Executive Function Composite Scores Research Articles

Reversibility of Cognitive Deficits and Functional Connectivity With Transfusion in Children With Sickle Cell Disease.

People with sickle cell disease (SCD) are at risk of cognitive dysfunction independent of stroke. Diminished functional connectivity in select large-scale networks and white matter integrity reflect the neurologic consequences of SCD. Because chronic transfusion therapy is neuroprotective in preventing stroke and strengthening executive function abilities in people with SCD, we hypothesized that red blood cell (RBC) transfusion facilitates the acute reversal of disruptions in functional connectivity while white matter integrity remains unaffected. Children with SCD receiving chronic transfusion therapy underwent a brain MRI measuring white matter integrity with diffusion tensor imaging and resting-state functional connectivity within 3 days before and after transfusion of RBCs. Cognitive assessments with the NIH Toolbox were acquired after transfusion and then immediately before the following transfusion cycle. Sixteen children with a median age of 12.5 years were included. Global assessments of functional connectivity using homotopy (p = 0.234) or modularity (p = 0.796) did not differ with transfusion. Functional connectivity within the frontoparietal network significantly strengthened after transfusion (median intranetwork Z-score 0.21 [0.17-0.30] before transfusion, 0.29 [0.20-0.36] after transfusion, p < 0.001), while there was not a significant change seen within the sensory motor, visual, auditory, default mode, dorsal attention, or cingulo-opercular networks. Corresponding to the change within the frontoparietal network, there was a significant improvement in executive function abilities after transfusion (median executive function composite score 87.7 [81.3-90.7] before transfusion, 90.3 [84.3-93.7] after transfusion, p = 0.021). Participants with stronger connectivity in the frontoparietal network before transfusion had a significantly greater improvement in the executive function composite score with transfusion (r = 0.565, 95% CI 0.020-0.851, p = 0.044). While functional connectivity and executive abilities strengthened with transfusion, there was not a significant change in white matter integrity as assessed by fractional anisotropy and mean diffusivity within 16 white matter tracts or globally with tract-based spatial statistics. Strengthening of functional connectivity with concomitant improvement in executive function abilities with transfusion suggests that functional connectivity MRI could be used as a biomarker for acutely reversible neurocognitive injury as novel therapeutics are developed for people with SCD.

Computerized assessment of executive functioning: Validation of the CNS Vital Signs executive functioning scores in a sample of community-dwelling older adults

Objective: Computerized assessment of cognitive functioning has gained significant popularity over recent years, yet options for clinical assessment of executive functioning (EF) are lacking. One computerized testing platform, CNS Vital Signs (CNS-VS), offers tests designed to measure EF but requires further validation. The goal of the present study was to validate CNS-VS executive scores against standard clinical measures of EF. We also sought to determine whether a modified CNS-VS composite score that included variables purported to measure inhibition, switching, and working memory would outperform the currently available CNS-VS Executive Function Index. Method: A sample of 73 cognitively healthy older adults completed four tests from the Delis-Kaplan Executive Function System, the Digit Span subtest from the Wechsler Adult Intelligence Scale-fourth edition, and three CNS-VS tasks purported to measure inhibition, switching, and working memory. Results: Performances on the CNS-VS tests were predicted by performances on standard paper-and-pencil measures. Although the currently available CNS-VS Executive Function Index predicted unique variance in a well-validated paper-and-pencil EF composite score, our Modified CNS-VS EF composite accounted for unique variance above and beyond the original CNS-VS Executive Function Index, while the reverse was not true. Conclusions: The present results support the construct validity of CNS-VS EF tests but also suggest that modifications to their current composite scores would improve the prediction of EF performance.

Vessel density mapping of small cerebral vessels on 3D high resolution black blood MRI

Small cerebral blood vessels are largely inaccessible to existing clinical in vivo imaging technologies. This study aims to present a novel analysis pipeline for vessel density mapping of small cerebral blood vessels from high-resolution 3D black-blood MRI at 3T. Twenty-eight subjects (10 under 35 years old, 18 over 60 years old) were imaged with the T1-weighted turbo spin-echo with variable flip angles (T1w TSE-VFA) sequence optimized for black-blood small vessel imaging with iso-0.5 mm spatial resolution (interpolated from 0.51×0.51×0.64 mm3) at 3T. Hessian-based vessel segmentation methods (Jerman, Frangi and Sato filter) were evaluated by vessel landmarks and manual annotation of lenticulostriate arteries (LSAs). Using optimized vessel segmentation, large vessel pruning and non-linear registration, a semiautomatic pipeline was proposed for quantification of small vessel density across brain regions and further for localized detection of small vessel changes across populations. Voxel-level statistics was performed to compare vessel density between two age groups. Additionally, local vessel density of aged subjects was correlated with their corresponding gross cognitive and executive function (EF) scores using Montreal Cognitive Assessment (MoCA) and EF composite scores compiled with Item Response Theory (IRT). Jerman filter showed better performance for vessel segmentation than Frangi and Sato filter which was employed in our pipeline. Small cerebral blood vessels including small artery, arterioles, small veins, and venules on the order of a few hundred microns can be delineated using the proposed analysis pipeline on 3D black-blood MRI at 3T. The mean vessel density across brain regions was significantly higher in young subjects compared to aged subjects. In the aged subjects, localized vessel density was positively correlated with MoCA and IRT EF scores. The proposed pipeline is able to segment, quantify, and detect localized differences in vessel density of small cerebral blood vessels based on 3D high-resolution black-blood MRI. This framework may serve as a tool for localized detection of small vessel density changes in normal aging and cerebral small vessel disease.

Scheltens ratings, clinical white matter hyperintensities and executive: Functioning in the Cache County Memory Study

ObjectiveExamine the association between neuropsychologically assessed executive function and clinically identifiable white matter burden from magnetic resonance imaging, using a visual rating system (Scheltens Rating System) applied to the Cache County Memory Study (CCMS) archival database.MethodWe used the Scheltens Ratings Scale to quantify white matter lesion burden in the CCMS sample and used this metric as a predictor of executive function. The sample included 60 individuals with dementia and 13 healthy controls.ResultsHigher Scheltens ratings were associated with poorer task performance on an Executive Function composite score of common neuropsychological tests. This association held true for both controls and dementing cases.ConclusionsThe current findings support extensive prior literature demonstrating the association between brain vascular health determined by white matter burden and clinical outcomes based on neuropsychological assessment of cognitive performance.

The effect of light exposure on cognitive outcomes at long term follow up in an at‐risk dementia population

AbstractBackgroundCircadian disturbances are a common occurrence in older adult population but are more prevalent in people with dementia. For some individuals, these occurrences begin many years prior to the onset of clinical symptoms and have been suggested as a potential risk factor. As light is the primary synchroniser of the circadian system, the current study aimed to examine if 14‐day light exposure could predict cognitive outcomes of older adults with varying risks of dementia at 2‐year follow‐up.MethodThe study was a retrospective analysis of 195 participants (age = 67, 60.7% female) who attended the Healthy Brain Ageing Clinic in Sydney. At baseline, participants were neurocognitively assessed and wore an actigraph for 14 days and then completed another neurocognitive test battery at their follow‐up. Binary logistic regression was used to determine if participants converted to either Mild Cognitive Impairment (MCI) or dementia was predicted from light exposure (average and maximum) and average time spent in &gt;1000 lux (OR = 1.00), adjusting for age, sex and years of education. Linear regression was used to investigate the relationship between light variables and differences in verbal memory, processing speed and executive function composite scores from baseline to 2 years.ResultLight exposure at 2 years prior did not appear to predict cognitive performance. There was a trend towards moderate to bright light increasing risk of cognitive decline.ConclusionFurther research is needed to understand light exposure and the relationship to circadian rhythms and cognition. As previous light therapy research has been inconclusive, future research will inform treatment approaches.

Examining the Effects of Hospitalization in ADNI Subjects: Characterizing Changes in Cognition and Glucose Metabolism Associated with Inpatient Hospital Stays

AbstractBackgroundRisk of inpatient hospitalization and dementia both increase with age, though no study has attempted to characterize lasting changes in regional brain metabolism occurring after inpatient hospitalization.MethodWe screened adverse events reported to the Alzheimer’s Disease Neuroimaging Initiative (ADNI), identifying subjects with minimum one‐night hospitalizations and two pre‐ and two post‐hospitalization ADNI visits. 523 visits from 133 subjects were included in neuropsychological analysis, with 55 subjects hospitalized for major surgery. An analogous “event date” was set in demographically matched control subjects using the median elapsed time from first visit to hospitalization; 352 visits from 88 controls were included. Memory and executive function composite scores were used to calculate pre‐ and post‐event cognitive trajectories. Pre‐ and post‐event FDG‐PET images were acquired and quantitatively examined using standardized volume of interest (sVOI) analysis. Students t‐tests were used to determine the difference in pre‐ and post‐event trajectories within groups and between groups.ResultWithin‐group analysis of inpatient subjects revealed significantly declined trajectory of memory and executive function after hospitalization (p&lt;0.001, p = 0.02), though the difference in pre‐ and post‐event trajectory did not differ significantly from the control group. There was no significant difference in change in trajectory between subjects with surgical and non‐surgical hospitalizations. To prevent the dilution of metabolic alterations that may begin on one‐side, the sVOI with the greatest decline between post‐ and pre‐event trajectory was chosen for all bilateral volumes. Within the inpatient group, significant decline in metabolic trajectory after hospitalization was observed in the inferior lateral anterior and medial anterior temporal volumes (p&lt;0.005, p&lt;0.0005). This change in metabolic trajectory in the anterior temporal volumes after hospitalization was not significantly different between surgical and non‐surgical subjects. Finally, the decline in trajectory observed in the inferior lateral and medial anterior temporal volumes in the inpatient group was significantly greater than the control group (p = 0.05, p = 0.005), in which no significant decline in trajectory was observed.ConclusionInpatient hospitalization is associated with accelerated decline in metabolic trajectory after discharge in two anterior temporal volumes, regardless of whether the hospitalization was associated with a major surgery.

50 Effects of Cerebrovascular Risk Factors and Alzheimer’s Disease Pathology on Executive Function and Memory Changes: Analysis of the National Alzheimer’s Coordinating Center Cohort

Objective:A common assumption in clinical neuropsychology is that cerebrovascular risk is adversely associated with executive function, while Alzheimer’s disease (AD) primarily targets episodic memory. The goal of the present study was to determine the cross-sectional and longitudinal validity of these assumptions using validated markers of cerebrovascular and AD burden.Participants and Methods:19271 longitudinally-followed participants from the National Alzheimer Coordinating Center (NACC) database (Mean age= 72.25; SD age= 10.42; 58% women; 51.6% CDR= 0, 33.7% CDR= 0.5, 14.7% CDR&gt; 1) were included. Cognitive outcomes were a composite memory score and an executive function composite score (UDS3-EF; Staffaroni et al., 2020). Baseline presence of cerebrovascular disease was indexed by the presence of moderate to severe white matter hyperintensities or lacunar infarct on brain MRI (yes/no), while baseline AD pathology was indexed by the presence of a positive amyloid PET scan or elevated CSF AD biomarkers (yes/no). We used linear mixed effect models to assess the effects of baseline cerebrovascular disease, baseline AD pathology, and their interactions with time in study (years post baseline) controlling for baseline age, sex, education, and baseline MoCA score.Results:Baseline cerebrovascular disease was significantly associated with a lower intercept on executive functioning (between-person effect) (p &lt; -0.001, 95% CI -0.37, -0.14) but not memory, while presence of AD biomarkers was associated with a lower memory intercept (p &lt; -0.001, 95% CI -0.52, -0.39) but not executive function. However, only presence of AD pathology at baseline was associated with faster longitudinal decline on both memory and executive functioning over time. Baseline cerebrovascular disease did not independently relate to rate of cognitive decline.Conclusions:Consistent with widely held assumptions, our between-person analyses showed that MRI evidence of cerebrovascular disease was associated with worse executive functioning but not memory, while biomarker evidence of AD pathology was associated with worse memory but not executive function. Longitudinally, however, AD is the primary driver of decline in both executive and memory function. These results extend our understanding of how pathology impacts cognition in aging cohorts and highlight the importance of using longitudinal models.

1 Executive Functioning and Anxiety/Depressive Symptoms as Mediators Between ADHD and Quality of Life: A 10-year Longitudinal Study

Objective:Attention-Deficit/Hyperactivity Disorder (ADHD) is associated with impaired executive functioning and anxiety/depressive symptoms, which may contribute to reduced quality of life. We tested the hypotheses that (1) a childhood diagnosis of ADHD is related to reduced quality of life in emerging adulthood and that (2) this relationship is mediated by impaired executive functioning and anxiety/depressive symptoms.Participants and Methods:We assessed 85 children and adolescents with ADHD and 50 typically developing peers at baseline (Mean age = 11.6 years, 58% males), two-year follow-up, and 10-year follow-up with neuropsychological tests of executive functioning, the Behavioral Rating Inventory of Executive Function (BRIEF), the Short Moods and Feelings Questionnaire (SMFQ), and the Revised Children’s Manifest Anxiety Scale, second edition (RCMAS-2), as well as the Perceived Quality of Life scale (PQoL) at the 10-year follow-up. Four neuropsychological tests of executive functioning, the Letter-Number Sequencing test (working memory), the Color-Word Interference test condition 3 (response inhibition), the Color-Word Interference test condition 4 (shifting), and the trail making test condition 4 (cognitive flexibility) were combined into a neuropsychological executive functioning composite score based on high factor loadings (&gt; .73). the parent-reported BRIEF indexes, the behavioral regulation index, and the metacognition index were used as measures of everyday executive functioning. We conducted independent samples t-tests to compare the groups and simple and parallel mediation analyses with full information maximum likelihood estimation to examine whether the different executive functioning measures and anxiety/depressive symptoms at two-year follow-up mediated the relationship between baseline ADHD and self-reported quality of life at 10-year follow-up.Results:Baseline ADHD was associated with more difficulties with executive functioning on a composite measure of neuropsychological tests (p &lt; .001, Hedges g = .79) and parent-reported everyday metacognitive (p &lt; .001, Hedges g = 2.37) and behavioral regulation executive functioning (p &lt; .001, Hedges g = 1.55), as well as self-reported anxiety (p &lt; .001, Hedges g = 1.05) and depressive symptoms (p &lt; .001, Hedges g = 1.00) at two-year follow-up. Baseline ADHD was associated with lower self-reported quality of life (p = .001, Hedges g = -.67) at 10-year follow-up. The mediation analysis showed that everyday metacognitive executive functioning (p = .011, ß = -.497) and an anxiety/depressive symptoms composite (p &lt; .001, ß = -.404) parallelly mediated the relationship between ADHD and quality of life.Conclusions:Impaired everyday executive functioning and anxiety/depressive symptoms may represent two distinct pathways to reduced quality of life in emerging adults with a childhood diagnosis of ADHD. These findings stress the importance of targeting both cognitive and emotional aspects in interventions for children and adolescents with ADHD to improve later quality of life.

APOEɛ4 Status and Plasma p-tau181 Levels May Influence Memory and Executive Function Decline in Older Adults Without Dementia.

Elevated tau phosphorylation has been linked to the Apolipoprotein E (APOE) ɛ4 allele, which is considered one of the most significant genes related to Alzheimer's disease (AD). However, it is uncertain whether the impact of increased plasma tau phosphorylated at threonine 181 (p-tau181) on memory and executive function decline would be greater among APOEɛ4 carriers. To investigate the effects of plasma p-tau181 and APOEɛ4 on memory and executive function. The longitudinal analysis included 608 older adults without dementia (aged 72±7 years; 47% female; follow-up period of 1.59±1.47 years) from the ADNI dataset, including 180 individuals with normal cognition and 429 individuals with mild cognitive impairment. Linear mixed-effects models were utilized to assess the contributions of APOEɛ4 status and plasma p-tau181 to longitudinal changes in memory composite score and executive function composite score. At baseline, the APOEɛ4+/Tau+ group exhibited poorer performance in memory composite score and executive function composite score, and an elevated load of cerebrospinal fluid Aβ and tau pathologies. To further understand longitudinal changes, we compared groups directly based on plasma p-tau181 and APOEɛ4 status (four groups: APOEɛ4-/Tau-, APOEɛ4-/Tau+, APOEɛ4+/Tau-, APOEɛ4+/Tau+). Both the memory composite score and executive function composite score showed a significantly greater decline in the APOEɛ4+/Tau+ group than in all other groups. Our findings indicate that there is an interaction between plasma p-tau181 levels and APOEɛ4 status, which contributes to the longitudinal changes of memory and executive function in older adults without dementia.

Cognitive determinants of decisional capacity in neurodegenerative disorders.

Cognitive contributions to decisional capacity are complex and not well understood. Capacity to consent for research has been linked to executive function, but executive function assessment tools are imperfect. In this study, we examine the relationship between decisional capacity and a newly developed executive function composite score and determine whether cognitive performance can predict impaired decisional capacity. This is a cross sectional study of participants at the National Institutes of Health with frontotemporal dementia-amyotrophic lateral sclerosis spectrum disorders enrolled between 2017 and 2022. A structured interview tool was used to ascertain research decisional capacity. Study participant Uniform Data Set (v3.0) executive function (UDS3-EF) composite score, Clinical Dementia Rating Scale©, and Neuropsychiatric Inventory was determined. A decrease in UDS3-EF composite score significantly increased the odds of impaired decisional capacity (OR = 2.92, 95% CI [1.66-5.13], p = 0.0002). Executive function was most impaired in frontotemporal dementia (-2.86, SD = 1.26) and least impaired in amyotrophic lateral sclerosis (-0.52, SD = 1.25) participants. The UDS3-EF composite score was also strongly correlated to the Clinical Dementia Rating Scale©. Decisional capacity is intrinsically related to executive function in neurodegenerative disorders, and executive dysfunction may predict a lack of decisional capacity alerting investigators of the need for additional scrutiny during the informed consent process.

Exploring Co-Regulation-Related Factors in the Mothers of ADHD Children-Proof of Concept Study.

Attention deficit hyperactivity disorder (ADHD) is a complex neurological condition interfering with family relationships and co-regulation capabilities. Therefore, exploring factors underpinning parental co-regulation ability is crucial for future fostering relationships in families of children with ADHD. This preliminary study aims to characterize and compare the executive-functions, anxiety, self-efficacy, and sensory modulation in mothers of children with and without ADHD. Mothers of children with (study group) and without (control-comparison, group) ADHD completed online self-reports, measuring executive-functions; parental self-efficacy; anxiety; and sensory modulation. The study group (N = 40) had lower self-efficacy compared to the control group (N = 27; p = 0.018), and the control group had lower sensory responsiveness (p = 0.025). Within both groups the Behavior Rating Inventory of Executive Function-Adult (BRIEF-A) Global Executive Function Composite score (GEC) and the Beck Anxiety Inventory (BAI) were moderately correlated. Further, within the study group correlations were found between the BRIEF-A-GEC and the Sensory Responsiveness Questionnaire (SRQ)-Aversive scores (r = 0.37, p ≤ 0.01), and between the BRIEF-A Behavioral-Rating-Index and the parental self-efficacy scores (r = 0.31, p ≤ 0.05). Within the control group, negative correlations were found between the BRIEF-A-GEC and SRQ-Hedonic scores (r= -0.44, p < 0.05). Self-efficacy, executive-functions, high sensory responsiveness and anxiety traits are interwoven and may impact parental co-regulation ability.

Executive Function Predicts Older Adults' Lure Discrimination Difficulties on the Mnemonic Similarity Task.

Older adults often have difficulty remembering the details of recently encountered objects. We previously found this with the Mnemonic Similarity Task (MST). Surprisingly, the older adults' MST Lure Discrimination Index (LDI) was significantly correlated with visual acuity but not with memory or executive function. Here we ran a replication with new, larger samples of young (N = 45) and older adults (N = 70). We then combined the original and replication older adult samples (N = 108) to critically examine the relative contributions of visual acuity, memory, and executive function composite scores to LDI performance using dominance analysis. This provided, to our knowledge, the first direct statistical comparison of all 3 of these factors and their interactions on LDI. Participants completed the MST and a battery assessing visual acuity, memory, and executive function. We examined age group differences on MST performance in the new (i.e., replication) young and older adult samples and performed multiple regression and dominance analysis on the combined older adult sample. Consistent with previous findings, the older adults showed significantly poorer LDI but preserved item recognition. LDI was significantly correlated with both memory and executive function but not with visual acuity. In the combined older adult sample, all 3 composites predicted LDI, but dominance analysis indicated that executive function was the most important predictor. Older adults' MST LDI difficulty may be predicted by their executive function and visual acuity. These factors should be considered when interpreting older adults' MST performance.

Different levels of cognitive reserve among typical and limbic‐predominant hypometabolic subtypes of Alzheimer’s Disease

AbstractBackgroundResidual approaches for estimating cognitive reserve (CR) are assumed to reflect relative resilience of individuals to neuropathological change in Alzheimer’s disease (AD). In the present study, we characterized differences in CR in people expressing distinct hypometabolic subtypes of AD‐related neurodegeneration.MethodWe analyzed MRI, FDG‐PET and cognitive performance data of Aβ‐positive participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort, including 58 cognitively normal (CN), 217 prodromal AD and 177 AD dementia participants. Participants’ FDG‐PET scans were classified into the two principal hypometabolic subtypes of AD – typical and limbic‐predominant – as determined previously by a data‐driven clustering analysis. W‐scores were calculated as standardized residuals from a regression model with temporoparietal gray matter (GM) volume adjusted to total intracranial volume (TIV) as the dependent variable and with memory and executive function composite scores, as well as covariates age, gender, TIV and dementia status as independent variables (Fig. 1). The scores were multiplied by “‐1” so that higher values indicated lower than expected temporoparietal GM volume at a given level of cognitive performance and therefore represented higher CR. We evaluated the effects of W‐scores on the risk of clinical progression and longitudinal cognitive decline while including temporoparietal GM as a covariate. We then compared the W‐scores between the two hypometabolic subtypes of AD.ResultHigher W‐scores, indicating higher CR, predicted a lower risk of prodromal AD participants for the progression to AD dementia (hazards ratio = 0.32, 95%CI = [0.19;0.52]). W‐scores were also associated with a slower longitudinal cognitive decline for memory (β = 0.11,p&lt;0.01) and language performance (β = 0.12,p = 0.017) in the subsample of CN and prodromal AD (Fig. 2). The typical hypometabolic subtype showed on average higher W‐scores than the limbic‐predominant subtype in prodromal AD and AD dementia groups.ConclusionConsistent with previous research, CR as assessed by W‐scores was predictive of a lower risk of clinical progression and slower longitudinal cognitive decline. The typical subtype demonstrated higher W‐scores, which suggests a stronger resilience to the impact of neuropathological change on cognition. Future analysis will investigate longitudinal changes in W‐scores and factors contributing to the observed differences, as well as potential explanations for subtype differences.

Active Gains in brain Using Exercise During Aging (AGUEDA): protocol for a randomized controlled trial.

Alzheimer's disease is currently the leading cause of dementia and one of the most expensive, lethal and severe diseases worldwide. Age-related decline in executive function is widespread and plays a key role in subsequent dementia risk. Physical exercise has been proposed as one of the leading non-pharmaceutical approaches to improve executive function and ameliorate cognitive decline. This single-site, two-arm, single-blinded, randomized controlled trial (RCT) will include 90 cognitively normal older adults, aged 65-80 years old. Participants will be randomized to a 24-week resistance exercise program (3 sessions/week, 60 min/session, n = 45), or a wait-list control group (n = 45) which will be asked to maintain their usual lifestyle. All study outcomes will be assessed at baseline and at 24-weeks after the exercise program, with a subset of selected outcomes assessed at 12-weeks. The primary outcome will be indicated by the change in an executive function composite score assessed with a comprehensive neuropsychological battery and the National Institutes of Health Toolbox Cognition Battery. Secondary outcomes will include changes in brain structure and function and amyloid deposition, other cognitive outcomes, and changes in molecular biomarkers assessed in blood, saliva, and fecal samples, physical function, muscular strength, body composition, mental health, and psychosocial parameters. We expect that the resistance exercise program will have positive effects on executive function and related brain structure and function, and will help to understand the molecular, structural, functional, and psychosocial mechanisms involved.

Childhood Executive Function Predicts Internalizing and Externalizing Symptoms in Emerging Adults With and Without Autism: A 10-Year Longitudinal Study

ABSTRACT Individuals with autism spectrum disorder (ASD) and typically developing individuals were assessed on three neuropsychological tests of executive function (EF) and on scales of autism symptoms and co-occurring internalizing and externalizing symptoms at baseline (T1; N = 88, Mage = 11.8 years, 73% males), 2-year (T2; 99% retention, Mage = 13.9 years), and 10-year follow-ups (T3; 75% retention, Mage = 21.4 years). An EF composite score from T1 significantly predicted internalizing symptoms at T2 (β = .228) and internalizing and externalizing symptoms at T3 (β = .431 and .478, respectively), when controlling for age and autism symptoms. OThe findings suggest that EF difficulties are a long-term risk factor for more co-occurring symptoms. .

EFFECT OF A 6-MONTH HOME-BASED WALKING PROGRAM ON COGNITIVE FITNESS IN OLDER ADULTS WITH CHRONIC KIDNEY DISEASE

Abstract We have previously demonstrated that cognitive status and white matter integrity are highly associated with physical fitness in older adult patients with chronic kidney disease (CKD). We present data from a two group RCT determining effect of a 6-month home-based walking intervention on physical and cognitive fitness compared to usual care. The intervention included use of a wearable activity monitor, weekly didactic phone meetings, interactive tools and monthly coach-delivered feedback. The intervention group had a 78% compliance rate to the 6-month exercise program (159.9 (149.2) minutes/week). Executive function composite score and global cognitive for intervention group &amp;gt; than control group. Additionally, global white matter integrity and functional connectivity improved in the intervention group and declined in the usual care group. We conclude that a home-based physical activity intervention can have significant improvement on cognitive health and neuroplasticity in older adults with CKD and lowering their risk of developing AD/ADRD

Dropout risk and effectiveness of retention strategies in the Memory Advancement by Intranasal Insulin in Type 2 Diabetes (MemAID) Clinical Trial

BackgroundEffective recruitment and retention strategies are essential in clinical trials. MethodsThe MemAID trial consisted of 12 visits during 24 weeks of intranasal insulin or placebo treatment and 24 weeks of post-treatment follow-up in older people with and without diabetes. Enhanced retention strategies were implemented mid study to address high drop-out rate. Baseline variables used in Cox regression models to identify dropout risk factors were: demographics and social characteristics, functional measures, metabolic and cardiovascular parameters, and medications. Results244 participants were randomized; 13 (5.3%) were discontinued due to adverse events. From the remaining 231 randomized participants, 65 (28.1%) dropped out, and 166 (71.9%) did not. The Non-retention group included 95 participants not exposed to retention strategies, of which 43 (45.2%) dropped out. The Retention group included 136 participants exposed to enhanced retention strategies, of which 22 (16.2%) dropped out. Dropout risk factors included being unmarried, a longer diabetes duration, using oral antidiabetics as compared to not using, worse executive function and chronic pain. After adjusting for exposure to retention strategies, worse baseline executive function composite score (p = 0.001) and chronic pain diagnosis (p = 0.032) were independently associated with a greater risk of dropping out. The probability of dropping out decreased with longer exposure to retention strategies and the dropout rate per month decreased from 4.1% to 1.8% (p = 0.04) on retention strategies. ConclusionsBaseline characteristics allow prediction of dropping out from a clinical trial in older participants. Retention strategies has been effective at minimizing the impact of dropout-related risk factors.Trial Registration: Clinical trials.gov NCT2415556 3/23/2015 (www.clinicaltrials.gov).

OR15-5 Cognitive Function in Reproductive Aged Individuals with Polycystic Ovary Syndrome

Abstract PCOS by Rotterdam criteria is defined by the presence of at least two of the following: oligomenorrhea, hyperandrogenism and polycystic ovaries. Although not required for diagnosis, PCOS often has metabolic manifestations, particularly insulin resistance. In studies of non-PCOS populations, it appears a nexus may exist between insulin resistance and neuropsychological outcomes, such as cognitive performance (particularly executive function skills), cognitive aging, and depression. Cognitive performance, such as verbal and spatial skills, may also be impacted by gonadal hormones. It is therefore surprising that the relationship between PCOS and neuropsychological outcomes has been only minimally investigated. This study was therefore designed to measure and compare cognition in Rotterdam-PCOS subjects with and without hyperandrogenism and to test the hypothesis that executive function performance (cognitive control, verbal fluency and working memory) is lower in those with hyperandrogenism. Methods Forty-eight sequential subjects with PCOS were recruited from a multi-disciplinary PCOS clinic. Those with clinical/biochemical hyperandrogenism (in addition to oligomenorrhea/polycystic ovaries) were designed "NIH-PCOS" (n=35); while those without hyperandrogenism (only oligomenorrhea and polycystic ovaries) were designated "non-androgenic PCOS" (n=13). Neuropsychological test administration and scoring were performed by trained personnel. Verbal and perceptual reasoning were measured with Wechsler Adult Intelligence Scale (WAIS); memory was measured by California Verbal Learning Trials (long delay recall), and processing speed by WAIS symbol search. Executive functions were measured with Delis-Kaplan System: Stroop and Trail Making (cognitive control); Design and Verbal Fluency (generativity); WAIS: Digit Span (working memory); and Weschler Memory Scale: Symbol Span (working memory). Sample-based z-scores were calculated for cognitive outcomes. We compared z-scores using linear regressions, adjusting for age, race, and years of education. A composite executive function score was calculated as the mean z-score on all six executive function tests. Results Groups were similar for age and BMI, but NIH-PCOS showed greater mean (SD) Homa-IR (4.2 (6.1) vs. 1.82 (1.9); p=.06), compared to non-androgenic PCOS. Cognitive performance was similar for measures of "pre-morbid" IQ, including verbal and perceptual reasoning, memory and processing speed. However, subjects with NIH-PCOS demonstrated lower relative performance for executive functions (β-coefficient for executive function composite z-score: -0.44, 95% CI: -0.79, -0.09; p=0.016). Subdomains showing decreased performance (β-coefficient) included verbal fluency (-0.62; p=.04), working memory (-0.75; p=.04) and cognitive control (-0.53; p=.05). We additionally assessed cognitive performance in relation to insulin resistance (Homa &amp;gt;2.1). Considering non-androgenic PCOS without insulin resistance as referent, NIH-PCOS subjects with insulin resistance showed the lowest performance on the executive function composite score, followed by those with NIH-PCOS without insulin resistance (p-trend = .001). Conclusion People with hyperandrogenic PCOS may experience challenges in executive functioning compared to non-androgenic counterparts. Additional research is needed to confirm findings in larger cohorts and to investigate the role of modifiable factors. Presentation: Sunday, June 12, 2022 12:00 p.m. - 12:15 p.m.

Lipid Peroxidation as a Marker of Apathy and Executive Dysfunction in Patients at Risk for Vascular Cognitive Impairment.

The co-occurrence of apathy and executive dysfunction, a correlate of vascular cognitive impairment (VCI), is highly prevalent, yet facilitating factors are largely unknown. This study investigates the relationship between lipid peroxidation, apathy, and executive dysfunction in patients at risk for VCI. In participants with coronary artery disease, who are at a high risk of VCI, apathy (Apathy Evaluation Scale), and executive function (composite z-score based on age and education population norms from trails making test B, animal naming, and phonemic fluency tests) were assessed. Serum concentrations of an early (lipid hydroperoxide (LPH)) and late (8-isoprostane (8-ISO)) lipid peroxidation marker, were measured and the 8-ISO/LPH ratio was calculated. Participants (n = 206, age±SD = 63.0±7.5, 80% men, total years of education = 15.9±3.4, AES score = 28.3±8.8, executive function = 0±1) demonstrated significantly different 8-ISO/LPH ratios between groups (F(3, 202) = 10.915, p &lt; 0.001) with increasing levels in the following order: no apathy or executive dysfunction, only executive dysfunction (executive function composite score≤-1), only apathy (AES≥28), and both apathy and executive dysfunction. A model adjusting for demographics showed that lipid peroxidation was associated with both apathy (B(SE) = 4.63 (0.954), t = 4.852, p &lt; 0.001) and executive function (B(SE) = -0.19 (0.079), t = -2.377, p = 0.018). However, when controlling for both demographics and vascular risk factors, lipid peroxidation was associated with only apathy (B(SE) = 3.11 (0.987), t = 3.149, p = 0.002). The results highlight a potentially important involvement of lipid peroxidation in the co-occurrence of apathy and executive dysfunction in those at risk for VCI.

0690 Greater variability of sleep disturbance is associated with executive functioning among people with schizophrenia

Abstract Introduction Sleep disturbance is common among people with schizophrenia (PwS) and has been found to be related to poorer cognition in both PwS and non-psychiatric comparison participants (NCs). However, previous findings have been inconsistent on which aspects of executive functioning are most impacted by sleep. Additionally, the relationship of sleep variability to cognition in PwS has yet to be explored. This study aims to further understand the link between cognitive dysfunction and disturbed sleep in PwS and inform future sleep interventions to improve functioning and disability in PwS. Methods The current sample includes 36 participants (18 PwS, 18 NCs) from the San Diego area who completed executive functioning assessments (Delis-Kaplan Executive Function System, D-KEFS). Participants wore a wrist-worn Fitbit activity tracker for a 7-day period to monitor their sleep and activity. Independent samples t-tests were used to examine differences in mean and variability of sleep measures (total sleep time or TST, wake after sleep onset or WASO, and efficiency) and cognitive function between patients and controls. Spearman correlations were run to identify preliminary relationships between cognitive performance and sleep in both groups. Results The PwS and NCs were comparable on sex (50% female, age (mean 53 ± 10 years) and race (majority Caucasian). PwS and NCs were similar in mean sleep and variability of sleep measures. PwS had significantly poorer performance in all cognitive domains (p &amp;lt; 0.05). In the PwS, more variable WASO and sleep efficiency were significantly correlated with worse performance on visual-motor sequencing and motor speed tasks (rs = -0.56 to -0.66). Additionally, trending relationships were found between better executive function composite scores with both longer mean TST (rs = 0.43) and higher mean sleep efficiency (rs = 0.30) over the monitoring period. Data collection is ongoing, and updated results will be presented at the conference. Conclusion Poor sleep is a prominent problem in PwS and has been associated with deficits in various cognitive domains. The present study examines the relationships of mean and variability of sleep with executive functioning. Preliminary results found strong associations between worse and more variable sleep and cognitive performance that may strengthen as sample size increases. Support (If Any) National Institutes of Health [NIMH K23MH119375-01 (PI: Ellen E. Lee), NIMH R01MH094151-01 (PI: Dilip Jeste)]