Executive Function Performance Research Articles

Does comorbid depression impact executive functioning (EF) in adults diagnosed with ADHD?: a comparison of EF across diagnoses in clinically-referred individuals

ABSTRACT Introduction Executive functioning (EF) is a salient factor in both ADHD as well as depressive disorders. However, sparse literature has examined whether depression severity impacts EF concurrently among adults with ADHD. The goal of this study was to examine differences in EF between adult patients diagnosed with ADHD and those diagnosed with a non-ADHD primary psychopathological condition, as a function of both ADHD presentation and depression severity in a diverse clinical sample. Method This crosssectional study included 404 adult patients clinically referred for neuropsychological evaluation to assist with differential diagnosis and/or treatment planning related to known or suspected ADHD. Various EF tasks and a measure of depression severity were administered. One-way MANOVA analyses were conducted to compare EF performance between individuals diagnosed with ADHD or a non-ADHD primary psychopathological condition, with additional analyses examining group differences based on ADHD presentation and depression severity. Regression analyses also examined the potential contribution of depression severity to each EF measure within each group. Results No significant EF performance differences were found when comparing individuals diagnosed with ADHD and those with a non-ADHD primary psychopathological condition, nor based on ADHD presentation. When comparing across groups using cut-offs for high or low depression, only one EF measure showed significant differences between groups. Further, depression severity generally did not predict reduced EF performances with the exception of verbal fluency and working memory performances in select groups. Conclusions This study demonstrated that individuals with ADHD generally perform comparably on EF measures regardless of the presence or absence of comorbid depression. These results suggest further examination of EF deficits when they emerge for adults with ADHD, especially beyond comorbid depression severity.

Neuropsychological Changes in Isolated REM Sleep Behavior Disorder: A Systematic Review and Meta-analysis of Cross-sectional and Longitudinal Studies.

The aim of this meta-analysis is twofold: (a) to assess cognitive impairments in isolated rapid eye movement (REM) sleep behavior disorder (iRBD) patients compared to healthy controls (HC); (b) to quantitatively estimate the risk of developing a neurodegenerative disease in iRBD patients according to baseline cognitive assessment. To address the first aim, cross-sectional studies including polysomnography-confirmed iRBD patients, HC, and reporting neuropsychological testing were included. To address the second aim, longitudinal studies including polysomnography-confirmed iRBD patients, reporting baseline neuropsychological testing for converted and still isolated patients separately were included. The literature search was conducted based on PRISMA guidelines and the protocol was registered at PROSPERO (CRD42021253427). Cross-sectional and longitudinal studies were searched from PubMed, Web of Science, Scopus, and Embase databases. Publication bias and statistical heterogeneity were assessed respectively by funnel plot asymmetry and using I2. Finally, a random-effect model was performed to pool the included studies. 75 cross-sectional (2,398 HC and 2,460 iRBD patients) and 11 longitudinal (495 iRBD patients) studies were selected. Cross-sectional studies showed that iRBD patients performed significantly worse in cognitive screening scores (random-effects (RE) model = -0.69), memory (RE model = -0.64), and executive function (RE model = -0.50) domains compared to HC. The survival analyses conducted for longitudinal studies revealed that lower executive function and language performance, as well as the presence of mild cognitive impairment (MCI), at baseline were associated with an increased risk of conversion at follow-up. Our study underlines the importance of a comprehensive neuropsychological assessment in the context of iRBD.

Is there a link between heart rate variability and cognitive decline? A cross-sectional study on patients with mild cognitive impairment and cognitively healthy controls.

Given that, up to date, there is no effective strategy to treat dementia, a timely start of interventions in a prodromal stage such as mild cognitive impairment (MCI) is considered an important option to lower the overall societal burden. Although autonomic functions have been related to cognitive performance, both aspects have rarely been studied simultaneously in MCI. The aim of the present study was to investigate cardiac autonomic control in older adults with and without MCI. Cardiac autonomic control was assessed by means of heart rate variability (HRV) at resting state and during cognitive tasks in 22 older adults with MCI and 29 healthy controls (HCs). Resting HRV measurement was performed for 5 minutes during a sitting position. Afterwards, participants performed three PC-based tasks to probe performance in executive functions and language abilities (i.e., Stroop, N-back, and a verbal fluency task). Participants with MCI showed a significant reduction of HRV in the frequency-domain (high frequency power) and nonlinear indices (SD2, D2, and DFA1) during resting state compared to HCs. Older individuals with MCI exhibited decreases in RMSSD and increases in DFA1 from resting state to Stroop and N-back tasks, reflecting strong vagal withdrawal, while this parameter remained stable in HCs. The results support the presence of autonomic dysfunction at the early stage of cognitive impairment. Heart rate variability could help in the prediction of cognitive decline as a noninvasive biomarker or as a tool to monitor the effectiveness of therapy and prevention of neurodegenerative diseases.

Executive function performance in middle-aged adults.

The study aimed to observe the effect of hierarchy of educational qualifications (graduate, postgraduate, and PhD) and gender on various executive function tests across middle-aged adults with or without comorbidity. A total of 66 middle-aged individuals volunteered for the study (mean age=48.45±5.45 years; 20 graduates, 28 postgraduates, and 18 PhD; 36 males and 30 females; 38 healthy adults and 28 adults with comorbidities). Each subject performed a test assessing short-term memory, spatial working memory, and multitasking abilities on the Cambridge Neuropsychological Test Automated Battery with rest periods in no specific order of tests. Key parameters of cognitive tests were analyzed for differences in educational qualifications (ANOVA), gender (t-test), and the effect of comorbidity as a covariate (ANCOVA). PhDs performed significantly better (p<0.05) in multitasking than graduates and had superior visuospatial working memory (fewer errors). Differences in simultaneous matching abilities, lower incongruence cost and multitasking cost were statistically significant in healthy females than in males. On considering adults with comorbidity, those with higher educational attainment retained the ability to multitask compared to their healthy counterparts, which was not seen in the group with lower educational attainment. Thus, higher educational attainment attenuated the influence of comorbidities and deterioration of executive functions in general in middle-aged adults.

Classification of Alzheimer's disease and frontotemporal dementia using routine clinical and cognitive measures across multicentric underrepresented samples: A cross sectional observational study.

Global brain health initiatives call for improving methods for the diagnosis of Alzheimer's disease (AD) and frontotemporal dementia (FTD) in underrepresented populations. However, diagnostic procedures in upper-middle-income countries (UMICs) and lower-middle income countries (LMICs), such as Latin American countries (LAC), face multiple challenges. These include the heterogeneity in diagnostic methods, lack of clinical harmonisation, and limited access to biomarkers. This cross-sectional observational study aimed to identify the best combination of predictors to discriminate between AD and FTD using demographic, clinical and cognitive data among 1794 participants [904 diagnosed with AD, 282 diagnosed with FTD, and 606 healthy controls (HCs)] collected in 11 clinical centres across five LAC (ReDLat cohort). A fully automated computational approach included classical statistical methods, support vector machine procedures, and machine learning techniques (random forest and sequential feature selection procedures). Results demonstrated an accurate classification of patients with AD and FTD and HCs. A machine learning model produced the best values to differentiate AD from FTD patients with an accuracy = 0.91. The top features included social cognition, neuropsychiatric symptoms, executive functioning performance, and cognitive screening; with secondary contributions from age, educational attainment, and sex. Results demonstrate that data-driven techniques applied in archival clinical datasets could enhance diagnostic procedures in regions with limited resources. These results also suggest specific fine-grained cognitive and behavioural measures may aid in the diagnosis of AD and FTD in LAC. Moreover, our results highlight an opportunity for harmonisation of clinical tools for dementia diagnosis in the region. This work was supported by the Multi-Partner Consortium to Expand Dementia Research in Latin America (ReDLat), funded by NIA/NIH (R01AG057234), Alzheimer's Association (SG-20-725707-ReDLat), Rainwater Foundation, Takeda (CW2680521), Global Brain Health Institute; as well as CONICET; FONCYT-PICT (2017-1818, 2017-1820); PIIECC, Facultad de Humanidades, Usach; Sistema General de Regalías de Colombia (BPIN2018000100059), Universidad del Valle (CI 5316); ANID/FONDECYT Regular (1210195, 1210176, 1210176); ANID/FONDAP (15150012); ANID/PIA/ANILLOS ACT210096; and Alzheimer's Association GBHI ALZ UK-22-865742.

Acute effects of moderate-intensity continuous physical exercise performed with different amounts of muscle mass on executive function in healthy young adults: a randomized trial.

We examined the effect of amount of muscle mass involved in moderate-intensity continuous physical exercise on executive function. To this end, fifty-five participants completed two acute physical exercise sessions on an airbike ergometer using the upper and lower limbs simultaneously and only the upper limbs, and a resting control session in a randomized order. The physical exercise session lasted 30 min and was performed at moderate intensity (between 64 %-76 % of maximal heart rate evaluated in graded maximal exercise testing). Participants took the Stroop test (congruent and incongruent trials) before and after the sessions to assess executive performance. For the congruent trial, both physical exercise interventions improved executive function performance (pre vs. post, p-value = 0.002 and 0.003 for physical exercise with upper limbs and physical exercise with upper and lower limbs, respectively). Furthermore, executive function performance was higher after the physical exercise interventions than after the control session (p-value = 0.002 and 0.004 for physical exercise with upper limbs and physical exercise with upper and lower limbs, respectively). For the incongruent trial, both physical exercise interventions also improved executive function performance (pre vs. post, p-value < 0.001 for physical exercise with upper limbs and physical exercise with upper and lower limbs, respectively). However, there were no significant differences after both physical exercise interventions and resting control session (p-value = 0.175). Executive function (congruent trial) was positively impacted by acute aerobic physical exercise regardless of the amount of muscle mass involved (upper limbs or upper plus lower limbs). Therefore, we recommend aerobic physical exercise with less or more muscle mass involved to improve cognitive function.

The Effects of Using a Cycling Desk at School on Executive Function, Physical Fitness, and Body Composition in Primary School Children: Impact of Socioeconomic Status.

Physical inactivity and sedentary behaviors are associated with adverse health outcomes in both adults and children. The purpose of this study was to investigate the effects of a 9-week program using a Cycle Desk during school time in French primary school children from high or low socioeconomic status (SES) on body composition, physical fitness (PF), and executive function. Seventy-five (n = 75) children completed a test battery before and after 9weeks of use of Cycle Desk to evaluate anthropometric characteristics, body composition, PF, and executive function. Body mass index increased significantly (P = .0095), while body fat decreased after the use of Cycle Desks (P < .0001). Specifically, lean mass increased in the high-SES group while it decreased in the low-SES group (P < .0001). After 9weeks, there was an improvement in motor skills (P < .0001), upper and lower limbs' strength (P < .0001), and executive function performance (P < .0001). More specifically, the low-SES group had a greater improvement in motor skills and maximal aerobic speed between T0 and T1, compared to the high-SES group (P = .001, P = .023, respectively). In contrast, the high-SES group had a greater improvement in executive function at 9weeks of use of Cycle Desk compared with the low-SES group (P = .0084). The promotion of low-intensity physical activity with the use of a Cycle Desk at school may help offset some adverse effects of excess sedentary behavior among children. Moreover, this strategy appears to be particularly effective in children from low-SES backgrounds. What's New: The use of a Cycle Desk during school time has no deleterious effects on PF as well as cognitive executive functions in primary children. Modifications are more beneficial in children from low SES.

Carotid Intima-Media Thickness (cIMT) and Cognitive Performance: A Population-Based Cross-Sectional Study From North India.

Atherosclerosis has been shown to impact cognitive impairment, with most of the evidence originating from European, African, or East Asian populations that have employed carotid intima-media thickness (cIMT) as a biomarker for atherosclerosis. Vascular disease is related to dementia/cognitive decline. There is no community-based study from India that has looked at the association of cIMT with cognitive performance. In this cross-sectional study between December 2014 and 2019, we recruited 7505 persons [(mean age 64.6 (9.2)y) and 50.9% women] from a community-dwelling population in New Delhi. These persons underwent carotid ultrasound to quantify cIMT and a cognitive test battery that tapped into memory, processing speed, and executive function. We also computed the general cognitive factor (g-factor), which was identified as the first unrotated component of the principal component analysis and explained 37.4% of all variances in the cognitive tests. We constructed multivariate linear regression models adjusted for age, sex, education, and cardiovascular risk factors. Additional adjustment was made for depression, anxiety, and psychosocial support in the final model. We found a significant association of higher cIMT with worse performance in general cognition (β=-0. 01(95% CI: -0.01; -0.01); P<0.001), processing speed (β=-0.20; 95% CI: -0.34; -0.07); P=0.003), memory (β=-0.29; 95% CI: -0.53; -0.05); P=0.016), and executive function (β=-0.54; 95% CI: -0.75; -0.33); P=<0.001). There was no statistically significant association of cIMT with Mini-Mental Status Examination score (β=0.02; 95% CI: -0.34; 0.40; 0.89). The cross-sectional study found significant associations of increased cIMT with worse performance in global cognition, information processing, memory, and executive function.

Fornix degeneration in risk factors of Alzheimer's disease, possible trigger of cognitive decline.

Risk factors of late-onset Alzheimer's disease (AD) such as aging, type 2 diabetes, obesity, heart failure, and traumatic brain injury can facilitate the appearance of cognitive decline and dementia by triggering cerebrovascular pathology and neuroinflammation. White matter (WM) microstructure and function are especially vulnerable to these conditions. Microstructural WM changes, assessed with diffusion weighted magnetic resonance imaging, can already be detected at preclinical stages of AD, and in the presence of the aforementioned risk factors. Particularly, the limbic system and cortico-cortical association WM tracts, which myelinate late during brain development, degenerate at the earliest stages. The fornix, a C-shaped WM tract that originates from the hippocampus, is one of the limbic tracts that shows early microstructural changes. Fornix integrity is necessary for ensuring an intact executive function and memory performance. Thus, a better understanding of the mechanisms that cause fornix degeneration is critical in the development of therapeutic strategies aiming to prevent cognitive decline in populations at risk. In this literature review, i) we deepen the idea that partial loss of forniceal integrity is an early event in AD, ii) we describe the role that common risk factors of AD can play in the degeneration of the fornix, and iii) we discuss some potential cellular and physiological mechanisms of WM degeneration in the scenario of cerebrovascular disease and inflammation.

Promoting psychological well-being in preschool children: study protocol for a randomized controlled trial of a mindfulness- and yoga-based socio-emotional learning intervention

BackgroundMental health issues in youths have cascading negative effects on school outcomes, professional life, and physical health. Psychological well-being (P-WB) is an important protective factor against mental illness. Preliminary research suggests that mindfulness- and yoga-based socio-emotional learning (SEL) interventions can each have a positive impact on preschoolers P-WB. The objective of this trial is to rigorously evaluate the effect of a 24-week combined mindfulness- and yoga- based SEL intervention in preschool children from a French socio-economically disadvantaged area.MethodsThe P-WB promotion intervention is compared to a wait-list control condition in a cluster randomized controlled trial (RCT). Sixty-four pre-Kindergarten classrooms are randomized to the intervention or control group. Primary outcomes measure self-management capacity and core P-WB components: connection, insight, engagement, and positive relationship. Secondary outcomes include measures of mental health, executive functioning, and school performance. Primary and secondary outcomes are assessed through teacher questionnaires, standardized observations of children in school context, and experimental tasks and by collecting results of the national evaluation at first grade. All children-level outcomes are evaluated at pre-intervention, at the end of the intervention, and 1 year later (follow-up analysis), to the exception of school performance which is evaluated at follow-up only. Intention-to-treat analyses, accounting for clustering within classes, will adopt a random effects linear regression model to examine outcomes for the intervention versus control children.DiscussionThis is the first trial to rigorously evaluate a combined mindfulness- and yoga-based P-WB promotion intervention, and the first RCT evaluating a SEL curriculum in French schools. Results may have key implications for P-WB promotion in preschool children.Trial registrationhttps://www.drks.de/ DRKS00028623. Retrospectively registered on 30 May 2022

Effects of 12 Weeks of Physical-Cognitive Dual-Task Training on Executive Functions, Depression, Sleep Quality, and Quality of Life in Older Adult Women: A Randomized Pilot Study

This study aims to examine the effects of 12 weeks of physical-cognitive dual-task training on cognition, depression, sleep quality, and quality of life in older women (n = 44; 66.20 ± 4.05 years). Of these, 22 were randomly allocated to the dual-task training (DT) group, and 22 participated in the activities of the education control group (CG). Assessments were performed at baseline, at the end of 12 weeks of intervention, and after 12 weeks of follow-up using the following instruments: Trail Making Test parts A and B, ΔTMT (B-A), Stroop test parts A, B, C, and ΔStroop (C-B), Geriatric Depression Scale (GDS), sleep quality (PSQI), quality of life (SF-36). The results showed a positive and significant time-group interaction for two cognitive domains (TMT and Stroop). No time-group interaction effect was indicated for depression and sleep quality perception. There was a positive and significant interaction effect between time and group for three SF-36 subcategories (physical function, physical role, and general health). Our training protocol was not able to improve depressive symptoms and sleep quality. On the other hand, DT training was able to promote the performance of executive functions and the physical and mental component summary of the quality of life with lasting effects of up to 12 weeks after the intervention.

COGNITIVE PROFILES OF SPOUSAL AND PARENTAL CAREGIVERS: AN HRS STUDY

Abstract Previous work analyzing the health and wellbeing correlates of caregiving has found increased rates of depression (Caputo, Pavalko, &amp; Hardy, 2016), anxiety (Joling et al., 2015), and elevated risks of health problems, specifically cardiovascular-related incidents like hypertension (Capistrant, Moon, &amp; Glymour, 2012), cardiovascular disease (Capistrant et al., 2012), and strokes (Haley et al., 2010). Research on specific cognitive effects that this responsibility may elicit has been less of an area of focus, especially when examining domains related to executive functioning. The present research investigated whether executive functioning mechanisms (such as processing speed, recall, and attention) are impacted in caregivers and if their function is mediated by interpersonal factors like birth year, gender, education, and depressive symptomology. Using the Health and Retirement Study, we compared spousal and parental caregivers of persons with medical conditions (n = 143) and non-caregivers (n = 975) who completed the 2015 Consumer and Activities Mail Survey (CAMS). Additional demographic and cognitive performance information was paired from the corresponding RAND 2016 data and the 2016 Harmonized Cognitive Assessment Protocol (HCAP) data. Preliminary ANCOVA results indicated, surprisingly, that spousal/parental caregivers were more likely to exhibit better executive function performance (p &amp;lt; .05) compared to non-caregivers, while delayed recall measures were not linked to caregiving status. These results indicate that intact executive function might be linked to one’s ability to provide caregiving for parents and/or spouses; while the HCAP was only administered at a single time point, future research should examine the longitudinal effects of caregiving on cognitive function.

Do executive function performance, gaze behavior, and pupil size change during incremental acute physical exercise?

Several studies have investigated the interaction between acute physical exercise and cognitive performance. However, few studies have investigated this issue during acute high-intensity exercise. In the present study, we evaluated executive functions (EFs) during incremental exercise in three different intensities [below lactate threshold (LT), at LT, and above LT], measuring EFs performance, gaze behavior, and pupil diameter. Twenty subjects were familiarized with the EFs test and participated in a graded maximal exercise test on a cycle ergometer on the first visit. On the second visit, they performed the EFs task at rest and while exercising at three different intensities using mobile eye-tracking glasses. Our results showed that the psychophysiological measures differed between the conditions. Regarding EFs performance, during exercise above LT, the subjects showed worse accuracy when compared with rest (p < .001) and below LT (p < .001). In addition, the response time (RT) at LT and above LT was shorter than in the rest condition (p < .050). Further, RT was faster (p=.002) in the above LT than in the below LT condition. In addition, the gaze behavior measures indicated that exercise, independently of the intensity, improves the number of fixations with shorter fixation durations compared to the rest condition (p < .050). Additionally, we found no significant differences in average and peak pupil diameter between conditions. In conclusion, exercise at LT improves the EFs performance while exercising above LT worsens EFs performance. However, there were no significant differences in average and peak pupil diameter between conditions.

COGNITIVE EFFECTS OF PM2.5 EXPOSURE FROM MID-LIFE TO EARLY OLD AGE

Abstract Air pollution exposure is a notable public health hazard with adverse effects on multiple health outcomes as well as with increased risk of developing cognitive impairment, Alzheimer’s disease, and related dementias. Few studies examine associations between air pollution exposure in midlife or the transition from midlife to old age. We examined associations between exposure in midlife and cognitive functioning in early old age in ~800 men from the Vietnam Era Twin Study of Aging. Measures included PM2.5 and NO2 exposure in the three years prior to the time 1 (mean age 56; range 51-61) assessment, and cognitive performance in 5 domains at time 1 and time 2 (mean age 68; range 65-72). Analyses adjusted for multiple health and lifestyle covariates. Cognitive performance in all domains was worse at age 68 than at age 56. There was a main effect of midlife PM2.5 on verbal fluency; greater PM2.5 exposure was associated with worse fluency. This association was at a trend level for NO2. In addition, we found significant PM2.5-by-APOE genotype interactions. Increased exposure to PM2.5 in midlife was related to lower executive function and working memory performance in APOE-ε4 carriers, but not non-carriers. Both early executive deficits and APOE-ε4 status have been associated with increased risk for progression to mild cognitive impairment and Alzheimer’s disease. The present results indicate that midlife PM2.5 exposure in men is an additional factor contributing to poorer frontal-executive function, and that APOEε4 carriers are more susceptible to the deleterious effects of PM2.5.

Controlling parenting and executive functioning in children born preterm

This study investigated the relations between mothers’ and fathers’ controlling behaviors and the executive functioning of children born preterm. Sixty-eight preterm children and their parents were assessed when the children were 3 ½ years old. The executive functioning was measured using the Head-to-Toes-Task and controlling parenting behaviors were measured through a standardized observation of a parent-child interaction. Hierarchical regression analysis showed that both mothers’ and fathers’ controlling behaviors were associated with worse child executive functioning performance, after controlling for the child’s cognitive ability. Findings suggest that both mothers and fathers play an important role in the development of executive functioning of children born prematurely, highlighting the need to consider both parents in the study of and intervention with these children.

Associations of audiometric hearing and speech-in-noise performance with cognitive decline among older adults: The Baltimore Longitudinal Study of Aging (BLSA).

Established associations between hearing loss and cognitive decline were primarily defined by pure-tone audiometry, which reflects peripheral hearing ability. Speech-in-noise performance, which reflects central hearing ability, is more limited in prior literature. We examined the longitudinal associations of audiometric hearing and speech-in-noise performance with cognitive decline. We studied 702 participants aged ≥60 years in the Baltimore Longitudinal Study of Aging 2012-2019. Global and domain-specific (language, memory, attention, executive function, visuospatial ability) cognitive performance were assessed by the cognitive assessment battery. Hearing thresholds at 0.5, 1, 2, and 4 kilohertz obtained from pure-tone audiometry were averaged to calculate better-ear pure-tone average (PTA) and participants were categorized as having hearing loss (>25 decibels hearing level [dB HL]) or normal hearing (≤25 dB HL). Speech-in-noise performance was assessed by the Quick Speech-in-Noise (QuickSIN) test, and participants were categorized as having below-median (worse) or above-median performance. Linear mixed effects models with random intercepts and slopes were used to assess baseline cognitive performance and cognitive decline by hearing status. Models adjusted for demographic, lifestyle and disease factors. Participants with audiometric hearing loss showed similar baseline cognitive performance but faster decline in global cognitive function, language, executive function, and attention. Participants with below-median QuickSIN score showed worse baseline cognitive performance in all domains and faster decline in global cognitive function, language, memory, executive function and attention. Audiometric hearing might be targeted to delay cognitive decline. Speech-in-noise performance might be a novel marker and might be more sensitive to memory decline.

Altered frontal connectivity as a mechanism for executive function deficits in fragile X syndrome.

Fragile X syndrome (FXS) is the leading inherited monogenic cause of intellectual disability and autism spectrum disorder. Executive function (EF), necessary for adaptive goal-oriented behavior and dependent on frontal lobe function, is impaired in individuals with FXS. Yet, little is known how alterations in frontal lobe neural activity is related to EF deficits in FXS. Sixty-one participants with FXS (54% males) and 71 age- and sex-matched typically-developing controls (TDC; 58% males) completed a five-minute resting state electroencephalography (EEG) protocol and a computerized battery of tests of EF, the Test of Attentional Performance for Children (KiTAP). Following source localization (minimum-norm estimate), we computed debiased weighted phase lag index (dWPLI), a phase connectivity value, for pairings between 18 nodes in frontal regions for gamma (30-55Hz) and alpha (10.5-12.5Hz) bands. Linear models were generated with fixed factors of group, sex, frequency, and connection. Relationships between frontal connectivity and EF variables also were examined. Individuals with FXS demonstrated increased gamma band and reduced alpha band connectivity across all frontal regions and across hemispheres compared to TDC. After controlling for nonverbal IQ, increased error rates on EF tasks were associated with increased gamma band and reduced alpha band connectivity. Frontal connectivity findings are limited to intrinsic brain activity during rest and may not generalize to frontal connectivity during EF tasks or everyday function. We report gamma hyper-connectivity and alpha hypo-connectivity within source-localized frontal brain regions in FXS compared to TDC during resting-state EEG. For the first time in FXS, we report significant associations between EF and altered frontal connectivity, with increased error rate relating to increased gamma band connectivity and reduced alpha band connectivity. These findings suggest increased phase connectivity within gamma band may impair EF performance, whereas greater alpha band connectivity may provide compensatory support for EF. Together, these findings provide important insight into neurophysiological mechanisms of EF deficits in FXS and provide novel targets for treatment development.

Brain functional connectivity alterations associated with neuropsychological performance 6-9months following SARS-CoV-2 infection.

Neuropsychological deficits and brain damage following SARS-CoV-2 infection are not well understood. Then, 116 patients, with either severe, moderate, or mild disease in the acute phase underwent neuropsychological and olfactory tests, as well as completed psychiatric and respiratory questionnaires at 223 ± 42 days postinfection. Additionally, a subgroup of 50 patients underwent functional magnetic resonance imaging. Patients in the severe group displayed poorer verbal episodic memory performances, and moderate patients had reduced mental flexibility. Neuroimaging revealed patterns of hypofunctional and hyperfunctional connectivities in severe patients, while only hyperconnectivity patterns were observed for moderate. The default mode, somatosensory, dorsal attention, subcortical, and cerebellar networks were implicated. Partial least squares correlations analysis confirmed specific association between memory, executive functions performances and brain functional connectivity. The severity of the infection in the acute phase is a predictor of neuropsychological performance 6-9months following SARS-CoV-2 infection. SARS-CoV-2 infection causes long-term memory and executive dysfunctions, related to large-scale functional brain connectivity alterations.

Lower baseline cerebral oxygen extraction and metabolic rate are associated with faster cognitive decline and brain atrophy over a longitudinal follow‐up period

AbstractBackgroundOxygen extraction fraction (OEF), cerebral blood flow (CBF), and cerebral metabolic rate of oxygen (CMRO2) are complexly interrelated. Low OEF and CMRO2 are promising early indicators of Alzheimer’s disease (AD) pathophysiology. To better understand how alterations in cerebral oxygen utilization relate to abnormal brain aging, we investigated baseline oxygen metabolism variables (OEF, CBF, CMRO2) in relation to longitudinal cognition and brain structure, and if these associations were different among individuals at genetic risk for sporadic AD (i.e., apolipoprotein E (APOE)‐ε4 carriers).MethodsVanderbilt Memory and Aging Project participants (n=244, 74±7 years, mean follow‐up=3.7 years) underwent serial neuropsychological testing and multimodal 3T brain MRI. We used T2‐relaxation‐under‐spin‐tagging to calculate OEF and pseudo‐continuous arterial spin‐labeling to assess grey matter CBF. CMRO2 was calculated as: CMRO2=OEF*CBF*arterial oxygen content. Linear mixed‐effects regression models related time x oxygen metabolism variable (one predictor per model) to longitudinal cognitive and brain MRI outcomes. Models were adjusted for baseline age, sex, race/ethnicity, education, Framingham Stroke Risk Profile, cognitive status, intracranial volume (for MRI outcomes), APOE‐ε4 status, and time. Models were repeated testing anAPOE‐ε4 status x oxygen metabolism variable x time interaction term.ResultsLower baseline OEF was associated with faster hippocampal atrophy (p=0.02). Lower baseline CBF was associated with faster cortical thinning in regions susceptible to AD‐related neurodegeneration (p=0.008). Lower baseline CMRO2 was associated with faster language decline (p=0.01) and hippocampal atrophy (p=0.01) and inferior lateral ventricle volume increase (reflecting faster atrophy of adjacent tissue; p=0.02). OEF interacted with APOE‐ε4 status on executive function (p=0.002), language (p=0.006), and visuospatial performances (p=0.02), and inferior lateral ventricle volume (p=0.007). CBF interacted with APOE‐ε4 status on executive function performance (p=0.0003). CMRO2 interacted with APOE‐ε4 status on temporal lobe volume (p=0.03). In stratified models, lower baseline OEF and CMRO2 tended to relate to faster brain health decline among APOE‐ε4 carriers.ConclusionsLower OEF, CBF, and CMRO2 are associated with worse brain health trajectories over a 4‐year follow‐up. Assessing oxygen metabolism variables in combination may provide more comprehensive insight into longitudinal brain aging and serve as an early biomarker of disease, particularly among older adults at genetic risk for AD.FundingT32‐AG058524, IIRG‐08‐88733, R01‐AG034962, R01‐NS100980

Declining Gait Speed is associated with Deteriorating Executive Performance in people with Mild Cognitive Impairment

AbstractBackgroundThe Motoric Cognitive Risk Syndrome has highlighted the link between cognitive and motor performance, and the associated incremental higher risk of developing dementia. There is considerable debate regarding what aspects of cognition (working memory, executive function, attention) are most associated with gait changes. This study investigates the relationship between mobility scores and cognitive profiles in individuals with Mild Cognitive Impairment (MCI) specifically with regard to executive performance and amnestic/non‐amnestic profiles.MethodParticipants diagnosed with MCI, (Clinical Dementia Rating scale global score of ≤0.5, sum of boxes score ≤4.0), attending a regional specialist memory service had a three‐meter Timed Up and Go (TUG) gait assessment and multi‐domain neuropsychiatric assessment undertaken. Amnestic neuropsychiatric profile was defined as Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) delayed memory subset score &lt;1SD i.e. ≤16th centile below norm for age/ education. Executive function performance was assessed using the Executive Interview (EXIT‐25) where higher scores reflect poorer executive performance.ResultData was reviewed for 161 patients with MCI; 53% (86/161) women. 80% (129/161) had an amnestic neuropsychiatric profile, mean age 73.8 ±7.2 (51‐94). 20% (32/161) had non‐amnestic MCI, mean age 74 ±7.07 (60‐87). There was no significant difference in TUG results between amnestic and non‐amnestic MCI patients (11.2 ±3.3 vs 10.7 ±3.1 p = NS). There was a significant increase in TUG values with worsening executive function performance [EXIT‐25 score 0–9 (88/161) mean TUG = 10.5 ±3.3 seconds vs EXIT‐25 score 10–14 (43/161) mean TUG = 11.9 ±2.8 seconds vs EXIT‐25 score 15–25 (30/161) mean TUG = 12.1 ±3.9 seconds; p = 0.021] which persisted after controlling for age, gender and other relevant cofactors.ConclusionReflective of the importance of frontal lobe integration to the respective tasks, subtle differences in gait performance are associated with executive function performance regardless of predominant amnestic or non‐amnestic MCI profile.