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Recent work suggests that the brain can be conceptualized as a network comprised of groups of sub-networks or modules. The extent of segregation between modules can be quantified with a modularity metric, where networks with high modularity have dense connections within modules and sparser connections between modules. Previous work has shown that higher modularity predicts greater improvements after cognitive training in patients with traumatic brain injury and in healthy older and young adults. It is not known, however, whether modularity can also predict cognitive gains after a physical exercise intervention. Here, we quantified modularity in older adults (N = 128, mean age = 64.74) who underwent one of the following interventions for 6 months (NCT01472744 on ClinicalTrials.gov): (1) aerobic exercise in the form of brisk walking (Walk), (2) aerobic exercise in the form of brisk walking plus nutritional supplement (Walk+), (3) stretching, strengthening and stability (SSS), or (4) dance instruction. After the intervention, the Walk, Walk+ and SSS groups showed gains in cardiorespiratory fitness (CRF), with larger effects in both walking groups compared to the SSS and Dance groups. The Walk, Walk+ and SSS groups also improved in executive function (EF) as measured by reasoning, working memory, and task-switching tests. In the Walk, Walk+, and SSS groups that improved in EF, higher baseline modularity was positively related to EF gains, even after controlling for age, in-scanner motion and baseline EF. No relationship between modularity and EF gains was observed in the Dance group, which did not show training-related gains in CRF or EF control. These results are consistent with previous studies demonstrating that individuals with a more modular brain network organization are more responsive to cognitive training. These findings suggest that the predictive power of modularity may be generalizable across interventions aimed to enhance aspects of cognition and that, especially in low-performing individuals, global network properties can capture individual differences in neuroplasticity.

Numerous studies have examined executive function (EF) abilities in cognitively healthy older adults and those living with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Currently, there are no standard accepted protocols for testing specific EFs; thus, researchers have used their preferred tool, which leads to variability in assessments of decline in a particular ability across studies. Therefore, there is a need for guidance as to the most sensitive tests for assessing EF decline. A search of the most current literature published between 2000 and 2022 on EF studies assessing cognitively healthy older adults and individuals living with MCI and AD was conducted using PubMed/Medline, PsycINFO, Embase, Web of Science, and Google Scholar. Emphasis was placed on the EF's dual-tasking, inhibition, shifting or switching, and working memory updating. Many tasks and their outcomes were reviewed. Of particular importance was the difference in outcomes for tasks applied to the same group of participants. These various EF assessment tools demonstrate differences in effectively identifying decline in EF ability due to the aging process and neurodegenerative conditions, such as MCI and AD. This review identifies various factors to consider in using particular EF tasks in particular populations, including task demand and stimuli factors, and also when comparing differing results across studies.

During aging, physical integrity and cognitive abilities, especially executive function, become compromised, directly influencing the quality of life of the elderly. One good strategy to ensure healthy aging is the practice of physical exercise. Activities to improve aerobic capacity and muscle strength are extremely important in old age. However, some genetic factors can interfere both positively and negatively with these gains. In this context, the polymorphism rs1815739 (R577X) of the α-actinin 3 gene (ACTN-3) is commonly studied and related to muscle phenotype. Thus, the present study aimed to investigate the effect of the ACTN-3 gene polymorphism on the functional fitness (measured by the Senior Fit test) and cognitive capacity (evaluated by the Stroop test) of the elderly (n = 347), both men and women. We did not find the effect of genotype on functional fitness, but we did observed a positive effect of the ACTN-3 gene polymorphism on executive function. The presence of the X allele of the ACTN3 gene in the elderly was related to a better performance in the Stroop test (shorter answer time). Our results showed that ACTN-3 gene polymorphism affects the executive function of the elderly but not their functional fitness.

ObjectiveThis study aims to explore whether body mass index (BMI) level affects the executive function and hippocampal subregion volume of subjective cognitive decline (SCD).Materials and methodsA total of 111 participants were included in the analysis, including SCD (38 of normal BMI, 27 of overweight and obesity) and normal cognitive control (NC) (29 of normal BMI, 17 of overweight and obesity). All subjects underwent the Chinese version of the Stroop Color-Word Test (SCWT) to measure the executive function and a high-resolution 3D T1 structural image acquisition. Two-way ANOVA was used to examine the differences in executive function and gray matter volume in hippocampal subregions under different BMI levels between the SCD and NC.ResultThe subdimensions of executive function in which different BMI levels interact with SCD and NC include inhibition control function [SCWT C-B reaction time(s): F(1,104) = 5.732, p = 0.018], and the hippocampal subregion volume of CA1 [F(1,99) = 8.607, p = 0.004], hippocampal tail [F(1,99) = 4.077, p = 0.046], and molecular layer [F(1,99) = 6.309, p = 0.014]. After correction by Bonferroni method, the population × BMI interaction only had a significant effect on the CA1 (p = 0.004). Further analysis found that the SCWT C-B reaction time of SCD was significantly longer than NC no matter whether it is at the normal BMI level [F(1,104) = 4.325, p = 0.040] or the high BMI level [F(1,104) = 21.530, p < 0.001], and the inhibitory control function of SCD was worse than that of NC. In the normal BMI group, gray matter volume in the hippocampal subregion (CA1) of SCD was significantly smaller than that of NC [F(1,99) = 4.938, p = 0.029]. For patients with SCD, the high BMI group had worse inhibitory control function [F(1,104) = 13.499, p < 0.001] and greater CA1 volume compared with the normal BMI group [F(1,99) = 7.619, p = 0.007].ConclusionThe BMI level is related to the inhibition control function and the gray matter volume of CA1 subregion in SCD. Overweight seems to increase the gray matter volume of CA1 in the elderly with SCD, but it is not enough to compensate for the damage to executive function caused by the disease. These data provide new insights into the relationship between BMI level and executive function of SCD from the perspective of imaging.

BackgroundExecutive function will gradually decline with the increase of age, which will have a negative impact on the quality of life and general health. Exercise intervention can improve executive function and prevent its deterioration, but the evidence from randomized controlled trials is not consistent.AimTo assess the effect of exercise intervention on executive function of healthy middle-aged and elderly people, and briefly describe its mechanism.MethodsA search was conducted using PubMed, Web of science and EBSCO. The searches were limited to English articles published from January 2010 to January 2022. The information is extracted from searched articles included or excluded based on certain criteria.ResultsThe search returned 2,746 records, of which 11 articles were included in the systematic review, and 8 articles were supplemented according to the references included and related reviews. The results show that different types of exercise intervention have positive effects on the executive function of the middle-aged and elderly people. The intervention prescriptions in most studies are executed in medium to low frequency, medium intensity and medium duration, while only 11% of the studies were followed up.ConclusionsThe intervention, which was executed twice a week with 30–60 min single intervention time and over 12 weeks total duration, showed a good intervention effect. Exercise intervention is to improve executive function by affecting the activation of brain network and the synthesis of neurotransmitters.

This is a follow-up study of our previous work, with a specific goal to examine whether older adults are able to maintain or show delayed cognitive and psychosocial benefits of executive function training and physical exercise over a period of 3.5 years on average. Thirty-four participants from the original training study (17 from the executive function training and 17 from the aerobic exercise group) returned and completed a single follow-up session on a set of cognitive and psychosocial outcome measures. The results of the returned follow-up sample showed some significant original training transfer effects in WCST-64 performance but failed to maintain these benefits at the follow-up session. Surprisingly, episodic memory performance showed some significant improvement at the follow-up relative to baseline, signaling delayed benefits. The findings add some novel implications for cognitive training schedule and highlight the possible importance of continuous engagement in long-term cognitive enhancement in healthy older adults.

Episodic memory and executive function are two cognitive domains that have been studied extensively in older adults and have been shown to decline in normally-aging older individuals. However, one of the problems with characterizing cognitive changes in longitudinal studies has been separating effects attributable to normal aging from effects created by repeated testing or practice. In the present study, 166 people aged 65 and older were enrolled over several years and tested at least 3 times at variable intervals (M = 3.2 yrs). The cognitive measures were composite scores. Each composite was made up of five neuropsychological tests, previously identified through factor analysis. For one pair of composite scores, variance attributable to age was removed from each subtest through regression analyses before z-scores were computed, creating two age-corrected composites. A second pair of composites were not age-corrected. Using linear mixed-effects models, we first explored retest effects for each cognitive domain, independent of age, using the age-corrected composites. We then modeled aging effects using the age-uncorrected composites after subtracting out retest effects. Results indicated significant retest effects for memory but not for executive function, such that memory performance improved across the three testing sessions. When these practice effects were removed from the age-uncorrected data, effects of aging were evident for both executive and memory function with significant declines over time. We also explored several individual difference variables including sex, IQ, and age at the initial testing session and across time. Although sex and IQ affected performance on both cognitive factors at the initial test, neither was related to practice effects, although young-older adults tended to benefit from practice to a greater extent than old-older adults. In addition, people with higher IQs showed slower age-related declines in memory, but no advantages in executive function. These findings suggest that (a) aging affects both memory and executive function similarly, (b) higher IQ, possibly reflecting cognitive reserve, may slow age-related declines in memory, and (c) practice through repeated testing enhances performance in memory particularly in younger-older adults, and may therefore mask aging effects if not taken into account.

ObjectiveThe objective of this study was to examine the activation and functional connectivity of the prefrontal and temporal lobe in young and elder people during the Stroop test using functional near-infrared spectroscopy (fNIRS).MethodsA total of 33 healthy volunteers (20 young people, mean age: 23.7 ± 3.9 years; 13 elder people, mean age: 63.9 ± 4.0 years) participated in the study. All subjects were asked to finish the Stroop Color Word Test. The oxygenated hemoglobin concentration (Delta [HbO2]) signals and the deoxygenated hemoglobin (Delta [HbR]) signals were recorded from temporopolar area (TA), pars triangularis Broca's area (Broca), dorsolateral prefrontal cortex (DLPFC), and frontopolar area (FA) by fNIRS. The coherence between the left and right frontotemporal lobe delta [HbO2] oscillations in four frequency intervals (I, 0.6–2 Hz; II, 0.145–0.6 Hz; III, 0.052–0.145 Hz; and IV, 0.021–0.052 Hz) was analyzed using wavelet coherence analysis and wavelet phase coherent.ResultsIn the Stroop test, the young group was significantly better than the elder group at the responses time, whether at congruent tasks or at incongruent tasks (congruent: F = 250.295, p < 0.001; incongruent: p < 0.001). The accuracy of the two groups differed significantly when performing incongruent tasks but not when performing congruent tasks (incongruent: F = 9.498, p = 0.001; congruent: p = 0.254). Besides, only elders show significant activation in DLPFC, Broca, FA, and TA (p < 0.05) during the Stroop test, but young people did not show significant differences. In the functional connectivity of task states, younger people had stronger connections between different brain regions in both the left and right brain compared with the elderly (p < 0.05). In particular, the left and right DLPFC showed stronger connection strength in most of the brain areas. The result suggested that younger people had stronger functional connectivity of brain areas than older people when completing the task.ConclusionAccording to these results, although the cortical activation in the elder people was higher than the young people, the young showed stronger connectivity in most of the brain areas than the elders. Both sides of DLPFC and right Broca area were the most significant cortical activation in Stroop test. It was suggested that the decrease in functional connectivity in the elder people resulted in the atrophy of white matter, to which we should pay more attention.

Numerous studies have examined executive function (EF) abilities in cognitively healthy older adults and those living with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Currently, there are no standard accepted protocols for testing specific EFs; thus, researchers have used their preferred tool, which leads to variability in assessments of decline in a particular ability across studies. Therefore, there is a need for guidance as to themost sensitive tests for assessing EF decline. A search of the most current literature published between 2000 and 2022 on EF studies assessing cognitively healthy older adults and individuals living with MCI and AD was conducted using PubMed/Medline, PsycINFO, Embase, Web of Science, and Google Scholar. Emphasis was placed on the EF's dual-tasking, inhibition, shifting or switching, and working memory updating. Many tasks and their outcomes were reviewed. Of particular importance was the difference in outcomes for tasks applied to the same group of participants. These various EF assessment tools demonstrate differences in effectively identifying decline in EF ability due to the aging process and neurodegenerative conditions, such as MCI and AD. This review identifies various factors to consider in using particular EF tasks in particular populations, including task demand and stimuli factors, and also when comparing differing results across studies. [ABSTRACT FROM AUTHOR]

BackgroundAcute medical illnesses, surgical interventions, or admissions to hospital in older individuals are frequently associated with a delirium. In this cohort study, we investigated the impact of specific cognitive domains and depression before the occurrence of delirium symptoms in an 8-year observation of older non-hospitalized individuals.MethodsIn total, we included 807 participants (48–83 years). Deficits in specific cognitive domains were measured using the CERAD test battery, and depressive symptoms were measured using Beck Depression Inventory and the Geriatric Depression Scale (GDS) before the onset of a delirium. Delirium symptoms were retrospectively assessed by a questionnaire based on the established Nursing Delirium Screening Scale.ResultsFifty-eight of eight hundred seven participants (7.2%) reported delirium symptoms over the 8-year course of the study. Sixty-nine percent (n = 40) of reported delirium symptoms were related to surgeries. In multivariate regression analysis, impaired executive function was an independent risk factor (p = 0.034) for the occurrence of delirium symptoms. Furthermore, age (p = 0.014), comorbidities [captured by the Charlson Comorbidity Index (CCI)] (p < 0.001), and depression (p = 0.012) were significantly associated with reported delirium symptoms.ConclusionEspecially prior to elective surgery or medical interventions, screening for impaired executive function and depression could be helpful to identify patients who are at risk to develop delirium symptoms.

Age-related alterations of functional brain networks contribute to cognitive decline. Current theories indicate that age-related intrinsic brain functional reorganization may be a critical marker of cognitive aging. Yet, little is known about how intrinsic interhemispheric functional connectivity changes with age in adults, and how this relates to critical executive functions. To address this, we examined voxel-mirrored homotopic connectivity (VMHC), a metric that quantifies interhemispheric communication, in 93 healthy volunteers (age range: 19–85) with executive function assessment using the Delis-Kaplan Executive Function System (D-KEFS) scales. Resting functional MRI data were analyzed to assess VMHC, and then a multiple linear regression model was employed to evaluate the relationship between age and the whole-brain VMHC. We observed age-related reductions in VMHC of ventromedial prefrontal cortex (vmPFC) and hippocampus in the medial temporal lobe subsystem, dorsal anterior cingulate cortex and insula in salience network, and inferior parietal lobule in frontoparietal control network. Performance on the color-word inhibition task was associated with VMHC of vmPFC and insula, and VMHC of vmPFC mediated the relationship between age and CWIT inhibition reaction times. The percent ratio of correct design scores in design fluency test correlated positively with VMHC of the inferior parietal lobule. The current study suggests that brain interhemispheric functional alterations may be a promising new avenue for understanding age-related cognitive decline.

A prominent feature of cognitive aging is the decline of executive function (EF) abilities. Numerous studies have reported that older adults perform poorer than younger adults in such tasks. In this cross-sectional study, the effect of age on four EFs, inhibition, shifting, updating, and dual-tasking, was examined in 26 young adults (mean 21.18 years) and 25 older adults (mean 71.56 years) with the utilization of a pair of tasks for each EF. The tasks employed for DT were the Psychological Refractory Period paradigm (PRP) and a modified test for everyday attention, for inhibition the Stroop and Hayling sentence completion test (HSCT), for shifting a task switching paradigm and the trail making test (TMT), and for updating the backward digit span (BDS) task and a n-back paradigm. As all participants performed all tasks, a further aim was to compare the size of the age-related cognitive decline among the four EFs. Age-related decline was observed in all four EFs in one or both of the tasks employed. The results revealed significantly poorer performance in the older adults in the response times (RTs) of the PRP effect, interference score of the Stroop, RT inhibition costs of the HSCT, RT and error-rate shifting costs of the task switching paradigm, and the error-rate updating costs of the n-back paradigm. A comparison between the rates of decline revealed numerical and statistically significant differences between the four EFs, with inhibition showing the greatest decline, followed by shifting, updating, and dual-tasking. Thus, we conclude that with age, these four EFs decline at different rates.

ObjectivesPrior work has demonstrated that executive function training or physical exercise can improve older adults’ cognition. The current study takes an exploratory approach to compare the feasibility and efficacy of online executive function training and low-intensity aerobic exercise for improving cognitive and psychosocial functioning in healthy older adults.MethodFollowing a standard pretest-training-posttest protocol, 40 older adults (aged 65 and above) were randomly assigned to an executive function or a physical training group. A battery of cognitive and psychosocial outcome measures were administered before and after training. During the 10 weeks of self-guided training at home (25–30 min/day, 4 days/week), the executive function training group practiced a set of adaptive online executive function tasks designed by Lumos Labs, whereas the physical training group completed an adaptive Digital Video Disc (DVD)-based low-intensity aerobic exercise program.ResultsTraining transfer effects were limited. Relative to low-intensity aerobic exercise, executive function training yielded cognitive improvement on the 64-card Wisconsin Card Sorting Task (WCST-64), a general executive function measure. Depression and stress levels dropped following both training programs, but this could be driven by decreased stress or excitement in performing the tasks over time.DiscussionThe results revealed limited cognitive benefits of the online executive function training program, specifically to a near transfer test of general executive control. Importantly, the current study supports the feasibility of home-based self-guided executive function and low-intensity physical training with healthy older adults.

Introduction: Recent research has recognized executive dysfunction as another component affected in Primary Progressive Aphasia (PPA). This systematic review aimed to examine what information distinctive neurophysiological markers can provide in the evaluation of executive function (EF) deficits in PPA, and to what effect executive function deficits can be assessed through the characteristics of functional markers. Methods: We conducted a systematic literature search following the PRISMA guidelines across studies that employed neuropsychological assessments and neurophysiological imaging techniques (EEG, MEG; PET, SPECT, fMRI, fNIRS) to investigate executive dysfunction correlates in PPA. Results: Findings from nine articles including a total number of 111 individuals with PPA met our inclusion criteria and were synthesized. Although research on the neural correlates of EF deficits is scarce, MEG studies revealed widespread oscillatory slowing, with increased delta and decreased alpha power, where alterations in alpha, theta, and beta activities were significant predictors of executive function deficits. PET findings demonstrated significant correlations between executive dysfunction and hypometabolism in frontal brain regions. fMRI results indicated elevated homotopic connectivity in PPA patients, with a broader and more anterior distribution of abnormal hippocampal connections of which were associated with reduced executive performance. Conclusion: Our study provides indirect support for the assumption regarding the significance of the frontal regions and inferior frontal junction in executive control and demonstrates that neurophysiological tools can be a useful aid to further investigate clinical-neurophysiological correlations in PPA. [ABSTRACT FROM AUTHOR]

Background: The mechanism of cognitive impairment in hemodialysis patients is multifactorial. The relationship between cerebral blood flow and the decline of cognitive function is poorly understood. Objective: To investigate the association between cerebral blood flow variation and decline of cognitive function in older patients undergoing hemodialysis. Methods: In this prospective observational cohort study of 121 older patients undergoing hemodialysis, we used transcranial Doppler ultrasound (TCD) to measure cerebral arterial mean flow velocity (MFV) throughout dialysis, assessed cognitive function at baseline and 12-month follow-up, and then analyzed associations between MFV and changes on cognitive scores. Results: TCD recordings demonstrated a significant reduction in MFV throughout dialysis, which were significantly correlated with cumulative ultrafiltration volume (rho 0.356, p < 0.001), ΔSBP (rho 0.251, p = 0.005), and ΔMAP (rho 0.194, p = 0.032). Compared with the baseline assessments, cognitive scores of participants at the 12-month follow-up were significantly worsened in global cognition (MOCA), some tests of memory (CFT-memory), executive function (TMT-B, SCWT-C, and SCWT-T), attention/processing speed (SDMT), and visuospatial function (CFT-copy) (p < 0.05). The worsening scores in global cognition (MOCA) (β = 0.066, 95% CI 0.018-0.113, p = 0.007) and some tests of memory (AVLT5) (β = 0.050, 95% CI 0.004-0.097, p = 0.035) and executive function (TMT-B, SCWT-C, SCWT-T) (β = 1.955, 95% CI 0.457--3.453, p = 0.011; β = 0.298, 95% CI 0.112-0.484, p = 0.002 and β = 1.371, 95% CI 0.429-2.303, p = 0.004, respectively) were significantly associated with the reduction of MFV. Conclusion: Hemodialysis may significantly reduce cerebral blood flow in older patients; Repetitive intradialytic decreases in CBF may be one of the mechanisms underlying the decline of cognitive function. [ABSTRACT FROM AUTHOR]

BackgroundPrevious studies have confirmed that physical exercise may be beneficial for brain health, but there is little data on this among older Chinese.ObjectiveThe purpose of this study was to explore the relationship between physical exercise and cognitive impairment, and to explore the possible mechanism by which physical exercise prevents cognitive decline.Materials and methods192 older adults with dementia, 610 older adults with mild cognitive impairment (MCI), and 2,218 healthy older adults were included in the study. Through standardized questionnaires, we obtained their general demographic information (such as gender, age, education, etc.), disease-related information (hypertension and diabetes) and physical exercise information (such as whether they did physical exercise and the frequency of physical exercise, etc.). The mini-mental state examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used to assess their overall cognitive function, while the Wechsler block diagram was used to assess their executive function. Moreover, 164 healthy, randomly selected older adults also underwent brain MRI scans at the same time, and the target brain regions included hippocampus, gray matter, and cerebellar cortex.ResultsBy using stepwise multiple logistics regression analysis, we found that physical exercise was associated with both MCI (p = 0.001*, OR = 0.689, 95%CI: 0.553–0.859) and dementia (p < 0.001*, OR = 0.501, 95%CI: 0.354–0.709), independent of gender, age, education, and other factors. The results of ROC curve showed that the area under the curve of physical exercise in predicting MCI and dementia was 0.551 (p < 0.001*, 95%CI: 0.525–0.577) and 0.628 (p = 0.001*, 95%CI: 0.585–0.671), respectively. The results of partial correlation analysis showed that physical exercise was associated with left cerebellar cortex (r = 0.163, p = 0.023), right cerebellar cortex (r = 0.175, p = 0.015) and Wechsler block diagram score (r = 0.235, p = 0.011). Moreover, the results of linear regression analysis mediation model showed that physical exercise may affect Wechsler block diagram score through influencing the thickness of right cerebellum cortex, and the latter may play a partial mediation effect (indirect B = 0.001, p = 0.045).ConclusionPhysical exercise might be a protective factor for mild cognitive impairment and dementia among the Chinese elderly, and there might be an association among physical exercise, executive function, and the thickness of the cerebellar cortex.

Background: Walking while performing cognitive and motor tasks simultaneously interferes with gait performance and may lead to falls in older adults with mild cognitive impairment (MCI). Executive function, which seems to play a key role in dual-task gait performance, can be improved by combined physical and cognitive training. Virtual reality (VR) has the potential to assist rehabilitation, and its effect on physical and cognitive function requires further investigation. The purpose of this study was to assess the effects of VR-based physical and cognitive training on executive function and dual-task gait performance in older adults with MCI, as well as to compare VR-based physical and cognitive training with traditional combined physical and cognitive training.Method: Thirty-four community-dwelling older adults with MCI were randomly assigned into either a VR-based physical and cognitive training (VR) group or a combined traditional physical and cognitive training (CPC) group for 36 sessions over 12 weeks. Outcome measures included executive function [Stroop Color and Word Test (SCWT) and trail making test (TMT) A and B], gait performance (gait speed, stride length, and cadence) and dual-task costs (DTCs). Walking tasks were performed during single-task walking, walking while performing serial subtraction (cognitive dual task), and walking while carrying a tray (motor dual task). The GAIT Up system was used to evaluate gait parameters including speed, stride length, cadence and DTCs. DTC were defined as 100 * (single-task gait parameters − dual-task gait parameters)/single-task gait parameters.Results: Both groups showed significant improvements in the SCWT and single-task and motor dual-task gait performance measures. However, only the VR group showed improvements in cognitive dual-task gait performance and the DTC of cadence. Moreover, the VR group showed more improvements than the CPC group in the TMT-B and DTC of cadence with borderline significances.Conclusion: A 12-week VR-based physical and cognitive training program led to significant improvements in dual-task gait performance in older adults with MCI, which may be attributed to improvements in executive function.

Background/objective: To examine the cognitive benefits of 6  months of prescribed intermittent exercise (10-min bouts totaling 150 weekly minutes) in community-dwelling older adults, comparing effects of low-intensity movement (LIM) and moderate-intensity aerobic exercise (aerobic exercise; AE) training; and exploring biological mechanisms of exercise-related cognitive improvement. Method: Twenty-five adults (>60  years old) participated in a 6-month controlled trial and were randomized into LIM or AE intermittent training. Cognition was assessed using a neuropsychological test battery including the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), California Verbal Learning Test, 2nd Edition (CVLT-II), and Delis-Kaplan Executive Function System (D-KEFS). Neuroimaging measures were collected using a 7  T human MRI scanner. Serologic neurotrophic and inflammatory factors were analyzed using Luminex multiplex assays [brain derived neurotrophic factor (BDNF); vascular endothelial growth factor (VEGF)]; interleukin-6 (IL-6), C-reactive protein (CRP), plasminogen activator inhibitor (PAI-1). Results: LIM and AE intermittent training had dissociable effects on cognition, with LIM resulting in improved learning and memory and AE resulting in improved executive functioning. Intervention groups differed on change in cognitive performance on CVLT-II learning and D-KEFS trail making test. Increase in right dorsolateral prefrontal cortex (DLPFC) surface area was linked to executive improvement (i.e., phonemic fluency) regardless of intervention group. A decline in circulating PAI-1 was linked to learning and memory improvement in response to LIM over 6 months. Conclusion: Moderate-intensity AE and LIM intermittent training likely have distinct cognitive benefits, though low-intensity activity is often included as a control group in exercise trials in aging. [ABSTRACT FROM AUTHOR]

A wealth of evidence has shown that a single bout of aerobic exercise can facilitate executive function. However, none of current studies on this topic have addressed whether the magnitude of the acute-exercise benefit on executive function and oculomotor performance is influenced by different aerobic exercise modes. The present study was thus aimed toward an investigation of the acute effects of high-intensity interval exercise (HIIE) vs. moderate-intensity continuous exercise (MICE) on executive-related oculomotor performance in healthy late middle-aged and older adults. Using a within-subject design, twenty-two participants completed a single bout of 30 min of HIIE, MICE, or a non-exercise-intervention (REST) session in a counterbalanced order. The behavioral [e.g., reaction times (RTs), coefficient of variation (CV) of the RT], and oculomotor (e.g., saccade amplitude, saccade latency, and saccadic peak velocity) indices were measured when participants performed antisaccade and prosaccade tasks prior to and after an intervention mode. The results showed that a 30-min single-bout of HIIE and MICE interventions shortened the RTs in the antisaccade task, with the null effect on the CV of the RT in the late middle-aged and older adults. In terms of oculomotor metrics, although the two exercise modes could not modify the performance in terms of saccade amplitudes and saccade latencies, the participants’ saccadic peak velocities while performing the oculomotor paradigm were significantly altered only following an acute HIIE intervention. The present findings suggested that a 30-min single-bout of HIIE and MICE interventions modulated post-exercise antisaccade control on behavioral performance (e.g., RTs). Nevertheless, the HIIE relative MICE mode appears to be a more effective aerobic exercise in terms of oculomotor control (e.g., saccadic peak velocities) in late middle-aged and older adults.

Background: Executive function tends to decline as people age. Transcranial direct current stimulation (tDCS) is assumed to have beneficial effects on various cognitive functions. Some prior investigations have shown that repeated sessions of tDCS enhance the executive function performance of healthy elderly people by mediating cognitive training gains. However, studies of the effect of long-term stimulation on executive function without cognitive training are absent.Objective: The purpose of this study was to explore whether the executive function of healthy older adults could be enhanced with long-term tDCS alone applied on the prefrontal cortex.Methods: Sixty-five cognitively normal older adults were enrolled and randomly assigned to two groups: an anodal tDCS group and a sham tDCS group. The participants in the two groups received anodal stimulation or sham stimulation over the left dorsolateral prefrontal lobe, for 30 min per day for 10 consecutive days. Executive function was tested before stimulation, immediately after stimulation and 3 months after stimulation. Three core components of executive function were tested using a two-back task for updating, a flanker task for inhibition, and a switching task for shifting.Results: Across the three tasks, we failed to discover any differences between the anodal and sham stimulation. Moreover, we found no statistically significant stimulation effect in the follow-up session.Conclusion: Our study does not support the assumption that multiple sessions of tDCS that are independent of cognitive training have a beneficial effect on executive function in healthy older adults, presumably because the effect of the stimulation lies in its amplification of training gains. It indicates that combining traditional cognitive training methods with brain stimulation may be a better approach to improve older adults’ executive function.

Aging is accompanied by structural brain changes that are thought to underlie cognitive decline and dementia. Yet little is known regarding the association between increasing age, structural brain damage, and alterations of functional brain connectivity. The aim of this study was to evaluate whether cortical thickness and white matter damage as markers of age-related structural brain changes are associated with alterations in functional connectivity in non-demented healthy middle-aged to older adults. Therefore, we reconstructed functional connectomes from resting-state functional magnetic resonance imaging (MRI) (rsfMRI) data of 976 subjects from the Hamburg City Health Study, a prospective population-based study including participants aged 45–74 years from the metropolitan region Hamburg, Germany. We performed multiple linear regressions to examine the association of age, cortical thickness, and white matter damage quantified by the peak width of skeletonized mean diffusivity (PSMD) from diffusion tensor imaging on whole-brain network connectivity and four predefined resting state networks (default mode, dorsal, salience, and control network). In a second step, we extracted subnetworks with age-related decreased functional connectivity from these networks and conducted a mediation analysis to test whether the effect of age on these networks is mediated by decreased cortical thickness or PSMD. We observed an independent association of higher age with decreased functional connectivity, while there was no significant association of functional connectivity with cortical thickness or PSMD. Mediation analysis identified cortical thickness as a partial mediator between age and default subnetwork connectivity and functional connectivity within the default subnetwork as a partial mediator between age and executive cognitive function. These results indicate that, on a global scale, functional connectivity is not determined by structural damage in healthy middle-aged to older adults. There is a weak association of higher age with decreased functional connectivity which, for specific subnetworks, appears to be mediated by cortical thickness.

IntroductionThe structural and functional damages of the striatum were evident in idiopathic REM sleep behavior disorder (iRBD). With the research on iRBD deepens, cognitive impairment in iRBD is getting increasing attention. However, the mechanism of cognitive impairment in iRBD was poorly understood.MethodsNeuropsychological assessment was carried out in 21 polysomnographies (PSGs) confirmed iRBD patients and 22 normal controls. Both regional homogeneity (ReHo) and seed-based functional connectivity (FC) rs-fMRI analyses were applied to explore the FC abnormalities and its association with cognition in iRBD patients. Positive ReHo clusters were set as seeds for further FC analysis.ResultsIdiopathic REM sleep behavior disorder patients presented cognitive deficits in attention/working memory, executive function, immediate memory, and visuo-spatial ability. ReHo analysis revealed abnormal spontaneous brain activities in the striatum (right caudate, left pallidum and bilateral putamen) in iRBD. FC analysis showed decreased striatum-related FCs in the frontal, temporal, occipital lobes, thalamus, anterior cingulate gyrus, as well as decreased intrinsic FCs between bilateral putamen and between caudate and pallidum. Deficits in attention/working memory, executive function, and immediate memory were associated with abnormal striatal-cortical FCs including frontal, temporal, and anterior cingulate cortices.ConclusionFunctional changes of striatum and cognitive impairment in iRBD were reconfirmed in the present study. Abnormal striatal-cortical networks, especially the striatal-frontal network, contribute to the working memory/executive function deficits in iRBDs. These findings supported the role of striatum not only in motor but also in cognition impairment in iRBD.

Aging is associated with both changes in affective experience and attention. An intrinsic brain network subserving these functions, the salience network, has not shown clear evidence of a corresponding age-related change. We propose a solution to this discrepancy: that aging differentially affects the connectivity of two dissociated subsystems of the salience network identified in our prior research (Touroutoglou et al., 2012). We examined the age-related changes in intrinsic connectivity between a dorsal and a ventral salience subsystem in a sample of 111 participants ranging in age from 18 years to 81 years old. We predicted that connectivity within the ventral subsystem is relatively preserved with age, while connectivity in the dorsal subsystem declines. Our findings showed that the connectivity within the ventral subsystem was not only preserved but it actually increased with age, whereas the connectivity within the dorsal subsystem decreased with age. Furthermore, age-related increase in arousal experience was partially mediated by age-related increases in ventral salience subsystem, whereas age-related decline in executive function was fully mediated by age-related decreases in dorsal salience subsystem connectivity. These findings explain previously conflicting results on age-related changes in the salience network, and suggest a mechanism for relatively preserved affective function in the elderly.

Recent work suggests that the brain can be conceptualized as a network comprised of groups of sub-networks or modules. The extent of segregation between modules can be quantified with a modularity metric, where networks with high modularity have dense connections within modules and sparser connections between modules. Previous work has shown that higher modularity predicts greater improvements after cognitive training in patients with traumatic brain injury and in healthy older and young adults. It is not known, however, whether modularity can also predict cognitive gains after a physical exercise intervention. Here, we quantified modularity in older adults (N = 128, mean age = 64.74) who underwent one of the following interventions for 6 months (NCT01472744 on ClinicalTrials.gov): (1) aerobic exercise in the form of brisk walking (Walk), (2) aerobic exercise in the form of brisk walking plus nutritional supplement (Walk+), (3) stretching, strengthening and stability (SSS), or (4) dance instruction. After the intervention, the Walk, Walk+ and SSS groups showed gains in cardiorespiratory fitness (CRF), with larger effects in both walking groups compared to the SSS and Dance groups. The Walk, Walk+ and SSS groups also improved in executive function (EF) as measured by reasoning, working memory, and task-switching tests. In the Walk, Walk+, and SSS groups that improved in EF, higher baseline modularity was positively related to EF gains, even after controlling for age, in-scanner motion and baseline EF. No relationship between modularity and EF gains was observed in the Dance group, which did not show training-related gains in CRF or EF control. These results are consistent with previous studies demonstrating that individuals with a more modular brain network organization are more responsive to cognitive training. These findings suggest that the predictive power of modularity may be generalizable across interventions aimed to enhance aspects of cognition and that, especially in low-performing individuals, global network properties can capture individual differences in neuroplasticity.

Behavioral variant frontotemporal dementia (bvFTD) is characterized by deep alterations in behavior and personality. Although revised diagnostic criteria agree for executive dysfunction as most characteristic, impairments in social cognition are also suggested. The study aimed at identifying those neuropsychological and behavioral parameters best discriminating between bvFTD and healthy controls. Eighty six patients were diagnosed with possible or probable bvFTD according to Rascovsky et al. (2011) and compared with 43 healthy age-matched controls. Neuropsychological performance was assessed with a modified Reading the Mind in the Eyes Test (RMET), Stroop task, Trail Making Test (TMT), Hamasch-Five-Point Test (H5PT), and semantic and phonemic verbal fluency tasks. Behavior was assessed with the Apathy Evaluation Scale, Frontal Systems Behavioral Scale, and Bayer Activities of Daily Living Scale. Each test’s discriminatory power was investigated by Receiver Operating Characteristic curves calculating the area under the curve (AUC). bvFTD patients performed significantly worse than healthy controls in all neuropsychological tests. Discriminatory power (AUC) was highest in behavioral questionnaires, high in verbal fluency tasks and the RMET, and lower in executive function tests such as the Stroop task, TMT and H5PT. As fluency tasks depend on several cognitive functions, not only executive functions, results suggest that the RMET discriminated better between bvFTD and control subjects than other executive tests. Social cognition should be incorporated into diagnostic criteria for bvFTD in the future, such as in the International Classification of Diseases (ICD)-11, as already suggested in the Diagnostic and Statistical Manual for Mental Disorders (DSM)-5.

Background: Multiple modalities of Alzheimer’s disease (AD) risk factors may operate through interacting networks to predict differential cognitive trajectories in asymptomatic aging. We test such a network in a series of three analytic steps. First, we test independent associations between three risk scores (functional-health, lifestyle-reserve, and a combined multimodal risk score) and cognitive [executive function (EF)] trajectories. Second, we test whether all three associations are moderated by the most penetrant AD genetic risk [Apolipoprotein E (APOE) ε4+ allele]. Third, we test whether a non-APOE AD genetic risk score further moderates these APOE × multimodal risk score associations.Methods: We assembled a longitudinal data set (spanning a 40-year band of aging, 53–95 years) with non-demented older adults (baseline n = 602; Mage = 70.63(8.70) years; 66% female) from the Victoria Longitudinal Study (VLS). The measures included for each modifiable risk score were: (1) functional-health [pulse pressure (PP), grip strength, and body mass index], (2) lifestyle-reserve (physical, social, cognitive-integrative, cognitive-novel activities, and education), and (3) the combination of functional-health and lifestyle-reserve risk scores. Two AD genetic risk markers included (1) APOE and (2) a combined AD-genetic risk score (AD-GRS) comprised of three single nucleotide polymorphisms (SNPs; Clusterin[rs11136000], Complement receptor 1[rs6656401], Phosphatidylinositol binding clathrin assembly protein[rs3851179]). The analytics included confirmatory factor analysis (CFA), longitudinal invariance testing, and latent growth curve modeling. Structural path analyses were deployed to test and compare prediction models for EF performance and change.Results: First, separate analyses showed that higher functional-health risk scores, lifestyle-reserve risk scores, and the combined score, predicted poorer EF performance and steeper decline. Second, APOE and AD-GRS moderated the association between functional-health risk score and the combined risk score, on EF performance and change. Specifically, only older adults in the APOEε4− group showed steeper EF decline with high risk scores on both functional-health and combined risk score. Both associations were further magnified for adults with high AD-GRS.Conclusion: The present multimodal AD risk network approach incorporated both modifiable and genetic risk scores to predict EF trajectories. The results add an additional degree of precision to risk profile calculations for asymptomatic aging populations.

Introduction: We investigated the relationship between loneliness, cognitive impairment, and regional brain volume among elderly individuals residing in the Korean community. Methods: Data from the ARIRANG aging-cognition sub-cohort, collected between 2020 and 2022, were utilized for the present study. Loneliness was assessed using the UCLA-Loneliness Scale (UCLA-LS) questionnaire and the relevant item from Center for Epidemiologic Studies Depression Scale Korean version (CES-D-K). Cognitive impairment was measured through Mini-Mental State Examination (K-MMSE-2) and Seoul Neuropsychological Screening Battery (SNSB-C), with five sub-categories: attention, memory, visuospatial function, language, and executive function. Logistic regression was employed for prevalence ratios related to cognitive impairment, while linear regression was used for regional brain volume including white matter hyperintensity (WMH) and cortical thickness. Results: Our analysis involved 785 participants (292 men and 493 women). We observed increased cognitive impairment assessed by K-MMSE-2 [UCLA- LS: odds ratio (OR) 3.133, 95% confidence interval (CI) 1.536-6.393; loneliness from CES-D: OR 2.823, 95% CI 1.426-5.590] and SNSB-C total score (UCLA-LS: OR 2.145, 95% CI 1.304-3.529) in the lonely group compared to the non-lonely group. Specifically, the lonely group identified by UCLA-LS showed an association with declined visuospatial (OR 1.591, 95% CI 1.029-2.460) and executive function (OR 1.971, 95% CI 1.036-3.750). The lonely group identified by CES-D-K was associated with impaired memory (OR 1.577, 95% CI 1.009-2.466) and executive function (OR 1.863, 95% CI 1.036-3.350). In the regional brain volume analysis, loneliness was linked to reduced brain volume in frontal white matter (left: -1.24, 95% CI -2.37 ~ -0.12; right: -1.16, 95% CI -2.31 ~ -0.00), putamen (left: -0.07, 95% CI -0.12 ~ -0.02; right: -0.06, 95% CI -0.11 ~ -0.01), and globus pallidus (-15.53, 95% CI -30.13 ~ -0.93). There was no observed association in WMH and cortical thickness. Conclusion: Loneliness is associated with cognitive decline and volumetric reduction in the frontal white matter, putamen, and globus pallidus. [ABSTRACT FROM AUTHOR]

Video games have been found to have positive influences on executive function in older adults; however, the underlying neural basis of the benefits from video games has been unclear. Adopting a task-based functional magnetic resonance imaging (fMRI) study targeted at the flanker task, the present study aims to explore the neural basis of the improved executive function in older adults with video game experiences. Twenty video game players (VGPs) and twenty non-video game players (NVGPs) of 60 years of age or older participated in the present study, and there are no significant differences in age (t = 0.62, p = 0.536), gender ratio (t = 1.29, p = 0.206) and years of education (t = 1.92, p = 0.062) between VGPs and NVGPs. The results show that older VGPs present significantly better behavioral performance than NVGPs. Older VGPs activate greater than NVGPs in brain regions, mainly in frontal-parietal areas, including the right dorsolateral prefrontal cortex, the left supramarginal gyrus, the right angular gyrus, the right precuneus and the left paracentral lobule. The present study reveals that video game experiences may have positive influences on older adults in behavioral performance and the underlying brain activation. These results imply the potential role that video games can play as an effective tool to improve cognitive ability in older adults.

Age-related declines in endothelial function can lead to cognitive decline. However, little is known about the relationships between endothelial function and specific neurocognitive functions. This study explored the relationship between measures of endothelial function (reactive hyperemia index; RHI), white matter (WM) health (fractional anisotropy, FA, and WM hyperintensity volume, WMH), and executive function (Trail Making Test (TMT); Trail B − Trail A). Participants were 36 older adults between the ages of 59 and 69 (mean age = 63.89 years, SD = 2.94). WMH volume showed no relationship with RHI or executive function. However, there was a positive relationship between RHI and FA in the genu and body of the corpus callosum. In addition, higher RHI and FA were each associated with better executive task performance. Tractography was used to localize the WM tracts associated with RHI to specific portions of cortex. Results indicated that the RHI-FA relationship observed in the corpus callosum primarily involved tracts interconnecting frontal regions, including the superior frontal gyrus (SFG) and frontopolar cortex, linked with executive function. These findings suggest that superior endothelial function may help to attenuate age-related declines in WM microstructure in portions of the corpus callosum that interconnect prefrontal brain regions involved in executive function.

Purpose: Previously, we have shown that the SNP rs10932201 genotype of the cyclic AMP responsive element binding protein 1 gene (CREB1) contributes to individual differences in executive and memory function at the neural system and behavioral levels in healthy, young adults. However, longitudinal effects of CREB1 genotypes on cognition have not yet been addressed. Furthermore we were interested in replicating associations between CREB1 genotypes and human cognition in previous cross-sectional studies and explore whether APOE𝜀4 status might modify these relations.Materials and Methods: We investigated whether common, independent tag SNPs within CREB1 (rs2253206, rs10932201, rs6785) influence individual differences in age-related longitudinal change and level of executive function and memory performance independent of baseline age, sex, APOE𝜀4 status, and education. Our analysis included data from cognitively unimpaired older adults participating in the Baltimore Longitudinal Study of Aging. Eleven measures from six cognitive tests (sample sizes range 617–786) were analyzed using linear mixed effects and generalized estimating equations models. Mean baseline age ranged from 50 to 69 years and mean time of follow-up (interval) ranged from 8 to 22 years.Results: We found significant effects of all three CREB1 SNPs on performance level and/or longitudinal change in performance based on eight measures assessing semantic memory, episodic memory, or both executive function and semantic memory. SNP rs10932201 showed the most significant and largest effect (Cohen’s d = -0.70, p < 0.01) on age-related longitudinal decline of semantic memory. Additionally, we show interactions between all three CREB1 SNPs and APOE𝜀4 status on age-related longitudinal declines and levels of memory and executive function.Conclusion: Our results suggest that CREB1 genotypes independently and by interactions with APOE𝜀4 status contribute to individual differences in cognitive aging.

Introduction: Studies on the aging brain often occur in active settings, but comparatively few investigate brain activity in resting states. However, exploring brain activity in a resting state offers valuable insights into spontaneous neural processes unaffected by task-specific influences. Objective: To investigate the relationship between self-care practices, cognitive function, and patterns of brain activity in healthy older adults, taking into account predictions from aging brain models. Methodology: 77 older adults aged 61 to 87 completing a self-care practices questionnaire, neuropsychological tests, and resting-state electroencephalogram (EEG) recordings. Participants were classified into two groups according to their self-care practices: traditional self-care (T-SC) and developmental self-care (D-SC). Results: Although neuropsychological tests did not yield significant differences between the D-SC and T-SC groups, patterns of brain activity revealed distinct behaviors. The T-SC group demonstrated patterns more consistent with established aging brain models, contrasting with the D-SC group, which exhibited brain activity akin to that observed in younger adults. Specifically, the T-SC group displayed hyperactivation related to memory and executive function performance, alongside heightened alpha power in posterior regions. Furthermore, bilateral frontal activation in the beta band was evident. Conclusions: The findings suggest a nuanced relationship between self-care practices and brain activity in older adults. While the T-SC group demonstrated brain activity patterns consistent with conservative aging, indicating the preservation of typical aging characteristics, the D-SC group displayed activity suggestive of a potential protective effect. This effect may be linked to self-care strategies that foster development and resilience in cognitive aging. [ABSTRACT FROM AUTHOR]

Apathy is a quantitative reduction in goal-directed behaviors, having three subtypes. Despite executive deterioration in healthy aging, researchers have not investigated the “cognitive-deficit” subtype of apathy in healthy populations, which would result from executive dysfunction. We hypothesized that a relationship between apathy and executive function (EF) would be found in healthy older adults, accompanied with neural deterioration with functional dysconnectivity between the striatum and frontal region as suggested by previous studies. A total of 100 healthy adults in a health examination system database were analyzed. The present study indicates that apathy is substantially associated with executive deterioration, which can be partially ascribed to decreased functional connectivity between the frontal and ventral striatum. Despite some limitations, our findings may contribute to research on healthy psychological aging.

During aging, physical integrity and cognitive abilities, especially executive function, become compromised, directly influencing the quality of life of the elderly. One good strategy to ensure healthy aging is the practice of physical exercise. Activities to improve aerobic capacity and muscle strength are extremely important in old age. However, some genetic factors can interfere both positively and negatively with these gains. In this context, the polymorphism rs1815739 (R577X) of the α-actinin 3 gene (ACTN-3) is commonly studied and related to muscle phenotype. Thus, the present study aimed to investigate the effect of the ACTN-3 gene polymorphism on the functional fitness (measured by the Senior Fit test) and cognitive capacity (evaluated by the Stroop test) of the elderly (n = 347), both men and women. We did not find the effect of genotype on functional fitness, but we did observed a positive effect of the ACTN-3 gene polymorphism on executive function. The presence of the X allele of the ACTN3 gene in the elderly was related to a better performance in the Stroop test (shorter answer time). Our results showed that ACTN-3 gene polymorphismaffects the executive function of the elderly but not their functional fitness. [ABSTRACT FROM AUTHOR]

Episodic memory and executive function are two cognitive domains that have been studied extensively in older adults and have been shown to decline in normally-aging older individuals. However, one of the problems with characterizing cognitive changes in longitudinal studies has been separating effects attributable to normal aging from effects created by repeated testing or practice. In the present study, 166 people aged 65 and older were enrolled over several years and tested at least 3 times at variable intervals (M = 3.2 yrs). The cognitive measures were composite scores. Each composite was made up of five neuropsychological tests, previously identified through factor analysis. For one pair of composite scores, variance attributable to age was removed from each subtest through regression analyses before z -scores were computed, creating two age-corrected composites. A second pair of composites were not age-corrected. Using linear mixed-effects models, we first explored retest effects for each cognitive domain, independent of age, using the age-corrected composites. We then modeled aging effects using the age-uncorrected composites after subtracting out retest effects. Results indicated significant retest effects for memory but not for executive function, such that memory performance improved across the three testing sessions. When these practice effects were removed from the age-uncorrected data, effects of aging were evident for both executive and memory function with significant declines over time. We also explored several individual difference variables including sex, IQ, and age at the initial testing session and across time. Although sex and IQ affected performance on both cognitive factors at the initial test, neither was related to practice effects, although young-older adults tended to benefit from practice to a greater extent than old-older adults. In addition, people with higher IQs showed slower age-related declines in memory, but no advantages in executive function. These findings suggest that (a) aging affects both memory and executive function similarly, (b) higher IQ, possibly reflecting cognitive reserve, may slow age-related declines in memory, and (c) practice through repeated testing enhances performance in memory particularly in younger-older adults, and may therefore mask aging effects if not taken into account. [ABSTRACT FROM AUTHOR]

Introduction: Evidence suggests urinary urgency is associated with cognitive impairment in a subtype of Parkinson’s disease (PD) patients. This study investigates if cognitive impairment independently predicts the presence of urinary dysfunction.Methods: We report data of 189 idiopathic PD patients, excluding those with concomitant diseases or medication interacting with bladder function. A standardized questionnaire was used to define the presence of urinary urgency. All patients underwent a comprehensive motor, cognitive non-motor and health-related quality of life (HRQoL) assessment. Multivariable linear regression analysis was performed to identify independent variables characterizing urinary urgency in PD (PD-UU), which were assigned as discriminant features to estimate their individual contribution to the phenotype of the PD-UU group.Results: Of 189 PD patients, 115 (60.8%) reported PD-UU. The linear regression analysis showed that among cognitive domains, executive function (EF; p = 0.04) had a significant negative association with PD-UU. In a second model, scores of the Montreal Cognitive Assessment (MoCA) significantly differentiated between study groups (p = 0.007) and also non-motor symptom (NMS) burden (p < 0.001). The third model consisted of reports of HRQoL, of which stigma was the only subscale of the Parkinson’s Disease Questionnaire (PDQ-39) differentiating between patients with and without PD-UU (p = 0.02). The linear discriminant analysis provided evidence that the combination of EF, NMS burden, nocturia, and stigma discriminated between groups with 72.4% accuracy.Conclusion: In our large, non-demented PD cohort, urinary urgency was associated with executive dysfunction (EF), supporting a possible causative link between both symptoms. A combination of neuropsychological and non-motor aspects identified patients with PD-UU with high discriminative accuracy.

A prominent feature of cognitive aging is the decline of executive function (EF) abilities. Numerous studies have reported that older adults perform poorer than younger adults in such tasks. In this cross-sectional study, the effect of age on four EFs, inhibition, shifting, updating, and dual-tasking, was examined in 26 young adults (mean 21.18  years) and 25 older adults (mean 71.56  years) with the utilization of a pair of tasks for each EF. The tasks employed for DT were the Psychological Refractory Period paradigm (PRP) and a modified test for everyday attention, for inhibition the Stroop and Hayling sentence completion test (HSCT), for shifting a task switching paradigm and the trail making test (TMT), and for updating the backward digit span (BDS) task and a n-back paradigm. As all participants performed all tasks, a further aim was to compare the size of the age-related cognitive decline among the four EFs. Age-related decline was observed in all four EFs in one or both of the tasks employed. The results revealed significantly poorer performance in the older adults in the response times (RTs) of the PRP effect, interference score of the Stroop, RT inhibition costs of the HSCT, RT and error-rate shifting costs of the task switching paradigm, and the error-rate updating costs of the n-back paradigm. A comparison between the rates of decline revealed numerical and statistically significant differences between the four EFs, with inhibition showing the greatest decline, followed by shifting, updating, and dual-tasking. Thus, we conclude that with age, these four EFs decline at different rates., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Idowu and Szameitat.)

Objective: White matter hyperintensities (WMH) are the most common neuroimaging manifestation of cerebral small vessel disease, and is frequently observed in Alzheimer's disease (AD). This study aimed to investigate the relationship between WMH and cognition and to verify the mediation of grey matter atrophy in this relationship. Methods: The diffusion tensor imaging (DTI) technique analyses white matter fiber tract to assess white matter integrity. Voxel-based morphometry was applied to measure the grey matter volume (GMV). A linear regression model was applied to examine the associations between WMH and GMV, and mediation analyses was performed to determine the mediating role of regional GMV in the effect of WMH on cognitive function. Results: Compared to the HC group, AD group have 8 fiber tract fractional anisotropy (FA) decreased and 16 fiber tract mean diffusivity (MD) increased. Compared to AD without WMH, AD with high WMH had 9 fiber tracts FA decreased and 13 fiber tracts MD increased. High WMH volume was negatively correlated with GMV in the frontal--parietal region. Low WMH volume was also negatively correlated with GMV except for the three regions (right angular gyrus, right superior frontal gyrus and right middle/inferior parietal gyrus), where GMV was positively correlated. Mediation analysis showed that the association between WMH and executive function or episodic memory were mediated by GMV in the frontal--parietal region. Conclusion: Damage to white matter integrity was more severe in AD with WMH. Differential changes in DTI metrics may be caused by progressive myelin and axonal damage. There was a negative correlation between WMH and grey matter atrophy in frontal--parietal regions in a volume-dependent manner. This study indicates the correspondence between WMH volume and GMV in cognition, and GMV being a key modulator between WMH and cognition in AD. This result will contribute to understanding the progression of the disease process and applying targeted therapeutic intervention in the earlier stage to delay neurodegenerative changes in frontal--parietal regions to achieve better treatment outcomes and affordability. [ABSTRACT FROM AUTHOR]

Background: Stable mild cognitive impairment (sMCI) and progressive mild cognitive impairment (pMCI) represent two distinct subtypes of mild cognitive impairment (MCI). Early and effective diagnosis and accurate differentiation between sMCI and pMCI are crucial for administering targeted early intervention and preventing cognitive decline. This study investigated the intrinsic dysconnectivity patterns in sMCI and pMCI based on degree centrality (DC) and effective connectivity (EC) analyses, with the goal of uncovering shared and distinct neuroimaging mechanisms between subtypes. Methods: Resting-state functional magnetic resonance imaging combined with DC analysis was used to explore the functional connectivity density in 42 patients with sMCI, 31 patients with pMCI, and 82 healthy control (HC) participants. Granger causality analysis was used to assess changes in EC based on the significant clusters found in DC. Furthermore, correlation analysis was conducted to examine the associations between altered DC/EC values and cognitive function. Receiver operating characteristic curve analysis was performed to determine the accuracy of abnormal DC and EC values in distinguishing sMCI from pMCI. Results: Compared with the HC group, both pMCI and sMCI groups exhibited increased DC in the left inferior temporal gyrus (ITG), left posterior cerebellum lobe (CPL), and right cerebellum anterior lobe (CAL), along with decreased DC in the left medial frontal gyrus. Moreover, the sMCI group displayed reduced EC from the right CAL to bilateral CPL, left superior temporal gyrus, and bilateral caudate compared with HC. pMCI demonstrated elevated EC from the right CAL to left ITG, which was linked to episodic memory and executive function. Notably, the EC from the right CAL to the right ITG effectively distinguished sMCI from pMCI, with sensitivity, specificity, and accuracy of 0.5806, 0.9512, and 0.828, respectively. Conclusion: This study uncovered shared and distinct alterations in DC and EC between sMCI and pMCI, highlighting their involvement in cognitive function. Of particular significance are the unidirectional EC disruptions from the cerebellum to the temporal lobe, which serve as a discriminating factor between sMCI and pMCI and provide a new perspective for understanding the temporal-cerebellum. These findings offer novel insights into the neural circuit mechanisms involving the temporal-cerebellum connection in MCI. [ABSTRACT FROM AUTHOR]

Background: Ischemic stroke and heavy alcohol consumption are both known risk factors for cognitive impairment. The issue gains importance because the prevalence of stroke and binge drinking have both increased among working-aged adults. Alarmingly, a recent cross-sectional study suggests the additive negative effects of binge drinking and comorbid brain disease on cognition. However, the long-term cognitive prognosis of the additive effects of stroke and binge drinking on adults remains unknown. Methods: In this prospective, two-center cohort study, we recruited consecutive 18-65-year-old patients with first-ever ischemic stroke along with demographically matched stroke-free controls. Patients participated in neuropsychological assessment at 6 months, 2 years, and 9 years after stroke, and in neurological assessment at acute care and at 9-year follow-up. Controls participated in a similar follow-up procedure. We examined the association between binge drinking, follow-up time, and long-term cognitive outcomes using repeated-measures analysis of variance. Results: We included 85 patients who had had their first-ever and only ischemic stroke (mean age 53 years at the incident stroke). Patients were divided into binge-drinking (n = 22) and non-binge-drinking groups (n = 63) based on the shortened version of the Alcohol Use Disorders Identification Test. Follow-up data in healthy controls (n = 31) was used to normalize the patients' test scores for effects of age, sex, and education. We compared cognitive changes between binge-drinking and non-binge-drinking patients over a 9-year follow-up. Non-binge-drinking patients outperformed binge-drinking patients across all follow-up points on most of the executive function tests and in one memory test: binge drinking had a significant main effect both on executive function (the phonemic fluency task, p = 0.002; the Trail Making Test, p = 0.013) and memory (the list learning task, p = 0.002). Conclusion: Binge drinking was associated with executive and memory dysfunction at three time points over a decade after a first-ever ischemic stroke. Subdiagnostic binge drinking might increase the adverse effects of a first-ever ischemic stroke on executive function and memory, evident over a decade poststroke. [ABSTRACT FROM AUTHOR]

Purpose: Rapid eye movement sleep behavior disorder (RBD) affects 30%–40% of patients with Parkinson’s disease (PD) and has been linked to a higher risk of cognitive impairment, especially executive dysfunction. The aim of this study was to investigate the brain activation patterns in PD patients with RBD (PDRBD+) compared to those without RBD (PD-RBD−) and healthy controls (HCs), and to analyze the correlation between changes in cerebral cortex activity and the severity of RBD. Methods: We recruited 50 PD patients, including 30 PD-RBD+, 20 PD-RBD−, and 20 HCs. We used functional near infrared spectroscopy during a verbal fluency task (VFT-fNIRS) and clinical neuropsychological assessment to explore the correlation between PD-RBD+ and executive function and changes in neural activity. Results: The VFT-fNIRS analysis revealed a significant reduction in activation among PD-RBD+ patients across multiple channels when compared to both the PD-RBD− and HC groups. Specifically, PD-RBD+ patients exhibited diminished activation in the bilateral dorsolateral prefrontal cortex (DLPFC) and the right ventrolateral prefrontal cortex (VLPFC) relative to their PD-RBD− counterparts. Furthermore, compared to the HC group, PD-RBD+ patients displayed reduced activation specifically in the right DLPFC. Significantly, a noteworthy negative correlation was identified between the average change in oxygenated hemoglobin concentration (1HbO2) in the right DLPFC of PD-RBD+ patients and the severity of their RBD. Conclusion: Our study offers compelling evidence that RBD exacerbates cognitive impairment in PD, manifested as executive dysfunction, primarily attributed to reduced prefrontal activation. These aberrations in brain activation may potentially correlate with the severity of RBD. [ABSTRACT FROM AUTHOR]

Introduction: With age, sensory, cognitive, and motor abilities decline, and the risk for neurodegenerative disorders increases. These impairments influence the quality of life and increase the need for care, thus putting a high burden on society, the economy, and the healthcare system. Therefore, it is important to identify factors that influence healthy aging, particularly ones that are potentially modifiable through lifestyle choices. However, large-scale studies investigating the influence of multi-modal factors on a global description of healthy aging measured by multiple clinical assessments are sparse. Methods: We propose a machine learning model that simultaneously predicts multiple cognitive and motor outcome measurements on a personalized level recorded from one learned composite score. This personalized composite score is derived from a large set of multi-modal components from the TREND cohort, including genetic, biofluid, clinical, demographic, and lifestyle factors. Results: We found that a model based on a single composite score was able to predict cognitive and motor abilities almost as well as a classical flexible regression model specifically trained for each single clinical score. In contrast to the flexible regression model, our composite score model is able to identify factors that globally influence cognitive and motoric abilities as measured by multiple clinical scores. The model identified several risk and protective factors for healthy aging and recovered physical exercise as a major, modifiable, protective factor. Discussion: We conclude that our low parametric modeling approach successfully recovered known risk and protective factors of healthy aging on a personalized level while providing an interpretable composite score. We suggest validating this modeling approach in other cohorts. [ABSTRACT FROM AUTHOR]

Deficits in executive functions occur in up to 93% of patients with Parkinson`s disease (PD). Apathy, a reduction of motivation and goal-directed behavior is an important part of the syndrome; affecting both the patients as well as their social environment.Executive functions can be subdivided into three different processes: initiation, shifting and inhibition. We examined the hypotheses, (1) that apathy in patients with Parkinson`s disease is only related to initiation and not to shifting and inhibition, and (2) that depression and severity of motor signs correlate with apathy.Fifty-one non-demented patients (19 = female) with PD were evaluated for apathy, depression and executive functions. Executive function variables were summarized with an index variable according to the defined executive processes. Linear regression with stepwise elimination procedure was used to select significant predictors.The significant model (R2 = .41; p < .01) revealed influences of initiation (b = - .79; p < .01), gender (b = - 7.75; p < .01), age (b = -.07; p < .05) and an age by gender interaction (b = .12; p < .01) on apathy in Parkinson`s disease. Motor signs, depression and level of education did not influence the relation. These results support an association of apathy and deficits of executive function in PD. Initiation strongly correlates with apathy, whereas depression does not. We conclude, that initiation dysfunction in a patient with Parkinson`s disease heralds apathy. Apathy and depression can be dissociated. Additionally, apathy is influenced by age and gender: older age correlates with apathy in men, whereas in women it seems to protect against it.

BackgroundPhysical activity may attenuate age-related cognitive decline by improving cerebrovascular function. The aim of this study was therefore to investigate effects of aerobic exercise training on cerebral blood flow (CBF), which is a sensitive physiological marker of cerebrovascular function, in sedentary older men.MethodsSeventeen apparently healthy men, aged 60–70 years and with a BMI between 25 and 35 kg/m2, were included in a randomized, controlled cross-over trial. Study participants were randomly allocated to a fully-supervised, progressive, aerobic exercise training or no-exercise control period for 8 weeks, separated by a 12-week wash-out period. Measurements at the end of each period included aerobic fitness evaluated using peak oxygen consumption during incremental exercise (VO2peak), CBF measured with pseudo-continuous arterial spin labeling magnetic resonance imaging, and post-load glucose responses determined using an oral glucose tolerance test (OGTT). Furthermore, cognitive performance was assessed in the domains of executive function, memory, and psychomotor speed.ResultsVO2peak significantly increased following aerobic exercise training compared to no-exercise control by 262 ± 236 mL (P < 0.001). CBF was increased by 27% bilaterally in the frontal lobe, particularly the subcallosal and anterior cingulate gyrus (cluster volume: 1008 mm3; P < 0.05), while CBF was reduced by 19% in the right medial temporal lobe, mainly temporal fusiform gyrus (cluster volume: 408 mm3; P < 0.05). Mean post-load glucose concentrations determined using an OGTT decreased by 0.33 ± 0.63 mmol/L (P = 0.049). Furthermore, executive function improved as the latency of response was reduced by 5% (P = 0.034), but no changes were observed in memory or psychomotor speed.ConclusionAerobic exercise training improves regional CBF in sedentary older men. These changes in CBF may underlie exercise-induced beneficial effects on executive function, which could be partly mediated by improvements in glucose metabolism. This clinical trial is registered on ClinicalTrials.gov as NCT03272061.

Objective: This study investigated whether acute exercise duration affects inhibition in late middle-aged adults.Methods: Over four separate days, 40 late middle-aged adults completed, in a counterbalanced order, three exercise sessions consisting of single bouts of moderate-to-vigorous intensity cycling, with the main acute exercise durations being 10, 20, and 45 min, and a control session consisting of 30 min of reading. Their inhibition performance was then evaluated by administration of the Stroop test following each session.Results: The participants had shorter mean response times for both the congruent and neutral conditions of the Stroop following the acute exercise lasting 20 min than they did after the control session. The acute exercise lasting 20 min also resulted in shorter response times for both conditions of the Stroop than the acute exercise lasting only 10 min. Meanwhile, the acute exercise lasting 45 min resulted in a shorter mean response time for the neutral Stroop condition than did the control session. Finally, the acute exercise lasting 20 min resulted in the shortest mean response time of all four sessions for the Stroop incongruent condition.Conclusion: The above findings suggest that the moderate-to-vigorous intensity acute exercise lasting 20 min facilitated multiple cognitive function domains in general, whereas the exercise sessions of shorter and longer duration had negligible effects on executive function in the late middle-aged adults. These results highlight the need to consider the duration of any moderate-to-vigorous intensity exercise when developing acute exercise programs to facilitate executive function in aged populations.

Objective: This study aims to explore whether body mass index (BMI) level affects the executive function and hippocampal subregion volume of subjective cognitive decline (SCD)., Materials and Methods: A total of 111 participants were included in the analysis, including SCD (38 of normal BMI, 27 of overweight and obesity) and normal cognitive control (NC) (29 of normal BMI, 17 of overweight and obesity). All subjects underwent the Chinese version of the Stroop Color-Word Test (SCWT) to measure the executive function and a high-resolution 3D T1 structural image acquisition. Two-way ANOVA was used to examine the differences in executive function and gray matter volume in hippocampal subregions under different BMI levels between the SCD and NC., Result: The subdimensions of executive function in which different BMI levels interact with SCD and NC include inhibition control function [SCWT C-B reaction time(s): F (1,104) = 5.732, p = 0.018], and the hippocampal subregion volume of CA1 [ F (1,99) = 8.607, p = 0.004], hippocampal tail [ F (1,99) = 4.077, p = 0.046], and molecular layer [ F (1,99) = 6.309, p = 0.014]. After correction by Bonferroni method, the population × BMI interaction only had a significant effect on the CA1 ( p < 0.001], and the inhibitory control function of SCD was worse than that of NC. In the normal BMI group, gray matter volume in the hippocampal subregion (CA1) of SCD was significantly smaller than that of NC [ F (1,104) = 0.029]. For patients with SCD, the high BMI group had worse inhibitory control function [ p = 0.040] or the high BMI level [ F (1,104) = 21.530, p < 0.001], and the inhibitory control function of SCD was worse than that of NC. In the normal BMI group, gray matter volume in the hippocampal subregion (CA1) of SCD was significantly smaller than that of NC [ F (1,99) = 4.938, p = 0.029]. For patients with SCD, the high BMI group had worse inhibitory control function [ F (1,104) = 13.499, p < 0.001] and greater CA1 volume compared with the normal BMI group [ F (1,99) = 7.619, p = 0.007]., Conclusion: The BMI level is related to the inhibition control function and the gray matter volume of CA1 subregion in SCD. Overweight seems to increase the gray matter volume of CA1 in the elderly with SCD, but it is not enough to compensate for the damage to executive function caused by the disease. These data provide new insights into the relationship between BMI level and executive function of SCD from the perspective of imaging., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Cai, Xu, Sun, Luo, Wang, Li, Lin and Liu.)

Objective: The objective of this study was to examine the activation and functional connectivity of the prefrontal and temporal lobe in young and elder people during the Stroop test using functional near-infrared spectroscopy (fNIRS)., Methods: A total of 33 healthy volunteers (20 young people, mean age: 23.7 ± 3.9 years; 13 elder people, mean age: 63.9 ± 4.0 years) participated in the study. All subjects were asked to finish the Stroop Color Word Test. The oxygenated hemoglobin concentration (Delta [HbO 2 ]) signals and the deoxygenated hemoglobin (Delta [HbR]) signals were recorded from temporopolar area (TA), pars triangularis Broca's area (Broca), dorsolateral prefrontal cortex (DLPFC), and frontopolar area (FA) by fNIRS. The coherence between the left and right frontotemporal lobe delta [HbO 2 ] oscillations in four frequency intervals (I, 0.6-2 Hz; II, 0.145-0.6 Hz; III, 0.052-0.145 Hz; and IV, 0.021-0.052 Hz) was analyzed using wavelet coherence analysis and wavelet phase coherent., Results: In the Stroop test, the young group was significantly better than the elder group at the responses time, whether at congruent tasks or at incongruent tasks (congruent: F = 250.295, p < 0.001; incongruent: p < 0.001). The accuracy of the two groups differed significantly when performing incongruent tasks but not when performing congruent tasks (incongruent: F = 9.498, p = 0.001; congruent: p = 0.254). Besides, only elders show significant activation in DLPFC, Broca, FA, and TA ( p < 0.05) during the Stroop test, but young people did not show significant differences. In the functional connectivity of task states, younger people had stronger connections between different brain regions in both the left and right brain compared with the elderly ( p < 0.05). In particular, the left and right DLPFC showed stronger connection strength in most of the brain areas. The result suggested that younger people had stronger functional connectivity of brain areas than older people when completing the task., Conclusion: According to these results, although the cortical activation in the elder people was higher than the young people, the young showed stronger connectivity in most of the brain areas than the elders. Both sides of DLPFC and right Broca area were the most significant cortical activation in Stroop test. It was suggested that the decrease in functional connectivity in the elder people resulted in the atrophy of white matter, to which we should pay more attention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Huang, Li, Xie, Qiao, Zheng, Su, Tang and Dou.)

This is a follow-up study of our previous work, with a specific goal to examine whether older adults are able to maintain or show delayed cognitive and psychosocial benefits of executive function training and physical exercise over a period of 3.5 years on average. Thirty-four participants from the original training study (17 from the executive function training and 17 from the aerobic exercise group) returned and completed a single follow-up session on a set of cognitive and psychosocial outcome measures. The results of the returned follow-up sample showed some significant original training transfer effects in WCST-64 performance but failed to maintain these benefits at the follow-up session. Surprisingly, episodic memory performance showed some significant improvement at the follow-up relative to baseline, signaling delayed benefits. The findings add some novel implications for cognitive training schedule and highlight the possible importance of continuous engagement in long-term cognitive enhancement in healthy older adults., Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yang.)

Background: Acute medical illnesses, surgical interventions, or admissions to hospital in older individuals are frequently associated with a delirium. In this cohort study, we investigated the impact of specific cognitive domains and depression before the occurrence of delirium symptoms in an 8-year observation of older non-hospitalized individuals. Methods: In total, we included 807 participants (48–83 years). Deficits in specific cognitive domains were measured using the CERAD test battery, and depressive symptoms were measured using Beck Depression Inventory and the Geriatric Depression Scale (GDS) before the onset of a delirium. Delirium symptoms were retrospectively assessed by a questionnaire based on the established Nursing Delirium Screening Scale. Results: Fifty-eight of eight hundred seven participants (7.2%) reported delirium symptoms over the 8-year course of the study. Sixty-nine percent (n = 40) of reported delirium symptoms were related to surgeries. In multivariate regression analysis, impaired executive function was an independent risk factor (p = 0.034) for the occurrence of delirium symptoms. Furthermore, age (p = 0.014), comorbidities [captured by the Charlson Comorbidity Index (CCI)] (p < 0.001), and depression (p = 0.012) were significantly associated with reported delirium symptoms. Conclusion: Especially prior to elective surgery or medical interventions, screening for impaired executive function and depression could be helpful to identify patients who are at risk to develop delirium symptoms. [ABSTRACT FROM AUTHOR]

Background: Previous studies have confirmed that physical exercise may be beneficial for brain health, but there is little data on this among older Chinese., Objective: The purpose of this study was to explore the relationship between physical exercise and cognitive impairment, and to explore the possible mechanism by which physical exercise prevents cognitive decline., Materials and Methods: 192 older adults with dementia, 610 older adults with mild cognitive impairment (MCI), and 2,218 healthy older adults were included in the study. Through standardized questionnaires, we obtained their general demographic information (such as gender, age, education, etc.), disease-related information (hypertension and diabetes) and physical exercise information (such as whether they did physical exercise and the frequency of physical exercise, etc.). The mini-mental state examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used to assess their overall cognitive function, while the Wechsler block diagram was used to assess their executive function. Moreover, 164 healthy, randomly selected older adults also underwent brain MRI scans at the same time, and the target brain regions included hippocampus, gray matter, and cerebellar cortex., Results: By using stepwise multiple logistics regression analysis, we found that physical exercise was associated with both MCI ( p = 0.001*, OR = 0.689, 95%CI: 0.553-0.859) and dementia ( p < 0.001*, OR = 0.501, 95%CI: 0.354-0.709), independent of gender, age, education, and other factors. The results of ROC curve showed that the area under the curve of physical exercise in predicting MCI and dementia was 0.551 ( p < 0.001*, 95%CI: 0.525-0.577) and 0.628 ( p = 0.001*, 95%CI: 0.585-0.671), respectively. The results of partial correlation analysis showed that physical exercise was associated with left cerebellar cortex ( r = 0.163, p = 0.023), right cerebellar cortex ( r = 0.175, p = 0.015) and Wechsler block diagram score ( r = 0.235, p = 0.011). Moreover, the results of linear regression analysis mediation model showed that physical exercise may affect Wechsler block diagram score through influencing the thickness of right cerebellum cortex, and the latter may play a partial mediation effect (indirect B = 0.001, p = 0.045)., Conclusion: Physical exercise might be a protective factor for mild cognitive impairment and dementia among the Chinese elderly, and there might be an association among physical exercise, executive function, and the thickness of the cerebellar cortex., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer SZ declared a shared parent affiliation with the authors WL, LY, and SX to the handling editor at the time of review., (Copyright © 2022 Li, Li, Chen, Yue and Xiao.)