Identifying persons with HIV (PWH) at increased risk for Alzheimer’s disease (AD) is complicated because memory deficits are common in HIV-associated neurocognitive disorders (HAND) and a defining feature of amnestic mild cognitive impairment (aMCI; a precursor to AD). Recognition memory deficits may be useful in differentiating these etiologies. Therefore, neuroimaging correlates of different memory deficits (i.e., recall, recognition) and their longitudinal trajectories in PWH were examined.

We examined 92 PWH from the CHARTER Program, ages 45–68, without severe comorbid conditions, who received baseline structural MRI and baseline and longitudinal neuropsychological testing. Linear and logistic regression examined neuroanatomical correlates (i.e., cortical thickness and volumes of regions associated with HAND and/or AD) of memory performance at baseline and multilevel modeling examined neuroanatomical correlates of memory decline (average follow-up = 6.5 years).

At baseline, thinner pars opercularis cortex was associated with impaired recognition (p = 0.012; p = 0.060 after correcting for multiple comparisons). Worse delayed recall was associated with thinner pars opercularis (p = 0.001) and thinner rostral middle frontal cortex (p = 0.006) cross sectionally even after correcting for multiple comparisons. Delayed recall and recognition were not associated with medial temporal lobe (MTL), basal ganglia, or other prefrontal structures. Recognition impairment was variable over time, and there was little decline in delayed recall. Baseline MTL and prefrontal structures were not associated with delayed recall.

Episodic memory was associated with prefrontal structures, and MTL and prefrontal structures did not predict memory decline. There was relative stability in memory over time. Findings suggest that episodic memory is more related to frontal structures, rather than encroaching AD pathology, in middle-aged PWH. Additional research should clarify if recognition is useful clinically to differentiate aMCI and HAND.

Affective responses to the menstrual cycle vary widely. Some individuals experience severe symptoms like those with premenstrual dysphoric disorder, while others have minimal changes. The reasons for these differences are unclear, but prior studies suggest stressor exposure may play a role. However, research in at-risk psychiatric samples is lacking.

In a large clinical sample, we conducted a prospective study of how lifetime stressors relate to degree of affective change across the cycle. 114 outpatients with past-month suicidal ideation (SI) provided daily ratings (n = 6187) of negative affect and SI across 1–3 menstrual cycles. Participants completed the Stress and Adversity Inventory (STRAIN), which measures different stressor exposures (i.e. interpersonal loss, physical danger) throughout the life course, including before and after menarche. Multilevel polynomial growth models tested the relationship between menstrual cycle time and symptoms, moderated by stressor exposure.

Greater lifetime stressor exposure predicted a more pronounced perimenstrual increase in active SI, along with marginally significant similar patterns for negative affect and passive SI. Additionally, pre-menarche stressors significantly increased the cyclicity of active SI compared to post-menarche stressors. Exposure to more interpersonal loss stressors predicted greater perimenstrual symptom change of negative affect, passive SI and active SI. Exploratory item-level analyses showed that lifetime stressors moderated a more severe perimenstrual symptom trajectory for mood swings, anger/irritability, rejection sensitivity, and interpersonal conflict.

These findings suggest that greater lifetime stressor exposure may lead to heightened emotional reactivity to ovarian hormone fluctuations, elevating the risk of psychopathology.

Both impulsivity and compulsivity have been identified as risk factors for problematic use of the internet (PUI). Yet little is known about the relationship between impulsivity, compulsivity and individual PUI symptoms, limiting a more precise understanding of mechanisms underlying PUI.

The current study is the first to use network analysis to (a) examine the unique association among impulsivity, compulsivity and PUI symptoms, and (b) identify the most influential drivers in relation to the PUI symptom community.

We estimated a Gaussian graphical model consisting of five facets of impulsivity, compulsivity and individual PUI symptoms among 370 Australian adults (51.1% female, mean age = 29.8, s.d. = 11.1). Network structure and bridge expected influence were examined to elucidate differential associations among impulsivity, compulsivity and PUI symptoms, as well as identify influential nodes bridging impulsivity, compulsivity and PUI symptoms.

Results revealed that four facets of impulsivity (i.e. negative urgency, positive urgency, lack of premeditation and lack of perseverance) and compulsivity were related to different PUI symptoms. Further, compulsivity and negative urgency were the most influential nodes in relation to the PUI symptom community due to their highest bridge expected influence.

The current findings delineate distinct relationships across impulsivity, compulsivity and PUI, which offer insights into potential mechanistic pathways and targets for future interventions in this space. To realise this potential, future studies are needed to replicate the identified network structure in different populations and determine the directionality of the relationships among impulsivity, compulsivity and PUI symptoms.

Anterior temporal lobectomy is a common surgical approach for medication-resistant temporal lobe epilepsy (TLE). Prior studies have shown inconsistent findings regarding the utility of presurgical intracarotid sodium amobarbital testing (IAT; also known as Wada test) and neuroimaging in predicting postoperative seizure control. In the present study, we evaluated the predictive utility of IAT, as well as structural magnetic resonance imaging (MRI) and positron emission tomography (PET), on long-term (3-years) seizure outcome following surgery for TLE.

Patients consisted of 107 adults (mean age=38.6, SD=12.2; mean education=13.3 years, SD=2.0; female=47.7%; White=100%) with TLE (mean epilepsy duration =23.0 years, SD=15.7; left TLE surgery=50.5%). We examined whether demographic, clinical (side of resection, resection type [selective vs. non-selective], hemisphere of language dominance, epilepsy duration), and presurgical studies (normal vs. abnormal MRI, normal vs. abnormal PET, correctly lateralizing vs. incorrectly lateralizing IAT) were associated with absolute (cross-sectional) seizure outcome (i.e., freedom vs. recurrence) with a series of chi-squared and t-tests. Additionally, we determined whether presurgical evaluations predicted time to seizure recurrence (longitudinal outcome) over a three-year period with univariate Cox regression models, and we compared survival curves with Mantel-Cox (log rank) tests.

Demographic and clinical variables (including type [selective vs. whole lobectomy] and side of resection) were not associated with seizure outcome. No associations were found among the presurgical variables. Presurgical MRI was not associated with cross-sectional (OR=1.5, p=.557, 95% CI=0.4-5.7) or longitudinal (HR=1.2, p=.641, 95% CI=0.4-3.9) seizure outcome. Normal PET scan (OR= 4.8, p=.045, 95% CI=1.0-24.3) and IAT incorrectly lateralizing to seizure focus (OR=3.9, p=.018, 95% CI=1.2-12.9) were associated with higher odds of seizure recurrence. Furthermore, normal PET scan (HR=3.6, p=.028, 95% CI =1.0-13.5) and incorrectly lateralized IAT (HR= 2.8, p=.012, 95% CI=1.2-7.0) were presurgical predictors of earlier seizure recurrence within three years of TLE surgery. Log rank tests indicated that survival functions were significantly different between patients with normal vs. abnormal PET and incorrectly vs. correctly lateralizing IAT such that these had seizure relapse five and seven months earlier on average (respectively).

Presurgical normal PET scan and incorrectly lateralizing IAT were associated with increased risk of post-surgical seizure recurrence and shorter time-to-seizure relapse.

Many people with HIV (PWH) are at risk for age-related neurodegenerative disorders such as Alzheimer’s disease (AD). Studies on the association between cognition, neuroimaging outcomes, and the Apolipoprotein E4 (APOE4) genotype, which is associated with greater risk of AD, have yielded mixed results in PWH; however, many of these studies have examined a wide age range of PWH and have not examined APOE by race interactions that are observed in HIV-negative older adults. Thus, we examined how APOE status relates to cognition and medial temporal lobe (MTL) structures (implicated in AD pathogenesis) in mid- to older-aged PWH. In exploratory analyses, we also examined race (African American (AA)/Black and non-Hispanic (NH) White) by APOE status interactions on cognition and MTL structures.

The analysis included 88 PWH between the ages of 45 and 68 (mean age=51±5.9 years; 86% male; 51% AA/Black, 38% NH-White, 9% Hispanic/Latinx, 2% other) from the CNS HIV Antiretroviral Therapy Effects Research multi-site study. Participants underwent APOE genotyping, neuropsychological testing, and structural MRI; APOE groups were defined as APOE4+ (at least one APOE4 allele) and APOE4- (no APOE4 alleles). Eighty-nine percent of participants were on antiretroviral therapy, 74% had undetectable plasma HIV RNA (<50 copies/ml), and 25% were APOE4+ (32% AA/Black/15% NH-White). Neuropsychological testing assessed seven domains, and demographically-corrected T-scores were calculated. FreeSurfer 7.1.1 was used to measure MTL structures (hippocampal volume, entorhinal cortex thickness, and parahippocampal thickness) and the effect of scanner was regressed out prior to analyses. Multivariable linear regressions tested the association between APOE status and cognitive and imaging outcomes. Models examining cognition covaried for comorbid conditions and HIV disease characteristics related to global cognition (i.e., AIDS status, lifetime methamphetamine use disorder). Models examining the MTL covaried for age, sex, and

relevant imaging covariates (i.e., intracranial volume or mean cortical thickness).

APOE4+ carriers had worse learning (ß=-0.27, p=.01) and delayed recall (ß=-0.25, p=.02) compared to the APOE4- group, but APOE status was not significantly associated with any other domain (ps>0.24). APOE4+ status was also associated with thinner entorhinal cortex (ß=-0.24, p=.02). APOE status was not significantly associated with hippocampal volume (ß=-0.08, p=0.32) or parahippocampal thickness (ß=-0.18, p=.08). Lastly, race interacted with APOE status such that the negative association between APOE4+ status and cognition was stronger in NH-White PWH as compared to AA/Black PWH in learning, delayed recall, and verbal fluency (ps<0.05). There were no APOE by race interactions for any MTL structures (ps>0.10).

Findings suggest that APOE4 carrier status is associated with worse episodic memory and thinner entorhinal cortex in mid- to older-aged PWH. While APOE4+ groups were small, we found that APOE4 carrier status had a larger association with cognition in NH-White PWH as compared to AA/Black PWH, consistent with studies demonstrating an attenuated effect of APOE4 in older AA/Black HIV-negative older adults. These findings further highlight the importance of recruiting diverse samples and suggest exploring other genetic markers (e.g., ABCA7) that may be more predictive of AD in some races to better understand AD risk in diverse groups of PWH.

Patients with Parkinson’s disease (PD) commonly show deficits on tests of visuospatial functioning. The Identi-Fi is a new measure of visual organization and recognition composed of two components. The Visual Recognition (VR) subtest asks persons to identify an object that has been broken its pieces and rearranged, akin to the Hooper Visual Organization Test, but using updated and colorful pictures. The Visual Matching (VM) subtest involves showing the same stimuli, but the examinee must select the correct response from among five choices (1 correct and 4 foils), placing greater demand on visuospatial discrimination. Together, the two subtests comprise the Visual Organization Index (VOI), reflecting overall visual processing and organization ability. The present study examined performance on the Identi-Fi in patients with PD and its association with other aspects of cognition.

Participants were 23 patients with PD (95% male; mean age = 69.7 years [SD = 7.8], range = 47-79) and 12 patients with cognitive concerns (CC) who were intact on neuropsychological testing (excluding consideration of Identi-Fi scores; 50% male, mean age = 71.08 [SD = 6.27], range = 60-78) seen for a neuropsychological evaluation at a large Northeastern medical center. As part of a larger battery, patients completed the Identi-Fi, Trail Making Test (TMT), Category Fluency, Test of Premorbid Functioning (TOPF), and Brief Visuospatial Memory Test, Revised (BVMT-R).

The PD group performed significantly worse than the CC group on VR and VM, as well as VOI, of the Identi-Fi (p < .001). Within the PD group, poorer VR, VM, and VOI performance was associated with lower scores on the TOPF (p < .05), BVMT-R learning (p < .05) and delayed recall (p < .05), as well as TMT Parts A and B (p < .05). VR was significantly correlated with Category Fluency (p < .05), while a trend was seen for the association between VOI and Category Fluency (p = .094).

Identi-Fi performance was worse in the PD group than the CC group, which is consistent with prior research indicating that visuospatial processing is often abnormal in patients with PD. Furthermore, findings indicate that poorer performance on the Identi-Fi in the PD group is associated with poorer cognitive functioning in other domains (i.e., visuospatial learning and memory, processing speed, cognitive flexibility, and semantic fluency), as well as lower premorbid intellectual functioning. While these findings suggest that the Identi-Fi is useful in identifying visuospatial dysfunction in PD, findings should be interpreted with caution given the small sample sizes and uneven gender distribution

Patients with Post-Acute COVID Syndrome (PACS) are reported to commonly experience a variety of cognitive, physical, and neuropsychiatric symptoms well beyond the acute phase of the illness. Notably, concerns involving mood, fatigue, and physical symptoms (e.g., pain, headaches) following COVID-19 appears to be especially prevalent. It is unclear, however, the extent to which such symptoms are associated with cognitive problems in patients with PACS. In the present study, we examined the prevalence of cognitive impairment in a sample of patients with PACS, as well as the relationship between cognitive functioning and several non-cognitive symptoms.

Participants were 38 patients with PACS [71.1% female; mean age = 48.03 years (SD = 11.60) and years of education = 15.26 years (SD = 2.60)] seen for a neuropsychological evaluation at a large Northeastern medical center at least three months from the time of COVID-19 diagnosis (per PCR test). As part of a larger battery, patients completed the Hopkins Verbal Learning Test- Revised (HVLT, learning and delayed recall), Trail Making Test (TMT; time to complete parts A and B), Controlled Oral Word Association Test (COWAT total correct), and Animals (total correct). They also were administered the Chalder Fatigue Scale-11 (CFS-11), Beck Depression Inventory-II (BDI-II), Beck Anxiety Inventory (BAI), and Patient Health Questionnaire (PHQ-15). The percentage of patients with scores in the impaired range (z < -1.5) on cognitive tests was determined. Correlations between cognitive and non-cognitive measures were also examined.

The most frequent impairment was seen for COWAT (21.2%), followed by TMT-A and TMT-B (both 13.9%), then category fluency (9.1%). No patients were impaired on HVLT-R Learning and only one (4%) for HVLT-R Delayed Recall. Overall, the sample endorsed considerable depression, anxiety, fatigue, as well as physical symptoms. Greater fatigue was associated with worse verbal learning, processing speed, cognitive flexibility, and verbal fluency (letter and category). Worse physical symptom severity was related to poorer verbal delayed recall and cognitive flexibility. Greater anxiety was also associated with worse cognitive flexibility, while more severe depression was related to poorer category fluency.

In our sample of patients with PACS, seen for evaluation several months since contracting COVID-19, phonemic fluency was the most common cognitive impairment, though less than a quarter were impaired on any given cognitive test. Importantly, several associations were observed between cognitive test performance and non-cognitive symptoms commonly endorsed by patients with PACS. These findings highlight the importance of assessing multiple factors potentially contributing to cognitive impairment in these patients. Interventions designed to address such symptoms may be helpful in ameliorating cognitive functioning in those with PACS.

Mild cognitive impairment (MCI) is characterized by subjective and objective memory concerns, though additional cognitive concerns are commonly reported, including changes in executive functions (EF). Rabin et al. (2006) showed that a sample of research participants with MCI endorsed problems with their EFs, especially working memory. Similarly, those with subjective cognitive dysfunction (SCD) also reported greater difficulty with aspects of their EF than a healthy comparison sample of older adults (HC). In the present study, we investigated subjective EF in clinical samples of older adults with MCI or SCD, which represents a more naturalistic sample relative to a research sample. Furthermore, we evaluated whether subjective EF varied in these groups depending on whether patients were "young-old" versus "old-old" given prior research indicating objective cognitive differences between these age groups.

Participants were 135 older adults (53 MCI, 52 SCD, and 30 HC) matched for age (p = .116) and education (p = .863). Dichotomous categorization of age used the sample median (72 years) as cutoff score with 72 participants in the young-old group (mean age = 65.8 ± 4.7 years) and 63 in the old-old group (mean age = 78.1 ± 3.7 years). Participants completed the Behavior Rating Inventory of Executive Function-Adult (BRIEF-A), assessing executive functions in everyday life over the past month. The BRIEF-A yields an overall score (Global Executive Composite [GEC]) composed of two index scores (Behavioral Regulation Index [BRI] and Metacognition Index [MI]) and nine clinical scales (Inhibit, Shift, Emotional Control, Self-Monitor, Initiate, Working Memory, Plan/Organize, Task Monitor, and Organization of Materials). A diagnosis by age-group multivariate analysis of variance (MANOVA) with post-hoc comparisons for diagnosis using a Tukey HSD correction was conducted using SPSS Version 24.

MCI and SCD groups endorsed worse EF on all three index scores (ps < .005) and all nine clinical scales (ps < .05) relative to the HC group, and the MCI group reported worse initiation relative to the SCD group. Additionally, worse executive functions on all three index scores (ps < .05) and four clinical scales (ps < .05; emotional control, self-monitoring, planning/organization, and task monitoring) were reported by the young-old group relative to the old-old group. No diagnosis by age-group interactions were observed.

Problems with aspects of EF were endorsed by older adults with MCI and SCD compared to HCs across all indices and clinical scales; however, only initiation was reported to be worse in MCI than those with SCD. Additionally, the young-old group endorsed having worse EF than the old-old group across BRIEF-A indices and several more specific aspects of EF, without a moderating effect of diagnosis. These findings highlight the importance of assessing subjective EF in older adults, as they may be early indicators of cognitive change, prior to objective evidence of cognitive decline. Furthermore, results also point to differences in how the young-old and old-old perceive their EF in everyday life.

Emotional functioning is linked to HIV-associated neurocognitive impairment, yet research on this association among diverse people with HIV (PWH) is scant. We examined emotional health and its association with neurocognition in Hispanic and White PWH.

Participants included 107 Hispanic (41% primarily Spanish-speakers; 80% Mexican heritage/origin) and 216 White PWH (Overall age: M = 53.62, SD = 12.19; 86% male; 63% AIDS; 92% on antiretroviral therapy). Emotional health was assessed via the National Institute of Health Toolbox (NIHTB)-Emotion Battery, which yields T-scores for three factor-based summary scores (negative affect, social satisfaction, and psychological well-being) and 13 individual component scales. Neurocognition was measured via demographically adjusted fluid cognition T-scores from the NIHTB-cognition battery.

27%–39% of the sample had problematic socioemotional summary scores. Hispanic PWH showed less loneliness, better social satisfaction, higher meaning and purpose, and better psychological well-being than Whites (ps <.05). Within Hispanics, Spanish-speakers showed better meaning and purpose, higher psychological well-being summary score, less anger hostility, but greater fear affect than English speakers. Only in Whites, worse negative affect (fear affect, perceived stress, and sadness) was associated with worse neurocognition (p <.05); and in both groups, worse social satisfaction (emotional support, friendship, and perceived rejection) was linked with worse neurocognition (p <.05).

Adverse emotional health is common among PWH, with subgroups of Hispanics showing relative strengths in some domains. Aspects of emotional health differentially relate to neurocogntition among PWH and cross-culturally. Understanding these varying associations is an important step towards the development of culturally relevant interventions that promote neurocognitive health among Hispanic PWH.

Life stress and blunted reward processing each have been associated with the onset and maintenance of major depressive disorder. However, much of this work has been cross-sectional, conducted in separate lines of inquiry, and focused on recent life stressor exposure, despite the fact that theories of depression posit that stressors can have cumulative effects over the lifespan. To address these limitations, we investigated whether acute and chronic stressors occurring over the lifespan interacted with blunted reward processing to predict increases in depression over time in healthy youth.

Participants were 245 adolescent girls aged 8–14 years old (Mage = 12.4, s.d. = 1.8) who were evaluated at baseline and two years later. The reward positivity (RewP), an event-related potential measure of reward responsiveness, was assessed at baseline using the doors task. Cumulative lifetime exposure to acute and chronic stressors was assessed two years later using the Stress and Adversity Inventory for Adolescents (Adolescent STRAIN). Finally, depressive symptoms were assessed at both baseline and follow-up using the Children's Depression Inventory.

As hypothesized, greater lifetime acute stressor exposure predicted increases in depressive symptoms over two years, but only for youth exhibiting a blunted RewP. This interaction, however, was not found for chronic stressors.

Lifetime acute stressor exposure may be particularly depressogenic for youth exhibiting a blunted RewP. Conversely, a robust RewP may be protective in the presence of greater acute lifetime stressor exposure.