People with bipolar disorder (BD) often show inaccurate subjective ratings of their objective cognitive function. However, it is unclear what information individuals use to formulate their subjective ratings. This study evaluated whether people with BD are likely using information about their crystallized cognitive abilities (which involve an accumulated store of verbal knowledge and skills and are typically preserved in BD) or their fluid cognitive abilities (which involve the capacity for new learning and information processing in novel situations and are typically impaired in BD) to formulate their subjective cognitive ratings.

Eighty participants diagnosed with BD and 55 control volunteers were administered cognitive tests assessing crystallized and fluid cognitive abilities. Subjective cognitive functioning was assessed with the Cognitive Failures Questionnaire (CFQ), daily functioning was rated using the Multidimensional Scale of Independent Functioning (MSIF) and the Global Assessment of Functioning Scale (GAF), and quality of life was assessed with the Quality of Life in Bipolar Disorder scale (QoL.BD).

The BD group exhibited considerably elevated subjective cognitive complaints relative to controls. Among participants with BD, CFQ scores were associated with fluid cognitive abilities including measures of memory and executive function, but not to crystallized abilities. After controlling for objective cognition and depression, higher cognitive complaints predicted poorer psychosocial outcomes.

Cognitive self-reports in BD may represent a metacognitive difficulty whereby cognitive self-appraisals are distorted by a person’s focus on their cognitive weaknesses rather than strengths. Moreover, negative cognitive self-assessments are associated with poorer daily functioning and diminished quality of life.

Neurocognitive dysfunction is a transdiagnostic finding in psychopathology, but relationships among cognitive domains and general and specific psychopathology dimensions remain unclear. This study aimed to examine associations between cognition and psychopathology dimensions in a large youth cohort.

The sample (N = 9350; age 8–21 years) was drawn from the Philadelphia Neurodevelopmental Cohort. Data from structured clinical interviews were modeled using bifactor confirmatory factor analysis (CFA), resulting in an overall psychopathology (‘p’) factor score and six orthogonal psychopathology dimensions: dysphoria/distress, obsessive-compulsive, behavioral/externalizing, attention-deficit/hyperactivity, phobias, and psychosis. Neurocognitive data were aggregated using correlated-traits CFA into five factors: executive functioning, memory, complex cognition, social cognition, and sensorimotor speed. We examined relationships among specific and general psychopathology dimensions and neurocognitive factors.

The final model showed both overall and specific associations between cognitive functioning and psychopathology, with acceptable fit (CFI = 0.91; TLI = 0.90; RMSEA = 0.024; SRMR = 0.054). Overall psychopathology and most psychopathology dimensions were negatively associated with neurocognitive functioning (phobias [p < 0.0005], behavioral/externalizing [p < 0.0005], attention-deficit/hyperactivity [p < 0.0005], psychosis [p < 0.0005 to p < 0.05]), except for dysphoria/distress and obsessive-compulsive symptoms, which were positively associated with complex cognition (p < 0.05 and p < 0.01, respectively).

By modeling a broad range of cognitive and psychopathology domains in a large, diverse sample of youth, we found aspects of neurocognitive functioning shared across clinical phenotypes, as well as domain-specific patterns. Findings support transdiagnostic examination of cognitive performance to parse variability in the link between neurocognitive functioning and clinical phenotypes.

Although obsessive–compulsive disorder (OCD) is highly prevalent in schizophrenia, its relationship with patients’ real-life functioning is still controversial.

The present study aims at investigating the prevalence of OCD in a large cohort of non-preselected schizophrenia patients living in the community and verifying the relationship of OCD, as well as of other psychopathological symptoms, with real-life functioning along a continuum of OCD severity and after controlling for demographic variables.

A sample of 327 outpatients with schizophrenia was enrolled in the study and collapsed into three subgroups according to OCD severity (subclinical, mild–moderate, severe). A series of structural equation modeling (SEM) was performed to analyze in each subgroup the association of obsessive–compulsive symptoms with real-life functioning, assessed through the Specific Levels of Functioning Scale and the UCSD Performance-Based Skills Assessment. Moreover, latent profile analysis (LPA) was performed to infer latent subpopulations. In the subclinical OCD group, obsessive–compulsive symptoms (OCS) were not associated with functioning, whereas in the mild–moderate OCD group, they showed a positive relationship, particularly in the domains of work and everyday life skills. The paucity of patients with severe OCD did not allow performing SEM analysis in this group. Finally, LPA confirmed a subgroup with mild–moderate OCS and more preserved levels of functioning.

These findings hint at a positive association between mild–moderate OCD and real-life functioning in individuals with schizophrenia and encourage a careful assessment of OCD in personalized programs to sustain daily life activities.

Cognitive training is a non-pharmacological intervention aimed at improving cognitive function across a single or multiple domains. Although the underlying mechanisms of cognitive training and transfer effects are not well-characterized, cognitive training has been thought to facilitate neural plasticity to enhance cognitive performance. Indeed, the Scaffolding Theory of Aging and Cognition (STAC) proposes that cognitive training may enhance the ability to engage in compensatory scaffolding to meet task demands and maintain cognitive performance. We therefore evaluated the effects of cognitive training on working memory performance in older adults without dementia. This study will help begin to elucidate non-pharmacological intervention effects on compensatory scaffolding in older adults.

48 participants were recruited for a Phase III randomized clinical trial (Augmenting Cognitive Training in Older Adults [ACT]; NIH R01AG054077) conducted at the University of Florida and University of Arizona. Participants across sites were randomly assigned to complete cognitive training (n=25) or an education training control condition (n=23). Cognitive training and the education training control condition were each completed during 60 sessions over 12 weeks for 40 hours total. The education training control condition involved viewing educational videos produced by the National Geographic Channel. Cognitive training was completed using the Posit Science Brain HQ training program, which included 8 cognitive training paradigms targeting attention/processing speed and working memory. All participants also completed demographic questionnaires, cognitive testing, and an fMRI 2-back task at baseline and at 12-weeks following cognitive training.

Repeated measures analysis of covariance (ANCOVA), adjusted for training adherence, transcranial direct current stimulation (tDCS) condition, age, sex, years of education, and Wechsler Test of Adult Reading (WTAR) raw score, revealed a significant 2-back by training group interaction (F[1,40]=6.201, p=.017, η2=.134). Examination of simple main effects revealed baseline differences in 2-back performance (F[1,40]=.568, p=.455, η2=.014). After controlling for baseline performance, training group differences in 2-back performance was no longer statistically significant (F[1,40]=1.382, p=.247, η2=.034).

After adjusting for baseline performance differences, there were no significant training group differences in 2-back performance, suggesting that the randomization was not sufficient to ensure adequate distribution of participants across groups. Results may indicate that cognitive training alone is not sufficient for significant improvement in working memory performance on a near transfer task. Additional improvement may occur with the next phase of this clinical trial, such that tDCS augments the effects of cognitive training and results in enhanced compensatory scaffolding even within this high performing cohort. Limitations of the study include a highly educated sample with higher literacy levels and the small sample size was not powered for transfer effects analysis. Future analyses will include evaluation of the combined intervention effects of a cognitive training and tDCS on nback performance in a larger sample of older adults without dementia.

In persons with severe psychiatric disorders, distinct neurocognitive profiles hold differential associations to positive, negative and disorganized symptom dimensions of psychosis. These patterns portend specific functional outcomes, treatment efficacy, and prognoses. Similar associations have not been established in multimorbid samples in which persons present with a complex array of psychiatric symptoms. The objective of this study was to (1) establish neurocognitive profiles in a multimorbid, marginalized sample and (2) investigate their pattern(s) of association with psychiatric symptom dimensions and psychosocial outcomes.

Participants (n=370; Mage = 45 years; 74% male) were precariously housed, substance-using adults with multimorbidity, recruited from Single-Room Occupancy hotels and a community court within the Downtown Eastside of Vancouver, BC, Canada. Data were collected as part of a longitudinal examination consisting of annual, bi-annual, and monthly neurocognitive, psychosocial, and psychiatric assessments. Neurocognitive scores were combined into five cognitive domains (Attentional Control [AC]; Processing Speed [PS]; Fluid Reasoning [Problem Solving and Reversal Learning; Gf]; Encoding and Retrieval [ER]; and Decision Making [DM]) and submitted to a latent profile analysis. The resulting profiles capturing neurocognition were validated on sociodemographic and clinical variables. Finally, the profiles were compared across previously validated, population-distinct factors derived from the Positive and Negative Syndrome Scale (PANSS), as well as on measures of psychosocial functioning.

An optimal goodness-of-fit was reached for a three-profile model (BLRT=127.86, p=.01). Profile 1 (n=207, 55.9%) showed stronger neurocognition (all p<.05), with a within-profile strength in Gf (p<.001). With the exception of ER, Profile 2 (n=109, 29.5%) exhibited inferior neurocognition across all indicators compared to Profile 1 (all p <.05); yet showed a relative, within-profile strength in Gf (p < .01). Profile 3 (n=54, 14.6%) generally displayed comparable impairments to Profile 2. Additionally, their performance on Gf was remarkably low compared to Profiles 1 and 2 (p<.001). Psychiatrically, compared to Profile 1, Profile 2 exhibited more positive/disorganized symptoms and general psychopathology, as well as higher total PANSS (all p <.05), whereas Profile 3 showed the poorest insight/awareness (p<.01). Profiles 2 and 3 had lower levels of adaptive functioning and work productivity compared to Profile 1 (all p<.01).

Three neurocognitive profiles were detected in a sample of precariously housed adults with multimorbidity: one profile of comparatively higher neurocognitive capacity, with less symptoms of psychosis and better psychosocial functioning; a second profile of comparatively poorer neurocognition and psychosocial functioning, with more symptoms of psychosis; and a third profile with a severe deficit in fluid reasoning and poor insight and awareness. Given their poor insight, the third profile may be comprised of particularly vulnerable persons at greater risk of unmet healthcare needs. Interventions to improve these individuals' understanding of their personal health risks might facilitate their capacity to access services. Conversely, individuals from Profile 2 may benefit from outreach programs focusing on medication access and adherence to address their symptoms of psychosis. In sum, our findings suggest that the confluence of neurocognition and psychiatric symptoms may implicate unique treatment approaches and outcomes in precariously-housed persons with multimorbid conditions.

Major Depressive Disorder (MDD) subtypes have been shown to differentially impact psychiatric symptom presentation, clinical features, and functional abilities. While there is extensive research regarding MDD subtypes and clinical characteristics, there has been limited information regarding the relationship between MDD subtypes and neurocognitive functioning. In particular, the neurocognitive impact of the subtype of treatment resistant depression (TRD), defined as MDD that is unresponsive to treatment, is unknown. The aim of this preliminary study was to address this gap by characterizing the neurocognitive profile of TRD. We characterized the performance of older adults with TRD on measures across multiple neurocognitive domains, and explored whether performance varied based on age and education.

Data utilized were drawn from a broader NIMH-funded, randomized, controlled study conducted at the University of New Mexico that investigated the clinical and cognitive outcomes of varying pulse amplitudes during acute electroconvulsive therapy (ECT) in adults with MDD. Participants in the study were age 50+ with a diagnosis of MDD, and further delineated by subtype as TRD. For this analysis, we utilized demographic and baseline neurocognitive data collected prior to start of treatment for those diagnosed with MDD, recurrent, severe (TRD). Neurocognitive measures included the Delis Kaplan Executive Function System (D-KEFS) Verbal Fluency and Color-Word Interference Subtests, Hopkins Verbal Learning Test-Revised (HVLT-R), and the Wechsler Adult Intelligence Scale 4th Edition (WAIS-IV) Digit Spans. Demographic-adjusted scaled scores were computed, and descriptive statistics were used to characterize the demographic and neurocognitive features of the sample. Multiple Analysis of Variance (MANOVA) was used to investigate difference in performance across neurocognitive measures based on level of education, with age as a covariate.

The sample (n = 42) had a mean age of 65 (SD=8), education level between12 and 14 years, 66.6% were female and 93% were Caucasian. DKEFS Verbal Fluency Category Switching Total Switching Accuracy fell in the Average range (Mean SS=9.5, SD=3.1), and Color Word Inhibition Total Completion Time fell in the Average range (Mean SS=8.5, SD=3.3). HVLT-R Total Recall Correct fell in the Mildly Impaired range (Mean T=35.5, SD=9.9) and Delayed Recall Correct fell in the Mildly to Moderately Impaired range (Mean T=32.9, SD=11.0). WAIS-IV Digit Span fell in the Average range (Mean SS=9.5, SD=2.2). Results indicated that age did not adjust outcomes on the neurocognitive variables, Wilks's λ=0.63, F(6, 23)=2.13, p=0.08. We found no evidence for significant effect of level of education on neurocognitive functioning when controlling for the covariate of age, Wilks's λ=-0.16, F(36, 103.7)=1.47, p=0.07.

To our knowledge, this is one of two studies to examine neurocognitive functioning in patients with TRD. The analysis indicated generally intact performance in the neurocognitive domains of executive function (inclusive of verbal fluency, cognitive flexibility, and inhibition), auditory attention and working memory, and Impaired performance on indices of verbal learning and memory. Age did not impact performance on neurocognitive measures, and there was no significant effect for level of education. Further research is warranted to confirm these findings and further explicate the neurocognitive profile of TRD.

Postoperative neurocognitive disorder is common after all forms of surgery in older adults. The mechanisms are multifactorial, and probably require pre-existing neuropathology, whether the patient is symptomatic or not. In Alzheimer's disease (AD) and other tauopathies, the microtubule-associated protein tau can undergo aberrant hyperphosphorylation potentially leading to the development of neurofibrillary pathology, one of the neuropathological hallmarks of the disease. Preclinical and human CSF studies suggest that anesthesia and surgery elicits an increment in CNS tauopathy, which may accelerate any preexisting neuropathology and produce a risk of delirium and the commonly reported changes in cognition.

In this session, the author will present a bench to beside review of how tau protein is altered by perioperative factors and its potential relationship to the impairment of cognition after surgery and anesthesia. Published and ongoing studies will be reviewed to result in a discussion as to why changes in tau protein are concerning in perioperative disorders of cognition.

The presenter will initially review pre-clinical studies focusing on the impact of anesthetics and surgery-induced inflammation on tau pathology and how the impairment of resolution of surgery-induced inflammation, notably decreased lipoxin A4 signaling, is altered by aging, gender, or an increase in the tau pathology burden. These preclinical studies have partially informed a multi-center federally funded observational clinical study, currently in progress, involving neuroimaging to determine whether pre-operative CNS tauopathy, as reflected by PET imaging, predicts delirium and other cognitive and functional outcomes. This translational study will also examine whether anesthesia and spine surgery produces a longitudinal change in the brain tau burden in older adults, as compared to control, nonoperative patients.

Bench to bedside research is needed in order to promote evidence-based care for patients at risk for ADRD.

Older age is associated with an increase in altruistic behaviors such as charitable giving. However, few studies have investigated the cognitive correlates of financial altruism in older adults. This study investigated the cognitive correlates of financial altruism measured using an altruistic choice paradigm in a community-based sample of older adults.

In the present study, a sample of older adults (N = 67; M age = 69.21, SD = 11.23; M education years = 15.97, SD = 2.51; 58.2% female; 71.6% Non-Hispanic White) completed a comprehensive neuropsychological assessment and an altruistic choice paradigm in which they made decisions about allocating money between themselves and an anonymous person.

In multiple linear regression analyses that controlled for age, education, and sex, financial altruism was negatively associated with performance on cognitive measures typically sensitive to early Alzheimer’s Disease. These included CVLT-II Short Delay Free Recall (Beta=-0.26, p=0.03); CVLT-II Long Delay Cued Recall (Beta=-0.32, p=0.04), Craft Story 21 Delayed Recall (Beta=-0.32, p=0.01), and Animal Fluency (Beta=-0.27, p=0.02). Findings held when responses were grouped according to how much was given (Gave Equally, Gave More, Gave Less) for word list memory and story memory measures.

Findings of this study point to a negative relationship between financial altruism and cognitive functioning in older adults on measures known to be sensitive to Alzheimer’s Disease (AD). Findings also point to a potential link between financial exploitation risk and AD in older age.

Migraine refers to recurrent, unilateral headache attacks, lasting 4-72 hours, that have a pulsating quality and can occur with or without aura. Aura is a symptom, usually preceding the onset of a migraine, where there is an experience of gradually spreading focal neurological symptoms which typically last less than one hour. A meta-analysis was conducted which quantitatively synthesized literature documenting performance on clinical measures of processing speed (PS) in individuals with migraine with (MwA) and without aura (MwoA).

Data for this study came from a larger study that compared overall neuropsychological functioning in primary headache disorders (PHD) and healthy controls (HC). We searched OneSearch and PubMed using a uniform search-strategy to locate original research comparing cognition between PHD and HC. Analyses were modeled under random effects. Hedge’s g was used as a bias-corrected estimate of effect size. We assessed between-study heterogeneity using Cochran’s Q and I2. Egger’s regression test was used to assess publication bias (i.e., the association between standard error and effect size). High heterogeneity in effects was analyzed for possible moderating variables using metaregression and sub-group analyses.

The initial search interval spanned inception-May 2021 and yielded 6692 results. Twelve studies met inclusion criteria, included clinical measures of PS, and included PHD subgroups with MwA and/or MwoA (MwA n = 279, MwoA n = 655, HC n = 2159). MwA demonstrated moderately worse performance in PS overall when compared to HC (k = 7, g = -0.41, p = 0.028). MwoA also demonstrated worse performance in PS overall when compared to HC but the effect size was small (k = 12, g = -0.21, p = 0.006). Heterogeneity of MwoA studies was low (Q = 15.12, I2 = 21.19) while heterogeneity of MwA studies was high (Q = 21.91, I2 = 72.61). Meta-regressions of MwA studies indicated clinical age and disease duration to be related to effect sizes such that studies with older clinical participants and longer disease durations yielded greater (negative) differences. Egger’s regression intercept noted a possible association effect size and standard error for MwA articles (t = 3.60, p = 0.02) and MwoA articles (t = 5.21, p < 0.005). Trim-and-fill procedure estimated 0 MwA studies to be missing due to publication bias (adjusted g = -0.41, p = 0.028) while 7 MwoA studies were estimated to be missing due to publication bias (adjusted g = -0.03, Q = 34.79).

Individuals with migraine demonstrated worse performances on tests of PS compared to controls. Effect sizes were generally moderate in strength for MwA while effect sizes were generally small in strength for MwoA. This quantitative summary confirmed that individuals with migraine experience slowed processing speed in general and this effect is magnified when aura is a presenting symptom.

Converging evidence across languages suggests that the word length effect (WLE; rate of number of syllables, phonemes, or pronunciation times per word) significantly contributes to estimates of verbal working memory (WM) capacity limits in the storage phase, but not in the manipulation phase (i.e., word length effect decay), of WM. Direct examination of the WLE on verbal WM performance within monolingual Spanish-speakers has not been reported. We investigated the psychophysical mechanisms of capacity consumption in Spanish-speakers across three syllabic word length rates to clarify the relative contributions of the WLE to storage (digit span forward) versus manipulation (digit span backward) memory phases within one language of monolingual speakers.

Monolingual Spanish-speaking adults (N = 84) born in Latin American countries and age 18-65 completed testing over Zoom. Inclusion criteria required proficiency in the Spanish-language; exclusion criteria were bilingualism, multilingualism, TONI-4 IQ < 85, or history of head injury/LOC. A within-group design measured the WLE across three cognitive load conditions in the forward and backward directions of the digit span test varying in Spanish syllabic word length: the Mexican WAIS-IV Digit Span Test (“Standard Load”), and two modified measures with either a ∼20% decrease (“Low Load”) or ∼20% increase (“High Load”) in total syllables/digit relative to the Standard Load.

A reverse WLE was observed on syllable accuracy percentage task performance (p < 0.01), such that longer word length led to higher capacity limits during storage WM. A WLE, not decay, was found on both raw score (p < .001) and syllable accuracy percentage (p < 0.01) task performances during manipulation WM, where longer word length led to lower capacity limits.

The reverse WLE was attributed to higher-order, executive-function cognitive strategies (such as chunking) that superseded negative word length effects. A larger syllabic discrepancy during manipulation WM could have superseded executive-function strategies, rendering a traditional WLE. Our study contributed more precise capacity estimates and clearer understanding of successful WM performance within monolingual, Latin American-born Spanish-speakers, helping to reduce cultural disparities in neurocognitive and neuropsychological research. Future studies may extend these findings to examine how WM capacity resources can be harnessed to improve memory strategies in clinically-applied settings with Spanish-speaking populations.

Cognitive change affecting patients after anesthesia and surgery has been recognised for more than 100 yr. Research into cognitive change after anesthesia and surgery accelerated in the 1980s when multiple studies utilised detailed neuropsychological testing for assessment of cognitive change after cardiac surgery. This body of work consistently documented decline in cognitive function in elderly patients after anaesthesia and surgery, and cognitive changes have been identified up to 7.5 yr afterward. Importantly, other studies have identified that the incidence of cognitive change is similar after non-cardiac surgery. Other than the inclusion of non-surgical control groups to calculate postoperative cognitive dysfunction, research into these cognitive changes in the perioperative period has been undertaken in isolation from cognitive studies in the general population. This study aimed to develop similar terminology to that used in cognitive classifications of the general population for use in investigations of cognitive changes after anesthesia and surgery.

A multispecialty working group followed a modified Delphi procedure with no prespecified number of rounds comprised of three face-to-face meetings followed by online editing of draft versions. Two major classification guidelines [Diagnostic and Statistical Manual for Mental Disorders, fifth edition (DSM-5) and National Institute for Aging and the Alzheimer Association (NIA-AA)] are used outside of anesthesia and surgery and may be useful for the inclusion of biomarkers in research. For clinical purposes, it is recommended to use the DSM-5 nomenclature.

The working group recommends that 'perioperative neurocognitive disorders (PND)' be used as an overarching term for cognitive impairment identified in the preoperative or postoperative period. This includes cognitive decline diagnosed before operation (described as neurocognitive disorder); any form of the acute event (postoperative delirium) and cognitive and functional decline diagnosed up to 30 days after the procedure (delayed neurocognitive recovery (dNCR)) and up to 12 months (postoperative neurocognitive disorder (postoperative NCD).1 Further, the working group has undergone a further Delphi process to expand these recommendations for research purposes which will also be covered.

Perioperative neurocognitive disorders are the most common complication for patients aged 65y or more undergoing anesthesia and surgery. Moreover, they are associated with significant morbidity, mortality, loss of functional independence and extreme economic costs. A multi-disciplinary approach to PND, including neuropsychologists, is critical to reducing and preventing these disorders. Evered L, Silbert B, Knopman DS, et al. Recommendations for the nomenclature of cognitive change associated with anaesthesia and surgery-2018. Br J Anaesth 2018; 121: 1005-12

Among people with HIV (PWH), the apolipoprotein e4 (APOE-e4) allele, a genetic marker associated with Alzheimer’s disease (AD), and self-reported family history of dementia (FHD), considered a proxy for higher AD genetic risk, are independently associated with worse neurocognition. However, research has not addressed the potential additive effect of FHD and APOE-e4 on global and domain-specific neurocognition among PWH. Thus, the aim of the current investigation is to examine the associations between FHD, APOE-e4, and neurocognition among PWH.

283 PWH (Mage=50.9; SDage=5.6) from the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study completed comprehensive neuropsychological and neuromedical evaluations and underwent APOE genotyping. APOE status was dichotomized into APOE-e4+ and APOE-e4-. APOE-e4+ status included heterozygous and homozygous carriers. Participants completed a free-response question capturing FHD of a first- or second-degree relative (i.e., biologic parent, sibling, children, grandparent, grandchild, uncle, aunt, nephew, niece, half-sibling). A dichotomized (yes/no), FHD variable was used in analyses. Neurocognition was measured using global and domain-specific demographically corrected (i.e., age, education, sex, race/ethnicity) T-scores. t-tests were used to compare global and domain-specific demographically-corrected T-scores by FHD status and APOE-e4 status. A 2x2 factorial analysis of variance (ANOVA) was used to model the interactive effects of FHD and APOE-e4 status. Tukey’s HSD test was used to follow-up on significant ANOVAs.

Results revealed significant differences by FHD status in executive functioning (t(281)=-2.3, p=0.03) and motor skills (t(278)=-2.0, p=0.03) such that FHD+ performed worse compared to FHD-. Differences in global neurocognition by FHD status approached significance (t(281)=-1.8, p=.069). Global and domain-specific neurocognitive performance were comparable among APOE-e4 carriers and noncarriers (ps>0.05). Results evaluating the interactive effects of FHD and APOE-e4 showed significant differences in motor skills (F(3)=2.7, p=0.04) between the FHD-/APOE-e4+ and FHD+/APOE-e4- groups such that the FHD+/APOE-e4- performed worse than the FHD-/APOE-e4+ group (p=0.02).

PWH with FHD exhibited worse neurocognitive performance within the domains of executive functioning and motor skills, however, there were no significant differences in neurocognition between APOE-e4 carriers and noncarriers. Furthermore, global neurocognitive performance was comparable across FHD/APOE-e4 groups. Differences between the FHD-/APOE-e4+ and FHD+/APOE-e4- groups in motor skills were likely driven by FHD status, considering there were no independent effects of APOE-e4 status. This suggests that FHD may be a predispositional risk factor for poor neurocognitive performance among PWH. Considering FHD is easily captured through self-report, compared to blood based APOE-e4 status, PWH with FHD should be more closely monitored. Future research is warranted to address the potential additive effect of FHD and APOE-e4 on rates of global and domain-specific neurocognitive decline and impairment over time among in an older cohort of PWH, where APOE-e4 status may have stronger effects.

Youth with sickle cell disease (SCD) are at increased risk of neurocognitive difficulties with and without neurological complications. Research has identified disease-related, socioeconomic, and sociodemographic risk factors as independently having significant associations with brain physiology for youth with SCD. Notably, sleep has a profound effect on youth’s neurocognitive abilities including learning, executive function, memory, attention, and processing speed. Furthermore, youth with SCD are at an increased risk for poor sleep measured by self-report questionnaires and by polysomnography (PSG). Within the SCD literature, only a few studies have examined the relationship between sleep and cognition. Of these, the majority examined individuals with SCD and comorbid sleep disorder diagnoses. The aim of this study is to identify associations between subjective sleep measures and neurocognitive outcomes in youth with SCD.

This study investigated a cohort of 24 youth with SCD (ages 9-16, 11 males, 13 females; HbSS [63%], HbSB+ [8%], HbSC [21%], HbSB0 [8%]) who received sleep questionnaires and a neuropsychological evaluation. Exclusion criteria included a history of neurological disorder (e.g., overt stroke, seizures, or moyamoya disease) or prescribed psychotropic medication. Sleep questionnaires measuring sleep disturbance (e.g., sleep onset, sleep continuity, and sleep quality) and sleep-related impairments (e.g., daytime sleepiness, sleepiness interference with concentration, and difficulty with activities of daily living skills) were collected. Executive function, working memory, processing speed, and verbal comprehension measures were assessed. Demographics and disease-related risk factors were analyzed individually from medical records.

All analyses were controlled for age, the time between neuropsychological testing and sleep questionnaires, SCD genotype, and sex. Partial correlations were conducted to explore associations with neurocognitive outcomes. Verbal comprehension was significantly correlated with sleep disturbance (r= -.673, p=.001). Multiple linear regressions revealed that sleep disturbance significantly predicts verbal comprehension (ß= -.572, p=.003). Specifically, verbal comprehension decreased by 4.4 standard points for every one-point increase in sleep disturbance. Additionally, total sleep problems significantly predicted working memory (ß=-.414, p=.044) and processing speed (ß= -.411, p= .046). Specifically, working memory decreased by 3.5 standard points while processing speed decreased by 3.3 standard points for every one-point increase in total sleep problems reported. Sleep parameters did not significantly predict executive function.

Results support the association between poor sleep and neurocognitive difficulty in youth with SCD. Three of the participants in this study received a PSG, which further demonstrates the importance of the current findings. This study serves to identify potential risk factors for neurocognitive deficits and provides potential methods for identifying youth with SCD who may need to be referred for a PSG assessment. Research should replicate these findings with increased sample sizes including utilizing PSG and investigating neurobiological effects. Findings may inform future screening tools, treatment approaches, and advanced cognitive initiatives and resources for this population.

Prior research supports retirement may negatively impact cognitive functioning. The current study examined the relationship between retirement status and the level of cognitive dysfunction amongst individuals with Alzheimer’s disease (AD). For the purpose of this study, it was predicted that there would be significantly higher levels of cognitive dysfunction in retired participants after controlling for age.

Participants (ages 65 to 91) were drawn from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). The sample included 110 participants who were retired and 111 participants who were not retired. Cognitive dysfunction was assessed using the cognitive subscale of the modified Alzheimer’s Disease Assessment Scale (ADAS). A one-way ANCOVA analysis was conducted with cognitive dysfunction as the dependent variable and the age of the participants as a covariate.

The results of the one-way ANCOVA showed being retired was a significant predictor of greater cognitive dysfunction amongst individuals with AD after controlling for age (F(df=1, 218) = 231.143, p = < .001, p < .05) and accounted for 52% of the variance in the level of cognitive dysfunction.

Being retired is associated with higher levels of cognitive dysfunction in AD after accounting for the effects of age. As such, continued cognitive activity may slow the progression of cognitive declines amongst individuals with AD who are retired. There is a need for future longitudinal research to determine how late retirement may delay the progression of cognitive decline in AD by controlling for other moderator factors such as genetics and work-related stress.

Alzheimer’s disease (AD) pathophysiology, including β-amyloid (Aβ), can be appreciated with molecular PET imaging. Among older adults, the distribution of Aβ standard uptake value ratios (SUVR) is typically bimodal and a diagnostic cut is applied to define those who are amyloid ‘positive’ and ‘negative’. However, it is unclear whether the dynamic range of SUVRs in amyloid positive and negative individuals is meaningful and associated with cognition. Previous work by Insel and colleagues (2020) used screening data from the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) trial to demonstrate subtle associations between a cortical summary SUVR and cognition, particularly on the Free and Cued Selective Reminding Test (FCSRT). We followed up this study to determine the extent to which regional SUVR is associated with performance on the FCSRT in amyloid positive and negative participants screened for participation in the A4 study.

We accessed regional Aβ SUVR, including anterior cingulate, posterior cingulate, parietal, precuneus, temporal, and medial/orbital frontal regions, along with FCSRT15 and demographic data from 4492 A4 participants at screening. Participants were coded as amyloid positive (n=1329; 30%) or amyloid negative (n=3169; 70%) based on a summary SUVR of greater than or equal to 1.15. We used separate general linear models to examine the association of total or regional SUVR, amyloid positivity status, and the interaction of SUVR and amyloid status with FCSRT scores. We compared model fits across regions with the Akaike Information Criterion (AIC). We ran post hoc correlational analyses examining the relationship between SUVR and FCSRT scores stratified by amyloid status in the case of significant interactions. Results were similar with and without demographic adjustment.

There was a significant interaction of summary and all regional SUVR with FCSRT scores in addition to main effects of amyloid positivity. In all models, there were small negative associations between SUVR and memory in amyloid positive individuals. For amyloid negative individuals, there was a significant and very small negative association between SUVR and FCSRT scores only in the parietal lobes and precuneus regions. Model fits were generally similar across the different analyses.

In this sample of individuals screened for a secondary prevention trial of AD, there were consistent associations between Aβ SUVR in all regions and memory for those considered amyloid positive. However, for individuals considered amyloid negative, there were only very small associations between SUVR and memory in parietal and precuneus regions. We conclude that the dynamic range of amyloid may be relevant among those with diagnostic evidence of amyloidosis, but that subtle Aβ accumulation in posterior regions may relate to declining memory in “subthreshold” states.

Recent work has shown that dysfunctional brain EEG responses to anesthetic drugs can be an indicator of both preoperative cognitive impairment and postoperative delirium risk. However, since excessive anesthetic dosage can also cause abnormal EEG brain responses, it is unclear how to tell to what extent such abnormal brain EEG responses reflect latent neurocognitive impairment versus excessive anesthetic dosage. Further, it is unclear what underlying mechanisms might underlie the link between phenotypes (such as delirium and cognitive impairment) and these abnormal neurophysiologic responses to anesthetic drugs.

Dual center prospective cohort design. 139 total older surgical patients from two academic centers underwent intraoperative EEG monitoring with the bispectral index (BIS) EEG monitor during anesthesia and surgery, and postoperative delirium screening by geriatrician interview (Duke cohort) or by trained research staff (Mt Sinai cohort). We developed the Duke Anesthesia Resistance Scale (DARS), defined as the average BIS EEG values divided by the quantity 2.5 minus the age adjusted end tidal anesthetic gas concentration). We then examined the relationship between the DARS and postoperative delirium risk using the Youden index to identify an optimal low DARS threshold for delirium risk, and we used multivariable logistic regression to control for potential confounders.

Neither BIS scores nor inhaled anesthetic dosage differed significantly between patients with vs without postoperative delirium. Yet, patients with delirium had lower DARS scores than those who did not develop delirium (27.92 vs 32.88, p=0.015). A DARS threshold of 28.7 maximized the Youden index for the association between the DARS and delirium. In multivariable models adjusting for site (Duke vs Mt Sinai) and individual patient risk factors, DARS values <28.7 were associated with a 3.79 fold increased odds ratio (95% CI 1.63-9.10; p=0.03) for postoperative delirium. These results remained unchanged after adjusting for intraoperative medications including opioids, benzodiazepines, propofol, phenylephrine and ketamine. Patients with structural/functional MRI or CSF biomarker evidence of preclinical/prodromal Alzheimer's disease and/or neurovascular pathology were more likely to show altered anesthetic-induced EEG activity patterns.

Lower scores on a processed EEG-based scale of neurophysiologic resistance to anesthetic induced brain activity changes were independently associated with a nearly 4 fold increased delirium risk. The altered anesthetic-induced brain EEG patterns in patients who go on to develop postoperative delirium may reflect latent pre-clinical/pro-dromal Alzheimer's disease and/or neurovascular pathology.

A recent review called for a more robust assessment of cannabis use (CU), including amount and timing of recent use to assess neurocognitive effects of CU among people living with HIV (PWH) (Ellis et al., 2021). The current study addresses some issues raised by investigating between group neurocognitive differences among healthy controls and PWH who differ on their cannabis use histories, using strict inclusion criteria, robust classification of CU, and administration of an established neurocognitive test battery.

Among this community sample of adults (N=309), 58 were classified as CU+/HIV+ group (84.5% Male), 76 as CU-/HIV+ (57.9% M), 86 as CU+/HIV- (58.1% M), and 89 as CU-/HIV- (53.9% M). Exclusion criteria included history of past 12-month dependence and extensive lifetime dependence or significant use of illicit substances other than cannabis, severe or current mood or thought disorder, and other medical conditions that adversely impact neurocognitive functioning. Inclusion criteria for CU+ groups included <30-days since last CU, >10 times of CU in last month, 3 times of CU per month in last 12 months, > 1 year of CU, and > 500 times used in lifetime. CU parameters did not statistically differ between HIV+/CU+ and HIV-/CU+. CU- groups’ inclusion criteria required no CU in last 6 months, 196 lifetime number of times used, and no history of CU dependance. Lifetime CU did not statistically differ between CU-/HIV+ and CU-/HIV- groups. HIV+ groups did not differ significantly on HIV viral load in plasma or nadir CD4+ counts. Significant between group differences included age, sex, years of education, and amount of alcohol and nicotine use within 12 months. The aforementioned sociodemographic and substance use variables that differed between groups were covariates in analyses. A battery of 10 neurocognitive measures, two measures per each domain of learning, memory, motor, executive functioning, and processing speed. Global composite summary scores for overall neurocognitive performance were calculated by averaging M T-scores for each neurocognitive domain. Data transformations were used to address any violations of statistical assumptions.

To facilitate data reduction, neurocognitive task scores were standardized to T-scores using the M and SD of the CU-/HIV-group. An omnibus model of between-group comparisons on global neurocognitive task performance revealed no significant differences, F(3) = .16, p = .923. Subsequent Tukey’s post hoc test revealed no significant differences among the four groups. Results also revealed nonsignificant differences between groups in neurocognitive performance within each domain. However, the CU-/HIV- group performed significantly worse than the CU-/HIV+ group on the Executive Functioning domain, based on Tukey’s post hoc test.

We found no significant global neurocognitive differences among groups; however, there was some evidence for domain-specific neurocognitive differences in executive functioning. This contrasts somewhat with existing literature on HIV and cannabis-associated neurocognitive deficits. Several factors may have contributed to this, including our relatively healthy PWH sample. Future analyses will examine interactive effects of HIV severity and severity of CU on neurocognition. This analysis will better determine who, among PWH, are most at-risk for cannabis-associated neurocognitive effects and what factors may exacerbate them.

The objective of this study is to explore the impact on the mental health of caregivers of people with dementia during the period of mandatory preventive social isolation (ASPO) and to study which of these factors were predictors of caregiver overload.

During the first 3 months of the ASPO (June 2020 to september 2020). A sample of 112 caregivers (75.89% female; age 58.65 ± 14. 30) of patients with dementia from a Memory Center answered, remotely (online or telephone) a survey with the following questionnaires: the Zarit Caregiver Overload Scale (ZBI), Weekly hourly load dedicated to the care of patients with dementia), the use of time in unpaid activities through an activity diary, provided by Argentine National Institute of Statistics and Census (INDEC), the Caregiver Activities Survey (CAS) and the Anxiety, Depression and Stress Scale (DASS-21). These questionnaires evaluate the conditions and characteristics of caregiving tasks and their impact on the caregiver in the context of ASPO. Additionally, it was recorded whether the person with dementia, the caregiver, or persons living with them had had COVID-19.

Descriptively, a disparity in frequency was observed in the gender of caregivers of persons with dementia, i.e., caregiving is inequitably distributed between men (24.11%) and women (75.89%). This difference hinders direct comparison between men and women. A regularized L2 regression was performed for the identification of predictors of caregiver overload identifying the number of caregiving hours (β=0.090), DAS depression (β=0.085), DASS anxiety (β=0.099) DASS stress (β=0.164), fear of Covid (0.141) and lower patient cognitive performance according to MMSE (β=-0.41) and to lesser extent sex as the greatest contributors to patient overload. Additionally, a mediation analysis was performed in which the factors number of caregiving hours (CAS; r= 0.254,r= 0.292,r= 0.252,r= 0.252,r= -0.37), being a primary caregiver and fear of Covid-19 (r= 0.335,r= 0.432,r= 0.402,r= -0.496) were found to be mediators of the effect between anxiety, depression, stress (DASS) and overload (ZBI).

Caregivers of patients with dementia have suffered sequelae such as anxiety, stress, depression, and overload (caregivers’ burden) in the context of the COVID-19 virus spread and during mandatory preventive social isolation. Being a primary caregiver, dedicating more hours to caregiving, and fear of Covid-19 are factors that contribute significantly to caregiver burden and mediate between this burden and mood variables. Public policies to support caregivers and information about the disease could modify these variables and reduce caregiver burden.

Neurocognitive decline is prevalent in patients with metastatic cancers, attributed to various disease, treatment, and individual factors. Whether the presence of brain metastases (BrMets) contributes to neurocognitive decline is unclear. Aims of this study are to examine neurocognitive performance in BrMets patients and compare findings to patients with advanced metastatic cancer without BrMets. Here, we present baseline findings from an ongoing, prospective longitudinal study.

English-speaking adults with advanced metastatic cancers were recruited from the brain metastases and lung clinics at the Princess Margaret Cancer Centre. Participants completed standardized tests (WTAR, HVLT-R, BVMT-R, COWAT, Trailmaking test, WAIS-IV Digit Span) and questionnaires (FACT-Cog v3, EORTC-QLQ C30 and BN20, PROMIS Depression(8a) and Anxiety(6a)) prior to cranial radiotherapy for those who required it. Test scores were converted to z-scores based on published normative data and averaged to create a composite neurocognitive performance score and domain scores for memory, attention/working memory, processing speed and executive function. Neurocognitive impairment was defined according to International Cancer and Cognition Task Force criteria. Univariate and multivariate regressions were used to identify individual, disease and treatment variables that predict cognitive performance.

76 patients (mean (SD) age: 63.2 (11.7) years; 53% male) with BrMets were included. 61% experienced neurocognitive impairment overall; impairment rates varied across domains (38% memory, 39% executive functioning, 13% attention/working memory, 8% processing speed). BrMets quantity, volume, and location were not associated with neurocognitive performance. Better performance status (ECOG; ß[95%CI];-0.38[-0.70,-0.05], p=0.021), higher premorbid IQ (0.34[0.10,0.58], p=0.005) and greater cognitive concerns (0.02[-3.9e-04,0.04], p=0.051) were associated with better neurocognitive performance in univariate analyses. Only premorbid IQ (0.37[0.14,0.60], p=0.003) and cognitive concerns (0.02[0.0004, 0.03], p=0.05) remained significant in multivariate analysis. We also recruited 31 patients with metastatic non-small cell lung cancer (mNSCLC) with no known BrMets (age: 67.5 (8.3); 32% male) and compared them to the subgroup of BrMets patients in our sample with mNSCLC (N=32; age: 67.8 (11.7); 53% male). We found no differences in impairment rates (BrMets/non-BrMets: Cognitive Composite, 59%/55%; Memory, 31%/32%; Executive Functioning, 35%/29%; Attention/working memory, 16%/13%; Processing speed, 7%/6%; Wilcoxon rank-sum test, all p-value’s > 0.5). The presence or absence of BrMets did not predict neurocognitive performance. Among patients with mNSCLC, higher education (0.11[0.03,0.18], p=0.004) and premorbid IQ (0.36[0.12,0.61], p=0.003), fewer days since primary diagnosis (0.00290[-0.0052,-0.0005], p=0.015) fewer pack-years smoking history (0.01[0.02,-0.001], p=0.027) and greater cognitive concerns (0.02[7e-5,0.04], p=0.045) were associated with better neurocognitive performance in univariate analyses; only premorbid IQ (0.26[0.02,0.51], p=0.04) and cognitive concerns (0.02[0.01,0.04], p=0.02) remained significant in multivariate analysis.

Cognitive impairment is prevalent in patients with advanced metastatic cancers, particularly affecting memory and executive functioning. However, 39% of patients in our sample were not impaired in any domain. We found no associations between the presence of BrMets and neurocognitive function in patients with advanced cancers prior to cranial radiation. Premorbid IQ, a proxy for cognitive reserve, was associated with cognitive outcomes in our sample. Our longitudinal study will allow us to identify risk and resilience factors associated with neurocognitive changes in patients with metastatic cancers to better inform therapeutic interventions in this population.

Choice response time (RT) increases linearly with increasing information uncertainty, which can be represented externally or internally. Using a card-sorting task, we previously showed that Alzheimer’s disease (AD) dementia patients were more impaired relative to cognitively normal older adults (CN) under conditions that manipulated internally cued rather than externally driven uncertainty, but this study was limited by a between-subjects design that prevented us from directly comparing the two uncertainty conditions. The objective of this study was to assess internally cued and externally driven cued uncertainty representations in CN and mild cognitive impairment (MCI) patients.

Older participants (age > 60 years; N=49 CN, N=33 MCI patients) completed a card-sorting task that separately manipulated externally cued uncertainty (i.e., the number of sorting piles with equal probability of each stimulus type) or internally cued uncertainty (i.e., the probability of each stimulus type with fixed number of sorting piles) at three different uncertainty loads (low, medium, high). Exploratory analyses separated MCI patients by etiology into possible/probable cortical neurodegenerative process (i.e., AD, frontotemporal dementia; N=13) or nonneurodegenerative process (i.e., vascular, psychiatric, sleep, medication effect; N=20).

CN and MCI patients maintained a high level of accuracy on both tasks (M accuracy > .94 across conditions). MCI patients performed more slowly than CN on the externally and internally cued tasks, and both groups showed a significant positive association between uncertainty load and RT (p’s < .05). There was a group x load x uncertainty condition interaction (p = .05). For CNs, the slope of the linear association between load and RT was significantly steeper in the externally cued compared to internally cued condition. For MCI patients in contrast, RTs increased with load to a similar degree in both conditions. Exploratory analyses showed the MCI-neurodegenerative patients were significantly slower than MCI-nondegenerative and CN (p < .001). While the group x load x condition interaction was significant when comparing all three groups (p < .05), this was driven by the differences between CN and MCI patients described above; the MCI-neurodegenerative and non-neurodegenerative groups did not significantly differ in the strength of the RT-load association between the externally or internally cued conditions.

Overall, CN participants showed greater RT slowing with increasing load of externally driven than internally cued uncertainty. Though they were slower than CNs, MCI patients (even those with a possible/probable cortical neurodegenerative condition) were able to accurately perform an internally cued uncertainty task and did not show differential slowing compared to an externally driven task. This provides preliminary evidence that internal representations of probabilistic information are intact in patients with MCI due to a neurodegenerative condition, meaning they may not depend on cortical processes. Future work will increase the sample sizes of the MCI-neurodegenerative and non-degenerative groups.