Stress is well known to increase the severity of somatization and insomnia. A recent major stressor that could have influenced the severity of these presentations was world-wide COVID-19 Pandemic. Somatization is the physical expression of stress and emotional distress that can manifest itself throughout various corporal domains and can be a comorbidity to insomnia. Headaches represent some of the most common complaints associated with brain injuries and neurological disorders but are common in somaticized disorders as well. In large survey study we examined whether exercise was associated with severity of somatization and headaches. We hypothesized that both healthy individuals and those with insomnia who exercised during the pandemic would report less severe somatic symptoms and headaches than those who did not.

A large survey was sent out to 4,073 individuals to measure their experience in numerous domains during the COVID-19 pandemic. This survey included a short symptom questionnaire used to measure somatization and the Insomnia Scale Index to measure insomnia. These questionnaires were administered along with a “yes or no” question on whether the participants exercised regularly in that period. A univariate ANOVA was performed to analyze the data to determine if exercise during the pandemic was beneficial in the reduction of somatic symptoms and headache severity. Furthermore, these tests were run to determine if the effect was greater on those with insomnia.

The effect of insomnia and exercise on total somatic symptoms were significant at F(1, 3445)=650.5, p<0.001 and F(1, 3445)=26.1, p<0.001, respectively. For reported headache severity, there was a significant effect of exercise F(1, 4073)=14.5, p<0.001 and insomnia F(1, 4073)=160.5, p<0.001; therefore, those who exercised reported less severe headaches and those who suffered from insomnia reported more severe somatic symptoms. This meant that those who exercised reported less severe somatization and headaches than those who didn’t and those with insomnia reported more severe somatization and headaches than healthy individuals. However, the interaction between exercise and insomnia on overall somatization severity was not significant at F(1, 3445)=3.4, p=0.066 nor for reported headache severity F(1, 4073)=0.81, p=0.370. Despite there not being a significant interaction, the benefit of exercise was slightly greater on healthy individuals than those with insomnia.

Those with insomnia reported more severe headaches and overall somatic symptoms than non-insomniacs regardless of whether they exercised or not. Exercise did make a difference on the reported severity of headaches and somatization in both groups; however, the benefit of exercise on headaches and somatization was greater in individuals who do not suffer from insomnia. Thus, exercise was noted to be beneficial to those in the general population and those suffering from insomnia as it can potentially reduce the severity of somatization and headaches. Of course, this research was cross sectional and correlational, so the directionality of the effects cannot be inferred. For future research, it would be instrumental to use experimental methods to help determine the duration and type of exercise that may optimize its potential benefits on headaches and somatic symptoms.

Higher educational attainment is associated with reduced risk for Alzheimer's disease (AD) dementia, and its protective effect may act through alterations in cerebral blood flow (CBF) that allow for better coping with accumulating neuropathology. Additionally, there are sex differences in both the risk of developing AD as well as the potential protective effects of education. We therefore sought to investigate whether education moderates the association of hippocampal CBF and memory in cognitively unimpaired older adults, and to examine if these interactions were moderated by sex.

Cognitively unimpaired older adults from the Alzheimer's Disease Neuroimaging Initiative (ADNI; 51 men, 50 women) underwent neuropsychological evaluation and arterial spin labeling MRI, which was used to quantify bilateral hippocampal CBF. Sex was defined as sex at birth. Multiple linear regressions assessed (1) the independent associations among education, CBF, and memory performance separately in men and women and (2) the three-way interactions among CBF, sex, and education, followed by sex-stratified analyses. Three outcome measures were examined: Logical Memory Story A immediate and delayed recall, and Rey Auditory Verbal Learning Test (RAVLT) intrusions. All models adjusted for age and APOE epsilon-4 allele frequency, and all models with CBF additionally adjusted for cerebral metabolism (baseline FDG-PET composite) and pulse pressure.

CBF was not associated with education or memory in either women or men. There was a positive association between education and delayed memory in women (ß=0.14, t=2.64, p=0.008) as well as trending, positive associations between education and immediate memory in women (ß=0.09, t=1.79, p=0.074) and education and delayed memory in men (ß=0.09, t=1.94, p=0.054). Three-way interactions among sex, CBF, and education were significant on immediate recall (ß=2.55, t=2.53, p=0.013), delayed recall (ß=2.56, t=2.44, p=0.017), and RAVLT intrusions (ß=-2.28, t=-2.27, p=0.026). In women, there were interactions between education and hippocampal CBF on both immediate (ß=2.49, t=2.90, p=0.006) and delayed recall (ß=2.30, t=2.78, p=0.009), such that as education increased, the strength of the association between CBF and immediate memory increased. There was also an interaction between education and hippocampal CBF on RAVLT intrusions in women (ß=-2.42, t=-3.05, p=0.004), such that as education increased, the strength of the association between CBF and number of intrusions decreased; there was a main effect where in women with lower education, as CBF increased, the number of intrusions increased (ß=0.76, t=2.59, p=0.032); in women with higher education, there was no association between CBF and intrusions. In men, none of these two-way interactions were significant.

These results suggest that, in cognitively unimpaired older women, the relationship between hippocampal CBF and memory is moderated by education level, even when adjusting for several other factors. Specifically, higher education may serve as a protective factor in the hippocampal CBF-memory relationship, and this relationship was sex-dependent, occurring in women only. Further research is needed to examine these relationships longitudinally across the clinical continuum of AD. Additionally, this work needs to be conducted in more diverse samples to allow for analyses investigating the impact of education on the intersection of race/ethnicity and sex/gender.

Psychological wellness and strong cognitive skills are both important to successful aging. Although there are well-established relationships between psychiatric illness (e.g., depression, anxiety, PTSD) and cognitive dysfunction, few studies have focused on the relationships between positive psychological factors and neurocognitive function in older adults. Our goal was to explore associations between these two sets of measures in older adults.

Participants (n=111) were part of a longitudinal study of biopsychosocial functioning in independently living older adult residents of a Continuing Care Senior Housing Community. Participants were administered a cognitive screening test (Montreal Cognitive Assessment; MoCA), a comprehensive neuropsychological battery, and a set of published self-report scales measuring positive emotional and psychological function. Neuropsychological scores were appropriately normed, and composite scores were calculated for the following domains: language (Boston Naming Test, Delis-Kaplan Executive Function System [D-KEFS] Verbal Fluency), attention/working memory (Wechsler Adult Intelligence Scale-IV [WAIS-IV] Digit Span, DKEFS Visual Scanning), learning and delayed recall (Brief Visuospatial Memory Test-Revised, Hopkins Verbal Learning Test-Revised), processing speed (WAIS-IV Coding, D-KEFS Trails Number and Letter Sequencing, D-KEFS Color-Word Interference Test Color and Word Naming), and executive function (D-KEFS Color-Word Inhibition and Inhibition/Switching, DKEFS Letter/Number Switching). Self-Report scales included the Perceived Stress Scale, Center for Epidemiological Studies in Depression Scale, Emotional Support Scale, Connor-Davidson Resilience Scale, Coping Humor and Self-Efficacy Scales, Personal Mastery Scale, Meaning in Life Scale, Self-Rated Successful Aging, Satisfaction with Life, Cognitive Failures Questionnaire, and Lifetime Orientation Test-Revised. Due to the large number of psychological functioning measures, dimension reduction was undertaken via principal component analysis, resulting in a two-factor solution. Bivariate Pearson correlations were then computed between the two factor scores and each neurocognitive variable.

Factor 1 consisted of variables reflecting Positive Subjective Functioning. A higher score on Factor 1 (indicating higher self-rating of successful aging, fewer perceived cognitive failures, fewer reported depressive symptoms, less perceived stress/anxiety, more perceived emotional support, more satisfaction with life, more meaningfulness in life, and more search for meaning in life) was associated with better attention/working memory (r=0.226, p=0.049) and executive function (r=0.242, p=0.035). Factor 2 consisted of variables that reflected Positive Coping Skills. A higher score on Factor 2 (indicating more happiness, higher optimism, greater resilience, higher sense of personal mastery, more use of humor as a coping strategy, and greater coping self-efficacy) was associated with better performance on tests of language (r=0.325, p=0.004), learning (r=0.313, p=0.006) and delayed recall (r=0.241, p=0.035) of visual and verbal information, and better MoCA performance (r=0.440, p<0.001). Neither factor was associated with processing speed.

Higher levels of subjective functioning and positive outlook/coping skills were associated with better neuropsychological performance. Given that late life is a time of risk for cognitive decline, future research should consider the influence of positive psychological functioning on neurocognitive outcomes and vice versa, as these relationships may have neurobiological and therapeutic implications for overall function in later life.

Anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARE) is a complex, yet treatable autoimmune disorder characterized by a fairly abrupt onset of a constellation of symptoms attributable to diffuse brain dysfunction (Tarantino et al., 2021). Despite the potential for a severe disease course, most patients have a favorable outcome with substantial recovery (Dalmau et al., 2011; Titulaer et al., 2013). Nevertheless, there is limited literature discussing the long-term outcomes in patients with anti-NMDARE, particularly in pediatric patients. The primary objective of this study is to examine and describe behavioral, emotional, adaptive, and executive functioning outcomes in pediatric and young adult patients with this disease. This study also sought to provide information on the perceived health-related quality of life (HRQoL) of patients and their parents and investigate the impact of anti-NMDARE on parents and family functioning.

All individuals known to have been diagnosed and treated for anti-NMDARE at The Children’s Hospital of Philadelphia (CHOP) between January 1, 2005, and October 1, 2020, were contacted with both patients and their parents/guardians invited to participate. Eighteen pediatric patients between the ages of 6 and 26 and/or their parents/caregivers participated in the study. Of the 18 patients represented in the sample, 50% were white/Caucasian, and 67% were female. The mean duration of time since symptom onset was 7.1 years. Primary outcomes were measured through standardized questionnaires of emotional, behavioral, and adaptive functioning (BASC-3) and executive functioning (BRIEF2 or BRIEF-A). Secondary outcomes related to family functioning and HRQoL were measured through (PedsQL™ and PedsQL™ Family Impact Module.)

All aggregate T-scores for the BASC and BRIEF placed children with anti-NMDARE within an age-appropriate range regarding behavioral, emotional, adaptive, and executive functioning outcomes. Children with anti-NMDARE were not found to have lower HRQoL compared to their healthy same-age peers. Moreover, parents of children with anti-NMDARE did not endorse a prolonged impact of this illness on family functioning and adjustment.

This study aimed to better understand the neurobehavioral profile and the long-term outcomes of children diagnosed with anti-NMDARE, with the ultimate goal of advancing understanding of this encephalitis. Consistent with findings from several reviewed studies on long-term follow-up, the present study suggests that most children with a history of anti-NMDARE show good functional recovery over time. However, data on the neurobehavioral sequelae, quality of life, and adaptive behavior in patients diagnosed with anti-NMDARE are still sparse, especially at pediatric age. In order to understand and learn to manage the needs of patients with anti-NMDARE, particularly regarding the impact this disease can have on daily life and school performance, additional neuropsychological research involving larger samples, longitudinal studies, and increased methodological consistency is required.

Cognitive tests on which performance is unrelated to brain pathology are considered “hold” tests and are often used to estimate cognitive abilities prior to injury or disease. Amongst the most commonly used “hold” tests are measures of irregular word reading, such as the Test of Premorbid Functioning (TOPF). Measures of irregular word reading assess ability to accurately pronounce phonetic irregularities based on prior experience and word knowledge, and tend to be insensitive to most forms of brain pathology (Lezak, 2012). However, research examining whether a relationship exists between neurodegenerative diseases and decline in irregular word reading is limited. The few studies completed have demonstrated a decline in irregular word reading in neurodegenerative disease in general (Berg, Durant, Banks, & Miller, 2016) and Alzheimer’s dementia specifically (McFarlane, Welch, & Rodgers, 2006). However, no known research has been published examining whether irregular word reading and TOPF scores differ depending on cognitive classifications commensurate with DSM-V diagnoses (i.e., mild or major neurocognitive disorder, etc.), or presumed neurological etiology.

Patients were enrolled from the University of Colorado Hospital Neuropsychology Clinic. This study was a retrospective review of consecutive referrals over the age of 65 to the University of Colorado Hospital Neuropsychology Clinic from 2019 to present. The TOPF was administered along with a full neuropsychological battery and patients were clinically classified by severity of cognitive impairment (e.g., Normal, Mild Neurocognitive Disorder, Major Neurocognitive Disorder) and presumed neurologic etiology (e.g., Alzheimer’s disease (AD), Parkinson’s disease (PD), vascular cognitive impairment (VCI), and mixed dementia (AD and VCI). TOPF Raw scores were used for all analyses. Correlation analysis was conducted to determine significant relationships between various demographic variables and TOPF performance. ANCOVA analyses were conducted to examine differences on TOPF performance by diagnostic classification and differences on TOPF performance by presumed neurologic etiology.

Correlation determined a significant relationship between TOPF performance and education (r = .51, p < .001), but not age (p = .092) or gender (p = .680). ANCOVA revealed a significant effect of TOPF performance on diagnostic group classification after controlling for education, F(2, 504)= 26.45, p < .001. Post hoc analysis revealed that those diagnosed with Major Neurocognitive Disorder performed the worst on the TOPF (M=39.801 ± .958), followed by those diagnosed with Mild Neurocognitive Disorder (M= 45.371 ± .767), while those diagnosed as cognitively normal performed the best (M= 49.826 ± .993). Additional ANCOVA analysis revealed a significant effect of TOPF performance on presumed neurologic etiology after controlling for education, F(3,148)=6.07, p = .001. Post hoc analyses revealed that participants with suspected AD (M= 40.728 ± 1.613) and those with suspected VCI (M= 32.804 ± 3.480) performed worse on the TOPF compared to those with suspected PD (M=46.964 ± 1.506), (p=.042 and p = .004, respectively).

Results suggest that TOPF performance in older individuals is sensitive to cognitive impairment. Furthermore, these results suggest that this sensitivity may be further influenced by presumed neurologic etiology. These findings are consistent with prior studies which demonstrated a decline in irregular word reading in individuals with neurodegenerative diseases.

Late-life depression is a complex condition impacted by both mental and physical health outcomes and psychosocial factors. Psychosocial predictors of depression are reliant on cultural factors including socioeconomic variables, stigmas, and cultural values. Most research on late-life depression and its effect on cognitive functioning has been completed in so-called Western, Educated, Industrialized, Rich, and Democratic (WEIRD) populations and findings may not generalize to older adults living in other areas of the world. The current study explored predictors of depressive symptoms as well as the association between depressive symptoms and neuropsychological functioning in Congolese older adults.

A total of 319 participants (mean age=72.7±6.15, mean education in years=7.6±4.56; 47% female) were randomly recruited. Depressive symptoms were assessed with the Geriatric Depression Scale. Given the exploratory nature of the current study, forward stepwise linear regression models were run to assess predictors of depressive symptoms. The independent variables assessed as potential predictors included age, years of education, gender, participant income, parental income, living arrangement (i.e., alone or with others), functional abilities (FAQ), fragility, and self-rated overall health. Analyses were run in the overall sample as well as stratified by gender. The association between depressive symptoms and performance on the Community Screening Instrument for Dementia (SCID) was also explored.

Higher depressive symptoms were found in women (ß=.228, p=0.036), those with lower parental income (ß=-.156, p=.005), higher fragility (ß=-.237, p<.001), and worse overall health (ß=-.311, p=.020). Among women, lower parental income, (ß=-.230, p=.002), higher fragility (ß=-.312, p<.001), and lower overall health (ß=-.235, p=.004) predicted higher depressive symptoms, while in men only higher fragility (ß=-.164, p=.041) and living alone (ß=-.184, p=.022) predicted higher depressive symptoms. There was also a significant association between depressive symptoms and lower scores on the CSID (ß=-.189, p=.001)

Similar to results in WEIRD populations, general health and fragility predicted depressive symptoms in Congolese older adults. However, parental income (more so than participant income) also predicted depressive symptoms in Congolese older adults, particularly in women, while living alone was a predictor in Congolese older men. It is possible that the difference in depressive symptoms between men and women is driven by underreporting of depressive symptoms among men. Our results also showed that there was an association between depressive symptoms and global cognitive functioning similar to prior findings in WEIRD populations. Our results are important for clinicians assessing depressive symptoms in patients in or from Congo or sub-Saharan Africa.

This study examines the clinical validity of the NIH Toolbox Cognition Battery measures in patients with oncological diagnoses and tumor predisposition syndromes, including Neurofibromatosis, Type 1 (NF1).

Participants included 158 patients (61% male, 67% White) ages 3 to 25 years (M = 8.38, SD = 4.32) who underwent neuropsychological evaluation between 2019 and 2022. Patients with brain tumors (n = 50) and leukemias (n = 49) accounted for 2/3 of the sample. The remainder had solid tumors, lymphomas, or cancer predisposition syndrome. Forty-eight had a diagnosis of NF1. Performance-based measures of attention, executive functioning, and processing speed were administered as part of neuropsychological evaluations. Patients were administered between 1 to 4 NIH Toolbox Cognition measures, including Flanker Inhibitory Control and Attention Test (Flanker), Dimensional Change Card Sort Test (DCCS), Pattern Comparison Processing Speed Test (PCCS), and List Sorting Test. Parent-reported measures of attention and EF were also obtained. Z-scores were used to compare performance across measures that assessed equivalent constructs. The rates of weak performance (>1 SD below the mean) using Toolbox measures were compared to rates of weak performance on traditional neuropsychological measures (e.g., Digit Span), and rates of functional impairment (e.g., parent-reported concerns, ADHD diagnosis).

FSIQ, Coding, and NEPSY Inhibition correlated with all 4 Toolbox measures, while Digit Span correlated with List Sorting, DCCS, and Flanker. DCCS and PCCS correlated with verbal fluency measures. NF1 patients scored lower than non-NF1 patients on Flanker, F(1,126) = 13.01, p<.001 and DCCS, F(1,150) = 6.85, p = .01. Toolbox performance did not differ significantly by age group. Rates of identified weakness were relatively similar on Toolbox measures, some traditional measures, and parent-reported attention problems. In identifying those with and without weakness, the agreement between Flanker and other measures ranged from 52% (Auditory Attention) to 66% (Coding). Agreement between DCCS and traditional measures ranged from 47% (Letter Fluency) to 80% (Switching). For PCCS, concordance ranged from 45% (Semantic Fluency) to 69% (Switching). List Sorting had 80% agreement with Digit Span and Coding.

List Sorting had the highest agreement with parent-reported attention problems (76%), EF problems (72%), and ADHD diagnosis (79%). There was relatively high concurrence between DCCS and ADHD diagnosis (69%) and parent-reported attention problems (60%) and EF problems (65%) and between Flanker and ADHD diagnosis (67%). PCCS had less agreement with functional outcomes, ranging from 49% for EF problems to 58% for attention problems and ADHD diagnosis. In comparison, Digit Span had 64% agreement for EF problems, 70% for attention problems, and 73% for ADHD diagnosis.

The NIH Toolbox Cognition Battery can be used to identify neurocognitive weaknesses in pediatric oncology patients and provide clinically meaningful data. Evaluation of the Toolbox measures’ sensitivity to change over time is warranted, as monitoring the progression of cognitive late effects is particularly salient in cancer survivorship.

Socialization is a crucial factor in children’s language acquisition. Lack of socialization could affect language development, causing a delay that can be spotted early by identifying neurological soft signs (NSS). This study aimed to compare NSS and language performance between two samples of children (pre and post-pandemic) since the lockdown carried out by Covid-19 restricted socialization in post-pandemic kids.

Two groups of 30 children (aged 3 to 5 years old, ten children per age group; 50% boys and 50% girls) were assessed with the NSS and language subtest from the SNB-MX battery (Salvador, Tovar, Segura, Armengol & Ledesma, 2019). The first group was selected and evaluated before the covid lockdown; the second group was selected and assessed after the lockdown. Hence the second group of children was less exposed to socialization since schools changed to digital format. We compared the language performance of both groups.

Results include the comparison between samples pre and post-pandemic. Post-pandemic children performed lower in language skills. We also found a correlation between the language and NSS.

We conclude that socialization is an essential factor in language development. Also, identifying Neurological Soft Signs could help predict language delay. We thank project PAPIIT IN308219 for sponsoring this research.

Fluoride exposure has been associated with thyroid dysfunction, but fluoride's impact on thyroid function in pregnancy is unclear, especially during early gestation when the fetus is dependent on maternal thyroid hormone. We examined the potential thyroid-disrupting effects of maternal fluoride exposure in pregnancy and tested whether thyroid disruption in pregnancy mediates the association between maternal fluoride exposure and child intelligence quotient (IQ) among Canadian mother-child dyads living in areas with optimal fluoridation.

We measured fluoride concentrations in drinking water and in spot urine samples collected in each trimester from pregnant women enrolled in the Maternal-Infant Research on Environmental Chemicals study. We also measured thyroid hormone (thyroid stimulating hormone [TSH], free thyroxine [FT4], and total thyroxine [TT4]) levels during the first trimester of pregnancy and categorized women as euthyroid (n=1301), subclinical hypothyroid (n=100), or primary hypothyroid (n=28). Those categorized as primary hypothyroid were combined with an additional 79 women who reported clinical diagnoses at time of study enrolment (total n=107). In a sample of 1508 women, we used logistic regression to estimate the association between fluoride exposure and risk of either subclinical or primary hypothyroidism, separately, and linear regression to estimate associations between fluoride exposure and women's thyroid hormone levels (TSH, FT4, TT4). We tested effect modification by child sex and thyroid peroxidase (TPO) antibody status. In a subsample of 439 mother-child pairs, we measured child Full-Scale IQ (FSIQ) at 3-4 years of age using the Wechsler Preschool and Primary Scale of Intelligence. We used linear regression to test associations between maternal hypothyroidism or thyroid hormone levels, and children's FSIQ scores. Finally, mediation analysis in the counterfactual framework was used to estimate the proportion of the effect of maternal fluoride exposure on child FSIQ mediated by maternal hypothyroidism, through evaluation of the natural direct (not through hypothyroidism) and indirect (through hypothyroidism) effects.

Using categorical measures of thyroid status, a 0.5 mg/L increase in water fluoride concentration was associated with a 1.64 (95% confidence interval [CI], 1.04 to 2.58) increased odds of primary hypothyroidism. This association was stronger among women with normal TPO antibody levels (< 5.61 IU/mL) (odds ratio, 2.80; 95% CI, 1.24 to 6.36). In contrast, we did not find a significant association between maternal urinary fluoride and hypothyroidism. For continuous measures of thyroid hormone levels, a 1 mg/L increase in maternal urinary fluoride was associated with a 35% (p=0.01) increase in TSH among women pregnant with a female fetus. In our subsample analyses, children born to women with primary hypothyroidism had lower FSIQ than children of euthyroid women, especially among boys (B, 8.78; 95% CI, -16.78 to -0.79). In contrast, maternal TSH, FT4, and TT4 levels were not significantly associated with child FSIQ scores. Maternal primary hypothyroidism did not significantly mediate the relationship between maternal water fluoride concentration and child FSIQ (p natural indirect effect= .35).

Fluoride in drinking water may increase the risk of hypothyroidism in pregnancy. Thyroid dysfunction in pregnancy may be one mechanism underlying developmental neurotoxicity of fluoride.

Understanding the factors contributing to optimal cognitive function throughout the aging process is essential to better understand successful cognitive aging. Processing speed is an age sensitive cognitive domain that usually declines early in the aging process; however, this cognitive skill is essential for other cognitive tasks and everyday functioning. Evaluating brain network interactions in cognitively healthy older adults can help us understand how brain characteristics variations affect cognitive functioning. Functional connections among groups of brain areas give insight into the brain’s organization, and the cognitive effects of aging may relate to this large-scale organization. To follow-up on our prior work, we sought to replicate our findings regarding network segregation’s relationship with processing speed. In order to address possible influences of node location or network membership we replicated the analysis across 4 different node sets.

Data were acquired as part of a multi-center study of 85+ cognitively normal individuals, the McKnight Brain Aging Registry (MBAR). For this analysis, we included 146 community-dwelling, cognitively unimpaired older adults, ages 85-99, who had undergone structural and BOLD resting state MRI scans and a battery of neuropsychological tests. Exploratory factor analysis identified the processing speed factor of interest. We preprocessed BOLD scans using fmriprep, Ciftify, and XCPEngine algorithms. We used 4 different sets of connectivity-based parcellation: 1)MBAR data used to define nodes and Power (2011) atlas used to determine node network membership, 2) Younger adults data used to define nodes (Chan 2014) and Power (2011) atlas used to determine node network membership, 3) Older adults data from a different study (Han 2018) used to define nodes and Power (2011) atlas used to determine node network membership, and 4) MBAR data used to define nodes and MBAR data based community detection used to determine node network membership.

Segregation (balance of within-network and between-network connections) was measured within the association system and three wellcharacterized networks: Default Mode Network (DMN), Cingulo-Opercular Network (CON), and Fronto-Parietal Network (FPN). Correlation between processing speed and association system and networks was performed for all 4 node sets.

We replicated prior work and found the segregation of both the cortical association system, the segregation of FPN and DMN had a consistent relationship with processing speed across all node sets (association system range of correlations: r=.294 to .342, FPN: r=.254 to .272, DMN: r=.263 to .273). Additionally, compared to parcellations created with older adults, the parcellation created based on younger individuals showed attenuated and less robust findings as those with older adults (association system r=.263, FPN r=.255, DMN r=.263).

This study shows that network segregation of the oldest-old brain is closely linked with processing speed and this relationship is replicable across different node sets created with varied datasets. This work adds to the growing body of knowledge about age-related dedifferentiation by demonstrating replicability and consistency of the finding that as essential cognitive skill, processing speed, is associated with differentiated functional networks even in very old individuals experiencing successful cognitive aging.

Abusive head trauma (AHT) is a form of inflicted brain injury that is associated with significant neurological impairment. Given that injuries occur during infancy, cognitive deficits may not become fully apparent for years. It is useful to understand injury factors related to outcomes. A recent study by Eismann et al. (2020) used length of PICU stay as a measure of injury severity and found that it is predictive of short-term and long-term outcomes in AHT. The current study aimed to examine injury severity factors related to acute outcomes (<3 months since injury) within a population of infants admitted to an inpatient rehabilitation unit (IRU).

The sample consisted of 45 infants (32 male, 13 female) hospitalized with suspected AHT. Age at injury was 0-21 months (MED= 4.89 months, SD = 5.48). The majority of patients (93%) had moderate to severe injury based on length of PICU stay (4+ days) [3]. Patients were administered the Mullen Scales of Early Learning (MSEL) during IRU admission, within 3 months of injury (range: 13-68 days; MED: 31 days). Pearson bivariate correlations were used to examine the relationship between MSEL subscales (ELC: Early Learning Composite; VR: Visual Reception; RL: Receptive Language; EL: Expressive Language; FM: Fine Motor; GM: Gross Motor) and the following factors: days since injury and hospitalization time (days in PICU, PICU/General Pediatrics, IRU, total hospitalization). P-values less than .05 were considered significant.

Scores on the MSEL Early Learning Composite ranged from exceptionally low to high average (Standard Score Range: <49-111; MED: 82; SD = 18.79). Unlike prior studies, time in PICU and time in PICU/General Pediatrics were not associated with any MSEL subscales. MSEL was moderately correlated with days in IRU (ELC: r = -.44; VR: r = -.37; RL: r = -.32; EL: r = -.36; GM: r = -.29) and total hospitalization time (ELC: r = -.46; VR: r = -.42; RL: r = -.36; EL: r = -.37; GM: r = -.31), such that longer hospitalization was associated with lower scores. Greater days since injury was also associated with lower MSEL scores (ELC: r = -.45; VR: r = -.42; RL: r = -.40; EL: r = -.36; FM: r = -.33; GM: r = -.35).

These results suggest that within an inpatient rehabilitation setting, longer total hospitalization time (including time on IRU) is moderately associated with worse acute neurobehavioral outcomes. While length of PICU stay has been associated with short-term outcomes in the outpatient setting (Eismann et al., 2020), this was not found in the current inpatient sample which had more severe injuries (longer PICU stay, inpatient rehabilitation admission). Interestingly, children assessed further out from injury had worse scores on the MSEL, which has previously been noted. Though this seems counterintuitive, it may reflect that participants with more severe injuries had a longer delay before they were capable of engaging in a neurodevelopmental assessment. These findings have implications for prognosticating early outcomes of AHT in an inpatient rehabilitation setting.

Patient-reported outcome measures provide valuable insights into health status after neurologic disease, but their relationships with function-based outcome measures remain incompletely understood. Here we evaluate the relationship between these two classes of measure using dimensionality-reduction techniques in patients after acute stroke and examine their associated patterns of neuroanatomical injury.

Fifty-four adults with upper extremity motor deficits were serially assessed at four time points after stroke with functional outcome measures (Upper Extremity Fugl-Meyer, Barthel Index, modified Rankin Scale, Box and Blocks, 9- Hole Peg, Grip Strength) as well as patient-reported measures (PROMIS-Global Physical, Mental, and Social Health, Patient Health Questionnaire-9) of health status. At each timepoint after stroke, exploratory and confirmatory factor analysis were performed to identify and confirm the underlying factorial structure of the entire battery of outcome measures. Multivariate linear regression analysis was used to determine the amount of variance explained by clinical and demographic characteristics on extracted factors. Voxel-Based Lesion Symptom Mapping was used to examine the relationship between factors and patterns of neuroanatomical injury.

In the battery of stroke outcome measures, two factors were identified and retained, accounting for >78% of the overall variance across outcomes at every timepoint. Function-based measures loaded onto Factor 1 separately from patient-reported measures which loaded onto Factor 2. Results were consistent at each serial timepoint after stroke. Pre-stroke disability (p=0.03) and amount of damage to the corticospinal tract (p=0.001), explained significant variance in performance on Factor 1 (function-based outcomes), whereas education (p=0.01) and socioeconomic status (p=0.04) explained significant variance in performance on Factor 2 (PROMs). While function-based measures were related to injury to subcortical brain regions known to be important for motor function, patient-reported measures were related to injury to cortical brain regions including the insula and inferior parietal lobe, known to be important for affective processing and social cognition.

Two distinct factors representing function-based and patient-reported measures of health status were extracted from the study battery of stroke outcome measures scored across the first year post-stroke. Each factor was associated with injury to brain regions concordant with the content of the represented assessments. These findings emphasize the distinct behavioral elements and neuroanatomical underpinnings of function-based and patient-reported outcome measures after stroke and have potential implications for precision rehabilitation.

Working memory is a vital construct in efficient verbal memory encoding (Cotton & Ricker, 2021). Working memory is impacted by attentional capacities (Riccio, Cohen, Garrison, & Smith, 2005). Mood symptoms impact efficient information processing and consolidation of memory (Hubbard, 2016; Lukasik, 2019). This study examines self-reported symptoms of depression, anxiety, and stress as possible moderators of the relationship between working memory and a verbal list-learning task.

Archival data from 415 adults (Mage= 56.10, SD=18.05; Medu= 15.5 SD=2.2; 53% female; 73% white) were collected at an outpatient clinic. Sex and race were not available in a small percentage of cases included in analyses. The Wechsler Adult Intelligence Scale 4th Edition Digit Span subtest was given to assess attention and working memory. Although Digit Span Forward is a measure of simple attention, not working memory, it was included in initial analyses because the subtest was given as a whole. The three components of Digit Span total, Forward, Backward, and Sequencing were also investigated separately, with the two latter scores being better representations of working memory. Learning was assessed via the California Verbal Learning Test (CVLT-II) total T-Score (Trials 1-5). Mood was assessed via the Depression Anxiety and Stress Scales (DASS-42).

Results of a hierarchical linear regression showed a significant effect between total Digit Span performance and total learning on the CVLT-II in the Block 1 (F(3, 411)=14.383, p =<.001 , AR2=.095). Standardized beta weights and p-values for Digit Span Forward, Backward, and Sequencing were (ß=-.50, p=.374), (ß= .159, p=.009), and (ß=.210, p<.001) respectively. In Block 2, when the DASS variables were introduced, the model remained significant F(3,408)=2.602, p=.05 , AR2=.017). The DASS anxiety and stress subscales had significant beta weights in the model (ß=-.172, p=.015) and (ß=.144, p=.039) respectively, with depression being insignificant (ß=--.023, p=.724).

Mood symptoms have been shown to be an important consideration when assessing working memory and verbal learning performance (Massey, Meares, Batchelor, & Bryant, 2015). Present results demonstrate that when accounting for working memory, anxiety and stress were significant predictors of performance on a measure of verbal learning. Additionally, as the components best representing working memory, Digit Span Sequencing and Backward were significantly correlated with verbal learning, whereas a measure best representing simple attention, Digit Span Forward, was not significantly correlated with verbal learning.

Recent conceptualizations of concussion symptoms have begun to shift from a latent perspective (which suggests a common cause; i.e., head injury), to a network perspective (where symptoms influence and interact with each other throughout injury and recovery). Recent research has examined the network structure of the Post-Concussion Symptom Scale (PCSS) cross-sectionally at pre-and post-concussion, with the most important symptoms including dizziness, sadness, and feeling more emotional. However, within-subject comparisons between network structures at pre-and post-concussion have yet to be made. These analyses can provide invaluable information on whether concussion alters symptom interactions. This study examined within-athlete changes in PCSS network connectivity and centrality (the importance of different symptoms within the networks) from baseline to post-concussion.

Participants were selected from a larger longitudinal database of high school athletes who completed the PCSS in English as part of their standard athletic training protocol (N=1,561). The PCSS is a 22-item self-report measure of common concussion symptoms (i.e., headache, vomiting, dizziness, etc.) in which individuals rate symptom severity on a 7-point Likert scale. Participants were excluded if they endorsed history of brain surgery, neurodevelopmental disorder, or treatment history for epilepsy, migraines, psychiatric disorders, or alcohol/substance use. Network analysis was conducted on PCSS ratings from a baseline and acute post-concussion (within 72-hours post-injury) assessment. In each network, the nodes represented individual symptoms, and the edges connecting them their partial correlations. Estimations of the regularized partial correlation networks were completed using the Gaussian graphical model, and the GLASSO algorithm was used for regularization. Each symptom’s expected influence (the sum of its partial correlations with other symptoms) was calculated to identify the most central symptoms in each network. Recommended techniques from Epskamp et al. (2018) were completed for assessing the accuracy of the estimated symptom importance and relationships. Network Comparison Tests were conducted to observe changes in network connectivity, structure, and node influence.

Both baseline and acute post-concussion networks contained negative and positive relationships. The expected influence of symptoms was stable in both networks, with difficulty concentrating having the greatest expected influence in both. The strongest edges in the networks were between symptoms within similar domains of functioning (e.g., sleeping less was associated with trouble falling asleep). Network connectivity was not significantly different between networks (S=0.43), suggesting the overall degree to which symptoms are related was not different at acute post-concussion. Network structure significantly differed at acute post-concussion (M=0.305), suggesting specific relationships in the acute post-concussion network were different than they were at baseline. In the acute post concussion network, vomiting was less central and sensitivity to noise and mentally foggy more central.

PCSS network structure at acute post-concussion is altered, suggesting concussion may disrupt symptom networks and certain symptoms’ associations with the experience of others after sustaining a concussive injury. Future research should compare PCSS networks later in recovery to examine if similar structural changes remain or return to baseline structure, with the potential that observing PCSS network structure changes post-concussion could inform symptom resolution trajectories.

Accurately interpreting change in cognitive functioning is an essential aspect of clinical care for older adults. Several approaches to identifying ‘true’ cognitive change in a single cognitive measure are available (e.g., reliable change methods, regression-based norms); however, neuropsychologists in clinical settings often rely on simple score differences rather than advanced analytical procedures especially since they examine multiple test performances. This study sought to establish quick-reference normative criteria to help neuropsychologists identify how frequently significant change occurs across multiple cognitive measures in cognitively normal older adults.

Data were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Participants were 401 older adults who were classified as cognitively normal at baseline and at 24-month follow-up. In ADNI, these clinical classifications are made separately from the assessment of cognitive performance, including cognitive change. The sample was 50.1% female, 93.5% non-Hispanic White, 4.0% non-Hispanic Black, 1.5% Asian American, and 1.0% other race/ethnicity, with a mean age of 76.0 years (SD = 4.9). Mean education was 16.4 years (SD = 2.7). The cognitive battery included: Boston Naming Test, Category Fluency Test, Trails A & B, Clock Drawing Test, and Auditory Verbal Learning Test, Trial 1-5 Total and Delayed Recall. Change scores between baseline performance and 24-month follow-up were calculated for each measure. The natural distribution of change scores was examined for each measure and cut points representing the 5th and 10th percentile were applied to each distribution to classify participants who exhibited substantial declines in performance on a given measure. We then examined the multivariate frequency of statistically rare change scores for each individual.

As expected in a normal sample, overall cognitive performance was generally stable between baseline and 24-month followup. Across cognitive measures, 43.6% of participants had at least one change score fall below the 10th percentile in the distribution of change scores, and 21.9% had at least one score below the 5th percentile. 13.0% of participants had two or more change scores that fell below the 10th percentile, in comparison to 4.5% with two or more below the 5th percentile. 3.2% of participants had three or more change scores below the 10th percentile, versus 0.5% of participants who had three change scores below the 5th percentile.

Among cognitively normal older adults assessed twice at a 24-month interval with a battery of seven measures, it was not uncommon for an individual to have at least one score fall below the 10th percentile (43% of the sample) or even the 5th percentile (21%) in the natural distribution of change scores. However, only 3.2% of normals had more than two declines in test performance below the 10th percentile, and less than 1% of the sample at more than one change score at the 5th percentile. This suggests that individuals who exhibit more multivariate changes in performance than these standards are likely experiencing an abnormal rate of cognitive decline. Our findings provide a preliminary quick-reference approach to identifying clinically significant cognitive change. Future studies will explore additional batteries and examine multivariate frequencies of change in clinical populations.

Psychosocial stress has been associated with impaired cognition and risk for neurodegenerative disease. However, the intermediate pathways underlying this relationship are not yet well understood. Chronic exposure to stress causes endocrine and immune dysregulation that can lead to heightened systemic inflammation. Moreover, chronic, low-grade inflammation has been linked to neurodegeneration, impaired neurogenesis and cognitive decline. Given the strength of the individual links between stress, inflammation and cognition, the current study tested the hypothesis that inflammatory biomarkers would mediate the relationship between perceived stress and executive functions.

Data from the Midlife in the United States Study (MIDUS) (N=863; Mean age= 52.72) provided measures of perceived psychological stress, inflammatory biomarkers [C-reactive protein (CRP) and interleukin-6 (IL-6)] and executive functions. Structural equation modeling (SEM) was used to test for the mediating effect of inflammation on the relationship between perceived stress and executive functions. Exploratory analyses were conducted to investigate whether sex-differences were driving these relationships. Mediation analyses adjusted for age and history of smoking.

In the full sample of men and women, there was a significant indirect effect of perceived stress on executive functions through inflammation [ß=-0.021, z=-2.841, p=0.005]. Further examination revealed that this effect was present in women [B=-0.039, z=-2.680, p=0.007] but not men [ß=-0.003, z=-0.558, p=0.577]. While inflammation was negatively associated with executive functions in both men and women [ß=-0.126, z=-1.930, p=0.050; ß=-0.279, z=-0.558, p>0.001], pathways linking perceived stress to inflammation and executive functions were only significant in women [ß=0.014, z=-3.190, p=0.001; ß=-0.192, z=-3.355, p=0.001].

These findings suggest that inflammatory biomarkers are a viable pathway for explaining how experiencing stress can negatively affect executive functions. Results indicate that women may be particularly vulnerable to the inflammatory and cognitive consequences of stress. As such, psychosocial stress and associated inflammation may be important targets for improving cognitive health outcomes, particularly in women.

Parkinsonism and Parkinson's disease (PD) have been described as consequences of repetitive head impacts (RHI) from boxing, since 1928. Autopsy studies have shown that RHI from other contact sports can also increase risk for neurodegenerative diseases, including chronic traumatic encephalopathy (CTE) and Lewy bodies. In vivo research on the relationship between American football play and PD is scarce, with small samples, and equivocal findings. This study leveraged the Fox Insight study to evaluate the association between American football and parkinsonism and/or PD Diagnosis and related clinical outcomes.

Fox Insight is an online study of people with and without PD who are 18+ years (>50,000 enrolled). Participants complete online questionnaires on motor function, cognitive function, and general health behaviors. Participants self-reported whether they "currently have a diagnosis of Parkinson's disease, or parkinsonism, by a physician or other health care professional." In November 2020, the Boston University Head Impact Exposure Assessment was launched in Fox Insight for large-scale data collection on exposure to RHI from contact sports and other sources. Data used in this abstract were obtained from the Fox Insight database https://foxinsight-info.michaeljfox.org/insight/explore/insight.jsp on 01/06/2022. The sample includes 2018 men who endorsed playing an organized sport. Because only 1.6% of football players were women, analyses are limited to men. Responses to questions regarding history of participation in organized football were examined. Other contact and/or non-contact sports served as the referent group. Outcomes included PD status (absence/presence of parkinsonism or PD) and Penn Parkinson's Daily Activities Questionnaire-15 (PDAQ-15) for assessment of cognitive symptoms. Binary logistic regression tested associations between history and years of football play with PD status, controlling for age, education, current heart disease or diabetes, and family history of PD. Linear regressions, controlling for these variables, were used for the PDAQ-15.

Of the 2018 men (mean age=67.67, SD=9.84; 10, 0.5% Black), 788 (39%) played football (mean years of play=4.29, SD=2.88), including 122 (16.3%) who played youth football, 494 (66.0%) played high school, 128 (17.1%) played college football, and 5 (0.7%) played at the semi-professional or professional level. 1738 (86.1%) reported being diagnosed with parkinsonism/PD, and 707 of these were football players (40.7%). History of playing any level of football was associated with increased odds of having a reported parkinsonism or PD diagnosis (OR=1.52, 95% CI=1.14-2.03, p=0.004). The OR remained similar among those age <69 (sample median age) (OR=1.45, 95% CI=0.97-2.17, p=0.07) and 69+ (OR=1.45, 95% CI=0.95-2.22, p=0.09). Among the football players, there was not a significant association between years of play and PD status (OR=1.09, 95% CI=1.00-1.20, p=0.063). History of football play was not associated with PDAQ-15 scores (n=1980) (beta=-0.78, 95% CI=-1.59-0.03, p=0.059) among the entire sample.

Among 2018 men from a data set enriched for PD, playing organized football was associated with increased odds of having a reported parkinsonism/PD diagnosis. Next steps include examination of the contribution of traumatic brain injury and other sources of RHI (e.g., soccer, military service).

The goal of our study was to examine the possible effects of a strategies-based training intervention on objective memory performance and subjective memory in healthy older adults. While slight declines in memory naturally occur in the aging process, these changes may impact the quality of life for older adults.

Patients (n = 11, aged 50-80, mean age = 70.73, SD = 4.41) with subjective memory complaints were recruited from memory clinics within an academic medical center. All participants engaged in one-on-one, three one-hour memory training sessions over the course of several weeks to undergo strategies-based training intervention (e.g., mnemonics). All participants completed neuropsychological battery of tests at baseline and at post-intervention (about 8-10 weeks after baseline). Tests included the Montreal Cognitive Assessment (MoCA), the Hopkins Verbal List Test (HVLT-R), the Visual Reproduction subtest of the Weschler Memory Scale (WMS-IV), and the Multiphasic Memory Questionnaire.

Data were analyzed using a mixed between-within subjects ANOVA and t-tests. Groups were created based on the participant’s MoCA score. While a total of 11 participants completed baseline testing and the memory training sessions, two did not return for post-intervention testing; as such their data were excluded from analyses. Older adults with a MoCA score of 26-30 (n = 6), but not older adults with a MoCA score 25 and below (n = 3), had a significant improvement in visual learning and encoding, F (1, 7) = 10.028, r = .50, p < .05. The high MoCA performers demonstrated an improved performance in their immediate visual memory from baseline (M = 10, SD = 3.53) to post-intervention (M = 12, SD = 3.35), t(9) = .895, p = .001 (two-tailed). Ratings of memory satisfaction among high MoCA performers also increased from baseline (M = 48, SD = 11.47) to post-intervention (M = 51, SD = 5.43), t(9) = .707, p < .05 (two-tailed). Among both groups, a significant increase in perceived memory ability was demonstrated from baseline (M = 50, SD =10.1) to post-intervention (M = 54, SD = 12.35), t(8) = .807, p < .05 (two-tailed).

These findings indicate that a brief memory training program may improve visual encoding and subjective memory in healthy older adults with memory concerns. Individuals with subjective memory concerns who undergo a cognitive training program seem to demonstrate improved encoding of nonverbal material. These participants also reported a greater memory satisfaction and improved perceived memory ability after completion of a memory training program. Interestingly, these findings were only seen in adults whose MoCA performance was within normal limits. Although a systematic review suggests the improvement of memory performances on cognitively impaired participants (Simon, Yokomizo, & Bottino, 2012), this may not have been demonstrated in the current study due to a low sample size and/or to the brief duration of the cognitive training. Future directions include increasing sample size and offering booster sessions to explore whether cognitively impaired adults may benefit from repetition.