Negative Cognitive Outcomes Research Articles

Traumatic and Adverse Childhood Experiences and Developmental Differences in Psychiatric Risk

While adverse childhood experiences (ACEs) are known to impart significant risk for negative mental health and cognitive outcomes in youth, translation of ACE scores into clinical intervention is limited by poor specificity in predicting negative outcomes. This work expands on the ACE framework using a data-driven approach to identify 8 different forms of traumatic and adverse childhood experiences (TRACEs) and reveal their differential associations with psychiatric risk and cognition across development. Building upon the traditional ACEs model, this study aimed to characterize unique components of commonly co-occurring TRACEs and to examine moderation of longitudinal change in mental health and cognitive development during adolescence. This work draws from youth and their caregivers who completed up to 4 annual behavioral assessments from 2016 to 2021 as part of the ongoing Adolescent Brain Cognitive Development (ABCD) study. Data collection was performed at 21 regionally-distributed sites across the United States. Analyses for this work were conducted January 2023 through November 2023. Youth participants in the ABCD study's exposure to 268 different TRACEs, which were distilled into adversity components using nonlinear principal components analysis. Mixed-effects and latent change score models considered TRACEs components as moderators of longitudinal change in internalizing and externalizing mental health problems, as well as longitudinal change in cognitive ability. Data were distilled from 11 876 youth participants, who were grouped into dyads with a caregiver. ABCD study youth participants were 9 to 10 years old at baseline assessment (year 0) and 12 to 13 years old at ABCD year 3. A total of 5679 participants (47.8%) were female. Analyses revealed that TRACEs organized into 8 thematic adversity components (e.g., family conflict, interpersonal violence). At baseline assessment (year 0), exposure to nearly every adversity component was associated with poorer mental health and diminished cognitive ability. Yet across time, it was observed that different forms of adversity were variably linked to both increases and decreases in internalizing and externalizing problems. For example, while peer aggression (t = 5.31) and family conflict (t = 5.67) were associated with increases in both internalizing and externalizing problems over early adolescence, community threat (t = 2.82) and poverty (t = 2.07) were linked to decreased problems, potentially representing adaptive suppression of symptoms. Finally, adversity types related to resource deprivation (eg, poverty, caregiver maladjustment) were associated with declines in cognitive ability over early adolescence. In this cohort study, distinct forms of TRACEs differentially moderated developmental changes in psychiatric risk and cognitive ability in different ways, offering the possibility for precision-based prediction of risk for youth. Such findings could be used in targeted early prevention and intervention strategies for at-risk youth.

Loneliness in sport: A systematic mixed studies review

ABSTRACT Loneliness is an established risk factor for mental and physical health problems. Individuals involved in sport face many unique stressors, some of which could exacerbate the risk of loneliness. To bring clarity to published evidence in this area, inform future research, and develop applied recommendations to prevent and reduce loneliness in the sport community, we sought to systematically review, synthesise, and appraise research on loneliness in sport. Following electronic database and manual searches to identify literature on loneliness in the sport community up to August 2024, we included and thematically synthesised data from 194 studies (N = 88,516). Social loneliness was the most common conceptualisation of loneliness within the literature. We identified socio-cultural, institutional, interpersonal, and intrapersonal risk factors associated with loneliness. There was less evidence for protective factors, but the available evidence was categorised into interpersonal and intrapersonal factors. Finally, there was substantial evidence concerning adverse consequences associated with loneliness in sport, including: impaired mental health and well-being; adverse social outcomes; negative cognitive, affective, and motivational outcomes; and maladaptive behavioural outcomes. Overall, this review advances knowledge by synthesising, for the first time, evidence on loneliness in sport and offers theoretical, methodological, and practical contributions that extend understanding of loneliness.

The multifaceted effects of fluoxetine treatment on cognitive functions.

Fluoxetine, the prototypical selective serotonin reuptake inhibitor (SSRI), is widely used to treat major depressive disorder (MDD) and a variety of other central nervous system conditions, primarily due to its established clinical safety profile. Although its efficacy in treating depression is well-recognized, the impact of fluoxetine on cognitive functions remains inconsistent and elusive. In this review, we first examine the well-substantiated biological mechanisms underlying fluoxetine's antidepressant effects, which include serotonin reuptake inhibition and activation of TrkB receptors-key to brain-derived neurotrophic factor (BDNF) signaling. Subsequently, we delve into the cognitive side effects observed in both preclinical and clinical studies, affecting domains such as memory, attention, and executive functions. While certain studies indicate cognitive improvements in patients with underlying disorders, there is also evidence of negative effects, influenced by variables like gender, duration of treatment, age, disease pathology, and the specifics of cognitive testing. Significantly, the negative cognitive outcomes reported in preclinical research often involve healthy, non-diseased animals. This review underscores the necessity for heightened caution in fluoxetine prescription and further investigation into its potentially detrimental cognitive effects, even when used prophylactically.

A - 30 Head-Injury Exposure and Later-in-Life Cognitive and Psychiatric Outcomes among Former Collegiate Football Players

Abstract Purpose Current understanding of potential long-term negative cognitive and psychiatric outcomes following head-injury exposure is limited, and this study aimed to evaluate these relationships in former collegiate football players. Method Former collegiate football players completed the College Level Aging Athlete Study (CLEAATS) survey including playing career, concussion/medical/psychiatric history, self-reported cognitive functioning, and measures of depression, anxiety symptoms, positive affect/resilience, emotional dysregulation, and objective cognitive function. A head-injury exposure estimate (HIEE, modified from Kerr et al., 2015) was calculated to determine total sports-related head-injury exposure. Partial correlations (controlling for age and education) examined the relationship between HIEE and cognitive functioning and emotional/mood symptoms. Results Participants (n = 216) were 50–87 years old (M = 63.4 [8.5]), 91% White, and well-educated (bachelor’s or graduate degree = 92%). HIEE (M = 763.8 [342.9]) was not correlated with any cognitive or emotional/mood symptom measures (p’s > 0.075). Depression (r = 0.65), anxiety (r = 0.48), and emotional dysregulation indices (r = 0.50) showed moderate positive correlations with subjective cognitive symptoms. Grit (r = −0.36) and positive affect/well-being (r = −0.49) were negatively correlated with cognitive symptom reporting. Conclusions HIEE was not found to be related to cognitive or emotional/mood outcomes, and results suggest that current emotional/mood symptoms have greater associations with subjective cognitive symptoms. Alternatively, positive affect/resilience were found to be negatively associated with cognitive symptoms, and may serve as protective factors against cognitive complaints. These findings are consistent with previous studies that have reported associations between cognitive symptoms, psychological distress, and resilience in former athletes, highlighting the importance of considering potential impact of current emotional/mood symptoms when evaluating retired players with cognitive concerns.

Sexual Dimorphism, Altered Hippocampal Glutamatergic Neurotransmission and Cognitive Impairment in APP Knock-In Mice.

It is well established that glutamatergic neurotransmission plays an essential role in learning and memory. Previous studies indicate that glutamate dynamics shift with Alzheimer's disease (AD) progression, contributing to negative cognitive outcomes. In this study, we characterized hippocampal glutamatergic signaling with age and disease progression in a knock-in mouse model of AD (APPNL-F/NL-F). At 2-4 and 18+ months old, male and female APPNL/NL, APPNL-F/NL-F, and C57BL/6 mice underwent cognitive assessment using Morris water maze (MWM) and Novel Object Recognition (NOR). Then, basal and 70 mM KCl stimulus-evoked glutamate release was measured in the dentate gyrus (DG), CA3, and CA1 regions of the hippocampus using a glutamate-selective microelectrode in anesthetized mice. Glutamate recordings support elevated stimulus-evoked glutamate release in the DG and CA3 of young APPNL-F/NL-F male mice that declined with age compared to age-matched control mice. Young female APPNL-F/NL-F mice exhibited increased glutamate clearance in the CA1 that slowed with age compared to age-matched control mice. Male and female APPNL-F/NL-F mice exhibited decreased CA1 basal glutamate levels, while males also showed depletion in the CA3. Cognitive assessment demonstrated impaired spatial cognition in aged male and female APPNL-F/NL-F mice, but only aged females displayed recognition memory deficits compared to age-matched control mice. Conclusions: These findings confirm a sex-dependent hyper-to-hypoactivation glutamatergic paradigm in APPNL-F/NL-F mice. Further, data illustrate a sexually dimorphic biological aging process resulting in a more severe cognitive phenotype for female APPNL-F/NL-F mice than their male counterparts. Research outcomes mirror that of human AD pathology and provide further evidence of divergent AD pathogenesis between sexes.

Association of Loneliness with Functional Connectivity MRI, Amyloid-β PET, and Tau PET Neuroimaging Markers of Vulnerability for Alzheimer's Disease.

Loneliness has been declared an "epidemic" associated with negative physical, mental, and cognitive health outcomes such as increased dementia risk. Less is known about the relationship between loneliness and advanced neuroimaging correlates of Alzheimer's disease (AD). To assess whether loneliness was associated with advanced neuroimaging markers of AD using neuroimaging data from Framingham Heart Study (FHS) participants without dementia. In this cross-sectional observational analysis, we used functional connectivity MRI (fcMRI), amyloid-β (Aβ) PET, and tau PET imaging data collected between 2016 and 2019 on eligible FHS cohort participants. Loneliness was defined as feeling lonely at least one day in the past week. The primary fcMRI marker was Default Mode Network intra-network connectivity. The primary PET imaging markers were Aβ deposition in precuneal and FLR (frontal, lateral parietal and lateral temporal, retrosplenial) regions, and tau deposition in the amygdala, entorhinal, and rhinal regions. Of 381 participants (mean age 58 [SD 10]) who met inclusion criteria for fcMRI analysis, 5% were classified as lonely (17/381). No association was observed between loneliness status and network changes. Of 424 participants (mean age 58 [SD = 10]) meeting inclusion criteria for PET analyses, 5% (21/424) were lonely; no associations were observed between loneliness and either Aβ or tau deposition in primary regions of interest. In this cross-sectional study, there were no observable associations between loneliness and select fcMRI, Aβ PET, and tau PET neuroimaging markers of AD risk. These findings merit further investigation in prospective studies of community-based cohorts.

Development of Malaysian-MIND diet scores for prediction of mild cognitive impairment among older adults in Malaysia.

Mild Cognitive impairment (MCI) is a pre-demented state in the elderly populace. The Mediterranean & Dietary Approaches to Stop Hypertension (DASH) Intervention for Neurodegenerative Delay (MIND) diet has shown promise in reducing the risk of MCI and Alzheimer's disease in older people. Notably, the existing MIND diet is not adapted to the specific needs of older adults in Malaysia, considering distinct food cultures and availability. Consequently, this study aimed to develop the Malaysian version of the MIND diet (MY-MINDD) scores and investigate their association with MCI in the older adult populace of Malaysia. A comprehensive pooled data analysis was conducted on combined data from 810 participants sourced from the longitudinal Long-Term Research Grant Scheme-Towards Useful Aging (LRGS-TUA) and Fundamental Research Grant Scheme (FRGS) studies. The MY-MINDD scores were developed by incorporating existing MIND diet food groups, their corresponding scoring mechanisms, and consideration of common Malaysian foods which are proven to be beneficial and detrimental to cognitive function. To substantiate the MY-MINDD scoring system, its association with MCI was evaluated using a series of validated neuropsychological test batteries. MY-MINDD consists of seven food groups promote brain health and four food groups exert negative cognitive outcomes. The study participants had an average age of 67.9 ± 4.7 years. The collective MY-MINDD score for all participants was 6.4 ± 0.1 (out of a maximum 11 points), revealing a lower score in individuals with MCI at 6.0 ± 1.7 compared to those without MCI at 6.6 ± 1.6 (p < 0.001). According to hierarchical multivariate binary logistic regression analysis, being in the highest tertile of MY-MINDD score was linked to reduced odds of MCI (odds ratio (OR) = 0.43, 95% confidence interval (CI): 0.26-0.72, p < 0.001) in the fully adjusted model in comparison to the lowest tertile. The development of the MY-MINDD scores for Malaysian older population revealed that a stronger adherence to this diet is linked to a reduced risk of MCI. Further substantiation of the MY-MINDD scores using more objective measures, such as neuroimaging approaches and other neuropsychological batteries, is necessary.

Clinical Outcomes and Tau Pathology in Retired Football Players: Associations With Diagnosed and Witnessed Sleep Apnea.

Obstructive sleep apnea (SA) is common in older men and a contributor to negative cognitive, psychiatric, and brain health outcomes. Little is known about SA in those who played contact sports and are at increased risk of neurodegenerative disease(s) and other neuropathologies associated with repetitive head impacts (RHI). In this study, we investigated the frequency of diagnosed and witnessed SA and its contribution to clinical symptoms and tau pathology using PET imaging among male former college and former professional American football players. The sample included 120 former National Football League (NFL) players, 60 former college players, and 60 asymptomatic men without exposure to RHI (i.e., controls). Diagnosed SA was self-reported, and all participants completed the Mayo Sleep Questionnaire (MSQ, informant version), the Epworth Sleepiness Scale (ESS), neuropsychological testing, and tau (flortaucipir) PET imaging. Associations between sleep indices (diagnosed SA, MSQ items, and the ESS) and derived neuropsychological factor scores, self-reported depression (Beck Depression Inventory-II [BDI-II]), informant-reported neurobehavioral dysregulation (Behavior Rating Inventory of Executive Function-Adult Version [BRIEF-A] Behavioral Regulation Index [BRI]), and tau PET uptake, were tested. Approximately 36.7% of NFL players had diagnosed SA compared with 30% of the former college football players and 16.7% of the controls. Former NFL players and college football players also had higher ESS scores compared with the controls. Years of football play was not associated with any of the sleep metrics. Among the former NFL players, diagnosed SA was associated with worse Executive Function and Psychomotor Speed factor scores, greater BDI-II scores, and higher flortaucipir PET standard uptake value ratios, independent of age, race, body mass index, and APOE ε4 gene carrier status. Higher ESS scores correlated with higher BDI-II and BRIEF-A BRI scores. Continuous positive airway pressure use mitigated all of the abovementioned associations. Among the former college football players, witnessed apnea and higher ESS scores were associated with higher BRIEF-A BRI and BDI-II scores, respectively. No other associations were observed in this subgroup. Former elite American football players are at risk of SA. Our findings suggest that SA might contribute to cognitive, neuropsychiatric, and tau outcomes in this population. Like all neurodegenerative diseases, this study emphasizes the multifactorial contributions to negative brain health outcomes and the importance of sleep for optimal brain health.

Approach to Sudden Hearing Loss Among Primary Care Physicians in Riyadh, Saudi Arabia.

A medical emergencyknown as sudden sensorineural hearing loss (SSNHL)affects the ears suddenly, has a considerable probability of negative cognitive and functional outcomes, and can influence the patient's quality of life. Primary care physicians play a crucial role in diagnosing SSNHL and initiating prompt and efficient management since they are the ones who would likely encounter it initially. This study aims to evaluate the present knowledge, diagnostic, and management perspective of SSNHL among primary care physicians in Riyadh, Saudi Arabia. A self-generated questionnaire with 17 questions was developed, and a link to the online survey was delivered to primary care physicians (PHPs) in Riyadh, SaudiArabia, concerning the management of SSNHL. The knowledge level regarding SSNHL was evaluated, in which 21 (25%) of the participants had a low knowledge level, 34 (40.5%) had moderate knowledge, and 29 (34.5%) had a high knowledge level. Among 84 participants, 20 (23.8%) were confident in their ability to administer and understand the findings of tuning fork tests (TFT) to differentiate between sensorineural hearing loss and conductive hearing loss, whereas 64 (76.2%) were unsure about it. In addition, to distinguish between sensorineural hearing loss and conductive hearing loss, 62 (73.8%) participants were confident, and 22 (26.2%) participants were skeptical about their ability to interpret a formal audiogram. Considering SSNHL as a medical emergency, in our survey, many family doctors would make proper referral and treatment decisions. However, TFTs were underutilized for guiding management decisions compared to other ways to distinguish between conductive and sensorineural hearing loss.

Longitudinal pathways of maltreated young children: Family stress processes and adverse childhood experiences.

An important issue associated with at-risk families in the child welfare system is the impact of familial stress processes on child developmental outcomes. The present study used the family stress model (FSM) to examine the impact of economic hardship, economic pressure, caregiver emotional distress, caregiver/partner conflict, caregiver harsh parenting, and adverse childhood experiences (ACEs) on child's cognitive, behavioral, and social outcomes. Data from the National Survey on Child and Adolescent Well-Being II were utilized, and 1,363 children (709 male, 654 female) ages 2-18 months (at Wave 1) were included in the present study. Three waves of data were analyzed in the longitudinal structural equation model, with economic hardship and economic pressure at Wave 1, caregiver emotional distress, caregiver/partner conflict, and caregiver harsh parenting at Wave 2 predicting ACEs and child outcomes at Wave 3. Results were overall consistent with the FSM in that economic hardship led to economic pressure, and caregiver emotional distress and caregiver/partner conflict led to harsh parenting, which subsequently led to ACEs. ACEs led to negative child cognitive outcomes, and for female children only, ACEs led to internalizing/externalizing behaviors. The results demonstrate that over time, familial stress processes led to negative child developmental outcomes in this sample. Study results also highlight the inextricable connection between mild harsh parenting behaviors and more severe forms of maltreatment on child outcomes. The prevention of child maltreatment is emphasized, with a specific focus on increasing positive parenting behaviors and decreasing caregiver emotional distress and caregiver/partner conflict. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Carbon Monoxide Exposure and Risk of Cognitive Impairment Among Cooks in Africa

We use air pollution exposure measurements and household survey data from four studies conducted across three countries in sub‐Saharan Africa (SSA) to analyze the association between carbon monoxide (CO) exposure from cooking with biomass and indicators of cognitive impairment. While there is strong evidence on the relationship between ambient air pollution exposure and cognitive impairment from studies in high‐income countries, relatively little research has focused on household air pollution (HAP) in low‐income country settings where risks of HAP exposure are high. This study is the first to our knowledge to focus on the association between HAP exposure (specifically CO exposure) and cognitive impairment across diverse settings in SSA. We use 24‐hour measurements of primary cooks’ exposure to CO across four study sites: urban Zambia (n = 493); urban Malawi (n = 130); rural Malawi (n = 102); and urban Rwanda (n = 2,576). We model the estimated percent carboxyhemoglobin (%COHb) of cooks and map values to a toxicological profile for risk of cognitive impairment. We find that across all study settings, cooks’ average %COHb levels are below levels of daily concern, but that cooks who use charcoal for preparing greater than 40% of meals are more likely to spend additional time at higher levels of risk. For the urban Zambia sample, we compare %COHb and frequency of charcoal use to a series of cognitive test scores and find no consistent relationships between %COHb and cognitive test scores. High levels of daily CO exposure from cooks across SSA highlight the potential for longer‐term negative cognitive (and other) health outcomes motivating additional research and efforts to characterize and mitigate risk.

Epigenome-Wide DNA Methylation Dynamics of Cannabis Addicts: Adolescents Performing a Socio-Educational Measure of Deprivation of Liberty - Case Study

Cannabis use is most likely to begin during adolescence or emerging adulthood; and such use during these developmental periods has been associated with some negative physical, mental, and cognitive health outcomes. Some of these long-term negative effects of this consumption during adolescence may be explained by epigenetic changes through a process called DNA methylation. However, little is known about the epigenetic impact of drug use during adolescence. The current study examined associations between DNA methylation and cannabis use during adolescence. Analyses focused on two genes, AHRR and NR2B because their methylation has been implicated in illicit drug use. Participants included twenty-seven adolescents separated into two groups, cannabis users and control. After identifying the subjects who would participate in the research, the general research framework was formed. The inclusion criteria were age between 13 and 18 years old. Those individuals diagnosed with cannabis dependence comprised the CUD (Cannabis Use Disorder) group, verified through a urine test for cannabis. Participants in the CONT group were healthy individuals, who did not have a history and/or criteria for diagnosing chemical dependency. DNA methylation values were measured with salivary DNA and averaged for each gene. Relationships between cannabis use and DNA methylation were tested using multivariate regressions, adjusting for sociodemographic data, and age. Adolescents with psychoactive substance use face a considerable risk of co-occurring mental health problems, something that may involve a more difficult life situation, social problems, as well as a worse result in complying with socio-educational measures.

EXPLORING THE EXPERIENCES OF PERCEIVED NEIGHBORHOOD SAFETY OF BLACK ADULTS: RESULTS FROM THE THINK PHRESH STUDY

Abstract Racial residential segregation is a complex socio-economic phenomenon that affects many communities across the U.S. Such residential segregation is a result of historic policies in the United States including redlining and inequitable urban redevelopment. Black adults who live in segregated areas face challenges and experience psychosocial stressors, including poverty, crime, and feeling unsafe in one’s neighborhood which are risk factors for many negative health and cognitive outcomes. To date, few studies have explored perspectives on experiences of racial residential segregation, and specifically, neighborhood safety trajectories that may relate to healthy aging. This qualitative study used data from a sample of participants in adulthood and older adulthood (aged 35-89, Mage= 64 years) from two predominantly black, low-income neighborhoods that have had different histories with regard to disinvestment and systemic racist policies. We used 60 in-depth interviews to explore perceptions around neighborhood safety trajectories and their perceived impact on aging outcomes. The results highlight several dimensions of perceived changes in neighborhood safety over time and how these are perceived to relate to aging outcomes, e.g., psychological stress. The findings also show a few differences between the two neighborhoods concerning policing strategies, individual behaviors, and resource availability, all of which may contribute to perceptions of safety. Implications of this work highlight the importance of developing culturally relevant interventions that target upstream social determinants of healthy aging and health disparities.

MEDIATING EFFECTS OF QUALITY OF LIFE IN THE ASSOCIATION OF DEBTS AND LATER MEMORY FUNCTION IN CHINA, ENGLAND, AND THE US

Abstract Non-mortgage debts were linked to negative cognitive health outcomes in later-life older adults. It is unclear how they may be associated with later-life memory function through psychosocial pathways, and whether the associations vary by health care system and policy environment. We examined the mediating effects of depressive symptoms and dissatisfaction with life in the association between non-mortgage debts and subsequent memory function among adults aged 65-101 years in the US, China, and England. Data were from harmonized, nationally representative longitudinal studies of aging in the US (Health and Retirement Study; n=8,388), China (China Health and Retirement Longitudinal Study; n=1,180), and England (English Longitudinal Study of Aging; n=3,390). Non-mortgage debt burden was defined as any pre-existing or new non-mortgage debts in two years (2010-2012 for the US and England; 2011-2013 for China). Memory function was measured by 20-point immediate and delayed word recall summary scores over a subsequent 5- or 6-year follow-up period. Within each country, we used sampling-weighted, multivariable-adjusted causal mediation analysis (product method) to estimate the total and direct effects of non-mortgage debts on memory function, and the indirect effects mediated by depressive symptoms and dissatisfaction with life. We observed significant mediating effects of depressive symptoms on the association between non-mortgage debts and memory function in China only. Dissatisfaction with life had a significant mediating effect on this association in US and China, not in England. Although more investigation is needed, the relationships between non-mortgage debts and later-life memory function through psychosocial pathways may differ across macro-level socioeconomic structures.

Associations of AHA’s Life’s Essential 8 health behaviors with cognitive function among U.S. Black and White midlife adults

AbstractBackgroundLife’s Simple 7 (LS7), originally proposed as the seven most important predictors of heart health, is associated with negative cognitive outcomes (Thacker et al., 2014). The recently updated Life’s Essential 8 (LE8) includes sleep. Limited research has investigated the association between LE8 and cognition, particularly within Black and White adults. We hypothesize that higher composite LE8 scores will be associated with better cognitive performance, particularly within Black adults.MethodCross‐sectional analyses were conducted including adults from the Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) study conducted in Baltimore, MD. Study participants (36‐76 years old; 41% male; 61% Black) completed all LE8 (Lloyd‐Jones et al., 2022) and global cognition measurements in wave 4 data collection (2013‐2017). Cognitive performance on a computerized cognitive battery (Joggle Research) yielded a total global cognition score and individual domains (e.g., working memory, attention). Linear regression analyses were stratified by race and poverty status (below 125% Federal poverty guidelines), education attainment (high school), and reading literacy (median split) respectively. Covariates included age, sex, sleep apnea, and depression. All reported models were fully adjusted.ResultAmong Black adults, higher LE8 scores (better CVH) were associated with better working memory only among individuals living above the poverty level (all b unstandardized; b = 0.008, p = .016), or only with high school education (b = 0.009, p = .027). Among White adults, higher LE8 score was associated with better working memory, particularly among individuals living above poverty level (b = 0.014, p = .002), having an education above high school (b = 0.019, p = .002), or high literacy (b = 0.021, p&lt;.001) . Additionally, higher LE8 scores were associated with better attention, and higher global cognition score among individuals living above poverty (b = 0.015, p = .042; b = 0.039, p = .025) or with a high literacy on (b = 0.023, p = .014; b = 0.049, p = .027).ConclusionHigher score of LE8 was associated with better working memory among both U.S. Black and White adults. However, higher LE8 scores were associated with performance across a larger variety of cognitive domains within White adults from diverse socioeconomic indicators. These findings illustrate unique LE8 and cognition associations when disentangling socioeconomic heterogeneity within racial groups.

6 Examining Relationships Between Perceived Discrimination, Metabolic Syndrome, and Cognition

Objective:Discrimination on the basis of race, gender identity, and age, among others, has been associated with negative cognitive outcomes. However, the mechanisms by which perceived discrimination impacts cognition are not yet well understood. Discrimination can lead to chronic stress, which disrupts glucocorticoid pathways and induces susceptibility to metabolic dysregulation. On the basis of this prior work, and the known associations between metabolic syndrome and cognition, the current study examined the hypothesis that metabolic syndrome mediates the relationship between discrimination and cognition.Participants and Methods:1,063 adults (Mean age = 54.92 years, SD = 11.68) who participated in the Midlife in the United States project were included. Confirmatory factor analysis was used to examine the acceptability of a bifactor model of metabolic syndrome using four subfactors (insulin resistance, adiposity, dyslipidemia, and blood pressure). The mediating effect of the metabolic syndrome latent factor on the association between discrimination and cognition was tested using PROCESS (Hayes, 2013). Exploratory analyses were conducted to examine which cognitive domains and which metabolic syndrome subfactors were driving these relationships. Mediation analyses adjusted for age, race, sex, and education.Results:The three most frequently reported reasons for discrimination were gender (n = 209), age (n = 174), and race (n = 129). The CFA of metabolic symptoms was deemed acceptable based on previously outlined goodness of fit criteria (CFI = 0.986, TLI = 0.976, RMSEA = 0.040, SRMR = 0.034). Results of the mediation analysis indicated a significant indirect effect of major events discrimination on the total cognition composite through the general metabolic syndrome factor (B = -0.0029, 95% CI [-0.0016, -0.0066]). Further examination revealed that this relationship was driven through an indirect path of metabolic syndrome on the relationship between discrimination and executive functioning (B = -0.0024, 95% CI -0.0059, -0.0001]). We examined which subfactors were driving these relationships and found that there were significant indirect effects of major events discrimination on total cognition through the insulin resistance (B = -0.0028, 95% CI -0.0065, -0.0003]) and dyslipidemia factors (B = -0.0026, 95% CI -0.0064, -0.0002]).Conclusions:Our findings provide evidence that metabolic syndrome can help explain differences in cognitive functioning based on experiences of discrimination, even after adjusting for relevant demographic factors. Results from this study suggest that understanding the impact of perceived discrimination on metabolic syndrome and developing lifestyle interventions that can improve metabolic syndrome may be helpful in reducing stress-related cognitive disparities.

Cardiac output, cerebral blood flow and cognition in patients with severe aortic valve stenosis undergoing transcatheter aortic valve implantation: design and rationale of the CAPITA study.

Approximately one-third of patients with symptomatic severe aortic valve stenosis who are scheduled for transcatheter aortic valve implantation (TAVI) have some degree of cognitive impairment. TAVI may have negative cognitive effects due to periprocedural micro-emboli inducing cerebral infarction. On the contrary, TAVI may also have positive cognitive effects due to increases in cardiac output and cerebral blood flow (CBF). However, studies that systematically assess these effects are scarce. Therefore, the main aim of this study is to assess cerebral and cognitive outcomes in patients with severe aortic valve stenosis undergoing TAVI. In the prospective CAPITA (CArdiac OutPut, Cerebral Blood Flow and Cognition In Patients With Severe Aortic Valve Stenosis Undergoing Transcatheter Aortic Valve Implantation) study, cerebral and cognitive outcomes are assessed in patients undergoing TAVI. One day before and 3months after TAVI, patients will undergo echocardiography (cardiac output, valve function), brain magnetic resonance imaging (CBF, structural lesions) and extensive neuropsychological assessment. To assess longer-term effects of TAVI, patients will again undergo echocardiography and neuropsychological assessment 1year after the procedure. The co-primary outcome measures are change in CBF (in ml/100 g per min) and change in global cognitive functioning (Z-score) between baseline and 3‑month follow-up. Secondary objectives include change in cardiac output, white matter hyperintensities and other structural brain lesions. (ClinicalTrials.gov identifier NCT05481008) CONCLUSION : The CAPITA study is the first study designed to systematically assess positive and negative cerebral and cognitive outcomes after TAVI. We hypothesise that TAVI improves cardiac output, CBF and cognitive functioning.

18 Vascular Risk, Cerebral White Matter, and Executive Functioning in Vietnam-Era Veterans with Traumatic Brain Injury and/or Post-Traumatic Stress Disorder: A Department of Defense Alzheimer’s Disease Initiative (DoD-ADNI) Study

Objective:Research indicates that Veterans with a history of traumatic brain injury (TBI) are at increased risk for dementia. Although the precise mechanisms underlying this relationship are poorly understood, remote TBI may exacerbate normal age-related changes to cerebral white matter (WM) and result in cognitive decline. However, Veterans commonly experience a constellation of mental (e.g., post-traumatic stress disorder [PTSD] and depression) and vascular (e.g., diabetes, hypertension, obesity) health conditions that have also been implicated in pathologic cerebral WM and cognitive aging trajectories. Therefore, the present study sought to (1) clarify the effects of remote TBI within the context of PTSD, depression, and vascular risk on WM micro- and macrostructure, and (2) explore if WM integrity is associated with cognition in a sample of Vietnam-Era Veterans.Participants and Methods:The sample consisted of 195 male Veterans ages 60-80 (mean age=69.3) enrolled in the Department of Defense-Alzheimer’s Disease Neuroimaging Initiative (DoD-ADNI) study. 102 Veterans met criteria for TBI by sustaining a head-injury that resulted in a loss of consciousness, alteration of consciousness, or post-traumatic amnesia. Current and/or lifetime PTSD was designated by scores &gt;30 on the Clinician-Administered PTSD Scale. The Geriatric Depression Scale was used as a continuous measure of depression. A vascular risk score (0-3) was calculated based on diabetes, hypertension, and obesity (BMI &gt;30 kg/m2). An executive functioning composite was created by averaging sample-specific z-scores for Trail Making Tests (A and B), with higher scores indicating worse performance. Voxelwise analysis of WM microstructure (fractional anisotropy [FA]) was conducted with Tract-Based Spatial Statistics (TBSS), using non-parametric permutation testing with threshold-free cluster enhancement. SPM’s Lesion Segmentation Tool was used to investigate WM macrostructure (WM hyperintensity [WMH] volume). Lesion probability maps were masked to restrict WMH volume calculations to WM. Robust regression using M-estimation and predictive R2 calculated using 10-fold cross-validation examined WMH volume, predictor, and cognitive associations. Age was a covariate in all WM analyses, and education was a covariate in all cognitive analyses.Results:TBSS analysis revealed widespread, significant negative relationships between vascular risk and FA across numerous WM tracts (p’s&lt;0.05). These associations remained significant after adjusting for TBI history, PTSD, and depression. TBSS identified significant positive relationships between executive functioning performance and FA across similar brain regions (p’s&lt;0.05). Robust regressions revealed that vascular risk significantly predicted WMH volume (p=0.006; ß=0.161; R2=0.093), whereas TBI history, PTSD, and depression did not (p’s=0.107-0.166; ß's=-0.089-0.101). WMH volume significantly predicted executive functioning (p=0.002; ß=0.216; R2=0.105), whereas TBI history, PTSD, depression, and vascular risk did not (p’s=0.123-0.888; ß's=-0.012-0.125).Conclusions:Our results suggest that vascular health, relative to remote TBI, PTSD, and depression, may be more robustly associated with cerebral WM micro- and macrostructure in older Veterans. Furthermore, poorer WM integrity is associated with poorer cognitive performance. These findings underscore the importance of vascular health interventions in preventing negative brain and cognitive aging outcomes in Veterans, independent of TBI history. Future studies might leverage other neuroimaging modalities (e.g., functional MRI) to further investigate the effects of vascular health on aging in Veterans with a history of TBI.

Preventive putative effect of agmatine on cognitive and molecular outcomes in ventral tegmental area of male offspring following physical and psychological prenatal stress.

Prenatal stress (PS) results from a maternal experience of stressful events during pregnancy, which has been associated with an increased risk of behavioral disorders including substance abuse and anxiety in the offspring. PS is known to result in heightened dopamine release in the ventral tegmental area (VTA), in part through the effects of corticotropin-releasing hormone, which directly excites dopaminergic cells. It has recently been suggested that agmatine plays a role in modulating anxiety-like behaviors. In this study, we investigated whether agmatine could reduce negative cognitive outcomes in male mice prenatally exposed to psychological/physical stress, and whether this could be associated with molecular changes in VTA. Agmatine (37.5mg/kg) was administrated 30min prior to PS induction in pregnant Swiss mice. Male offspring were evaluated in a series of behavioral and molecular assays. Findings demonstrated that agmatine reduced the impairment in locomotor activity induced by both psychological and physical PS. Agmatine also decreased heightened conditioned place preference to morphine seen in PS offspring. Moreover, agmatine ameliorated the anxiety-like behavior and drug-seeking behavior induced by PS in the male offspring. Molecular effects were seen in VTA as the enhanced brain-derived neurotrophic factor (BDNF) induced by PS in the VTA was reduced by agmatine. Behavioral tests indicate that agmatine exerts a protective effect on PS-induced impairments in male offspring, which could be due in part to agmatine-associated molecular alterations in the VTA. Taken together, our data suggest that prenatal treatment with agmatine exerts protective effect against negative consequences of PS on the development of affective circuits in the offspring.

Associations of Food Insecurity and Memory Function Among Middle to Older–Aged Adults in the Health and Retirement Study

ImportanceFood insecurity is a leading public health issue in the US. Research on food insecurity and cognitive aging is scarce, and is mostly cross-sectional. Food insecurity status and cognition both can change over the life course, but their longitudinal relationship remains unexplored.ObjectiveTo examine the longitudinal association between food insecurity and changes in memory function during a period of 18 years among middle to older–aged adults in the US.Design, Setting, and ParticipantsThe Health and Retirement Study is an ongoing population-based cohort study of individuals aged 50 years or older. Participants with nonmissing information on their food insecurity in 1998 who contributed information on memory function at least once over the study period (1998-2016) were included. To account for time-varying confounding and censoring, marginal structural models were created, using inverse probability weighting. Data analyses were conducted between May 9 and November 30, 2022.Main outcomes and MeasuresIn each biennial interview, food insecurity status (yes/no) was assessed by asking respondents whether they had enough money to buy food or ate less than they felt they should. Memory function was a composite score based on self-completed immediate and delayed word recall task of a 10-word list and proxy-assessed validated instruments.ResultsThe analytic sample included 12 609 respondents (mean [SD] age, 67.7 [11.0] years, 8146 [64.60%] women, 10 277 [81.51%] non-Hispanic White), including 11 951 food-secure and 658 food-insecure individuals in 1998. Over time, the memory function of the food-secure respondents decreased by 0.045 SD units annually (β for time, −0.045; 95% CI, −0.046 to −0.045 SD units). The memory decline rate was faster among food-insecure respondents than food-secure respondents, although the magnitude of the coefficient was small (β for food insecurity × time, −0.0030; 95% CI, −0.0062 to −0.00018 SD units), which translates to an estimated 0.67 additional (ie, excess) years of memory aging over a 10-year period for food-insecure respondents compared with food-secure respondents.Conclusions and RelevanceIn this cohort study of middle to older–aged individuals, food insecurity was associated with slightly faster memory decline, suggesting possible long-term negative cognitive function outcomes associated with exposure to food insecurity in older age.