, CI 95% 0.01;0.18), model 2 (β = 0.10, CI 95% 0.02;0.19) and model 3 (β = 0.10, CI 95% 0.03;0.21) (Table 2).ConclusionOur results suggest that better global cognition might be associated with some socially common and cheaper activities. Despite the study limitations, in a scenario where structured continuing education might not be readily available, these results indicate that PCSAs should be a target of future studies as a potential source of cognitive reserve.

The association of blood‐based biomarkers of neuropathology with cognitive performance and dementia in a diverse, population‐based sample of US adults

AbstractBackgroundThe association of blood‐based biomarkers of neuropathology with cognition and dementia, including potential variation by race/ethnicity (whites, blacks and Hispanics), has not been examined in large, diverse, population‐based samples of adults.MethodThe sample included Health and Retirement Study (HRS) respondents over age 50 with blood‐based neuropathology biomarker, demographic, and cognitive data (n = 4,214). A𝛃‐40, A𝛃‐42, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were measured in plasma (Quanterix Neurology 4‐Plex E kit), and phosphorylated tau (pTau‐181) was measured in serum (Quanterix Advantage V2.0 kit). Cognitive tests included immediate and delayed word recall, serial 7s, and backward counting (total score 0‐27). Dementia classification relied on a diagnostic algorithm previously validated in HRS. Linear and unconditional logistic regressions were weighted to account for sample design and used to model associations between the biomarkers and the cognitive score/dementia classification after controlling for age, sex, and batch effects.ResultAbout 80% of the sample was white, 10% black, and 10% Hispanic. Correlations were modest among pTau‐181, NfL, and GFAP (r = 0.29‐0.46).When the biomarkers were analyzed individually, higher A𝛃‐42/A𝛃‐40 ratio was associated with higher cognitive score among whites. Higher NfL was associated with lower cognitive score in the total sample and in each race/ethnic group (whites, blacks and Hispanics). Higher pTau‐181 was associated with lower cognitive score in the total and white sample. Higher GFAP was related to lower cognitive score in the total, white, and Hispanic samples. In a model that included all four biomarkers, GFAP remained significantly related to cognitive performance in the total sample, and NfL remained significantly related to cognitive performance in the total sample and in each race/ethnic group.When the biomarkers were analyzed individually, higher NfL was associated with higher likelihood of dementia in the total sample. Higher pTau‐181 was associated with higher likelihood of dementia among whites. Higher GFAP was associated with dementia in the total and white samples, alone and in the fully adjusted model with all four biomarkers.ConclusionThese results show the importance of examining blood‐based biomarkers of neuropathology as predictors of cognitive performance and dementia in diverse, population‐based samples.

Unlocking the link: how hippocampal glutathione-glutamate coupling predicts cognitive impairment in multiple sclerosis patients.

Cognitive impairment is a common symptom of multiple sclerosis and profoundly impacts quality of life. Glutathione (GSH) and glutamate (Glu) are tightly linked in the brain, participating in cognitive function. However, GSH-Glu couplings in cognitive brain regions and their relationship with cognitive impairment in relapsing-remitting multiple sclerosis (RRMS) remains unclear. Forty-one RRMS patients and 43 healthy controls underwent magnetic resonance spectroscopy to measure GSH and Glu levels in the posterior cingulate cortex, medial prefrontal cortex and left hippocampus. Neuropsychological tests were used to evaluate the cognitive function. The Glu/GSH ratio was used to indicate the coupling between GSH and Glu and was tested as a predictor of cognitive performance. The results show that RRMS patients exhibited reduced hippocampal GSH and Glu levels, which were found to be significant predictors of worse verbal and visuospatial memory, respectively. Moreover, GSH levels were dissociated from Glu levels in the left hippocampus of RRMS patients. Hippocampal Glu/GSH ratio is significantly correlated with processing speed and has a greater predictive effect. Here we show the hippocampal Glu/GSH ratio could serve as a new potential marker for characterizing cognitive impairment in RRMS, providing a new direction for clinical detection of cognitive impairment.

B - 86 Association of Fronto-Parietal Network White Matter Tract Connectivity with Executive Functioning and Working Memory in a Diverse Sample.

We evaluated whether Fronto-Parietal Network (FPN) connectivity is associated with cognitive performance within an ethnically diverse sample. Linear regression modeling of 50 FPN white matter tract connectivity measures (volume, anisotropy, diffusivity) predicted executive functioning (EF) and working memory (WM) data including Trails Making Test parts A and B (TMTA/TMTB), Digit Span (DSF/DSB/DST), and Digit Symbol Substitution (DSS) in an ethnically diverse sample (n = 2715, African American = 515, Non-Hispanic White = 1096, Mexican American = 1104). Maximum Likelihood Factoring (MLF) controlled for collinearity within connectivity measures. The best predictors of cognitive performance were thickness of the right caudal anterior cingulate (CAC) (p < 0.001 with DSF, DST, DSS) and mean diffusivity of the right superior longitudinal fasciculus (rSLF) (p < 0.001 with DSF, DST, TB). Within cognitive tests, DSF had the greatest number of significant relationships with connectivity measures (mean diffusivity of the superior longitudinal fasciculus, thickness of the right caudal anterior cingulate, and thickness of the right rostral anterior cingulate, each at p < 0.001). Three factors emerged from MLF which each had multiple significant relationships with cognitive task variables. However, variance accounted for was minimal (R2< 0.01). Relationships between FPN white matter tract connectivity with EF and WM scores are replicable in ethnically heterogeneous samples. Both the CAC and rSLF have previously been shown to be implicated in frontoparietal working memory functionality, however the lateralization of the functional relationship shown above appears to be unique to this sample. Further ethnically heterogenous neuroimaging studies are necessary to determine the uniqueness of these findings.

Resting state EEG complexity as a predictor of cognitive performance

Sustained spontaneous activity in the resting state brain represents the intrinsic state of the brain during most cognitive tasks. Electroencephalogram (EEG) measures of the resting state have shown potential as biomarkers for the evaluation of cognitive performance, but there is a lack of validation across health and different diseased populations. This study aims to decode cognitive function from resting-state EEG activity, and demonstrates that nonlinear dynamic features of EEG signals can be used to predict cognitive performance in healthy young adults, elderly adults with mild cognitive impairment (MCI), and patients with major depressive disorder (MDD) using the extreme gradient boosting (XGBoost) prediction model. In particular, the results showed that performance in cognitive task can be predicted by the resting-state EEG-based measures in these three populations (correlation coefficients between predicted values and observed true values were: r=0.39, p < 0.01; r=0.76, p < 0.001; and r=0.40, p < 0.001; respectively). Furthermore, we observed a U-shaped or inverted U-shaped distribution of multiscale fuzzy entropy index (MFEI) in healthy, aging and diseased populations, which symbolizes the law of complexity and health. The results suggest that the dynamic complexity of resting state EEG oscillations can predict certain dimensions of cognitive function in both health and mental illness, and highlights the nonlinear relationship between neurological measures and cognitive health status. These findings may provide insights into the development of treatments to improve cognition.

Microglial activation in the frontal cortex predicts cognitive decline in frontotemporal dementia.

Frontotemporal dementia is clinically and neuropathologically heterogeneous, but neuroinflammation, atrophy, and cognitive impairment occur in all of its principal syndromes. Across the clinical spectrum of frontotemporal dementia, we assess the predictive value of in vivo neuroimaging measures of microglial activation and grey-matter volume on the rate of future cognitive decline. We hypothesised that inflammation is detrimental to cognitive performance, in addition to the effect of atrophy. Thirty patients with a clinical diagnosis of frontotemporal dementia underwent a baseline multi-modal imaging assessment, including [11C]PK11195 positron emission tomography (PET) to index microglial activation, and structural magnetic resonance imaging (MRI) to quantify grey-matter volume. Ten people had behavioural variant frontotemporal dementia, ten the semantic variant of primary progressive aphasia and ten had the non-fluent agrammatic variant of primary progressive aphasia. Cognition was assessed at baseline and longitudinally with the revised Addenbrooke's Cognitive Examination (ACE-R), at an average of 7-month intervals (for an average of ∼2 years, up to ∼5 years). Regional [11C]PK11195 binding potential and grey-matter volume were determined, and these were averaged within four hypothesis-driven regions of interest: bilateral frontal and temporal lobes. Linear mixed-effect models were applied to the longitudinal cognitive test scores, with [11C]PK11195 binding potentials and grey-matter volumes as predictors of cognitive performance, with age, education and baseline cognitive performance as covariates. Faster cognitive decline was associated with reduced baseline grey-matter volume and increased microglial activation in frontal regions, bilaterally. In frontal regions, microglial activation and grey-matter volume were negatively correlated, but provided independent information, with inflammation the stronger predictor of the rate of cognitive decline. When clinical diagnosis was included as a factor in the models, a significant predictive effect was found for [11C]PK11195 BPND in the left frontal lobe (-0.70, p=0.01), but not for grey-matter volumes (p>0.05), suggesting that inflammation severity in this region relates to cognitive decline regardless of clinical variant. The main results were validated by two-step prediction frequentist and Bayesian estimation of correlations, showing significant associations between the estimated rate of cognitive change (slope) and baseline microglial activation in the frontal lobe. These findings support preclinical models in which neuroinflammation (by microglial activation) accelerates the neurodegenerative disease trajectory. We highlight the potential for immunomodulatory treatment strategies in frontotemporal dementia, in which measures of microglial activation may also improve stratification for clinical trials.

Balance performance and grip strength as predictors of cognitive function among community-dwelling older adults in the USA.

To investigate how balance and grip strength predicts the probability of cognitive function impairment (i.e., executive function: mild and mild-to-moderate impairment, and delayed recall) over eight years in community-dwelling older adults in the US, controlling for sex and race/ethnicity. The National Health and Aging Trends Study dataset (2011 - 2018) was employed. Dependent variables included the Clock Drawing Test (Executive Function) and Delayed Word Recall Test. Longitudinal ordered logistic regression examined the association between cognitive function and predictors (i.e., balance and grip strength) over eight waves (n=9800, 1,225 per wave). Those who could complete side-by-side standing and semi-tandem tasks were 33% and 38% less likely to have mild or mild-to-moderate executive function impairment, respectively, relative to those who could not complete these tests. One score decrease in grip strength increased the executive function impairment risk by 13% (Odds Ratio: 0.87, CI: 0.79-0.95). Those who completed the side-by-side tasks were 35% (Odds Ratio: 0.65, CI: 0.44-0.95) less likely to experience delayed recall impairments than those who could not complete this test. With one score decrease in grip strength, the risk of delayed recall impairment was increased by 11% (OR: 0.89, CI: 0.80-1.00). A combination of these two simple tests (i.e., semi-tandem stance and grip strength) can screen for cognitive impairment among community-dwelling older adults to identify people with mild and mild-to-moderate cognitive impairment in clinical settings.

Prolonged duration of post-traumatic amnesia: A sensitive classification for predicting cognitive outcomes in children recovering from traumatic brain injury.

A paucity of data exists regarding the duration of post-traumatic amnesia (PTA) as a predictor of cognitive functioning among children after traumatic brain injury (TBI). The study aimed to assess the relationship between PTA duration and areas of neurocognitive function among the pediatric population in the sub-acute phase of recovery and rehabilitation. Data were collected from medical files on 103 children aged 5.5-16.5 hospitalized at a pediatric rehabilitation department with a diagnosis of moderate-severe TBI (msTBI) between the years 2004-2019. The Children Orientation and Amnesia Test was used to evaluate PTA duration. Measures of high-order cognitive abilities of attention and executive function were collected using the Test of Everyday Attention-Child version (TEA-Ch). Three PTA duration groups were assembled out of a cluster analysis: "Long PTA" (M = 21 days), "Very Long PTA" (M = 47 days), and "Extremely Long PTA" (M = 94 days). Analyses revealed that the "Long PTA" group preformed significantly better than the "Very Long PTA" and "Extremely Long PTA" groups on all TEA-Ch measures, that is, Selective Attention, Attentional Control Switching, and Sustained Attention. This study is the first to demonstrate that PTA duration is a useful predictor of high-order cognitive functions among children with msTBI in the sub-acute phase of recovery and rehabilitation. The findings emphasize the importance of using a more sensitive classification of prolonged PTA durations to improve outcome prediction and allocation of resources to those who can benefit most after severe brain injuries.

Gadget addiction among school-going children and its association to cognitive function: a cross-sectional survey from Bangladesh

BackgroundPeople are becoming more dependent on technology than ever before. Today’s children and adults are heavily plugged into electronics, which raises concerns for their physical and cognitive development. This cross-sectional...

Age-related brain atrophy is not a homogenous process: Different functional brain networks associate differentially with aging and blood factors

Aging is characterized by a progressive loss of brain volume at an estimated rate of 5%per decade after age 40. While these morphometric changes, especially those affecting gray matter and atrophy of the temporal lobe, are predictors of cognitive performance, the strong association with aging obscures the potential parallel, but more specific role, of individual subject physiology. Here, we studied a cohort of 554 human subjects who were monitored using structural MRI scans and blood immune protein concentrations. Using machine learning, we derived a cytokine clock (CyClo), which predicted age with good accuracy (Mean Absolute Error = 6 y) based on the expression of a subset of immune proteins. These proteins included, among others, Placenta Growth Factor (PLGF) and Vascular Endothelial Growth Factor (VEGF), both involved in angiogenesis, the chemoattractant vascular cell adhesion molecule 1 (VCAM-1), the canonical inflammatory proteins interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFα), the chemoattractant IP-10 (CXCL10), and eotaxin-1 (CCL11), previously involved in brain disorders. Age, sex, and the CyClo were independently associated with different functionally defined cortical networks in the brain. While age was mostly correlated with changes in the somatomotor system, sex was associated with variability in the frontoparietal, ventral attention, and visual networks. Significant canonical correlation was observed for the CyClo and the default mode, limbic, and dorsal attention networks, indicating that immune circulating proteins preferentially affect brain processes such as focused attention, emotion, memory, response to social stress, internal evaluation, and access to consciousness. Thus, we identified immune biomarkers of brain aging which could be potential therapeutic targets for the prevention of age-related cognitive decline.

Social isolation and cognitive function in middle aged and older adults in the Wisconsin Alzheimer’s Disease Research Center: Implications for the pandemic

AbstractBackgroundSocial isolation and loneliness contribute to cognitive decline, and social isolation represents a key modifiable risk factor for dementia. Substantial interruptions in social engagement due to the COVID‐19 pandemic have heightened awareness of this issue, but common later‐life events may also reduce social connectedness. The neurocognitive impacts of such disruptions are unclear. Using the validated NIH Emotion Toolbox, we examined perceived social support and changes in perceived support as predictors of cognitive function in a sample of middle aged and older adults.Method672 participants from the Wisconsin Alzheimer’s Disease Research Center (ADRC) completed cognitive tests and Emotion Toolbox questionnaires at 2+ visits between 2017 and 2021 (mean interim = 1.7 years). Predictors comprised t‐scores on three perceived social support scales: Emotional Support, Instrumental Support, and Loneliness. Cross‐sectional analyses examined associations between social support and cognitive outcomes including memory (RAVLT Immediate and Delayed Recall) and processing speed/executive function (Trails A&amp;B times). Using median t scores from the first and last available visit to categorize social support as high or low (for Loneliness, low loneliness was categorized as “high” social support), support over time was classified as stable‐high, stable‐low, or “change” (high‐low or low‐high). Mixed‐effects regression models examined the demographic‐adjusted predictor‐outcome relationships between social support and cognition across visits.ResultIn this ADRC sample (mean age 65.2, SD = 9.2; Table 1), all three social support scores associated cross‐sectionally (Table 2) with Trails A and B performance. Relative to stable‐high participants, those reporting either stable‐low or declines from high to low social support exhibited poorer performance on measures of processing speed/executive function. Conversely, participants in the low‐high group performed comparably on cognitive tests to those in the stable‐high group (Table 3; Figure 1).ConclusionSocial support associated with processing speed/executive function in this sample. Participants who reported a change in social support performed comparably to those with either stable high or stable low support, suggesting that processing speed/executive function associated with social support may be modifiable in the shorter term. These findings underscore the cognitive cost of social isolation and highlight the substantial benefits of maintaining ‐ and improving ‐ social connections among middle aged and older adults.