Neurocognitive Test Performance Research Articles

Empirically derived symptom profiles in adults with attention-Deficit/hyperactivity disorder: An unsupervised machine learning approach

Background Attention-deficit/hyperactivity disorder (ADHD) is associated with various cognitive, behavioral, and mood symptoms that complicate diagnosis and treatment. The heterogeneity of these symptoms may also vary depending on certain sociodemographic factors. It is therefore important to establish more homogenous symptom profiles in patients with ADHD and determine their association with the patient’s sociodemographic makeup. The current study used unsupervised machine learning to identify symptom profiles across various cognitive, behavioral, and mood symptoms in adults with ADHD. It was then examined whether symptom profiles differed based on relevant sociodemographic factors. Methods Participants were 382 adult outpatients (62% female; 51% non-Hispanic White) referred for neuropsychological evaluation for ADHD. Results Employing Gaussian Mixture Modeling, we identified two distinct symptom profiles in adults with ADHD: “ADHD-Plus Symptom Profile” and “ADHD-Predominate Symptom Profile.” These profiles were primarily differentiated by internalizing psychopathology (Cohen’s d = 1.94-2.05), rather than by subjective behavioral and cognitive symptoms of ADHD or neurocognitive test performance. In a subset of 126 adults without ADHD who were referred for the same evaluation, the unsupervised machine learning algorithm only identified one symptom profile. Group comparison analyses indicated that female patients were most likely to present with an ADHD-Plus Symptom Profile (χ2 = 5.43, p < .001). Conclusion The machine learning technique used in this study appears to be an effective way to elucidate symptom profiles emerging from comprehensive ADHD evaluations. These findings further underscore the importance of considering internalizing symptoms and patients’ sex when contextualizing adult ADHD diagnosis and treatment.

Disparities in DMT treatment: Demographic and neurocognitive differences between MS patients currently treated versus not treated with disease-modifying therapies

BackgroundCurrent treatment guidelines recommend consideration of disease-modifying therapy (DMT) for all multiple sclerosis (MS) patients, but barriers to access have begun to be identified. In particular, prior studies have found that people with higher education have better access to DMTs, perhaps explained by the association of higher education with higher income. And while the majority of people with MS are women, being male is also associated with higher income. These factors argue for the need to better understand whether there are differences in DMT uptake based on sex and education. Finally, in addition to well-documented benefits of DMTs for slowing disease progression, there is growing evidence to suggest benefits of DMTs for cognitive functioning. ObjectiveDetermine whether rates of DMT treatment differ based on education and sex. Secondarily, we investigate whether neurocognitive test performance differs in treated versus not treated groups. MethodsIn cross-sectional data, mixed effects linear regression evaluated differences in education and sex of those treated versus not treated with DMTs. Models included the following predictors: age, disease duration, MS subtype, sex/education, disability, atrophy, and T2 lesion volume. Propensity score weights were extracted to obtain unbiased estimates of the relationship between DMT status and each outcome of interest. The same models evaluated performance differences between groups on an iPad-based processing speed test (PST) and manual dexterity test (MDT). ResultsControlling for covariates, individuals with less education (OR=1.09, 95 % CI=[1.03, 1.14], p = 0.003) and women (OR=0.80, 95 % CI=[0.72, 0.90], p < 0.001) were less likely to be currently treated with DMTs. Small effect size association was shown for DMT treatment with better performance on PST (beta=0.09, CI=[0.06, 0.13], p < 0.001) and MDT (beta=0.05, CI=[0.01,0.08], p = 0.011). ConclusionsWomen and people with lower education had a lower likelihood of being currently treated with DMTs. After controlling for all relevant variables, an independent (small) association of DMT treatment to better performance on tests of processing speed and fine motor dexterity was found. Reasons for disparities remain to be investigated in future work, and may include employment status, health insurance coverage, or sex differences in risk tolerance.

Neurocognitive Concussion Test Performance for Student Athletes on the Autism Spectrum.

To examine baseline neurocognitive functioning among adolescent athletes on the autism spectrum based on self-reported level of academic performance. Participants in this cross-sectional, observational study were 6,441 adolescent athletes with a self-reported diagnosis of autism who completed pre-season neurocognitive testing using Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT); 4,742 reported a co-occurring learning disorder (LD), and 6,612 individuals without autism or LD were included as a control group. The majority (57%) self-reported Average Academic Performance, 39% Above Average, and 4% Below Average performance. Athletes with self-reported autism (with or without LD; 12.2%) were 2.74x (95% CI: 2.17-2.82) more likely to fall below cutoffs for ImPACT Embedded Invalidity Indicators (EVIs), with a significant interaction between self-reported Diagnosis and Academic Performance; individuals with co-occurring autism and LD who reported Below Average Academic Performance had the greatest likelihood of scoring below cutoffs (22%), followed by ASD without LD (14.8%) and Controls (14.6%) with Below Average Academic Performance. Analyses of variance (ANOVAs) revealed main effects of Diagnosis and Academic Performance on neurocognitive performance, with interactions on all ImPACT Composite Scores except Processing Speed. Athletes with self-reported ASD are more likely to fall below ImPACT EVIs and score worse on ImPACT, with greater likelihood/worse performance related to level of academic functioning. Academic performance should be considered when interpreting neurocognitive testing data, to best index neuropsychological functioning associated with concussion in this population. The current findings highlight the importance of individual participant baseline neuropsychological testing for individuals on the autism spectrum.

Neurological involvement among non-hospitalized adolescents and young adults 6 months after acute COVID-19.

The post-COVID-19 condition (PCC) is characterized by debilitating persistent symptoms, including symptoms suggesting neurological aberrations such as concentration difficulties, impaired memory, pain, and sleep disturbances. The underlying mechanisms remain elusive. This study aimed to investigate brain injury biomarkers, neurocognitive test performance, and self-reported neurological and neuropsychological symptoms in young people with PCC. A total of 404 non-hospitalized adolescents and young adults aged 12-25 years who tested positive for SARS-CoV-2, along with 105 matched SARS-CoV-2 negative individuals, were prospectively enrolled and followed-up for 6 months (Clinical Trials ID: NCT04686734). All participants underwent comprehensive assessment encompassing clinical examinations, questionnaires, neurocognitive testing and blood sampling. Serum samples were immunoassayed for the brain injury biomarkers neurofilament light chain (Nfl) and glial fibrillary acidic protein (GFAp). At 6 months, cross-sectional analyses of serum Nfl/GFAp, neurocognitive test results and symptom scores were performed across groups based on adherence to PCC criteria as well as initial SARS-CoV-2 test results. Also, associations between Nfl/GFAp, neurocognitive test results, and symptom scores were explored. A total of 381 SARS-CoV-2 positive and 85 SARS-CoV-2 negative were included in the final analysis at 6 months, of whom 48% and 47%, respectively, adhered to the PCC criteria. Serum levels of Nfl and GFAp were almost equal across groups and did not differ from reference values in healthy populations. Also, neurocognitive test results were not different across groups, whereas symptom scores were significantly higher in patients fulfilling PCC criteria (independent of initial SARS-CoV-2 status). No significant associations between Nfl/GFAp, neurocognitive test results, and symptom scores were found. Normal brain injury biomarkers and neurocognitive performance 6 months after mild COVID-19 implies that the persistent symptoms associated with PCC are not concurrent with ongoing central nervous system damage or permanent disruption of cognitive functions. This finding contradicts the notion of neuroinflammation as a likely explanation for the persistent symptoms.

A comparison of two obesity-related hypoventilation disorders: Impact on sleep, quality of life and neurocognitive outcomes and the effects of positive airway pressuretherapy.

Symptom impact and neurocognitive function have not been previously compared between patients with obesity-associated hypoventilation disorders (obesity hypoventilation syndrome [OHS]) and hypoventilation in the setting of obesity and obstructive airways disease (OHAD). The aim of this study is to compare baseline sleep-related symptoms, health-related quality of life, and neurocognitive function between OHS and OHAD and the impact of PAP therapy on these outcomes. Epworth Sleepiness Scale (ESS), Pittsburgh Sleepiness Quality Index (PSQI), SF36, and various neurocognitive tests, in addition to anthropometric, polysomnography, lung function, and blood gas data from participants with OHS and participants with OHAD, were included in the analysis. These data were originally collected in their respective randomized clinical trials, comparing the efficacy of different PAP modes (bilevel PAP vs. CPAP) in resolving hypercapnia. Between groups (OHS vs OHAD), pre- and post-treatment (with 3 months of positive airway pressure) comparisons were made using linear mixed modeling. 45 OHS participants (mean age 51 years old, 33% female, BMI 52kg/m2, FER 0.81, PaCO2 54 mmHg, AHI 87/h) and 32 OHAD participants (mean age 61years old, 31% female, BMI 43kg/m2, FER 0.60, PaCO2 54 mmHg, AHI 59/h) were included in the analysis. Both OHS and OHAD had similar baseline ESS (14(5.6) vs. 12(5.4)), Global PSQI (10(3.2) vs. 11(4.8)), SF36 and neurocognitive test performances (other than OHAD had lower digit symbol substitution test performance). Treatment with PAP therapy resulted in similar ESS, Global PSQI, and SF36 improvements in both groups. Neurocognitive performance did not significantly improve after PAP therapy in either group. The symptom impact between two separate hypoventilation disorders (OHS and OHAD), in terms of sleepiness, sleep quality, quality of life, and cognitive function, were similar. OHS and OHAD had similar treatment responses in these parameters after 3 months of PAP therapy.Nocturnal ventilatory support in OHS.

ASSOCIATIONS BETWEEN CLINICAL FUNCTIONING AND AD BIOMARKERS AMONG HISPANIC AND WHITE NON-HISPANIC OLDER ADULTS

Abstract Objectives Hispanics are 1.5x more likely to develop Alzheimer’s disease (AD) when compared to White non-Hispanics (WNHs). There is also evidence to support that cognitive performance disproportionately reflects neuropathology among Hispanics and that functional decline is concurrent with the accumulation of AD biomarkers. The current study aimed to examine relationships between AD biomarkers and a functional measure among Hispanic and WNH older adults. It was hypothesized that the functional measure would be strongly related to AD biomarkers among Hispanics. Methods The modified clinical dementia rating scale (mCDR) was administered in the participants primary language (English or Spanish) to WNH (n=203) and Hispanic (n=258) older adults who were cognitive normal or diagnosed with Mild Cognitive Impairment (MCI) or dementia. Invariance SEM models were used to compare the pattern of relationships between the mCDR and neurocognitive test performance, MRI volumes, and amyloid load adjusting for age, education, ApoE4 status, and intracranial volume. Results Model fit was good and not significantly worsened by imposing strict structural invariance. Nested model comparisons indicated that regression weights and correlations among measures differed by group, suggestive of moderation by Hispanic status. Among Hispanic participants, sex (♌=-0.17, p&amp;lt;.05) and Amyloid load (♌=0.25, p&amp;lt;.001) significantly predicted mCDR scores. MRI volumes significantly predicted MCDR scores among both Hispanic (♌=-0.51, p&amp;lt;.001) and WNH participants (♌= -0.42, p&amp;lt;.001). Conclusions Functional measures like the mCDR may better correlate with Amyloid load among Hispanic older adults than among WNHs, while the correlation with MRI volumes may be comparable in both groups.

Cross-validating the Clinical Assessment of Attention Deficit–Adult symptom validity scales for assessment of attention deficit/hyperactivity disorder in adults

ABSTRACT Introduction The Clinical Assessment of Attention Deficit-Adult is among the few questionnaires that offer validity indicators (i.e., Negative Impression [NI], Infrequency [IF], and Positive Impression [PI]) for classifying underreporting and overreporting of attention-deficit/hyperactivity disorder (ADHD) symptoms. This is the first study to cross-validate the NI, IF, and PI scales in a sample of adults with suspected or known ADHD. Method Univariate and multivariate analyses were conducted to examine the independent and combined value of the NI, IF, and PI scores in predicting invalid symptom reporting and neurocognitive performance in a sample of 543 adults undergoing ADHD evaluation. Results The NI scale demonstrated better classification accuracy than the IF scale in discriminating patients with and without valid scores on measures of overreporting. Only NI scores significantly predicted validity status when used in combination with IF scores. Optimal cut-scores for the NI (≤51; 30% sensitivity / 90% specificity) and IF (≥4; 18% sensitivity / 90% specificity) scales were consistent with those reported in the original manual; however, these indicators poorly discriminated patients with invalid and valid neurocognitive performance. The PI scale demonstrated acceptable classification accuracy in discriminating patients with invalid and valid scores on measures of underreporting, albeit with an optimal cut-score (≥27; 36% sensitivity / 90% specificity) lower than that described in the manual. Conclusion Findings provide preliminary evidence of construct validity for these scales as embedded validity indicators of symptom overreporting and underreporting. However, these scales should not be used to guide clinical judgment regarding the validity of neurocognitive test performance.

52 Internalizing Psychopathology is Highly Related to Subjective Cognitive Impairment and the Discrepancy Between Objective and Subjective Cognitive Impairment: A Preliminary Cross-Sectional Study.

Objective:Eliciting perceived cognitive complaints is a routine part of a clinical neuropsychological evaluation, presumably because complaints are informative of underlying pathology. However, there is no strong empirical support that subjective cognitive impairment (SCI) is actually related to objective cognitive impairment as measured by neurocognitive tests. Instead, internalizing psychopathology is thought to predominately influence the endorsement of SCI. Specifically, individuals with greater symptoms of depression and anxiety, when accounting for comorbidities, have a higher disposition to overestimate their degree of cognitive impairment as compared to objective testing. Yet, there are few existing studies that have determined which factors influence both SCI and the discrepancy between subjective and objective cognitive impairment in general outpatient populations. The current study examined the relationship between subjective and objective cognitive impairment in a clinically diverse sample of outpatients. We additionally explored the associations between SCI and relevant intrapersonal factors including internalizing psychopathology, number of medical comorbidities, and demographics. Finally, we quantified the degree of discrepancy between subjective and objective impairment and examined this discrepancy in relation to the intrapersonal factors.Participants and Methods:The sample comprised 142 adult women and men (age range 18–79 years) seen in an outpatient neuropsychology clinic for a diverse range of referral questions. Scores on the cognition portion of the WHO Disability Assessment Schedule (WHODAS 2.0) were used to index SCI. A composite score from 14 measures across various domains of cognitive functioning served as an objective measure of cognitive functioning. Internalizing psychopathology was measured via a standardized composite of scores from screening measures of anxiety and depression. Medical comorbidities were indexed by the number of different ICD diagnostic categories documented in patients' medical records. Demographics included age, sex, race, and years of formal education. Objective-subjective discrepancy scores were computed by saving standardized residuals from a linear regression of neurocognitive test performance on the WHODAS 2.0 scores.Results:A hierarchical linear regression revealed that objective cognitive impairment was not significantly related to SCI (p &gt; .05), explaining less than 2% of the variance in SCI ratings. Likewise, participants' demographics (age, sex, education, race) and number of comorbidities were not significantly related to their SCI ratings, explaining about 6% of the variance. However, participants' level of internalizing psychopathology was significantly associated with SCI (F[10, 131] = 4.99, p &lt; .001), and explained approximately 20% of the variance in SCI ratings. Similarly, the degree of discrepancy between subjective and objective cognitive impairment was primarily influenced by internalizing psychopathology (F[9, 132] = 5.20, p &lt; .001, R2 = 21%) and largely unrelated to demographics and number of comorbidities, which explained about 6% of the variance.Conclusions:These findings are consistent with prior research suggesting that SCI may be more indicative of the extent of internalizing psychopathology rather than actual cognitive impairment. Taken together, these results illuminate potential treatment and diagnostic implications associated with assessing perceived cognitive complaints during a neuropsychological evaluation.

P065 A Comparison of Two Obesity Related Hypoventilation Disorders – Impact on Sleep, Quality of Life and Neurocognitive Outcomes and the Effects of PAP Therapy

Abstract Introduction Symptom burden and neurocognitive function have not been previous compared between patients with obesity-associated hypoventilation disorders (obesity hypoventilation syndrome, OHS), and hypoventilation in the setting of obesity and obstructive airways disease (OHAD). The aim of this study is to compare baseline sleep-related symptoms, health-related quality of life and neurocognitive function between OHS and OHAD and the impact of PAP therapy on these outcomes. Methods ESS, PSQI, SF36, and various neurocognitive tests, in addition to anthropometric, polysomnography, lung function and blood gas data from 45 patients with OHS and 32 patients with OHAD, were included in the analysis. Between groups (OHS vs OHAD), pre- and post-treatment (with 3 months of positive airway pressure) comparisons were made using linear mixed modelling. Results Both OHS and OHAD had similar baseline ESS (14(5.6) vs. 12(5.4)), Global PSQI (10(3.2) vs 11(4.8)), SF36 and neurocognitive test performances (other than OHAD had lower digit symbol substitution test performance). Treatment with PAP therapy resulted in similar improvements in ESS, Global PSQI, and SF36 in both groups. Neurocognitive performance did not significantly improve after PAP therapy in either group. Discussion The symptom burden between two separate hypoventilation disorders (OHS and OHAD), in terms of sleepiness, sleep quality, quality of life and cognitive function, were similar. OHS and OHAD had similar treatment responses in these parameters after 3 months of PAP therapy.

The Effect of Adverse Childhood Experiences on ADHD Symptom Reporting, Psychological Symptoms, and Cognitive Performance Among Adult Neuropsychological Referrals

Objective: Adverse childhood experiences (ACEs) are early life experiences that influence mental health outcomes, though there are mixed findings reported in relation to attention deficit hyperactivity disorder (ADHD) symptoms. The current study compared adults who experienced ACEs on measures of ADHD symptom reporting, psychological symptoms, and neurocognitive test performance. Method: The sample (n = 115) had mean age of 28.42 (SD = 6.46); educational attainment of 16.47 years (SD = 1.99); and was 35% male/65% female and racially/ethnically diverse. Participants completed measures of ACEs, ADHD symptoms, psychopathology, and perceived stress, as well as neuropsychological tests. Results: The high ACEs group endorsed higher levels of childhood/adulthood inattentive, impulsive, and hyperactive symptoms, and overall childhood symptoms when compared to the low ACEs group. Conclusions: This study provides a more comprehensive understanding of the association between ACEs and cognitive/mental health outcomes. Greater ACEs resulted in higher ADHD symptom reporting but not significantly greater psychological symptoms or worse neurocognitive performance.

High School GPA But Not Neurocognitive Test Performance Differs By Concussion History

High School GPA But Not Neurocognitive Test Performance Differs By Concussion History

LMAP-20 EVIDENCE-BASED MULTIVARIATE NORMAL TISSUE COMPLICATION PROBABILITY (NTCP) STUDY OF DOMAIN-SPECIFIC COGNITIVE DECLINE AFTER PARTIAL BRAIN RT

Abstract Beyond the hippocampus, there are no evidence-based dose constraints for eloquent structures which subserve memory and attention/processing speed. We performed a multivariate normal tissue complication probability analysis of post-RT neurocognitive decline, examining dosimetric predictors of eloquent brain regions in a prospective longitudinal clinical trial. 78 patients with primary brain tumors receiving fractionated RT completed a comprehensive neurocognitive evaluation and high-resolution volumetric and diffusion MRI at baseline and 6 months post-RT. Image processing using validated automated segmentation parcellated individual white matter (WM) tracts, cortical regions, and hippocampi. Neurocognitive test performance was scored using reliable change indices adjusted for practice effects: negative scores indicate decline. Univariate logistic regression and multivariate model building were performed. On univariate analysis mean and max dose to multiple regions of the corpus callosum (CC) correlated with attention/processing speed decline including Dmax to anterior CC (p=0.011) and central CC (p=0.010), and Dmax/Dmean to mid-anterior CC (p=0.006 and 0.010). Dmean to left fornix was associated with memory decline (p=0.023), as were increasing age and chemotherapy. On multivariate analysis for attention, automated bootstrapped logistic regression showed the most frequently selected variable was Dmean to mid-anterior CC. Performance at nested cross-validation by AUC was 0.80 (0.75-0.84); LASSO model performance by AUC was 0.76 (0.72-0.81) with Dmean to the mid-anterior CC being the most frequent variable. The top five most important variables in Random Forest were Dmean to mid-anterior CC, all WM, combined CC and Dmax to CC and posterior CC. Model performance by AUC was 0.66 (0.60-0.71). We present the first, to our knowledge, multivariate NTCP model for decline in attention/processing speed, and dosimetric predictors of memory decline beyond the hippocampus. Dose to several eloquent ROIs significantly correlated with post-RT impairment. These data can guide future cognitive-sparing strategies for brain RT.

Hearing, β-Amyloid Deposition and Cognitive Test Performance in Black and White Older Adults: The ARIC-PET Study.

Hearing loss is a risk factor for dementia; whether the association is causal or due to a shared pathology is unknown. We estimated the association of brain β-amyloid with hearing, hypothesizing no association. As a positive control, we quantified the association of hearing loss with neurocognitive test performance. Cross-sectional analysis of Atherosclerosis Risk in Communities-Positron Emission Tomography study data. Amyloid was measured using global cortical and temporal lobe standardized uptake value ratios (SUVRs) calculated from florbetapir-positron emission tomography scans. Composite global and domain-specific cognitive scores were created from 10 neurocognitive tests. Hearing was measured using an average of better-ear air conduction thresholds (0.5-4 kHz). Multivariable-adjusted linear regression estimated mean differences in hearing by amyloid and mean differences in cognitive scores by hearing, stratified by race. In 252 dementia-free adults (72-92 years, 37% Black race, and 61% female participants), cortical or temporal lobe SUVR was not associated with hearing (models adjusted for age, sex, education, and APOE ε4). Each 10 dB HL increase in hearing loss was associated with a 0.134 standard deviation lower mean global cognitive factor score (95% CI: -0.248, -0.019), after adjustment for demographic and cardiovascular factors. Observed hearing-cognition associations were stronger in Black versus White participants. Amyloid is not associated with hearing, suggesting that pathways linking hearing and cognition are independent of this pathognomonic Alzheimer's-related brain change. This is the first study to show that the impact of hearing loss on cognition may be stronger in Black versus White adults.

Attenuated post-movement beta rebound reflects psychomotor alterations in major depressive disorder during a simple visuomotor task: a MEG study

BackgroundPsychomotor alterations are a common symptom in patients with major depressive disorder (MDD). The primary motor cortex (M1) plays a vital role in the mechanism of psychomotor alterations. Post-movement beta rebound (PMBR) in the sensorimotor cortex is abnormal in patients with motor abnormalities. However, the changes in M1 beta rebound in patients with MDD remain unclear. This study aimed to primarily explore the relationship between psychomotor alterations and PMBR in MDD.MethodsOne hundred thirty-two subjects were enrolled in the study, comprising 65 healthy controls (HCs) and 67 MDD patients. All participants performed a simple right-hand visuomotor task during MEG scanning. PMBR was measured in the left M1 at the source reconstruction level with the time–frequency analysis method. Retardation factor scores and neurocognitive test performance, including the Digit Symbol Substitution Test (DSST), the Making Test Part A (TMT-A), and the Verbal Fluency Test (VFT), were used to measure psychomotor functions. Pearson correlation analyses were used to assess relationships between PMBR and psychomotor alterations in MDD.ResultsThe MDD group showed worse neurocognitive performance than the HC group in all three neurocognitive tests. The PMBR was diminished in patients with MDD compared to HCs. In a group of MDD patients, the reduced PMBR was negatively correlated with retardation factor scores. Further, there was a positive correlation between the PMBR and DSST scores. PMBR is negatively associated with the TMT-A scores.ConclusionOur findings suggested that the attenuated PMBR in M1 could illustrate the psychomotor disturbance in MDD, possibly contributing to clinical psychomotor symptoms and deficits of cognitive functions.

Decreased serum allopregnanolone and progesterone levels in male patients with bipolar disorder and their effects on cognitive functions

The progression of bipolar disorder (BD) is characterized by recurrent episodes of depression, mania, and hypomania, thus affecting the daily functionality of individuals. Previous studies have shown that a large proportion of patients diagnosed with BD who are in clinical remission experience significant functional disorders. The present study aimed to investigate the relationships between cognitive impairment and serum progesterone, allopregnanolone and BDNF levels in male bipolar disorder patients who are in the euthymic period. Our study included 41 euthymic male patients with bipolar disorder and 40 age, sex, body mass index (BMI) and smoking-matched male healthy control subjects. Neuropsychiatric tests such as the Stroop Test TBAG Form, Auditory Verbal Digit Span Test- Form B (VADS-B) and Cancellation Test were administered to all participants, and 5-7ml of peripheral venous blood sample was taken from all participants. Serum allopregnanolone, progesterone and BDNF levels were also measured in all participants. Serum allopregnanolone and progesterone levels were found to be lower in bipolar patients, and it was observed that the serum level of allopregnanolone decreased as the disease duration increased. The serum BDNF levels were similar between groups. The cognitive functions assessed using the Stroop, VADS-B and cancellation tests were found to be better in healthy subjects. The neurocognitive test performances of all participants were strongly positively correlated with allopregnanolone levels. The present study supports the hypothesis that allopregnanolone acts as an endogenous mood stabilizer.

Cognitive Function in People With Familial Risk of Depression

Cognitive impairment in depression is poorly understood. Family history of depression is a potentially useful risk marker for cognitive impairment, facilitating early identification and targeted intervention in those at highest risk, even if they do not themselves have depression. Several research cohorts have emerged recently that enable findings to be compared according to varying depths of family history phenotyping, in some cases also with genetic data, across the life span. To investigate associations between familial risk of depression and cognitive performance in 4 independent cohorts with varied depth of assessment, using both family history and genetic risk measures. This study used data from the Three Generations at High and Low Risk of Depression Followed Longitudinally (TGS) family study (data collected from 1982 to 2015) and 3 large population cohorts, including the Adolescent Brain Cognitive Development (ABCD) study (data collected from 2016 to 2021), National Longitudinal Study of Adolescent to Adult Health (Add Health; data collected from 1994 to 2018), and UK Biobank (data collected from 2006 to 2022). Children and adults with or without familial risk of depression were included. Cross-sectional analyses were conducted from March to June 2022. Family history (across 1 or 2 prior generations) and polygenic risk of depression. Neurocognitive tests at follow-up. Regression models were adjusted for confounders and corrected for multiple comparisons. A total of 57 308 participants were studied, including 87 from TGS (42 [48%] female; mean [SD] age, 19.7 [6.6] years), 10 258 from ABCD (4899 [48%] female; mean [SD] age, 12.0 [0.7] years), 1064 from Add Health (584 [49%] female; mean [SD] age, 37.8 [1.9] years), and 45 899 from UK Biobank (23 605 [51%] female; mean [SD] age, 64.0 [7.7] years). In the younger cohorts (TGS, ABCD, and Add Health), family history of depression was primarily associated with lower performance in the memory domain, and there were indications that this may be partly associated with educational and socioeconomic factors. In the older UK Biobank cohort, there were associations with processing speed, attention, and executive function, with little evidence of education or socioeconomic influences. These associations were evident even in participants who had never been depressed themselves. Effect sizes between familial risk of depression and neurocognitive test performance were largest in TGS; the largest standardized mean differences in primary analyses were -0.55 (95% CI, -1.49 to 0.38) in TGS, -0.09 (95% CI, -0.15 to -0.03) in ABCD, -0.16 (95% CI, -0.31 to -0.01) in Add Health, and -0.10 (95% CI, -0.13 to -0.06) in UK Biobank. Results were generally similar in the polygenic risk score analyses. In UK Biobank, several tasks showed statistically significant associations in the polygenic risk score analysis that were not evident in the family history models. In this study, whether assessed by family history or genetic data, depression in prior generations was associated with lower cognitive performance in offspring. There are opportunities to generate hypotheses about how this arises through genetic and environmental determinants, moderators of brain development and brain aging, and potentially modifiable social and lifestyle factors across the life span.

Neurocognitive test performance following cancer among middle-aged and older adults in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and the SOL-Investigation of Neurocognitive Aging Ancillary Study.

Cancer patients and survivors often experience acute cognitive impairments; however, the long-term cognitive impact remains unclear particularly among Hispanics/Latinos. We examined the association between cancer history and neurocognitive test performance among middle-aged and older Hispanic/Latinos. Participants included 9639 Hispanic/Latino adults from the community-based and prospective Hispanic Community Health Study/Study of Latinos. At baseline (2008-2011; V1), participants self-reported their cancer history. At V1 and again at a 7-year follow-up (2015-2018; V2), trained technicians administered neurocognitive tests including the Brief-Spanish English Verbal Learning Test (B-SEVLT), Word Fluency Test (WF), and Digit Symbol Substitution Test (DSS). We used survey linear regression to estimate the overall, sex-specific, and cancer site-specific [i.e., cervix, breast, uterus, and prostate] adjusted associations between cancer history and neurocognitive test performance at V1 and changes from V1 to V2. At V1, a history of cancer (6.4%) versus no history of cancer (93.6%) was associated with higher WF scores (β = 0.14, SE = 0.06; p = 0.03) and global cognition (β = 0.09, SE = 0.04; p = 0.04). Among women, a history of cervical cancer predicted decreases in SEVLT-Recall scores (β = -0.31, SE = 0.13; p = 0.02) from V1 to V2, and among men, a history of prostate cancer was associated with higher V1 WF scores (β = 0.29, SE = 0.12; p = 0.02) and predicted increases in SEVLT-Sum (β = 0.46, SE = 0.22; p = 0.04) from V1 to V2. Among women, a history of cervical cancer was associated with 7-year memory decline, which may reflect the impacts of systemic cancer therapies. Among men, however, a history of prostate cancer was associated with improvements in cognitive performance, perhaps due in part to engaging in health promoting behaviors following cancer.

First-Line Immunotherapy with Check-Point Inhibitors: Prospective Assessment of Cognitive Function.

Approximately 40% of patients with cancer are eligible for check-point inhibitor (CPI) therapy. Little research has examined the potential cognitive impact of CPIs. First-line CPI therapy offers a unique research opportunity without chemotherapy-related confounders. The purpose of this prospective, observational pilot was to (1) demonstrate the feasibility of prospective recruitment, retention, and neurocognitive assessment for older adults receiving first-line CPI(s) and (2) provide preliminary evidence of changes in cognitive function associated with CPI(s). Patients receiving first-line CPI(s) (CPI Group) were assessed at baseline (n = 20) and 6 months (n = 13) for self-report of cognitive function and neurocognitive test performance. Results were compared to age-matched controls without cognitive impairment assessed annually by the Alzheimer's Disease Research Center (ADRC). Plasma biomarkers were measured at baseline and 6 months for the CPI Group. Estimated differences for CPI Group scores prior to initiating CPIs (baseline) trended to lower performance on the Montreal Cognitive Assessment-Blind (MOCA-Blind) test compared to the ADRC controls (p = 0.066). Controlling for age, the CPI Group's 6-months MOCA-Blind performance was lower than the ADRC control group's 12-months performance (p = 0.011). No significant differences in biomarkers were detected between baseline and 6 months, although significant correlations were noted for biomarker change and cognitive performance at 6 months. IFNγ, IL-1β, IL-2, FGF2, and VEGF were inversely associated with Craft Story Recall performance (p < 0.05), e.g., higher levels correlated with poorer memory performance. Higher IGF-1 and VEGF correlated with better letter-number sequencing and digit-span backwards performance, respectively. Unexpected inverse correlation was noted between IL-1α and Oral Trail-Making Test B completion time. CPI(s) may have a negative impact on some neurocognitive domains and warrant further investigation. A multi-site study design may be crucial to fully powering prospective investigation of the cognitive impact of CPIs. Establishment of a multi-site observational registry from collaborating cancer centers and ADRCs is recommended.

Association between reproductive factors in women and risk of brain ageing and dementia

AbstractBackgroundWomen have a higher prevalence of dementia than men. We determined the association between female reproductive factors and risk of cognitive outcomes, including incident dementia, in a community‐based sample of cognitively healthy individuals.MethodLifetime reproductive factors including age of menarche, age of menopause, reproductive lifespan (age of menopause minus age of menarche), number of live births, post‐menopausal hormone replacement therapy use, and serum estradiol and estrone concentrations were measured in 796 dementia‐free women [mean age 68.4 (SD 5.7) yr] from the Framingham Heart Study Offspring cohort at examination cycle seven (1998‐2001). We related reproductive factors to subsequent risk of incident dementia. Structural MRI brain measures and neurocognitive test performance were included as secondary outcomes.ResultDuring a median 10 [Q1‐Q3, 8.04‐10.0] year follow‐up, 138 participants developed dementia. On Cox proportional‐hazards analysis adjusting for age and education, a longer reproductive lifespan was associated with a reduced risk of incident dementia (HR 0.94, 95% CI 0.91‐0.98, p = 0.004) while earlier age of menopause of ≤49 vs 50‐51 years was associated with an increased dementia risk (HR 2.56, 95% CI 1.12‐5.88, p = 0.027). Earlier menopause (≤49 versus 50‐51 years) was cross‐sectionally associated with lower hippocampal volume (β±SE, ‐0.123±0.057, p = 0.03). Compared to no live births, 1‐2 live births (5.85±2.03, p = 0.004) and ≥3 live births (5.17±2.06, p = 0.01) were associated with greater total cerebral brain volume. Use of post‐menopausal HRT (0.15±0.055, p = 0.007) and elevated serum estradiol (0.058±0.027, p = 0.03) and estrone concentrations (0.078±0.029, p = 0.006) were cross‐sectionally associated with improved abstract reasoning (Similarities test). Compared to no live births, 1‐2 live births (0.20±0.08, p = 0.018) and ≥3 live births (0.25±0.08, p = 0.003) were also associated with superior visuospatial performance.ConclusionGreater exposure to estrogen throughout a woman’s reproductive life was associated with a lower risk of incident dementia and cross‐sectionally associated with larger brain volumes and enhanced cognitive performance. Our results suggest positive cognitive benefits of greater lifetime estrogen exposure and highlight the potential role of estrogen exposure in modifying the risk of dementia.

Accuracy of immediate self-assessment of neurocognitive test performance: Associations with psychiatric diagnosis and longitudinal psychotic symptoms

Participants with schizophrenia (SCZ) and bipolar disorder (BD) have challenges in self-evaluation of their cognitive and functional abilities, referred to as introspective accuracy (IA). Although psychotic symptoms are commonly found to be uncorrelated with cognitive performance, many models of the development of delusions focus on failures in self-assessment and responses biases during momentary monitoring. We performed a single 4-test cognitive assessment on 240 participants (schizophrenia n = 126; bipolar disorder n = 114) and asked them to make a judgment about their performance immediately after completion of each task. We related performance and these judgments to results of Ecological Momentary Assessments (EMA) of the momentary occurrence of psychotic symptoms (Voices, paranoid ideas, other delusions) collected over up to 90 surveys over a 30 days prior to the single cognitive assessment. We examined test performance and the accuracy of self-assessment at that assessment, looking at diagnostic differences in performance and mis-estimation of performance. Participants with bipolar disorder had better cognitive performance, but there were no differences in mis-estimation. Analyses of the correlation between cognitive performance and self-assessment were all significant and better cognitive performance predicted reduced errors in self-assessment. Examination of the 30-day course of psychotic symptoms and IA could only be performed in participants with schizophrenia, revealing correlations between more common occurrences of all three psychotic symptoms and increased absolute values for IA errors. These data are consistent with theories of cognitive response biases and the formation of delusions.