Higher education is strongly associated with better cognitive function in older adults. Previous research has also showed that positive psychosocial factors, such as selfefficacy and emotional and instrumental support, are beneficial for late-life cognition. There is prior evidence of a buffering effect of self-efficacy on the relationship between educational disadvantage and poor cognition in older adults, however it is not known if other psychosocial factors modify the schooling-cognition relationship. We hypothesized that higher levels of emotional and instrumental support will diminish the association between lower education and lower cognitive test scores among older adults.

553 older adults without dementia (42.1% non-Latinx Black, 32.2% non-Latinx White, 25.7% Latinx; 63.2% women; average age 74.4 (SD 4.3)) from the Washington Heights-Inwood Columbia Aging Project. Neuropsychological tests assessed four cognitive domains (language, memory, psychomotor processing speed, and visuospatial function). Self-reported emotional and instrumental support were assessed with measures from NIH Toolbox. Linear regression estimated interactions between education and the two support measures on cognition in models stratified by cognitive domain and racial and ethnic group. Covariates included age, sex/gender, and chronic health conditions (e.g. heart disease, stroke, cancer, etc.).

Education was associated with cognition across racial and ethnic groups. For every one year of schooling, the processing speed z-score composite was 0.33 higher among Latinx participants, 0.10 among non-Latinx Black participants, and 0.03 higher among non-Latinx White participants. The education-cognition relationship was generally similar across cognitive domains with larger effects in non-Latinx Black and Latinx participants than in White participants. Low education was associated with slower processing speed among Black participants with low emotional support (B = 0.224, 95% CI [0.014, 0.096]), but there was no association between low education and processing speed among Black older adults with high levels of emotional support (beta for interaction = -.142, 95% CI [-0.061, -0.001]). A similar pattern of results was observed for instrumental support (beta for interaction = -.207, 95% CI [-0.064, 0.010]). There were no interactions between support and education on other cognitive domains or among Latinx and White participants.

We found that higher levels of emotional and instrumental support attenuate the detrimental effect of educational disadvantages on processing speed in older Black adults. This may occur via benefits of social capital, which provides access to health resources and knowledge, increased social interaction, an emotional outlet allowing the ability to better cope with stress. Longitudinal analyses are needed to examine temporal patterns of associations. In addition, improving equitable access to high quality schools will improve later-life cognitive outcomes for future generations of older adults. However, for the growing number of Black older adults who will not experience the benefits of structural improvements in the education system, emotional and instrumental support may represent a modifiable psychosocial factor to reduce their disproportionate burden of cognitive morbidity.

Neuropsychology is in a nascent stage of understanding the mechanisms that link social forces, psychosocial experiences, and brain health. Discrimination is associated with lower quality of life, higher stress, and worse physical health outcomes in Latinx, but contradictory findings in prior research complicate our understanding of its relationship to cognition. These contradictory results may be explained by heterogeneity within the broad category of Latinx, a cultural identity that requires more nuanced conceptualization. Immigration status is a primary social identifier for Latinx people that carries significant stigma. However, prior research found enculturation promotes better physical and mental health outcomes in immigrants compared to their US-born counterparts, which may protect immigrant Latinx from the cognitive costs of discrimination. The current study hypothesized that the effect of discrimination on cognition will be stronger in US-born Latinx compared to immigrant Latinx.

We partnered with 1,023 neurologically healthy, community dwelling Latinx adults (M age=56.1(±10.7); M education=12.5(±3.7); 69% women) in a prospective cohort study in NYC investigating risks factors for Alzheimer’s disease. Immigration status was determined by self-report of birthplace. Measures of attention, language, and memory were administered by bilingual examiners in the participants’ self-selected preferred language of English (n = 388) or Spanish (n=635). Discrimination, measured with the Everyday Discrimination Scale and Major Experiences of Discrimination Scale, was chronicity coded to weigh experiences of discrimination according to yearly chronicity. Linear regression models were employed for US-born and immigrant participants to assess the relationship between both discrimination measures and each cognitive measure.

Compared to US-born Latinx (n = 224), immigrant Latinx (n = 799; primarily from the Dominican Republic) were older, had fewer years of school, had lower income, and were much more likely to have chosen to be assessed in Spanish. Immigrants reported experiencing significantly fewer everyday and major experiences of discrimination than nonimmigrants. In unadjusted models, discrimination did not predict cognitive performance among US-born Latinx. Among immigrant Latinx, more major experiences of discrimination across the lifetime predicted better phonemic (F(2,362) = 4.167, p<0.05, R2=0.017) and semantic fluency (F(2,362) = 3.304, p<0.05, R2=0.013) but was not associated with measures of attention or memory.

Discrimination is an important life stressor for Latinx people living in the US, particularly when its impact is summed across intersectional identities. The current study is among the first to explore the potential cognitive impact of discrimination within a group of Latinx adults. The described relationship between discrimination and language performance in this cohort may be confounded by the language in which cognitive tests were administered. Future studies should consider how discrimination measures may be limited in their ability to accurately capture the experiences of US-born and immigrant Latinx groups and expand the measurement of cognition to additional domains.

Code-switching is when bilingual individuals alternate between two languages in the same conversation. Some studies find that code-switching frequency is associated with executive functioning, while others do not. Individual attitudes towards bilingual language use and code-switching may explain the inconsistency in the literature. For instance, greater positive attitudes towards code-switching may be associated with more likelihood to engage in that practice and thus strengthen the cognitive benefit in executive function. Additionally, code-switching between English and Spanish has been stigmatized in the U.S., therefore it is unclear what sociocultural factors may predict positive attitudes. In this study, we assessed Latinx bilinguals’ attitudes on code-switching and investigated their relationship with code-switching frequency, sociodemographic and linguistic factors, and executive functioning.

Participants were 525 community-dwelling English-Spanish bilingual Latinx adults from the Offspring study (Mage= 55.38 (10.42); Meducation= 12.62 (3.34); 71% women; 41% tested in English, 75% immigrant). A language history questionnaire assessed for bilingualism and code-switching frequency. Participants completed 7 questions on code-switching attitudes on a 7-point Likert scale ranging from Strongly Disagree to Strongly Agree (e.g., “switching between languages in a conversation is an important part of my identity”), that were summed for a total score with higher scores indicating more positive attitudes. Executive functioning was assessed with the NIH Toolbox Cognition battery, verbal fluencies, and the digit span test. Sociodemographic and linguistic factors included age, sex, education, immigrant status, parental years of education, English and Spanish proficiency (average score on self-reported ratings on speaking, reading, writing, and understanding), and testing language. General linear models evaluated the association of code-switching attitudes on executive function, after adjusting for relevant covariates.

Positive code-switching attitudes were correlated with greater code-switching, r(499)=.33, p<.001. Younger age r(499)=-.11, being born in the US t(493)=-2.05, greater English proficiency r(497)=.15, and English dominance t(499)=2.22, were associated with more positive code-switching attitudes (all p’s <.05). Sex, education, parental years of education, and Spanish proficiency were not associated with code-switching attitudes. Overall models of attitudes with executive function indicated that positive code-switching attitudes were associated with worse visual working memory (b = -0.08, t(169) = -2.75, 95% CI [0.14, -0.02]) after adjusting for age, sex, education, immigration status, parental years of education and testing language. Code-switching attitudes were not significantly associated with other executive function measures.

Among a community-based sample of bilingual middle-aged Latinx adults, positive attitudes towards code-switching were associated with greater likelihood of code-switching in conversations, higher English proficiency, being US born, younger age, and English language dominance but negatively associated with visual working memory. These findings indicate that code-switching attitudes are influenced by sociodemographic and linguistic factors. Additionally, the negative association between code-switching attitudes and visual working memory provides support for previous studies showing code-switching as a disadvantage to cognition. Results of this study suggest that detailed characterization of sociocultural factors and aspects of bilingualism can provide further clarity in determining if there is a potential bilingual cognitive advantage. Future research should examine the relationship of code-switching with other aspects of bilingualism (e.g., age of acquisition).

South Africa has a multi-lingual population where fewer than 10% of the population speak English as a first language. This poses a challenge regarding language usage for a verbal fluency task. This study investigated the difference in number of words produced by independent groups of non-English examinees required to produce words in English, or in their first language, on a category verbal fluency task.

A study on South African non-English first language participants was conducted using the Category Verbal Fluency test (animals) for a sample of nonclinical adults (N = 264) aged 18-60 years with 8-12 years of disadvantaged (poorly resourced) quality of education. Participants either had an African indigenous first language, or Afrikaans (a Dutch derivative) as a first language. The data were derived from one group of either African indigenous or Afrikaans first language participants who were required to use English for word production (Group A English) (n = 159; African indigenous n = 135; Afrikaans n = 24) and another group of participants who were required to use their first language (Group B First Language) (n = 105; African indigenous n = 83; Afrikaans n = 22). The comparative data were stratified for age ranges 18-20, 21-30, 31-40, 41-50 and 51-60 years. Level of education was broadly equivalent across the comparative groups. T-test analyses compared the number of words produced between the English versus indigenous African groups, and English versus Afrikaans first language groups for each age category.

The comparison for the indigenous African first language participants, revealed no significant differences in word production for words produced in English or first language regardless of age. In the comparison for the Afrikaans first language participants there was a highly consistent tendency for better word production in Afrikaans than in English. These results indicate that socio-cultural factors may be influential for English language proficiency on a verbal fluency task, rather than the effect of first language usage “per se”.

Since the dismantling of the Apartheid system in South Africa thirty years ago, English has become the main language used in government and business and is the preferred language of tuition in schools for those speaking English or an African indigenous language, whereas during the Apartheid era, two official languages were used for government, business, and schooling (Afrikaans and English). Currently, many Afrikaans speaking individuals continue to have Afrikaans as the preferred primary language of tuition in the schools and it persists as the preferred language for use in many Afrikaans dominated business arenas. This study attests to a high level of English fluency amongst those South Africans with an indigenous African first language, who clearly are as fluent in word production using English as they are when using their first language, in contrast to the indications for Afrikaans speaking individuals. Practitioners need to be alert to sociocultural factors that can impact on the optimal use of language in test situations, which may not necessarily be the first language.

Neurocognitive deficits commonly occur following pediatric stroke and can impact many neuropsychological domains. Despite awareness of these deleterious effects, neurocognitive outcome after pediatric stroke, especially hemorrhagic stroke, is understudied. This clinical study aimed to elucidate the impact of eight factors identified in the scientific literature as possible predictors of neurocognitive outcome following pediatric stroke: age at stroke, stroke type (i.e., ischemic vs. hemorrhagic), lesion size, lesion location (i.e., brain region, structures impacted, and laterality), time since stroke, neurologic severity, seizures post-stroke, and socioeconomic status.

Ninety-two patients, ages six to 25 and with a history of pediatric stroke, chose to participate in the study and were administered standardized neuropsychological tests assessing verbal reasoning, abstract reasoning, working memory, processing speed, attention, learning ability, long-term memory, and visuomotor integration. A standardized parent questionnaire provided an estimate of executive functioning. Statistical analyses included spline regressions to examine the impact of age at stroke and lesion size, further divided by stroke type; a series of one-way analysis of variance to examine differences in variables with three levels; Welch’s t-tests to examine dichotomous variables; and simple linear regressions for continuous variables.

Lesion size, stroke type, age at stroke, and socioeconomic status were identified as predictors of neurocognitive outcome in our sample. Large lesions were associated with worse neurocognitive outcomes compared to small to medium lesions across neurocognitive domains. Exploratory spline regressions suggested that ischemic stroke was associated with worse neurocognitive outcomes than hemorrhagic stroke. Based on patterns shown in graphs, age at stroke appeared to have an impact on outcome depending on the neurocognitive domain and stroke type, with U-shaped trends suggesting worse outcome across most domains when stroke occurred at approximately 5 to 10 years of age. Socioeconomic status positively predicted outcomes across most neurocognitive domains. Participants with seizures had more severe executive functioning impairments than youth without seizures. Youth with combined cortical-subcortical lesions scored lower on abstract reasoning than youth with cortical and youth with subcortical lesions, and lower on attention than youth with cortical lesions. Neurologic severity predicted scores on abstract reasoning, attention, processing speed, and visuomotor integration, depending on stroke type. There was no evidence of differences on outcome measures based on time since stroke, lesion laterality, or lesion region defined as supra-versus infratentorial.

The current study contributed to the scientific literature by identifying lesion size, stroke type, age at stroke, and socioeconomic status as predictors of neurocognitive outcome following pediatric stroke. Future research should examine other possible predictors of neurocognitive outcome that remain unexplored. Multisite collaborations would provide larger sample sizes and allow teams to build models with better statistical power and more predictors. Enhancing understanding of neurocognitive outcomes following pediatric stroke is a first step towards improving appraisals of prognosis.

Findings are clinically applicable as they provide professionals with information that can help assess individual expected patterns of recovery and thus refer patients to appropriate support services.

Motor impairments are one of the most common adverse outcomes after pediatric arterial ischemic stroke (AIS), affecting approximately half of survivors. The development of motor and cognitive skills is closely interrelated, and they share common neural substrates. The objective of this study was to examine whether motor functioning after the acute phase of stroke is associated with school-age intellectual abilities. We also examined associations between concurrent motor functioning and intellectual abilities. Finally, we explored clinical features associated with motor impairments.

Participants were 64 children, 34 childhood AIS (Meanage= 11.90[2.38]); 30 perinatal AIS (Meanage= 8.75[2.22]), from the Children’s Stroke Program at SickKids Hospital. Motor functioning was assessed with the Pediatric Stroke Outcome Measure sensorimotor subscale at two timepoints, Time 1 or early recovery (childhood group between 30 days post-stroke to 1 year; perinatal group between 2-5 years of age) and Time 2, closest to neuropsychological testing. Intellectual abilities were measured using the Wechsler Intelligence Scale for Children 4th or 5th edition. Associations between motor and intellectual functioning were examined separately in childhood and perinatal AIS groups. Clinical features associated with motor impairment were examined across the full sample.

Motor functioning during early recovery was significantly associated with processing speed (r= -.391, p= .036) in the perinatal group and with overall intellectual functioning (r= -.414, p= .018) verbal intellectual abilities (r= -.444, p= .011), working memory (r= .393, p= .026), and processing speed (r= -.351, p= .042) in the childhood group. There were no associations between concurrent motor and intellectual functioning in the perinatal group, and only with processing speed (r= -.525, p= .002) in the childhood group. When motor functioning was dichotomized as no/mild motor deficit and moderate/severe motor deficit at Time 1, children in the perinatal group with moderate/severe motor deficit had significantly lower perceptual reasoning scores (f[28]= 2.15, p= .040) and participants in the childhood group with moderate/severe motor deficit had significantly lower perceptual reasoning (f[32]= 2.35, p= .025) and processing speed (f[32]= 2.14, p= 0.41) scores. There were no differences between no/mild and moderate/severe motor deficit groups for either perinatal or childhood AIS at Time 2. Clinical features associated with moderate/severe motor deficit at Time 1 were cortical+subcortical infarcts, large lesions, presenting with hemiparesis and seizures at time of neuropsychological assessment, and accessing occupational therapy and physical therapy.

Results suggest that motor functioning during early stroke recovery is associated with intellectual outcome, whereas motor functioning at time closest to neuropsychological assessment is not. This may be related neuroplastic changes post-injury, likely in frontal-subcortical connections, that result in observable motor deficits after stroke and affect subsequent hierarchal brain maturational processes thereby impacting later cognitive outcome. Different patterns of associations between motor functioning and specific intellectual abilities in perinatal and childhood groups suggest possible age-mediated effects on this relationship.

Despite knowledge concerning the prevalence and adverse consequences of pediatric stroke, there is limited awareness of the immediate and long-term effects on social-emotional functioning and psychological adjustment. Evidence from the broader childhood literature suggests that young individuals living with disabilities or neurological conditions are at considerably greater risk for emotional and behavioral concerns and lower quality of life. Qualitative research methodology can elucidate personal and subjective aspects of experience that cannot be entirely represented through quantitative measures. Although the parent experience of pediatric stroke has been qualitatively investigated, we endeavored to fill a gap in the pediatric stroke literature by focusing on the youth voice. The current project aimed to qualitatively explore emotional, behavioral, and social outcomes in pediatric stroke and identify personal and environmental factors that can influence psychological risk and resilience.

Individual interviews were conducted with 14 children, aged 8 to 18 years, with a history of ischemic stroke. The semi-structured interview protocol aimed to capture the lived experience of survivors and encompassed open-ended questions about daily life, memories, perceptions, and psychosocial experiences. Interviews spanned 40-60 minutes in length, were audio recorded, transcribed verbatim, and qualitatively analyzed using reflexive Thematic Analysis methodology. Coding, theme generation, and data visualization were completed using NVivo12 software.

Participants discussed their views and understanding of their stroke, the perceived impact of stroke on their daily life, and the meaning-making process surrounding this experience. Children shared their perceptions regarding their abilities, challenges, life circumstances, aspirations, and relations to peers. Prominent themes encompassed shyness and social anxiety, cognitive and learning troubles, test anxiety, concealing feelings of sadness, the stigma of physical disability and its impact on social participation, bullying, and loneliness/isolation. Insight into adaptive coping mechanisms was present, as was emphasis on family closeness and the importance of supportive peers. Participants described feeling unique and were proud of their values and personal identity. Gratitude was expressed regarding stroke medical care and rehabilitative services, with an emergent theme surrounding the desire to give back to society.

Taken together, our qualitative study findings illustrate the profound impact that pediatric stroke can have on children’s emotional experiences, personal identity, self-efficacy, learning, behavior, and psychosocial functioning. Despite these challenges, an enormous degree of resiliency was also demonstrated in youth’s insights into coping and adaptation to challenge. Our findings speak to the importance of psychological assessment and treatment planning surrounding internalizing symptoms in children with stroke. Given the potential for pervasive changes in various aspects of daily life, a comprehensive understanding of the personal psychological experiences and perceptions of pediatric stroke patients is essential, as it will facilitate opportunity for timely interventions that can improve coping and adaptive outcome. Implications will be discussed with regard to empowering pediatric stroke survivors, enhancing public education efforts about childhood acquired brain injury, and reducing stigma associated with disability and use of required supports.

Childhood ischemic and hemorrhagic stroke is often associated with neuropsychological and cognitive deficits. Stroke induces an inflammatory response in the central and peripheral nervous systems. High levels of inflammatory markers in the plasma have been associated with poorer cognitive outcomes. The role of inflammation in neurological prognosis of stroke has been studied previously; however, there is a limited understanding of the association between inflammatory markers and neuropsychological outcome post-stroke. The present review examined the existing literature on the association between inflammatory markers and post-stroke functioning.

Data bases (PsycINFO, PubMed, Web of Science, and Ovid) were reviewed in October 2020. Articles were restricted to English-language literature. Articles were included regardless of recruitment setting, number of strokes, mechanism of stroke, timing of blood collection and outcome assessment. The articles focused on patients with stroke (between the ages of 0 to 95), measured post-stroke outcome by neurological and cognitive outcome measures (i.e., it included findings on any aspect of cognition such as memory, information processing, or attention), and on pro-inflammatory cytokines and c-reactive proteins as measures of inflammation. The systematic literature search retrieved 954 articles to review against inclusion criteria. Descriptive statistics were performed using IBM SPSS 27.0 Statistics Software.

A total of 18 articles were included in this review. The population age ranged from 21 to 95, and, when reported (n=17), mean participant age was 66.31. Among stroke patient populations, ischemic stroke was most researched (n=15). The most widely investigated biomarkers were CRP (n=9), IL-6 (n=8), TNF- a (n=7), IL-1 b (n=5), and IL-10 (n=5). The time of initial blood collection ranged from on admission to within 3 months poststroke. Equal number of studies used both neurological and cognitive tests (n=7), or only neurological (n=7), 2 studies only used cognitive tests, and one study used all three types of measures. The most commonly used cognitive test was the Mini Mental State Examination, MMSE (n=7). The next commonly used cognitive test was the Montreal Cognitive Assessment (MoCA), (n=4). Only two studies used a comprehensive neuropsychological battery.

There is a lack of research into diverse stroke populations. All the studies examined the association between inflammatory markers and the post-stroke outcomes in adult populations and mostly in patients with ischemic stroke. The lack of research on pediatric and young adult stroke represents a significant gap in understanding predictors of neurological and cognitive outcomes. Further, the review revealed a lack of comprehensive neurocognitive assessment post stroke, with most studies measuring neuropsychological outcome using brief cognitive instruments. Our findings highlight a critical need for addressing the above gaps to help elucidate the role of inflammatory markers in the neuropsychological prognosis of stroke in younger populations.

Epilepsy, and specifically drug-resistant epilepsy (DRE), is associated with an increased risk of psychiatric dysfunction, likely due to a combination of physiological mechanisms, emotional reactions to disease burden, and bi-directional influences. Women with epilepsy warrant special consideration due to many factors, including hormonal influences on seizure susceptibility, reproductive health considerations, and unique psychiatric and clinical profiles. However, there is yet to be large-scale research characterizing women with DRE. The present study characterized psychiatric conditions, treatment, and hospitalization data in a Veterans Health Administration (VHA)-wide sample of women Veterans and then compared results to a male Veteran sample to explore sex differences.

Data from 52,579 Veterans enrolled in VHA care between FY2014 and 2nd Quarter FY2020 were gathered from the VHA Corporate Data Warehouse administrative data. The sample was comprised of 5,983 women (11.4%) and 46,596 men (88.6%). Demographics, psychiatric diagnoses, psychiatric medications, ER visits, and hospitalizations were characterized. Chi-square analyses were used to examine group differences between men and women.

The vast majority of the women Veteran sample had at least one psychiatric diagnosis (86.1%), with over half of the sample diagnosed with depression (68.3%), PTSD (54.1%), and/or anxiety disorders (57.7%). When compared to men, women Veterans were more likely to have a psychiatric diagnosis (86.1% vs. 68.1%), evidenced a higher number of co-morbid psychiatric conditions (2.4 vs. 1.6), and were prescribed more psychiatric medications (3.4 vs. 2.3; all significant at p<0.001). All individual psychiatric diagnoses were more prevalent in women than men and, notably, suicidality was also higher in women (13.5% vs. 10.0%; p < 0.001). Women Veterans also had a higher number of ER visits (6.9 vs. 5.5; p < 0.001) and psychiatric hospitalizations than men (.4 vs. .3, p < 0.001).

The present study represents the largest known investigation to date of women with DRE and is also the largest study of women Veterans with any form of epilepsy. It highlights a vast psychiatric burden in this subset of women Veterans, with high rates of psychiatric comorbidity, lending to downstream effects on psychiatric medication burden and risk for emergency care usage and psychiatric hospitalization. Comparisons to men emphasize that women are differentially impacted by the psychiatric toll of DRE and warrant special consideration. The markedly higher rates of depressive disorders and suicidality in women Veterans with DRE is especially notable when considering risk of harm and mortality. Overall, the present work adds to the paucity of literature of women Veterans with seizures and gaps in the broader DRE research base, with implications for specialized screening and maximizing treatment interventions in this population.

The women who served in the 19901991 Persian Gulf War (GW) are unique in that they were the first group to have fewer restrictions in terms of military occupations and exposure to combat. Of the nearly 41,000 US troops who were women deployed to the GW, many were serving in frontline positions and were exposed to the same toxicants as their male counterparts. Toxicant exposures such as pesticide sprays and creams, oil well fires, diesel fuels, chemical and biological warfare (CBW) agents and anti-nerve gas (PB) pills have been found to result in cognitive impairments across a range of neuropsychological tests. Our research team has been following cohorts of women who were deployed to the GW and correlated exposures with neuropsychological outcomes. Overall, in small cohorts of women veterans we found that higher levels of exposures to pesticide sprays and creams and CBW are correlated with short-term memory, mood, and motor deficits. These findings were different from those of their male counterparts. In a recently developed data-repository we have compiled larger groups of women veterans to validate our prior findings.

The current study is an analysis of data from a national bio/data-repository (Boston Biorepository Recruitment and Integrative Network for Gulf War Illness; BBRAIN) which includes key data samples from prior GW studies that have been merged and combined into retrospective datasets. Data include general health and chronic symptom questionnaires, demographics, deployment and self-reported exposure histories (separated into no exposure, fewer than 7 days exposure and greater than or equal to 7 days exposure), as well as key neuropsychological test variables. Three separate datasets were combined to include 62 women. Exposures to chemical alarms, oil well fires, pesticide cream or spray, pesticide fogging, and PB pills were self-reported. Linear regression models were produced for each continuous cognitive outcome, modeled on a given exposure, and controlling for age, education level, PTSD, and other exposures.

Of the 62 women, the majority were White (77%). 74% of women surveyed were employed and 55% were married. 63% of women had at least a high school education. Deployed women who had > 7 days of exposure to pesticide sprays, CBW, smoke from oil well fires, and PB pills were more likely to show deficits in the areas of verbal learning and short-term memory (p < .03) and those with exposure to CBW, smoke from oil well fires, pesticides creams and PB pills had more errors on a test of executive functioning (p < .01). These data differ from the findings from cohorts of men.

These data validate the findings of our prior studies and add credence to the need for separate analyses for men and women. The unique outcomes may lead to individualized treatments for women veterans that may also help women with similar exposures from other deployments in addition to women with occupational exposures.

All premenopausal women who survive traumatic brain injury (TBI) will eventually experience menopause. Challenges experienced by women with TBI are superimposed on challenges associated with hormonal changes in midlife. Some women with stressful life contexts such as TBI are more vulnerable to the added burdens of the menopause transition, potentiating its effects. Although it may be argued that TBI research correctly overrepresents the male experience given disparities in injury rates (4:1), there are important differences in how females and males age, their specific health needs, and the psychosocial context of midlife. Development of evidence-based interventions begins with understanding the experience of menopause after TBI, including where and when key problems may emerge.

All participants were women 40-60 years old, not taking hormones (i.e., replacement therapy or other systematic hormones), with intact ovaries. Women with TBI were > 2 years post injury, whose menstrual period returned after injury, and were living in the community. Severity of injury ranged from complicated-mild to severe TBI. Pre/peri and postmenopausal status was determined by presence/absence of menstrual period in previous 6 months, respectively. Eighteen common menopause symptoms (vasomotor, somatic, psychological, and cognitive) were assessed for presence and frequency (rarely-always), along with Quality of Life in Neurological Disorders (Neuro-QOL) Sleep Disturbance and Traumatic Brain Injury Quality of Life (TBIQOL) Anxiety, Depression, and Fatigue scales.

Overall, women with TBI (n = 68) showed greater presence and frequency of symptoms than women without TBI (n = 153), with fewer within-group differences by menopausal status. Among pre/peri-menopausal women, TBI and non-TBI groups did not significantly differ and showed small effect sizes on symptoms associated with changes in estrogen during menopause, including hot flashes, night sweats, bowel and bladder sequelae, and breast tenderness. However, pre/peri-menopausal women with TBI also endorsed body aches and headaches, as well as troubles with memory, focus, fatigue, cognitive concerns, sleep, and anxiety significantly more than their pre/peri-menopausal counterparts (all medium effect sizes). Among postmenopausal women, those with TBI had significantly greater frequency of hot flashes, crying spells, poor memory, worry, moodiness, panic attacks, sleep disturbance, and anxiety than women without TBI. Within TBI, only hot flashes and breast tenderness were greater in postmenopausal versus pre/peri-menopausal women. Within non-TBI, postmenopausal status was associated with significantly greater hot flashes, night sweats, restlessness, poor memory, irritability, sleep disturbance, and anxiety, with greater fatigue but not significantly.

The findings support a model of TBI and menopause in which symptoms most closely associated with estrogen decline in pre/peri-menopause are generally similar between women with and without TBI, and symptoms that overlap with common TBI sequelae were generally more often present and frequently experienced among women with TBI versus non-TBI. We did not observe a synergistic or potentiating effect of TBI on menopause symptoms in post-menopause. These findings offer insight that contextualizes the experience of menopause symptoms among women with TBI. Such insights are essential for the development of treatment approaches that maximize health and wellbeing during the menopause transition for women with TBI.

The vast majority of existing research on outcomes following concussion is androcentric with women notably understudied in all settings where concussion commonly occurs, including sport, military, and civilian domains. Clinical care for concussed women is, by extension, far less evidenced-based as it is largely extrapolated from male-dominated studies. We therefore sought to center concussion outcomes of women in big data sources in this investigation to capitalize on both sample size and breadth of setting in which concussion occurs.

We identified all studies with publicly released data as of 4/7/21 that included both male and female adults, enough information to determine severity of injury consistent with concussion/mild traumatic brain injury (TBI), a measure of postconcussive symptoms (PCS), and objective measures of neurocognitive functioning from the Federal Interagency Traumatic Brain Injury Research (FITBIR) Informatics System. FITBIR is a collaborative effort of the National Institutes of Health (NIH) and the Department of Defense (DoD), developed to share data across the entire TBI research community. This resulted in inclusion of six studies with a total of 9370 participants, 32% female. PCS data was drawn from the Neurobehavioral Symptom Inventory (NSI), the Rivermead Post-Concussion Symptoms Questionnaire (RPSQ), and the Sport Concussion Assessment Tool - 3rd Edition (SCAT 3), specifically the 22-item participant symptom evaluation rated on a 7-point scale. The questionnaires were harmonized and the following symptom domains emerged: Somatic, Cognitive, and Affective. Data were analyzed using linear mixed-effects models.

We found a small to medium sized significant effect of sex, with women reporting higher symptoms overall. Mean symptom endorsement scores were higher overall on the NSI in comparison to the RPSQ and SCAT (ps < .001). Follow-up analyses revealed sex differences were largest for cognitive symptoms, followed by somatic symptoms, then affective symptoms. We also found significant main effects of population (military>sport/civilian, p = .003) and sex (women>males, p < .001) on the overall composite, as well as a significant population-by-sex interaction such that female service members/veterans endorsed the highest rates of symptoms (p < .001). Similar patterns of significance and effect sizes were observed for the somatic and affective composites. Cognitive symptom composites showed a similar pattern, but with smaller effect sizes overall. Racial and ethnic diversity was also limited in the sample.

In one of the largest samples of women to date, we found a small to medium effect of sex on symptom reporting such that women reported higher levels of postconcussive symptoms than males. Notably, however, the women in military/Veteran samples endorsed the highest levels of symptoms. Despite using a large publicly available dataset to maximize the representation of women, the current sample was still predominantly male and racial and ethnic diversity among the sample was not consistent with expected broader population demographics. Dramatically more concerted efforts need to be made to engage women in all spheres of concussion research (military, civilian, and sport). Strategies to be more inclusive in concussion research will be highlighted.

There are critical and perplexing sex/gender differences in Alzheimer’s disease (AD). Women show a more favorable clinical profile in preclinical AD particularly with verbal memory, but a steeper decline post mild cognitive impairment (MCI) diagnosis and, ultimately, higher rates of AD. Longitudinal studies are needed to understand sex differences across the AD trajectory. Using data from the Alzheimer’s Disease Neuroimaging Initiative, we identified profiles of memory trajectories among those with evidence of preclinical AD or MCI at baseline and how these trajectories differ by sex.

In our sample of 659 participants (age range: 55-90, mean age=72.9 [SD=7.4], 95% non-Hispanic White; mean follow-up=41.2 [SD=32.3] months), 233 were labelled “preclinical” AD (51% women) at baseline based on a cognitively normal status but positivity for either the cerebrospinal fluid p-Tau/Aß42, Amyloid PET or Tau PET biomarkers, and 426 participants (44% women) were MCI at baseline based on Jak/Bondi criteria. We applied latent class growth curve modeling to the heterogeneous change in the Rey Auditory Verbal Learning Test (RAVLT) Immediate and Delayed Recall within preclinical and MCI groups separately. Models in MCI group included Non-Linear Spline to account for differential change rates within subgroups. Models were compared on Bayesian Information Criterion, Entropy, and Class distribution to determine a best-fitting model. Effects of sex on trajectories were the primary outcomes. All models included APOE4 carrier status and age.

Women outperformed men on Immediate and Delayed Recall at baseline in the preclinical and MCI groups (ps<.05). Within the preclinical group, 3-class models representing stable, decline, and accelerated decline provided optimal fit for both Immediate and Delayed Recall. Whereas, on average, preclinical women showed more stable Immediate Recall than men (beta=6.24, SE=.82, p<.0001), they were more likely to be in the Immediate Recall accelerated decline class (23.4% vs. 16.25%; female:male; Chi-square=36.29, p<.00001). On average, preclinical women and men did not differ in Delayed Recall trajectories (beta=.31, SE=.30, p=.28); however, preclinical women were more likely to be in the stable Delayed Recall class (11.04% vs. 6.5%; Chi-Square=19.19, p<.0001). Within the MCI group, 2-class models representing a stable decline group and an accelerated decline group provided optimal fit for both outcomes. Whereas, on average, MCI women showed more stable Immediate Recall than men (beta=3.55, SE=.79, p<.0001), they were more likely to be in the Immediate Recall accelerated decline class, although not significantly. Women and men did not differ, on average, in their Delayed Recall trajectories; however, women were significantly more likely to be in the Delayed Recall accelerated decline class (Chi-square=32.24, p<.0001).

Our findings indicate that sex is an important determinant of the variability observed in early-stage AD trajectories; however, sex differences varied by Immediate versus Delayed Recall likely due, in-part, to psychometric test properties. Our results suggest that, when looking at sex differences in AD trajectories on average, women’s superior stability in verbal learning masks their higher likelihood of rapid decline. Our findings have implications for our ability to optimally diagnose and track disease progression in both sexes.

Neuropsychologists have difficulty detecting cognitive decline in high-functioning older adults, in whom substantially greater neurological change may need to occur before performance on cognitive tests are low enough to indicate cognitive impairment. For high-functioning older adults, subjective cognitive concerns (SCC) may indicate decline that is not detected by the presence of low cognitive test scores but may be related to the absence of high scores and the presence of latent neurological changes. We hypothesized that high-functioning older adults with SCC would have fewer high scores than those without concerns, but a comparable number of low scores. These findings would indicate that objective decline has occurred but would not be detected by a traditional focus on low scores. We also hypothesized that SCC would be associated with lower frontoparietal network volume, thickness, and connectivity, indicating latent neurological change underlying subjective cognitive concerns.

Participants from an imaging sub-study of an ongoing longitudinal aging study were selected if they had high estimated premorbid functioning, defined as either (a) estimated intelligence >75th percentile on the North American Adult Reading Test (n=48) or (b) having a college degree (n=62). This resulted in 68 participants subdivided based on SCC, defined as one or more self-reported SCC on the Medical Outcomes Study Cognitive Functioning Scale (MOS-Cog). Participants with SCC (n=35; 73.9 years-old, SD=9.6, range: 60-95; 62.9% female; 94.3% White) and without SCC (n=33; 71.0 years-old, SD=7.2, range: 61-85, 75.8% female; 100% White) completed a neuropsychological test battery of memory and executive functions, including the Rey Auditory Verbal Learning Test, Trail Making Test Parts A and B, Controlled Oral Word Association Test, Digit Span, and Letter-Number Sequencing, and underwent structural MRI. MR images were analyzed for frontoparietal network volume, thickness, and connectivity.

Participants with and without SCC were compared on the number of low test scores (i.e., at or below the 16th percentile) and high test scores (i.e., at or above the 75th percentile), finding a comparable number of low scores, t=1.66, p=.103, d=.40, but a lower number of high scores among participants with SCC, t=2.95, p=.004, d=.71. Participants with SCC had lower bilateral mean frontoparietal network volumes (left: t=2.98, p=.004, d=.74; right: t=2.63, p=.011, d=.66) and cortical thickness (left: t=2.65, p=.010, d=.66; right: t=2.18, p=.033, d=.54), but did not differ from those without SCC in terms of network connectivity.

SCC have been reported as a potential risk factor for dementia in older adults. High-functioning older adults with SCC presented with fewer high scores than those without SCC but had a comparable number of low scores. Among high-functioning older adults, subjective cognitive decline may correspond with objective cognitive change not detected by the traditional emphasis on low scores, but rather the absence of high scores. SCC were also related to underlying changes in the volume and thickness of the frontoparietal network, but not connectivity. In high-functioning older adults, subjective cognitive decline may correspond with a reduction from high average functioning in some domains and underlying neurological changes.

There is increasing recognition of cognitive and pathological heterogeneity in early-stage Alzheimer’s disease and other dementias. Data-driven approaches have demonstrated cognitive heterogeneity in those with mild cognitive impairment (MCI), but few studies have examined this heterogeneity and its association with progression to MCI/dementia in cognitively unimpaired (CU) older adults. We identified cluster-derived subgroups of CU participants based on comprehensive neuropsychological data and compared baseline characteristics and rates of progression to MCI/dementia or a Dementia Rating Scale (DRS) of <129 across subgroups.

A hierarchical cluster analysis was conducted using 11 baseline neuropsychological test scores from 365 CU participants in the UCSD Shiley-Marcos Alzheimer’s Disease Research Center (age M=71.93 years, SD=7.51; 55.9% women; 15.6% Hispanic/Latino/a/x/e). A discriminate function analysis was then conducted to test whether the individual neuropsychological scores predicted cluster-group membership. Cox regressions examined the risk of progression to consensus diagnosis of MCI or dementia, or to DRS score <129, by cluster group.

Cluster analysis identified 5 groups: All-Average (n=139), Low-Visuospatial (n=46), Low-Executive (n=51), Low-Memory/Language (n=83), and Low-All Domains (n=46). The discriminant function analysis using the neuropsychological measures to predict group membership into these 5 clusters correctly classified 85.2% of the participants. Subgroups had unique demographic and clinical characteristics. Relative to the All-Average group, the Low-Visuospatial (hazard ratio [HR] 2.39, 95% CI [1.03, 5.56], p=.044), Low-Memory/Language (HR 4.37, 95% CI [2.24, 8.51], p<.001), and Low-All Domains (HR 7.21, 95% CI [3.59, 14.48], p<.001) groups had greater risk of progression to MCI/dementia. The Low-Executive group was also twice as likely to progress to MCI/dementia compared to the AllAverage group, but did not statistically differ (HR 2.03, 95% CI [0.88,4.70], p=.096). A similar pattern of results was found for progression to DRS score <129, with the Low-Executive (HR 2.82, 95% CI [1.26, 6.29], p=.012), Low-Memory/Language (HR 3.70, 95% CI [1.80, 7.56], p<.001) and Low-All Domains (HR 5.79, 95% CI [2.74, 12.27], p<.001) groups at greater risk of progression to a DRS score <129 than the All-Average group. The Low-Visuospatial group was also twice as likely to progress to DRS <129 compared to the All-Average group, but did not statistically differ (HR 2.02, 95% CI [0.80, 5.06], p=.135).

Our results add to a growing literature documenting heterogeneity in the earliest cognitive and pathological presentations associated with Alzheimer’s disease and related disorders. Participants with subtle memory/language, executive, and visuospatial weaknesses all declined at faster rates than the All-Average group, suggesting that there are multiple pathways and/or unique subtle cognitive decline profiles that ultimately lead to a diagnosis of MCI/dementia. These results have important implications for early identification of individuals at risk for MCI/dementia. Given that the same classification approach may not be optimal for everyone, determining profiles of subtle cognitive difficulties in CU individuals and implementing neuropsychological test batteries that assess multiple cognitive domains may be a key step towards an individualized approach to early detection and fewer missed opportunities for early intervention.

Type 2 diabetes (T2D) is a risk factor for cognitive impairment/dementia and has been shown to modify the impact of Alzheimer’s disease (AD) biomarkers on cognition and everyday functioning. Studies examining amyloid-ß (Aß), one of the hallmark AD pathologies, have shown mixed results regarding associations of Aß biomarkers with cross-sectional cognition as well as T2D, though Aß is generally associated with future cognitive declines. The purpose of the present study is to examine whether T2D impacts the associations between amyloid positron emission tomography (PET) and cognition in older Veterans.

The current study included 202 mostly male Vietnam-Era Veterans from the Department of Defense-Alzheimer’s Disease Neuroimaging Initiative (DOD ADNI) study (age M=69.38 years, SD=4.37; 40% with self-reported T2D) who completed neuropsychological testing and florbetapir PET imaging. The Aß PET standardized uptake variable ratio (SUVR) was measured using a previously-validated summary SUVR calculated by dividing the mean uptake across 4 AD-vulnerable cortical regions by whole cerebellar uptake. General linear models examined whether T2D moderated the relationship of Aß PET with memory, attention/executive functioning, and language composite scores. Models adjusted for age, education, apolipoprotein E e4 carrier status, vascular risk burden, depressive symptoms, post-traumatic stress disorder (PTSD) symptom severity, and history of traumatic brain injury (TBI).

There was no main effect of diabetes on memory, attention/executive functioning, or language performance, and higher Aß PET SUVR was only associated with worse attention/executive functioning performance (ß=-.146, 95% CI [-.261, -.031], p=.013). The Aß PET x T2D interaction was significant for attention/executive functioning such that higher Aß PET SUVR was associated with lower attention/executive functioning scores, but only in those with T2D (ß=-.116, [-.225, -.006], p=.038). This interaction was not significant for language or memory.

The results show that Aß may negatively impact attention/executive functioning, but this effect was only found in Veterans with T2D. Prior work has suggested that T2D may be more associated with tau biomarkers than markers of Aß, so it is possible that the current results are due to a compounding effect of Aß pathology plus microvascular and/or tau pathology. Notably, the sample was relatively young, a relatively large proportion had elevated PTSD symptoms and/or a TBI history (which have both been shown to relate to attention/executive function), and the measures that made up the attention/executive composite (Trail Making Test A and B) have been shown to be particularly sensitive - all of which may have contributed to the domain-specific effects. Future research is needed to investigate the role that tau and vascular pathology may play in cognition among individuals with T2D. Longitudinal studies are also needed to better understand the timing and progression of these relationships.

History of traumatic brain injury (TBI) is associated with increased risk of dementia, but few studies have evaluated whether TBI history alters the course of neurocognitive decline, and existing literature on this topic is limited to short follow-up and smaller samples. The primary aim of this study was to evaluate whether a history of TBI (TBI+) influences neurocognitive decline later-in-life among older adults with or without cognitive impairment [i.e., normally aging, Mild Cognitive Impairment (MCI), or dementia].

Participants included individuals from the National Alzheimer’s Coordinating Center (NACC) who were at least 50 years old and with 3 to 6 visits (M number of visits = 4.43). Participants with any self-reported history of TBI (n = 1,467) were matched 1:1 to individuals with no reported history of TBI (TBI-) from a sample of approximately 45,000 participants using case-control matching based on age (+/- 2 years), sex, education, race, ethnicity, cognitive diagnosis [cognitively normal (CN), MCI, or all-cause dementia], etiology of cognitive impairment, functional decline (Clinical Dementia Rating Scale, CDR), number of Apolipoprotein E4 (APOE ε4) alleles, and number of annual visits (3 to 6). Mixed linear models were used to assess longitudinal neuropsychological test composites (using NACC normative data) of executive functioning/attention/speed (EFAS), language, and memory in TBI+ and TBI- participants. Interactions between TBI and demographics, APOE ε4 status, and cognitive diagnosis were also examined.

Following matching procedures, TBI+ (n=1467) and TBI- (n=1467) groups were nearly identical in age (TBI+ M = 71.59, SD = 8.49; TBI- M = 71.63, SD = 8.44), education (TBI+ M = 16.12, SD = 2.59; TBI- M = 16.10, SD = 2.52), sex (both 55% male), race (both 90% White), ethnicity (both 98% non-Hispanic), APOE ε4 alleles (both 0 = 62%, 1 = 33%, 2 = 5%), baseline cognitive diagnoses (both CN = 60%, MCI = 18%, dementia = 12%), and global CDR (TBI+ M = 0.30, SD = 0.38, TBI- M = 0.30, SD = 0.38). At baseline, groups had similar Z-scores of in EFAS (TBI+ Mefas = -0.02, SD = 1.21; TBI- Mefas = -0.04, SD = 1.27), language (TBI+ MLanguage = -0.48, SD = 0.98; TBI- MLanguage = -0.55, SD = 1.05), and memory (TBI+ MMemory = -0.45, SD = 1.28; TBI- MMemory = -0.45, SD =1.28). The course of change in neuropsychological functioning worsened longitudinally, but did not differ between TBI groups (p’s > .110). There were no significant interactions between TBI history and age, sex, education, race/ethnicity, number of APOE ε4 status, or cognitive diagnosis (all p’s > .027).

In this matched case-control design, our findings suggest that a history of TBI, regardless of demographic factors, APOE ε4 status, and cognitive diagnosis, does not significantly alter the course of neurocognitive functioning later-in-life in older adults with and without cognitive impairment. Future clinicopathological longitudinal studies with well characterized TBI histories and the associated clinical course are needed to help clarify the mechanism by which TBI may increase dementia risk for some individuals, without affecting course of decline.

Tissue inhibitor of metalloproteinases 2 (TIMP2) is produced peripherally, crosses the blood-brain barrier, and improves synaptic plasticity and hippocampal-dependent cognition in aged mice; however, the role of TIMP2 in human cognitive aging is unclear. We examined associations of circulating TIMP2 levels in blood with a known plasticity-inducing behavior, physical activity, and cognitive functioning among older adults along the Alzheimer’s disease continuum.

Participants included 84 community-dwelling older adults (meanage = 78.8; 57% female; 82% cognitively normal; 14% MCI; 4% mild dementia; 35% PET Aß+) enrolled in the UC San Francisco Memory and Aging Center. All participants completed 30 days of observational FitbitTM monitoring to quantify physical activity (average daily steps), as well as a comprehensive in-person visit including blood draw (proteins assayed on SOMAscan platform), [18F]AV-45 positron emission tomography (PET) to quantify brain beta-amyloid (centiloids), and neuropsychological assessment. Composite cognitive z-scores were calculated for memory (California Verbal Learning Test-II [CVLT-II] and Benson Figure Recall), semantic processing (animal fluency and Boston Naming Test), and executive functioning (digits backwards span, Stroop inhibition, modified trail making test, lexical fluency, and design fluency). Multiple linear regression examined TIMP2 as a function of physical activity, covarying for age and PET centiloids. Additional regression models separately examined cognitive z-scores as a function of TIMP2, covarying for age, sex, education, PET centiloids, and body mass index (BMI).

TIMP2 was not significantly correlated with age, sex, education, or PET centiloids (ps > 0.05); however, TIMP2 was negatively correlated with BMI (r = -0.23, p = 0.036). Greater average daily steps related to higher levels of TIMP2 (b = 0.30, 95%CI = 0.04-0.55, p = 0.022). TIMP2 also related to better semantic processing (b = 0.28, 95%CI = 0.04-0.51, p = 0.021) and executive functioning (b = 0.26, 95%CI = 0.03-0.49, p = 0.028). TIMP2 did not significantly relate to memory (p > 0.05).

Greater physical activity was associated with higher concentrations of blood factor TIMP2, which in turn related to better cognitive functioning independent of Alzheimer’s disease pathology burden. These results support previous mouse models by broadly replicating relationships between TIMP2 and cognition in humans, while also uniquely demonstrating an association between TIMP2 and physical activity, a modifiable protective factor in both typical and diseased cognitive aging. Our domain-specific results, however, suggest that benefits of TIMP2 in humans may involve a broader neuroanatomical network than the hippocampal-specific effects previously shown in mice. Although exact mechanisms of TIMP2 need further examination, TIMP2 is known to be enriched in human umbilical cord plasma, has been shown to be involved in cell-growth promoting activities, and may relate to increased neural plasticity in older age. Further examination of TIMP2 and other novel blood-based proteins as potential therapeutic targets for improved cognitive aging, including in the presence of Alzheimer’s disease, is warranted.