Executive Function Abilities Research Articles

Circadian Rest and Activity Rhythms and Cognitive Change in the Baltimore Longitudinal Study of Aging

Alterations in 24-hour movement patterns, or circadian rest/activity rhythms (RARs), commonly occur with aging. Using linear mixed effects (LME) modeling, we examined associations of baseline RARs with longitudinal change in cognition. Participants (N=424; 47% male, baseline age 72.8±10.1 years) were from the Baltimore Longitudinal Study of Aging and completed 5.6±0.8 nights of wrist actigraphy at baseline. Tests of memory, executive function, attention, language, and visuospatial ability were administered at baseline and subsequent visits (3.7±1.7 years of follow-up in those with >1 visit (n=295)). In unadjusted random intercept and slope LME models, greater RAR stability predicted slower memory decline, and higher activity during participants’ least active 5 hours (L5) predicted slower decline in visuospatial ability. After covariate adjustment, higher activity in participants’ most active 10 hours (M10) and higher L5 predicted slower decline in visuospatial ability (p<.05). Further research is needed on RARs as risk factors for later-life cognitive decline.

Depressive Symptoms Moderate the Association Between Lifetime Discrimination and Inhibition Among Older Adults

Discrimination has been identified as a potentially modifiable environmental stressor that reduces cognitive function. As the burden of discrimination can extend from early to late life, understanding its role in cognition in late life is critical. Further, understanding the potential moderating influence of depressive symptoms, which are common among older adults, on the linkage between discrimination and cognition, may provide further insight into the potential patterns of psychosocial stress and negative affect that may promote cognitive decline and dementia. Thus, we sought to examine whether depressive symptoms moderate linear relations of lifetime discrimination to cognitive function in the domains of visuospatial, verbal, and working memory, executive function, and psychomotor ability, adjusting for age, sex, race, and education. Participants were 165 older adults (34% male) with a mean age of 68.43y. Participants completed a health screening, a battery of cognitive tests, a psychosocial assessment, and cardiovascular testing relevant to the larger study. Linear regression results showed a significant interaction between lifetime discrimination and depressive symptoms (p<.05) related to the Stroop interference score, a measure of inhibition. A probe of the interaction showed that greater lifetime discrimination was associated with better inhibition among participants with fewer depressive symptoms. This paradoxical finding is consistent with scant research that shows exposure to discrimination may heighten performance, and is more common among individuals that have achieved more, both educationally and vocationally. Greater depressive symptomatology may reduce this paradoxical association. Future research should explore this question both longitudinally and in a larger sample.

Depressive Symptoms Moderate the Association Between Lifetime Discrimination and Inhibition Among Older Adults

Cognition relates longitudinally and cross-sectionally to physical and psychological health among older adults. The Vascular Hypothesis of Aging (Drewelies & Gerstorf, 2020) suggests that illnesses of a vascular nature (e.g., stroke, hypertension, severe varicose veins) negatively affect cognitive abilities. Awareness of age-related change (AARC) is also related to cognition. What is not known is whether the presence of a vascular illness and daily cognitive abilities interact to predict daily awareness of age-related changes. The purpose of this study is to examine the daily fluctuations of cognition, (i.e., memory failures) and their interaction with vascular illness to predict daily awareness of age-related changes. Data were analyzed from 104 participants (M age = 64.67, 60-90 years) who completed online self-report questionnaires. On Day 1, participants answered baseline questionnaires regarding presence of vascular illness, and on Days 2-9 completed measures regarding AARC losses and memory failures. Multilevel models revealed main effects of daily memory failures on awareness of age-related losses, such that on days with more memory failures, older adults reported more age-related losses. We also found a main effect for vascular illness, such that those with a vascular illness reported higher levels of daily age-related losses. We did not find a significant interaction between vascular illness and daily memory failures on daily reported age-related losses. Our results provide preliminary evidence that the vascular hypothesis of aging may also extend to perceptions of age-related changes. Future research could consider examining daily symptoms of vascular illness as they unfold over time.

The role of infant attention and parental sensitivity in infant cognitive development in the Netherlands and China

Infant attention and parental sensitivity are important predictors of later child executive function (EF). However, most studies have investigated infant and parent factors in relation to child EF separately and included only mothers from Western samples. The current study examined whether both infant attention at 4 months and parental sensitivity at 4 and 14 months were related to infant EF (i.e., inhibition, working memory, and cognitive flexibility) at 14 months among 124 Dutch and 63 Chinese first-time mothers and fathers and their infants. Findings revealed that parental sensitivity at 4 months was not correlated with infant EF abilities at 14 months. However, infant attention at 4 months was significantly related to 14-month working memory, but not to inhibition and cognitive flexibility. Maternal sensitivity at 14 months was significantly related to 14-month inhibition, but not to working memory and cognitive flexibility. No country differences were found in the relation among 4-month infant attention, parental sensitivity, and EF outcomes. Results show that both infant and parent factors are associated with early EF development and that these correlates of early EF skills may be similar in Western and non-Western samples.

Topographical functional correlates of interindividual differences in executive functions in young healthy twins

Executive functions (EF) are a set of higher-order cognitive abilities that enable goal-directed behavior by controlling lower-level operations. In the brain, those functions have been traditionally associated with activity in the Frontoparietal Network, but recent neuroimaging studies have challenged this view in favor of more widespread cortical involvement. In the present study, we aimed to explore whether the network that serves as critical hubs at rest, which we term network reliance, differentiate individuals as a function of their level of EF. Furthermore, we investigated whether such differences are driven by genetic as compared to environmental factors. For this purpose, resting-state functional magnetic resonance imaging data and the behavioral testing of 453 twins from the Colorado Longitudinal Twins Study were analyzed. Separate indices of EF performance were obtained according to a bifactor unity/diversity model, distinguishing between three independent components representing: Common EF, Shifting-specific and Updating-specific abilities. Through an approach of step-wise in silico network lesioning of the individual functional connectome, we show that interindividual differences in EF are associated with different dependencies on neural networks at rest. Furthermore, these patterns show evidence of mild heritability. Such findings add knowledge to the understanding of brain states at rest and their connection with human behavior, and how they might be shaped by genetic influences.

Alzheimer’s disease polygenic scores predict changes in executive function across 12 years in late middle age

Genome-wide association studies are instrumental in quantifying genetic influences underlying Alzheimer's disease (AD), and applications of polygenic scores derived from association studies have already shed light on early disease pathology. For example, AD polygenic scores (AD-PGS) are associated with amnestic mild cognitive impairment (MCI) diagnoses in midlife. What remains unclear is how AD-PGS relate to objectively measured cognitive changes across midlife. Moreover, executive function abilities have been somewhat neglected despite prominent executive impairments in MCI and AD. Here we tested the hypothesis that an AD-PGS would be associated with executive function and episodic memory changes across late midlife.We examined 1412 men in the Vietnam Era Twin Study of Aging (VETSA) who were cognitively normal at their first assessment and had up to 3 cognitive assessments across 10-12 years (mean ages 56, 62, and 68). Latent growth models of executive function were based on 6 tasks spanning inhibition, shifting, and working memory subdomains and growth models of episodic memory were based on 7 subtests from the Logical Memory, Visual Reproductions, and California Verbal Learning tests. The AD-PRS (Lambert et al. 2013) significantly differentiated MCI and cognitively normal participants in earlier VETSA investigations.Latent growth models of executive function and memory indicated that, compared to baseline performance (i.e., intercept at mean age 56), 10-year variability in cognitive change was comparatively larger for executive function (e.g., slope variance/intercept variance ratio=39% for executive function, 22% for memory). Importantly, individuals with higher AD-PGS had sharper declines in executive functioning (r= -.24, 95% CI [-.41, -.08]) but not episodic memory (r= -.11, 95% CI [-.25, .04]). Baseline executive function (r=.00) and memory (r=-.02) were not associated with PD-PGS.AD genetic risk was associated with executive function changes, but not episodic memory changes, across midlife. These findings highlight the importance of considering executive function changes in midlife, especially for predicting disease progression and AD biology. Executive functions are one of the first cognitive abilities to decline in midlife in normal aging. This study is among the first to demonstrate that this decline also relates to AD genetic influences.

Association of blood cell parameters of peripheral inflammation with cognitive function

AbstractBackgroundChronic peripheral inflammation is associated with cognitive decline and increased risk of dementia. Easily measured circulating blood cell parameters, including the neutrophil to lymphocyte ratio (NLR), red cell distribution width (RDW), and mean platelet volume (MPV), reflect peripheral inflammation. We sought to investigate the cross‐sectional association between these measures and neuropsychological (NP) test performance in the Framingham Heart Study (FHS) Offspring, Third‐generation, and Omni cohorts.MethodWe identified FHS participants who attended an exam that included a complete blood cell count sample and underwent NP testing within five years of blood draw. Linear mixed effect models were used to investigate the association between the blood cell parameters (NLR, RDW, MPV) and individual NP test scores adjusting for age, sex, education, cohort, time between blood draw and NP testing, prevalent cardiovascular disease, APOE‐ε4 genotype, and C‐reactive protein, and accounting for familial correlation using a random effect. We additionally tested for interactions between age (≥ 60 years vs. &lt; 60 years) and blood cell parameters on NP scores and associations were reported separately by age group when significant (P for interaction ≤ 0.01).ResultAmong the 3531 participants (mean age 60.3 years, range 25 to 97 years, 47% male), 80% had at least some college and 22% were APOE‐ε4 carriers. We observed significant association between higher NLR and poorer NP performance on visual reproductions – delayed recall, Trails B ‐ Trails A, and Hooper visual organization test, that assess visual memory, executive function, and visuospatial abilities respectively (Table). There was also a significant association between higher RDW and poorer performance on digit symbol test assessing executive function. We observed different effects for the two age groups for the association between RDW and a metric of executive function (i.e., Trails B ‐ Trails A), where higher RDW correlated with decreased cognitive performance in participants aged ≥ 60 years (n=1865).ConclusionChronic peripheral inflammation as measured by NLR and RDW associates with lower cognitive function in FHS participants ≥ 60 years. In younger individuals, chronic peripheral inflammation may have a smaller effect on cognitive function.

The association between personality and longitudinal cognitive trajectories is independent of baseline brain variables

AbstractBackgroundPrevious work has shown that select personality and other interpersonal characteristics influence late‐life cognitive outcomes. However, it is not well understood whether these associations are dissociable from the effects of late‐life brain integrity. The current study examines whether personality characteristics are associated with cross‐sectional and longitudinal cognitive variables in a diverse cohort of older adults and whether these associations are independent of brain integrity as measured by structural MRI.Method157 participants (mean age 73.1±6.3 years) from the UC Davis ADC longitudinal Diversity Cohort were evaluated using the Spanish and English Neuropsychological Assessment Scales (SENAS) to assess verbal episodic memory, semantic memory, executive function, and spatial ability. The Big 5 personality measures were used to assess openness, conscientiousness, agreeableness, neuroticism, and extraversion as well as positive affect, sadness, meaning in life, and self‐efficacy. Baseline brain (MRI) variables including total gray matter volume, hippocampus volume and total white matter hyperintensity volume were also measured (n = 131). A parallel process, multi‐level model of the four longitudinal cognitive outcomes yielded intercept and linear slope random effects for each outcome. Slope random effects were highly correlated and summarized by a global slope second order factor. Global slope and individual intercepts were regressed on personality variables, covariates (age, gender, education, race/ethnicity, and recruitment source), and baseline brain variables.ResultPositive affect (p=0.004) and openness to new experience (p=0.009) demonstrated positive associations with longitudinal change in cognition that were independent of baseline brain variables and covariates (Table 2). Other personality variables, including conscientiousness, extraversion, neuroticism, agreeableness, sadness, meaning in life, and self‐efficacy did not demonstrate significant associations with cognitive change. Lower neuroticism and higher conscientiousness were associated with higher spatial ability intercepts, and lower sadness was associated with a higher episodic memory intercept, independent of covariates and brain variables.ConclusionPositive affect and openness are significantly associated with longitudinal cognitive trajectories, independent of demographics and cross‐sectional brain variables, including total gray matter volume, hippocampal volume, and total white matter hyperintensity volume. Future research will help to delineate how individual differences in personality and behavior relate to late‐life brain and cognitive changes.

Plasma P‐tau181 and NfL are central nodes in a network of diagnostic, biomarker, and demographic data

AbstractBackgroundIn Alzheimer’s disease (AD), plasma biomarkers of neurodegeneration and phosphorylated tau have initial support for their relationship to clinical diagnosis and cognitive outcomes over time (total tau [t‐tau], neurofilament light [NfL], and p‐tau). To date, only one study has assessed a network model with these data. Here, we assessed the network relations (i.e., conditional dependencies) between diagnostic variables, plasma biomarkers, neuropsychological test performance, and demographic variables using a Gaussian graphical model (GGM) with participants from the Boston University (BU) Alzheimer’s Disease Research Center (ADRC) Longitudinal Clinical Core Registry.MethodThe sample included individuals with normal cognition (n=235), MCI due to AD (n=181), and AD dementia (n=153). Participants completed a comprehensive battery of neuropsychological tests to assess global cognition, attention, executive function, episodic memory, and language abilities. Diagnoses were adjudicated during multidisciplinary diagnostic consensus conferences. Plasma samples were analyzed using the Simoa technique. Regularized GGMs were estimated with Pearson, polychoric, and polyserial correlations depending on whether the variables were continuous, ordinal, or mixed. Network stability was assessed with a non‐parametric bootstrap of standardized edge weights and a person‐dropping bootstrap of centrality measures with 10,000 samples. Latent dimensions were estimated with Markov chain Monte Carlo (MCMC) simulation.ResultAssessment of the model suggested adequate fit, χ2(184, N = 569) = 620.46, EBIC = 27,444.53, RMSEA = 0.06, TLI = 0.95. Metrics of strength, closeness centrality, and expected influence met established thresholds of stability. Among biomarkers, diagnosis was connected to p‐tau181, βz = 0.07, 95% CI [0.01, 0.12]. Assessment of network centrality suggested that p‐tau181 ranked relatively highly for betweenness centrality and expected influence and NfL ranked highly for betweenness centrality. In contrast, t‐tau was not connected to any functional or diagnostic variable and did not rank highly for centrality. The biomarker variables loaded similarly on the two latent dimensions and were clustered near consensus conference diagnosis.ConclusionUnlike t‐tau, plasma biomarkers p‐tau181 and NfL were influential as “central junctions” for other connections in a network of diagnostic, biomarker, and demographic data. The findings support recent research that posits p‐tau181 and NfL reflect distinct aspects of AD progression (respectively, AD pathology and neurodegeneration).

Impact of mild behavioral impairment on longitudinal changes in cognitive performance

AbstractBackgroundRecent research has developed a better appreciation for non‐cognitive factors, such as neuropsychiatric symptoms (NPS), as early indicators for dementia. This has led to the development of criteria for mild behavioral impairment (MBI), or the late‐life onset of NPS. MBI has been associated with a unique cognitive phenotype, but research on longitudinal changes is limited. The goal of this study is to examine if MBI influences changes in cognitive abilities among older adults who are cognitively healthy (CH) or have mild cognitive impairment (MCI).MethodSecondary data analysis of participants (n=17,291) from the National Alzheimer’s Coordinating Center who were CH (n=11,771) or diagnosed with MCI (n=5,520). Almost 25% of the sample met the operationalized diagnostic criteria for MBI (n=4,274). Cognitive performance was evaluated using tasks of attention, episodic memory, executive function, language, visuospatial ability, and processing speed.ResultsCross‐sectionally, persons with MBI performed worse on tasks of attention, episodic memory, executive function, language, visuospatial ability, and processing speed compared to people without MBI. There were no significant interactions present between MBI and MCI on any of the tasks. Longitudinally up to 14 years, persons with MBI saw a greater decline on tasks of attention, executive function, language, episodic memory, and processing speed compared to individuals without MBI. Further, older adults with MBI performed significantly worse across time on tasks of executive function, language, and processing speed when compared to CH older adults without MBI. Persons with MBI and MCI performed significantly worse across time on tasks of executive function, language, processing speed, and visuospatial ability when compared to those with only MCI.ConclusionOlder adults with MBI performed worse on all cognitive domains, compared to those without MBI. Additionally, CH older adults with MBI saw a greater decline across time in the domains of executive function, language, and processing speed. In the MCI group, MBI was associated with a greater decline in all of these domains in addition to visuospatial ability. The results provide support for unique cognitive phenotypes for MBI in CH older adults and MCI, that may be indicative of preclinical and prodromal symptoms of dementia.

Cardiometabolic multimorbidity accelerates cognitive decline and progression to dementia in older adults

AbstractBackgroundThough cardiometabolic disorders (CMDs; including type 2 diabetes, heart disease, and stroke) have been individually associated with cognitive decline, their combined effect on the prodromal phase of dementia is unknown. We aimed to examine the extent to which CMD multimorbidity is associated with cognitive decline and the risk of cognitive impairment–no dementia (CIND) and its progression to dementia.MethodWithin the Swedish National Study on Aging and Care–Kungsholmen, 2934 dementia‐free adults aged ≥60—consisting of a cognitively intact (n=1821) and a CIND (n= 685) cohort—were followed over 12 years. At baseline and each follow‐up (every 3 or 6 years), participants were administered the Mini‐Mental State Examination (MMSE) and a neuropsychological test battery. CIND was defined as having no dementia and performance ≥1.5 SDs below age group‐specific means in at least one cognitive domain (episodic memory, processing speed, executive function, verbal fluency, or visuospatial ability). Dementia was diagnosed according to DSM‐IV criteria. CMDs were ascertained based on clinical examination, medication use, national patient registry data, and laboratory and instrumental tests. CMD multimorbidity was defined as the presence of ≥2 CMDs. Data were analyzed using multi‐adjusted linear mixed models, Cox regression, and Laplace regression, with adjustment for sociodemographic and vascular risk factors.ResultOf all participants, 813 (27.7%) had one, 221 had two (7.5%), and 23 (0.8%) had three CMDs at baseline. Compared to no CMDs, the presence of one (β= ‐0.22, 95% CI: ‐0.28 to ‐0.15), two (β= ‐0.28, 95% CI: ‐0.40 to ‐0.16), and three (β= ‐0.40, 95% CI: ‐0.77 to ‐0.03) CMDs was related to accelerated MMSE decline in a dose‐dependent fashion (p&lt;0.001). In Cox models, CMD multimorbidity was associated with nearly double the risk of both CIND (hazard ratio [HR] 1.71, 95% CI 1.22‐2.41) and the progression of CIND to dementia (1.89, 95% CI 1.17‐3.04). Furthermore, CMD multimorbidity anticipated the onset of CIND by 2.5 years and its progression to dementia by 2.2 years.ConclusionCardiometabolic multimorbidity accelerates cognitive decline and increases the risk of CIND and dementia, anticipating the occurrence of both CIND and dementia by more than two years.

Association of Neurofibrillary Tangle Distribution With Age at Onset-Related Clinical Heterogeneity in Alzheimer Disease: An Autopsy Study.

Patients with earlier age at onset of sporadic Alzheimer disease (AD) are more likely than those with later onset to present with atypical clinical and cognitive features. We sought to determine whether this age-related clinical and cognitive heterogeneity is mediated by different topographic distributions of tau-aggregate neurofibrillary tangles (NFTs) or by variable amounts of concomitant non-AD neuropathology. The relative distribution of NFT density in hippocampus and midfrontal neocortex was calculated, and α-synuclein, TAR DNA binding protein 43 (TDP-43), and microvascular copathologies were staged, in patients with severe AD and age at onset of 51-60 (n = 40), 61-70 (n = 41), and >70 (n = 40) years. Regression, mediation, and mixed effects models examined relationships of pathologic findings with clinical features and longitudinal cognitive decline. Patients with later age at onset of AD were less likely to present with nonmemory complaints (odds ratio [OR] 0.46 per decade, 95% confidence interval [CI] 0.22-0.88), psychiatric symptoms (β = -0.66, 95% CI -1.15 to -0.17), and functional impairment (β = -1.25, 95% CI -2.34 to -0.16). TDP-43 (OR 2.00, 95% CI 1.23-3.35) and microvascular copathology (OR 2.02, 95% CI 1.24-3.40) were more common in later onset AD, and α-synuclein copathology was not related to age at onset. NFT density in midfrontal cortex (β = -0.51, 95% CI -0.72 to -0.31) and midfrontal/hippocampal NFT ratio (β = -0.18, 95% CI -0.26 to -0.10) were lower in those with later age at onset. Executive function (β = 0.48, 95% CI 0.09-0.90) and visuospatial cognitive deficits (β = 0.97, 95% CI 0.46-1.46) were less impaired in patients with later age at onset. Mediation analyses showed that the effect of age at onset on severity of executive function deficits was mediated by midfrontal/hippocampal NFT ratio (β = 0.21, 95% CI 0.08-0.38) and not by concomitant non-AD pathologies. Midfrontal/hippocampal NFT ratio also mediated an association between earlier age at onset and faster decline on tests of global cognition, executive function, and visuospatial abilities. Worse executive dysfunction and faster cognitive decline in people with sporadic AD with earlier rather than later age at onset is mediated by greater relative midfrontal neocortical to hippocampal NFT burden and not by concomitant non-AD neuropathology.

Quality of life following awake surgery depends on ability of executive function, verbal fluency, and movement.

The outcome of awake surgery has been evaluated based on functional factors, return to work, and oncological aspects, and there have been no reports directly examining QOL. This study aimed to investigate the outcome of QOL following awake surgery and to determine the functional factors influencing QOL. Seventy patients with WHO grade II/III gliomas were included. For the assessment of QOL, we used the SF-36 and calculated summary and sub-component scores. Three summary component scores, including physical (PCS), mental (MCS), and role/social summary (RCS) component scores, were computed based on sub-component scores. Additionally, various assessments of neurological/neuropsychological function were performed. We performed univariate and multiple regression analyses to investigate the functional factors influencing the SF-36. PCS and MCS were maintained, but only RCS was low to 42.0±16.1. We then focused on the RCS and its sub-components: general health (GH), role physical (RP), social functioning (SF), and role emotional (RE). Multiple regression analysis showed following significant correlations between the sub-component scores and brain functions: GH to executive function and movement (p = 0.0033 and 0.032), RP to verbal fluency and movement (p = 0.0057 and 0.0010), and RE to verbal fluency (p = 0.020). Furthermore, when the sub-component scores were compared between groups with and without functional deficits related to GH, RP, and RE, each score was significantly lower in the groups with functional deficits (p = 0.012, 0.014, and 0.0049, respectively). In patients who underwent awake surgery, a subset of patients had low QOL because of poor RCS. Functional factors influencing QOL included executive function, verbal fluency, and movement.

Cerebral Blood Flow, Brain Volume, and Age Predicts Executive Function in Sickle Cell Anemia

Introduction: Individuals with sickle cell anemia (SCA) are at increased risk for deficits in multiple domains of neurocognitive functioning, including executive functions. In addition to assessing the effects of silent cerebral infarcts (SCI) and stroke on cognition, prior research has focused on hemoglobin and transcranial Doppler velocity as hemodynamic correlates. Recent studies have begun to use more precise measures of blood delivery to the brain (e.g., cerebral blood flow; CBF) to determine more sensitive indicators of cognitive risk prior to neurological injury. Nevertheless, empirical and meta-analytic findings suggest that these deficits increase with age, which can have broad impact on psychosocial functioning, including self-management and navigation through the transition from pediatric to adult medical care. This study aimed to assess brain volume as a mediator of the association between CBF and executive functioning in a sample of individuals with SCA. The secondary aim was to assess age as a moderator of hemodynamic and structural correlates of executive function.Methods: Children, adolescents, and young adults with SCA were enrolled prospectively. Each participant received a 3-Tesla non-contrast magnetic resonance imaging and magnetic resonance angiography of the brain, and a neurological examination by the study neurologist. Gray matter CBF was calculated from pseudo-continuous arterial spin labeling using the solution to the flow-modified Bloch equation after correcting for individual hematocrit. Three measures of brain volume were also computed from 3D-T1 images using Freesurfer version 7.1.1: total brain volume, gray matter volume, and white matter volume was calculated as the difference between the two. At a separate study visit, participants completed an age-appropriate Wechsler Working Memory Index (WMI). Pearson correlations assessed bivariate associations among variables, SPSS PROCESS macro was used to test gray matter volume as a mediator in the relation between CBF and working memory, and multiple linear regression analyses tested age as a moderator of the impact of CBF and brain volume on working memory.Results: Twenty-nine children and adolescents (ages 6 to 17 years) and 25 adults (ages 18 to 31 years) were enrolled. Five participants were excluded from analyses due to history of overt stroke that resulted in significant brain volume loss. Of 49 included participants, 20 had SCIs. Working memory was inversely correlated with age (r = -.30, p = .037) and CBF (r = -.36, p = .013), such that WMI decreased cross-sectionally with older age and higher CBF. Working memory was positively correlated with gray matter volume (r = .42, p = .002); however, it was not related to white matter volume (r = -.05, p = .715) or total brain volume (r = -.07, p = .642). Finally, patient age was positively correlated with CBF (r = .36, p = .014), but the association of age with gray matter volume did not reach statistical significance (r = -.27, p = .065). Analyses in Figure 1 show that although CBF and gray matter were directly related to working memory (path c and path b, respectively), gray matter volume did not mediate the association between CBF and working memory (path a*b). However, regression analyses (Table 1) showed that age moderated the association between gray matter volume and working memory, such that there was only a significant relation in children and adolescents. This association did not exist for young adults (Figure 2).Conclusions: Neurocognitive assessments has been cited as an important standard of care for children and adolescents with SCA. Given the increase in deficits with age, and the increase in mortality after transferring from pediatric to adult care, monitoring executive function abilities and potential impact on self-management should continue into adulthood. Findings from the current study provide preliminary evidence that cerebral hemodynamic compensation with elevated CBF may be insufficient to prevent gray matter volume loss in children and adolescents and decline in working memory ability. Some limitations of the current study include small sample size and whole brain gray and white matter volumes as opposed to specific regions relevant to executive functions (e.g., prefrontal cortex); however, findings from global measures provide promising evidence for future research on hemodynamic and structural predictors of executive function in SCA. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Executive Function and Self-Regulation: Bi-Directional Longitudinal Associations and Prediction of Early Academic Skills.

Despite a tendency to study executive function (EF) and self-regulation (SR) separately, parallel lines of research suggest considerable overlap between the two abilities. Specifically, both show similar developmental trajectories (i.e., develop rapidly in the early years), predict a broad range of overlapping outcomes across the lifespan (e.g., academic success, mental and physical health, and social competence), and have overlapping neural substrates (e.g., prefrontal cortex). While theoretical frameworks diverge in how they reconcile EF and SR – ranging from treating the two as functionally synonymous, to viewing them as related yet distinct abilities – there is no consensus and limited empirical evidence on the nature of their relationship and how this extends developmentally. The current study examined bi-directional longitudinal associations between early EF and SR, and their longitudinal associations with subsequent early academic skills, in a sample of 199 3- to 5-year-old pre-school children. The adopted measures permitted EF and SR to be modelled as composite indices for these analyses, thereby decreasing task-specific components of these associations. Early academic skills were captured by a standardized direct assessment. Bi-directional associations between EF and SR were found, with both accounting for unique variance in early academic skills 7 and 19months later. The current results provide important evidence to distinguish between EF and SR abilities, yet also for their reciprocal influence in situ and across early development.

Apolipoprotein E Genetic Variation and Its Association With Cognitive Function in Rural-Dwelling Older South Africans.

Apolipoprotein E (APOE) 𝜀4 allele carrier status is well known for its association with an increased likelihood of developing Alzheimer’s disease, but its independent role in cognitive function is unclear. APOE genetic variation is understudied in African populations; hence, this cross-sectional study in a rural South African community examined allele and genotype frequencies, and their associations with cognitive function. Cognitive function was assessed using two different screening methods to produce a total cognition score and four domain-specific cognition scores for verbal episodic memory, executive function, language, and visuospatial ability. Cognitive phenotype and APOE genotype data were used to determine whether APOE variation was significantly associated with cognitive function in this population. Observed allele frequencies for 1776 participants from the HAALSI study [age 40–80years (mean=56.19); 58.2% female] were 58.1% (𝜀3), 25.4% (𝜀4) and 16.5% (𝜀2). Allele distributions were similar to the African super population, but different from all non-African super populations from the 1,000 Genomes Project. The 𝜀3 homozygous genotype was most common (34.9%) and used as the base genotype for comparison in regression models. Four models were tested for each of the five cognitive phenotypes to explore association of APOE variation with cognitive function. In the first model assessing association with all genotypes for all individuals, marginally significant associations were observed for 𝜀2 homozygotes where executive function scored higher by ~0.5 standard deviations (p=0.037, SE=0.23), and for 𝜀3/𝜀4 heterozygotes where visuospatial ability scores were lower (p=0.046, SE=0.14). These did not survive correction for multiple testing. Regional African population differences were observed at the APOE locus. Marginally, significant associations between APOE genotype, and executive function and visuospatial ability indicate the need for larger studies to better examine these associations in African populations. Furthermore, longitudinal data could shed light on APOE genetic association with rate of change, or decline, in cognitive function.

Ladder Use in Older People: Type, Frequency, Tasks and Predictors of Risk Behaviours.

Ladder fall and injury risk increases with age. People who present to a hospital after an injurious ladder fall have been surveyed, but little is known about ladder use in the community. The purpose of this study was to: (1) document salient factors related to ladder safety, and (2) determine physical, executive function, psychological and frequency-of-use factors associated with unsafe ladder use in older people. One hundred and two older people (aged 65+ years) were recruited. Participants completed questionnaires on demographics, health, and ladder use (type, frequency, task, behaviours) and underwent assessments of physical and executive function ability. Results showed both older men and women commonly use step ladders (61% monthly, 96% yearly), mostly inside the home for tasks such as changing a lightbulb (70%) and decorating (43%). Older men also commonly use straight ladders (27% monthly, 75% yearly), mostly outside the home for tasks such as clearing gutters (74%) and pruning trees (40%). Unsafe ladder use was more common in males and individuals with greater ladder use frequency, greater quadriceps strength, better upper limb dexterity, better balance, better stepping ability, greater self-reported everyday risk-taking, a lower fear of falling, and fewer health problems compared to their counterparts (all p < 0.05). These findings document ladder use by older people and provide insight into unsafe ladder behaviours that may be amenable to interventions to reduce ladder falls and associated injuries.

Effects of Exergame-Based Dual-Task Training on Executive Function and Dual-Task Performance in Community-Dwelling Older People: A Randomized-Controlled Trial.

Objective: Aging is associated with decline in executive function that may lead to reduced dual-task performance. Regular exercise has been recommended for promoting or maintaining mental and physical health in older adults, yet only a fraction of older adults exercise regularly. Exergame training may have the potential to enhance exercise adherence. Therefore, the aim of this study was to examine the effects of exergame-based dual-task training on executive function and dual-task performance in community-dwelling older adults. Materials and Methods: This was a single-blinded, randomized-controlled trial. Twenty community-dwelling older adults were recruited and randomly assigned to one of two groups. All participants completed 36 trainings, including three 60-minute sessions/week over 12 weeks. Participants in the experimental group received exergame-based dual-task training, while those in the control group received home-based multicomponent exercise training. Measures of executive function, dual-task performance, and community walking ability were assessed before and after the intervention. Results: Significant group × time interactions (P = 0.000-0.027) with large effects were found in all selected outcome measures. Compared with the control group, the experimental group improved significantly in measures of general executive function (P = 0.014), inhibitory control (P = 0.037), cognitive dual-task performance (P < 0.001), and community walking ability (P = 0.002). Enhanced general executive function was highly correlated with either improved motor dual-task performance (r = 0.674) or improved cognitive dual-task performance (r = -0.701). Conclusion: These results suggested that exergame-based dual-task training improved both executive function and dual-task performance in older people. These positive effects could be transferred to enhance community walking ability. Clinical Trial Registration number: ACTRN 12617000095369.

A-18 Early Pattern of Cognitive Changes Associated with Insulin Resistance in a Sample of Young Adults

Abstract Objective Insulin resistance increases the risk of developing type 2 diabetes and subsequently cardiovascular and cerebrovascular disease. It is also linked to neurocognitive disorders and accelerated cognitive aging (Ekblad et al, 2017; Levine, Harrati, &amp; Crimmins, 2018). Using baseline data from a longitudinal study in a sample of 126 cognitively intact adults aged 25–50 years (36.5% males), we assessed cognitive performance in relation to insulin resistance to determine whether an early prodromal pattern of cognitive changes exists prior to advanced metabolic disease. Methods Steady state plasma glucose (SSPG) was used to measure insulin resistance. Multivariate regression analyses were conducted using age, years of education, body mass index (BMI), and SSPG as predictors of neuropsychological functioning. In-person and tele-neuropsychological assessment was administered using standard neuropsychological measures. Results Higher insulin resistance was associated with significantly worse attention (WAIS-III Digit Span total; B = -0.018, p = 0.03), executive functioning (D-KEFS Color-Word Inhibition/Switching; B = 0.047, p = 0.04) and dominant fine motor abilities (Purdue Pegboard; B = -0.008, p = 0.02). Higher insulin resistance was also associated with trend level worsening of other measures of executive functioning, namely D-KEFS Trails 4 (B = 0.099, p = 0.07) and DKEFS Color-Word Inhibition errors (B = 0.007, p = 0.09). Conclusions In young adults, higher insulin resistance was associated with declines in attention, executive functioning, and fine motor abilities. This early pattern of subtle cognitive changes associated with higher insulin resistance seen in this sample of younger adults is consistent with later cognitive declines found in type 2 diabetes and vascular neurocognitive disorder, namely declines in attention, executive functioning, and motor abilities with eventual memory declines in advanced disease.

Higher-order resting state network association with the useful field of view task in older adults.

Speed-of-processing abilities decline with age yet are important in performing instrumental activities of daily living. The useful field of view, or Double Decision task, assesses speed-of-processing and divided attention. Performance on this task is related to attention, executive functioning, and visual processing abilities in older adults, and poorer performance predicts more motor vehicle accidents in the elderly. Cognitive training in this task reduces risk of dementia. Structural and functional neural correlates of this task suggest that higher-order resting state networks may be associated with performance on the Double Decision task, although this has never been explored. This study aimed to assess the association of within-network connectivity of the default mode network, dorsal attention network, frontoparietal control network, and cingulo-opercular network with Double Decision task performance, and subcomponents of this task in a sample of 267 healthy older adults. Multiple linear regressions showed that connectivity of the cingulo-opercular network is associated with visual speed-of-processing and divided attention subcomponents of the Double Decision task. Cingulo-opercular network and frontoparietal control network connectivity is associated with Double Decision task performance. Stronger connectivity is related to better performance in all cases. These findings confirm the unique role of the cingulo-opercular network in visual attention and sustained divided attention. Frontoparietal control network connectivity, in addition to cingulo-opercular network connectivity, is related to Double Decision task performance, a task implicated in reduced dementia risk. Future research should explore the role these higher-order networks play in reduced dementia risk after cognitive intervention using the Double Decision task.