Brain health in diverse settings: How age, demographics and cognition shape brain function.

Diversity in brain health is influenced by individual differences in demographics and cognition. However, most studies on brain health and diseases have typically controlled for these factors rather than explored their potential to predict brain signals. Here, we assessed the role of individual differences in demographics (age, sex, and education; n = 1298) and cognition (n = 725) as predictors of different metrics usually used in case-control studies. These included power spectrum and aperiodic (1/f slope, knee, offset) metrics, as well as complexity (fractal dimension estimation, permutation entropy, Wiener entropy, spectral structure variability) and connectivity (graph-theoretic mutual information, conditional mutual information, organizational information) from the source space resting-state EEG activity in a diverse sample from the global south and north populations. Brain-phenotype models were computed using EEG metrics reflecting local activity (power spectrum and aperiodic components) and brain dynamics and interactions (complexity and graph-theoretic measures). Electrophysiological brain dynamics were modulated by individual differences despite the varied methods of data acquisition and assessments across multiple centers, indicating that results were unlikely to be accounted for by methodological discrepancies. Variations in brain signals were mainly influenced by age and cognition, while education and sex exhibited less importance. Power spectrum activity and graph-theoretic measures were the most sensitive in capturing individual differences. Older age, poorer cognition, and being male were associated with reduced alpha power, whereas older age and less education were associated with reduced network integration and segregation. Findings suggest that basic individual differences impact core metrics of brain function that are used in standard case-control studies. Considering individual variability and diversity in global settings would contribute to a more tailored understanding of brain function.

Relationship between default mode network and resting-state electroencephalographic alpha rhythms in cognitively unimpaired seniors and patients with dementia due to Alzheimer's disease.

Here we tested the hypothesis of a relationship between the cortical default mode network (DMN) structural integrity and the resting-state electroencephalographic (rsEEG) rhythms in patients with Alzheimer's disease with dementia (ADD). Clinical and instrumental datasets in 45 ADD patients and 40 normal elderly (Nold) persons originated from the PDWAVES Consortium (www.pdwaves.eu). Individual rsEEG delta, theta, alpha, and fixed beta and gamma bands were considered. Freeware platforms served to derive (1) the (gray matter) volume of the DMN, dorsal attention (DAN), and sensorimotor (SMN) cortical networks and (2) the rsEEG cortical eLORETA source activities. We found a significant positive association between the DMN gray matter volume, the rsEEG alpha source activity estimated in the posterior DMN nodes (parietal and posterior cingulate cortex), and the global cognitive status in the Nold and ADD participants. Compared with the Nold, the ADD group showed lower DMN gray matter, lower rsEEG alpha source activity in those nodes, and lower global cognitive status. This effect was not observed in the DAN and SMN. These results suggest that the DMN structural integrity and the rsEEG alpha source activities in the DMN posterior hubs may be related and predict the global cognitive status in ADD and Nold persons.

Association between executive and physical functions in people with Parkinson's disease.

PURPOSE: People with Parkinson's disease (PD) can develop cognitive and physical impairments. There is limited evidence on the association between executive function and physical function in people with PD. OBJECTIVE: We aimed to investigate the association between the executive and physical functions in people with Parkinson's disease (PD) by comparing healthy controls. METHOD: Thirty-three patients diagnosed with PD and 33 healthy controls were included in the study. PD group was divided into two subgroups according to their scores on executive tests as high performers (PD-HPs; n = 17) and low performers (PD-LPs; n = 16). The severity of motor symptoms disease severity, executive function, global cognitive function, reaction time, hand function, functional capacity, physical activity, and balance confidence was assessed by the validated instruments. RESULTS: The PD group had less physical function and executive function compared to healthy controls (p < 0.05). The PD-LPs group had less physical and cognitive function than the PD-HPs group (p < 0.05). The executive functions were significantly correlated with almost all variables in both people with PD and healthy people, and correlations were moderate to strong (p < 0.05). However, the correlation coefficients were relatively higher in people with PD compared to healthy controls. CONCLUSION: There was a significant association between executive and physical function in people with PD. Future studies should be conducted to determine whether the treatment of one of these dysfunctions affects the other.

Age-Related Aspects of Sex Differences in Event-Related Brain Oscillatory Responses: A Turkish Study.

Earlier research has suggested gender differences in event-related potentials/oscillations (ERPs/EROs). Yet, the alteration in event-related oscillations (EROs) in the delta and theta frequency bands have not been explored between genders across the three age groups of adulthood, i.e., 18-50, 51-65, and >65 years. Data from 155 healthy elderly participants who underwent a neurological examination, comprehensive neuropsychological assessment (including attention, memory, executive function, language, and visuospatial skills), and magnetic resonance imaging (MRI) from past studies were used. The delta and theta ERO powers across the age groups and between genders were compared and correlational analyses among the ERO power, age, and neuropsychological tests were performed. The results indicated that females displayed higher theta ERO responses than males in the frontal, central, and parietal regions but not in the occipital location between 18 and 50 years of adulthood. The declining theta power of EROs in women reached that of men after the age of 50 while the theta ERO power was more stable across the age groups in men. Our results imply that the cohorts must be recruited at specified age ranges across genders, and clinical trials using neurophysiological biomarkers as an intervention endpoint should take gender into account in the future.

Reconstructing brain functional networks through identifiability and deep learning.

We propose a novel approach for the reconstruction of functional networks representing brain dynamics based on the idea that the coparticipation of two brain regions in a common cognitive task should result in a drop in their identifiability, or in the uniqueness of their dynamics. This identifiability is estimated through the score obtained by deep learning models in supervised classification tasks and therefore requires no a priori assumptions about the nature of such coparticipation. The method is tested on EEG recordings obtained from Alzheimer's and Parkinson's disease patients, and matched healthy volunteers, for eyes-open and eyes-closed resting-state conditions, and the resulting functional networks are analysed through standard topological metrics. Both groups of patients are characterised by a reduction in the identifiability of the corresponding EEG signals, and by differences in the patterns that support such identifiability. Resulting functional networks are similar, but not identical to those reconstructed by using a correlation metric. Differences between control subjects and patients can be observed in network metrics like the clustering coefficient and the assortativity in different frequency bands. Differences are also observed between eyes open and closed conditions, especially for Parkinson's disease patients.

Brain clocks capture diversity and disparity in aging and dementia.

Brain clocks, which quantify discrepancies between brain age and chronological age, hold promise for understanding brain health and disease. However, the impact of multimodal diversity (geographical, socioeconomic, sociodemographic, sex, neurodegeneration) on the brain age gap (BAG) is unknown. Here, we analyzed datasets from 5,306 participants across 15 countries (7 Latin American countries -LAC, 8 non-LAC). Based on higher-order interactions in brain signals, we developed a BAG deep learning architecture for functional magnetic resonance imaging (fMRI=2,953) and electroencephalography (EEG=2,353). The datasets comprised healthy controls, and individuals with mild cognitive impairment, Alzheimer's disease, and behavioral variant frontotemporal dementia. LAC models evidenced older brain ages (fMRI: MDE=5.60, RMSE=11.91; EEG: MDE=5.34, RMSE=9.82) compared to non-LAC, associated with frontoposterior networks. Structural socioeconomic inequality and other disparity-related factors (pollution, health disparities) were influential predictors of increased brain age gaps, especially in LAC (R2=0.37, F2=0.59, RMSE=6.9). A gradient of increasing BAG from controls to mild cognitive impairment to Alzheimer's disease was found. In LAC, we observed larger BAGs in females in control and Alzheimer's disease groups compared to respective males. Results were not explained by variations in signal quality, demographics, or acquisition methods. Findings provide a quantitative framework capturing the multimodal diversity of accelerated brain aging.

Brain clocks capture diversity and disparities in aging and dementia across geographically diverse populations.

Brain clocks, which quantify discrepancies between brain age and chronological age, hold promise for understanding brain health and disease. However, the impact of diversity (including geographical, socioeconomic, sociodemographic, sex and neurodegeneration) on the brain-age gap is unknown. We analyzed datasets from 5,306 participants across 15 countries (7 Latin American and Caribbean countries (LAC) and 8 non-LAC countries). Based on higher-order interactions, we developed a brain-age gap deep learning architecture for functional magnetic resonance imaging (2,953) and electroencephalography (2,353). The datasets comprised healthy controls and individuals with mild cognitive impairment, Alzheimer disease and behavioral variant frontotemporal dementia. LAC models evidenced older brain ages (functional magnetic resonance imaging: mean directional error = 5.60, root mean square error (r.m.s.e.) = 11.91; electroencephalography: mean directional error = 5.34, r.m.s.e. = 9.82) associated with frontoposterior networks compared with non-LAC models. Structural socioeconomic inequality, pollution and health disparities were influential predictors of increased brain-age gaps, especially in LAC (R² = 0.37, F² = 0.59, r.m.s.e. = 6.9). An ascending brain-age gap from healthy controls to mild cognitive impairment to Alzheimer disease was found. In LAC, we observed larger brain-age gaps in females in control and Alzheimer disease groups compared with the respective males. The results were not explained by variations in signal quality, demographics or acquisition methods. These findings provide a quantitative framework capturing the diversity of accelerated brain aging.

Coherence in event-related EEG oscillations in patients with Alzheimer's disease dementia and amnestic mild cognitive impairment.

Objectives Working memory performances are based on brain functional connectivity, so that connectivity may be deranged in individuals with mild cognitive impairment (MCI) and patients with dementia due to Alzheimer's disease (ADD). Here we tested the hypothesis of abnormal functional connectivity as revealed by the imaginary part of coherency (ICoh) at electrode pairs from event-related electroencephalographic oscillations in ADD and MCI patients. Methods The study included 43 individuals with MCI, 43 with ADD, and 68 demographically matched healthy controls (HC). Delta, theta, alpha, beta, and gamma bands event-related ICoh was measured during an oddball paradigm. Inter-hemispheric, midline, and intra-hemispheric ICoh values were compared in ADD, MCI, and HC groups. Results The main results of the present study can be summarized as follows: (1) A significant increase of midline frontal and temporal theta coherence in the MCI group as compared to the HC group; (2) A significant decrease of theta, delta, and alpha intra-hemispheric coherence in the ADD group as compared to the HC and MCI groups; (3) A significant decrease of theta midline coherence in the ADD group as compared to the HC and MCI groups; (4) Normal inter-hemispheric coherence in the ADD and MCI groups. Conclusions Compared with the MCI and HC, the ADD group showed disrupted event-related intra-hemispheric and midline low-frequency band coherence as an estimate of brain functional dysconnectivity underlying disabilities in daily living. Brain functional connectivity during attention and short memory demands is relatively resilient in elderly subjects even with MCI (with preserved abilities in daily activities), and it shows reduced efficiency at multiple operating oscillatory frequencies only at an early stage of ADD. Supplementary Information: The online version contains supplementary material available at 10.1007/s11571-022-09920-0.

Normalized Theta but Increased Gamma Activity after Acetylcholinesterase Inhibitor Treatment in Alzheimer's Disease: Preliminary qEEG Study.

Acetylcholinesterase inhibitors (AChE-I) are the core treatment of mild to severe Alzheimer's disease (AD). However, the efficacy of AChE-I treatment on electroencephalography (EEG) and cognition remains unclear. We aimed to investigate the EEG power and coherence changes, in addition to neuropsychological performance, following a one-year treatment. Nine de-novo AD patients and demographically-matched healthy controls (HC) were included. After baseline assessments, all AD participants started cholinergic therapy. We found that baseline and follow-up gamma power analyzes were similar between groups. Yet, within the AD group after AChE-I intake, individuals with AD displayed higher gamma power compared to their baselines (P < .039). Also, baseline gamma coherence analysis showed lower values in the AD than in HC (P < .048), while these differences disappeared with increased gamma values of AD patients at the follow-up. Within the AD group after AChE-I intake, individuals with AD displayed higher theta and alpha coherence compared to their baselines (all, P < .039). These increased results within the AD group may result from a subclinical epileptiform activity. Even though AChE-I is associated with lower mortality, our results showed a significant effect on EEG power yet can increase the subclinical epileptiform activity. It is essential to be conscious of the seizure risk that treatment may cause.

A Real Environment Based Virtual Reality Psychosocial Treatment May Help Patients with Schizophrenia to Increase Social Functioning: A Preliminary Study. / Gerçek Çevre Temelli Sanal Gerçeklik Psikososyal Tedavisi Sizofreni Hastalarinin Sosyal Islevlerinin Artmasina Yardimci Olabilir: Bir Ön Çalisma.

disorders. The aim of the study is to investigate the impact of the VR Psychosocial Treatment Program (PTP) on psychosocial functioning and symptoms in people with schizophrenia. METHOD: Seven schizophrenia patients who have been admitted to the Schizophrenia Outpatient Unit of Dokuz Eylül University School of Medicine and met the diagnosis of schizophrenia according to DSM-V diagnostic criteria were included in the study. Psychosocial functionality level was assessed by PSP (Personal and Social Performance Scale), positive and negative symptom severity with PANSS (Positive and Negative Syndrome Scale), and social skills with SSC (Social Skills Checklist). VRPTP was continued for a total of 10 sessions and twice a week during five weeks. In this study, a real-environment-based VR-PTP for schizophrenia patients was developed. In the sessions, there were different realenvironment- based VR contents including social interaction components such as cafe, market, bazaar, public transportation. RESULTS: There was a statistically significant difference between the PSP scores before and after the VR application (p=0.018). None of the patients reported motion sickness during VR sessions due to the immersive nature of VR. There was no significant difference between pre and post VR PANSS total and subscale scores. CONCLUSION: In this preliminary study, we discovered that realenvironment- based VR-PTP is effective for improving the social skills of patients with schizophrenia. Cognitive enhancement programs and psychosocial functionality therapies may be carried out using virtual reality in the near future. VR can assist patients in coping with their symptoms and day-to-day challenges.

Attitudes toward pre-symptomatic screening for Alzheimer's dementia in five European countries: a comparison of family members of people with Alzheimer's dementia versus non-family members.

Introduction: Pre-symptomatic screening is getting more attention in healthcare as it detects the risk for developing neurodegenerative diseases like Alzheimer's disease (AD), which is very useful for treatment or prevention. AD screening could play an important role in individuals with at least one affected first-degree relative, but also without family history. As the demand for screening is rising worldwide, it is important to consider possible cross-cultural differences in attitudes toward pre-symptomatic screening in order to tailor healthcare services to the needs of each country. Objective: This study aims to investigate the attitudes of family members and non-family members of people with dementia toward pre-symptomatic screening and explore possible differences in attitudes across five European countries (Belgium, Germany, Greece, Spain, Turkey) using translated versions of the "Perceptions regarding pRE-symptomatic Alzheimer's Disease Screening" questionnaire (PRE-ADS). Methods: The multicultural sample (N = 650) was recruited from samples that were previously used in validation studies of the translated PRE-ADS versions. The subscale "Acceptability of Screening", consisting of five PRE-ADS items to specifically explore willingness to undergo screening, was created. Ιnternal consistency was measured, and structural validity was determined using Confirmatory Factor Analysis (CFA). Group comparisons were performed to investigate differences in attitudes toward pre-symptomatic AD screening regarding family history and country of origin using the PRE-ADS and the "Acceptability of Screening" mean scores. Results: Construct validity was acceptable for the PRE-ADS. Both the PRE-ADS (α = 0.76) and its subscale "Acceptability of Screening" (α = 0.90) had good internal consistency. Overall, 56.9% of the total sample expressed a positive intention toward pre-symptomatic AD screening. T-tests showed significantly higher mean scores of participants with an affected family member. An international comparison revealed differences in the "Acceptability of Screening" mean score across the five European countries. No cross-cultural differences were found for the PRE-ADS mean score after adjusting for confounding variables. Conclusion: The PRE-ADS and its subscale are reliable tools for assessing pre-symptomatic AD screening attitudes. Variations in the acceptability of screening seem to be linked to family history and cultural influences. Further research with larger samples is needed to explore underlying relationships.

The reliability of P300 and the influence of age, gender and education variables in a 50 years and older normative sample.

OBJECTIVES: The present study aims to investigate the effects of age, gender, and level of education on P300 in a healthy population, aged 50 years and over; and determine the reliability metrics for different conditions and measurement methods. METHOD: Auditory and visual oddball recordings of 171 healthy adults were investigated. A fully automated preprocessing was applied to elicit ERP P300. Maximum peak amplitude, latency and mean amplitudes were measured. Data were stratified by age, gender, and education to determine group-level differences by using repeat measures of ANOVA. The internal consistency of P300 was calculated by a split-half method using odd-even segments. Test-retest reliability was assessed by calculating the intraclass correlation coefficient (ICC). RESULTS: Maximum peak P300 amplitudes were higher in the 50-64 years age group compared to the >65 years age group; and females showed increased P300 amplitudes compared to males. P300 measures showed fair to good internal consistency and poor to good test-retest reliability. CONCLUSION: Age and gender should be taken into account when designing ERP studies with elderly individuals. P300 showed good internal consistency in general, between gender groups and age groups. Long-term test-retest reliability was lower but acceptable. These findings can be interpreted as the strength of P300 by being an objective and reliable method independent of cultural differences. Here we underline several factors that may affect P300 measures and discuss other possible factors that should be standardized for P300 to be used in clinical settings.

Validity, Reliability and Normative Data of the Stroop Test Çapa Version. / Stroop Testi Çapa Formu’nun Geçerlik-Güvenirlik ve Norm Çalismasi.

OBJECTIVE: The Stroop test Çapa version does not have normative data, despite its extensive use in clinical and research settings to assess executive functions. The aim of the present study was to test the validity and reliability of the Stroop test Çapa version and to establish stratified normative data in individuals aged between 18-83 years. METHOD: The norm determination phase of the study included 541 healthy participants, stratified by age, education, and gender. The relative contributions of the demographic variables on the completion times of Stroop subtests were assessed with multiple linear regression analysis. The main effects of age, education and gender variables and of interactions between these on the completion times of subtests were investigated with 6x3x2 ANOVA design. In addition, the concurrent validity, test-retest reliability and internal consistency of the test were examined. RESULTS: Multiple linear regression models that included age and education accounted for 23-42% of the completion time variances of all subtests. In the factorial ANOVA, main effects, as well as interaction effects of age and education were found on all subtests. For all Stroop subtests, the completion times were the shortest for the individuals in the 18-29 age group with the highest education level and longest for the individuals in the 70-83 age group with the lowest education level. The test demonstrated acceptable internal consistency and high test-retest reliability. CONCLUSION: Normative data of the Stroop Test Çapa Version were provided for the assessment of executive functions in young and middleaged adults and elderly population.

Timed Up and Go Test With a Cognitive Task: Correlations With Neuropsychological Measures in People With Parkinson's Disease.

Background The Timed Up and Go (TUG) test is a simple and widely used clinical test for the assessment of lower extremity function, balance, mobility, and fall risk in various populations. The TUG has been found as a valid and reliable measure in people with Parkinson's disease (PD). Besides, the addition of a cognitive task to the TUG (TUG-cognitive) enhances predictive validity related to fall risk in people with PD. However, further investigation is needed about the correlations of the TUG-cognitive test with neuropsychological measures in people with PD. Methods Thirty-three people with PD [modified Hoehn and Yahr scale, median (min-max)=2.5 (1.0-3.0)] participated in this cross-sectional study. The TUG was administered in the traditional way and with a cognitive task (counting backward by three from any number between 20 and 100). Neuropsychological measures included the Montreal Cognitive Assessment (MoCA), Trail Making Test (TMT), and the Simple Reaction Time (SRT) test for stepping. The self-reported number of falls in the last six months was also recorded. Results The TUG-cognitive [13.1 (SD=8.5) seconds] was significantly longer than the TUG-traditional [12.2 (SD=8.1) seconds] (p<0.01). The TUG-cognitive significantly correlated with the MoCA [(rho=-0.712), TMT part A (TMT-A; rho=0.722), TMT part B (TMT-B; rho=0.694), SRT (rho=0.794), and number of falls (rho=0.960)] (p<0.01). The TUG-traditional also significantly correlated with the MoCA (rho=-0.682), TMT-A (rho=0.684), TMT-B (rho=0.746), SRT (rho=0.755), and number of falls (rho=0.702) (p<0.01). Conclusion Both the TUG-cognitive and TUG-traditional strongly correlated with neuropsychological measures; while the correlations were slightly stronger for the TUG-cognitive, the difference was not significant. The TUG-cognitive can be used in the clinical practice as a simple and more informative alternative to the TUG-traditional in people with PD.

Electrophysiological and neuropsychological outcomes of severe obstructive sleep apnea: effects of hypoxemia on cognitive performance.

Obstructive sleep apnea syndrome (OSAS) is a sleep disorder characterized with upper airway obstructions. Some studies showed cognitive and electrophysiological changes in patients with OSAS; however, contradictory results were also reported. The purpose of the present study was twofold: (1) to investigate cognitive changes in severe OSAS patients by using neuropsychological tests and electrophysiological methods together, (2) to investigate influence of hypoxemia levels on cognition. Fifty-four severe OSAS patients and 34 age-, gender- and education matched healthy subjects were participated. OSAS patients were further divided into two subgroups according to minimum oxygen saturation levels. All participants underwent a detailed neuropsychological test battery. A classical visual oddball task was used to elicit ERP P300 and mean P300 amplitudes were measured from Fz, Cz and Pz electrode sites. OSAS patients showed reduced mean P300 amplitudes up to 43-51% on all electrode sites compared to healthy controls. Subgroup analysis revealed significant differences in neuropsychological test scores between healthy controls and high hypoxemia OSAS group, as well as between low and high hypoxemia groups. Moreover, both low and high hypoxemia OSAS groups had lower P300 amplitudes compared with healthy controls. P300 amplitudes showed a gradual decline in parallel with increasing hypoxemia severity; however, the difference between high and low hypoxemia OSAS groups did not reach significance. Moderate correlations were found between sleep parameters, neuropsychological test scores and P300 amplitudes. These results suggest that electrophysiological measures could be better indicators of cognitive changes than neuropsychological tests in OSAS, particularly in mildly affected patients.

Demonstration of Early Cognitive Impairment in Parkinson's Disease with Visual P300 Responses.

INTRODUCTION: Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease. Cognitive changes in PD are less observable than motor symptoms; thus, research on cognitive processes, which are known to be impaired from the early stages of PD, is minimal. The purpose of this study is to research the brain dynamics of cognitively normal PD patients and healthy elderly controls using event-related potentials (ERPs) and to evaluate their relationships with neuropsychological tests. METHODS: Eighteen cognitively normal PD patients and 18 age-, gender-, and education-matched healthy controls were included in the study. Detailed neuropsychological tests were applied to all participants. Electroencephalography (EEG) was performed according to the international 10-20 system, and a classical visual oddball paradigm was used in the experiments. ERP responses in the 0.5 to 25 Hz frequency range were examined. P300 amplitude and latency values were measured from the F3, Fz, F4, C3, Cz, C4, P3, Pz, P4, O1, Oz, and O2 electrode sites. In addition, the correlations between P300 responses and neuropsychological test scores were analyzed. RESULTS: Significant differences were found between the P300 amplitudes of cognitively normal PD patients and healthy elderly controls [F(1,31)=9.265; p=0.005]. P300 amplitudes were significantly lower for PD patients at the F3, FZ, Cz, C4, Pz, and P4 electrode sites than for healthy elderly controls. Moderate correlations were found between Stroop test score and P4 amplitude, digit span forward and C3 and Pz amplitude, and digit span backward and O1 amplitude. CONCLUSION: The major finding of this study was the detection of cognitive changes by electrophysiological methods in PD patients who were indicated to be cognitively normal by neuropsychological tests. These finding suggests that cognitive changes in PD patients, which are not yet reflected in neuropsychological tests, may be detected by electrophysiological methods in earlier stages.