Neurocognitive Test Battery Research Articles

Cognitive Function in Individuals with Chronic Hypoparathyroidism - A Prospective Observational Study.

"Brain fog" is a frequently reported, distressing experience among individuals with chronic hypoparathyroidism, characterized by reduced concentration and reduced ability to perform day-to-day tasks. However, evidence linking chronic hypoparathyroidism to cognitive impairment is limited and inconsistent. This study aimed to explore cognitive function in these patients using a validated neurocognitive test battery, compare results with a matched healthy control group, and analyze the frequency of cognitive impairment based on normative data. The participants' cognitive performance was tested using a cognitive test battery, including the Trail Making Test A/B, the Color-Word Interference Test, and the California Verbal Learning Test. These tests were used to evaluate the cognitive domains of "attention and processing speed," "verbal learning and memory, " and "executive function." In total, 30 individuals with hypoparathyroidism and 30 healthy controls were included. 24 patients were women (80.0%), with a median age of 44.5±13.1 and a median disease duration of 8.7 years (±5.3). Individuals with chronic hypoparathyroidism showed poorer cognitive performance in "attention and processing speed" (F(1,57) = 8.65, p = 0.005*, η² = 0.13) compared to healthy controls. A significantly higher percentage of patients had cognitive deficits in both "attention and processing speed" (56.7% vs. 3.3%) and "executive function" (60.0% vs. 16.7%). This study provides evidence that cognitive dysfunction, particularly in "attention and processing speed" is common in chronic hypoparathyroidism. Recognizing cognitive impairment in these patients is crucial, especially when discussing workability. Neuropsychological training as an adjunct therapy strategy may be beneficial in managing these cognitive deficits.

Abstract 4126628: Worse Cardiac Structure and Function is Associated with Decline in Multiple Domains of Cognitive Function: the Atherosclerosis Risk in Communities (ARIC) Study

Background: Cognitive impairment is cross-sectionally associated with worse cardiac structure/function. However, limited data exist regarding cardiac structure/function and longitudinal changes in cognitive function. Objective: Determine the association of cardiac structure and function with longitudinal changes in cognitive performance in late life. Methods: Among HF- and dementia-free participants in the community-based ARIC study who attended the 5th study visit (V5; 2011-2013), underwent protocol echocardiography, and completed a neurocognitive test battery at both V5 and study Visit 6 (V6; 2015-17), we assessed associations of cardiac structure and function measures with changes in both domain-specific and global cognitive scores between V5 and V6 using multivariable linear regression. Models were initially adjusted for demographics and education level, with additional models further adjusting for cardiovascular risk factors and disease at both V5 and V6. The neuropsychological test battery consisted of 10 neuropsychological tests that covered 3 domains of cognitive function: memory, executive functioning, and language. Factor scores were constructed for each cognitive domain, and their average represented a global composite score. Results: Among 2,988 included participants, mean age was 74±5 years, 60% were female, 20% reported Black race, and mean LVEF was 66±6%. Over a mean of 4.9±0.6 years (the V5 to V6 interval), raw scores declined for all neuropsychological tests. In fully adjusted models, worse diastolic function (larger LAVi) and LV remodeling (greater LV mass index) were associated with decline in executive function. Lower LVEF was associated with decline in language function, while worse LV longitudinal strain – a more sensitive measure of systolic dysfunction – was associated with decline in executive function, language function, and global cognition performance (all p<0.05; Table). Conclusion: Subclinical LV remodeling and dysfunction is associated with greater declines in cognitive function over 5 years in late life. Differential associations were observed by cognitive domains, with executive function decline most uniformly associated with impairments in cardiac structure/function.

Association between social networks and cognition among middle-aged and older adults in rural India.

Prior studies using global cognitive measures have shown that social connectedness is linked with cognitive performance. We investigate the role of different social network dimensions on performance across distinct cognitive domains among dementia-free middle-aged and older rural Indians. We utilized baseline assessment data of 2,525 participants (≥45 years) of an ongoing, prospective, aging cohort in rural India (Srinivaspura Aging, Neuro Senescence, and COGnition) for this study. We evaluated social networks using Cohen's Social Network Index on three dimensions: network diversity, network size, and network embeddedness. We measured cognitive performance on memory (narrative recall), visuospatial ability (geometric figure spatial recognition, visuospatial span), language (verbal fluency, semantic association, word comprehension, reading comprehension), and attention domains of a culturally adapted, computerized, neurocognitive test battery. Linear regression models, adjusted for age and sex, were used for statistical analysis. In the linear regression model adjusted for age and sex, we found that greater network diversity was significantly associated with better performance in narrative recall, geometric figure spatial recognition, reading comprehension, semantic association, and attention tests. Participants with a larger network size had significantly better performance in verbal fluency and semantic association tests. Further, participants with greater network embeddedness had better visuospatial span and verbal fluency. Individuals having a greater network diversity, larger network size, and greater network embeddedness had better cognitive performance in multiple distinct cognitive domains. Following up these participants with serial cognitive monitoring can help understand if social networks play a role in delaying cognitive decline and protecting against dementia. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Immune Activation Is Associated With Neurocognitive Performance in Ugandan Adolescents Living With HIV.

We examined relationships between neurocognition and immune activation in Ugandan adolescents with perinatally acquired HIV (PHIV). Eighty-nine adolescents in Kampala, Uganda (32 virally suppressed [<400 copies/mL] PHIV and 57 sociodemographically matched HIV-negative controls), completed a tablet-based neurocognitive test battery. Control-derived z-scores for 12 individual tests and a global/overall z-score were calculated. We measured plasma (soluble CD14 and CD163), monocyte (proportions of monocyte subsets), and T-cell (expression of CD38 and HLA-DR on CD4 + and CD8 + ) activation and gut markers. Spearman rank correlations and median regressions examined associations between test performance and immune activation. The median [IQR] age was 15 [13-16] years, and 40% were girls. The median time on antiretroviral therapy was 10 years [7-11] for PHIV; 87% had viral load <50 copies/mL. Compared with controls, global z-scores were lower among PHIV ( P = 0.05) and significantly worse on tests of executive functioning and delayed recall ( P 's ≤ 0.05). Overall, monocyte activation significantly correlated with worse test performance on global z-score (r = 0.21, P = 0.04), attention, processing speed, and motor speed (r = 0.2-0.3, P ≤ 0.01). T-cell activation was significantly correlated with worse performance on tests of learning, executive functioning, and working memory (r = 0.2-0.4, P ≤ 0.04). In PHIV, after adjusting for age, sex, and antiretroviral therapy duration, activated CD4 T cells remained associated with worse memory (β-0.3, 95% CI: -0.55 to -0.07, P = 0.01). PHIV with virologic suppression on antiretroviral therapy shows evidence of worse neurocognitive test performance compared with controls. Monocyte and T-cell activation is correlated with worse neurocognition in Ugandan youth with and without HIV, which has not been previously investigated in this setting.

Reliability and validity study of the Turkish version of the Schizophrenia Cognition Rating Scale (SCoRS-TR)

BackgroundSchizophrenia is characterized by significant dysfunction in cognitive domains. Despite its crucial role in prognosis, evaluating neurocognitive impairments is challenging in outpatient settings because of the time-consuming nature of neurocognitive assessments. SCoRS “Schizophrenia Cognition Rating Scale” is a scale that provides brief cognitive evaluation. This study aimed to establish the validity and reliability of the Turkish version of the “Schizophrenia Cognition Rating Scale” (SCoRS-TR) in patients with schizophrenia and examine the correlation between SCoRS and cognitive tests. MethodsData were collected from 130 patients with schizophrenia who met the DSM-5 criteria and 40 healthy controls. SCoRS rating, Positive and Negative Syndrome Scale (PANSS), and a neurocognitive test battery were administered. ResultsFindings indicated that SCoRS-TR is a reliable and valid scale for the Turkish population. The scale demonstrated strong internal consistency, with Cronbach's alpha values ranging from 0.937 to 0.940. High interrater reliability (ranging from 0.90 to 0.98) and test-retest reliability (ranging from 0.976 to 0.990) were observed. SCoRS-TR significantly discriminated patients from healthy controls (p<0.001). SCoRS-TR exhibited significant correlations to neurocognitive tests. DiscussionResults indicated that SCoRS-TR had significant reliability and validity scores that may be useful for evaluating daily life functioning related to cognitive dysfunction in patients with schizophrenia. This approach may be useful for neurocognitive evaluation and monitoring in clinical follow-up and outpatient settings.

Sleep disturbances and psychomotor retardation in the prediction of cognitive impairments in patients with major depressive disorder.

Symptoms of depression and comorbid anxiety are known risk factors for cognitive impairment in major depressive disorder (MDD). Understanding their relationships is crucial for developing targeted interventions to mitigate cognitive impairments in MDD patients. We expect that the severity of sleep disturbances and other depressive symptoms will be positively correlated with the degree of cognitive impairments. We also hypothesize that anxiety symptoms, especially psychic anxiety, is a key factor in predicting cognitive performance in MDD patients and may indirectly contribute to cognitive impairment by affecting sleep disturbances and other potential factors. To determine which dimension of the depressive and anxiety symptoms predicts cognitive impairment during a depressive episode. A comprehensive neurocognitive test battery assessed executive function, attention, processing speed, and memory in 162 medication-free MDD patients and 142 matched healthy controls. The 24-item Hamilton Depression Rating Scale was used to assess depressive symptoms, and the 14-item Hamilton Anxiety Scale was used to assess anxiety symptoms. Linear regression analyses and mediation analyses were conducted to evaluate the impact of depressive and anxiety symptoms, as well as their interactions, on cognitive impairments. Among the depressive symptoms, sleep disturbances were associated with poorer executive function (P = 0.004), lower processing speed (P = 0.047), and memory impairments (P < 0.001), and psychomotor retardation (PR) was associated with lower processing speed in patients with MDD (P = 0.019). Notably, PR was found to mediate the impact of sleep disturbances on the processing speed. Regarding anxiety symptoms, psychic anxiety, rather than somatic anxiety, was associated with cognitive impairments in all aspects. Sleep disturbances mediated the effect of psychic anxiety on executive function [β = -0.013, BC CI (-0.027, -0.001)] and memory [β = -0.149, BC CI (-0.237, -0.063)], while PR mediated its effect on processing speed (β = -0.023, BC CI (-0.045, -0.004)]. Sleep disturbances may be a key predictor of poorer executive function, lower processing speed, and memory loss, while PR is crucial for lower processing speed during a depressive episode. Psychic anxiety contributes to all aspects of cognitive impairments, mediated by sleep disturbances and PR.

Diagnostic Accuracy of Neurocognitive and Executive Functions to Discriminate Women With and Without Fibromyalgia Syndrome: A Secondary Analysis.

Objective: The aim of the current study was to determine the capability of neurocognitive variables and executive functions to differentiate women with and without fibromyalgia syndrome (FMS). Methods: A secondary diagnostic accuracy analysis was conducted. A battery of neurocognitive and executive function tests (the D2 Attention test, the Rey-Osterrieth Complex Figure for visual perception, "Digits D/R/I" tests of the WAIS-IV battery for working memory, the 5-Digit test for mental inhibition, the Symbol Search for processing speed, and the Zoo Test for planning/decision-making) were collected in 129 women with FMS and 111 without FMS. The area under the receiver operating characteristic (ROC) curve, optimal cut-off point, sensitivity, specificity, and positive and negative likelihood ratios (LR) for each variable were calculated. Results: Between-group differences were identified in ROCF_Copy (p = 0.043), ROCF_Recall (p = 0.004), d2_TR (p = 0.019), d2_TA (p = 0.007), d2_TOT (p = 0.005), d2_CON (p = 0.004), d2_C (p = 0.042), Symbol Search (p = 0.008), Decoding _FDT (p = 0.001), Retrieving_FDT (p = 0.001), and Inhibiting_FDT (p = 0.024). The result showed that FDT-based outcomes (Retrieving_FDT: ROC 0.739, sensitivity 85.3%, specificity 48.6%; Decoding_FDT: ROC 0.724, sensitivity 50.4%, specificity 16.2%; Inhibiting_FDT: ROC 0.708, sensitivity 56.6%, specificity 22.5%) were the variables able to differentiate between women with and without FMS. Conclusions: Although women with FMS exhibited deficits in attention, long-term visual memory, processing speed, and mental inhibition when compared with women without FMS, only mental inhibition scores showed moderate diagnostic accuracy to discriminate between women with and without FMS. Future studies investigating these results in clinical settings are needed to identify the clinical relevance of these findings.

Relationship between 25-OH-D3 levels and cognitive functions in children with obesity

Aims: The inconsistent results about neurocognitive functions in children with obesity may be suggestive of factors like vitamin deficiencies rather than the disorder itself. So we aimed to investigate the 25(OH)D3 levels and cognitive functions in obese children in the present study. Methods: Seventy-two children were included to this study. Forty-one of them were obese children and 31 children were with normal weight. The patients were diagnosed as obese according to body mass index &gt;95 percentile, considering the sex and age-specific growth curves for Turkish children. The participants completed the battery tests of the central nervous system vital signs (CNSVS), a neurocognitive test battery, via computer. The battery calculates seven domain scores (Memory, Psychomotor speed, Processing speed, Reaction time, Complex attention, Executive function, Cognitive flexibility) and a summary score (Neurocognition Index). 25(OH)D3 levels were measured in residual samples using a Shimadzu HPLC system with the aid of a 25(OH)D3 kit. The scores were compared by using commercial software (IBM SPSS Statistics 18). Results: The mean 25-OH-vitamin D levels were 13.41±7.91 µg/L in obese children and 20.31±5.92µg/L in controls. Vitamin D3 levels were significantly lower in obese children than in control group (p

Therapeutic Cerebral Fluid Puncture in Patients with Idiopathic Intracranial Hypertension: No Short-Term Effect on Neurocognitive Function.

Idiopathic intracranial hypertension (IIH) is typically characterized by headaches and vision loss. However, neurocognitive deficits are also described. Our study aimed to test the influence of therapeutic lumbar puncture on the latter. A total of 15 patients with IIH were tested with a battery of neurocognitive tests at baseline and after therapeutic lumbar drainage. Hereby, Logical Memory of the Wechsler Memory Scale-Revised Edition (WMS-R), the California Verbal Learning Test Short Version (CVLT), alertness, selective attention, and word fluency were used. Changes in cognitive functioning in the course of CSF pressure lowering were analysed and compared with age, sex, and education-matched healthy controls. Before intervention, scores of Logical Memory, the RWT, and the HADS-D were significantly lower in IIH patients compared to matched controls. After short-term normalization of CSF pressure, the RWT improved significantly. Additionally, significant positive correlations were found between headache intensity and subjective impairment, as well as between BMI and CSF opening pressure. Our findings confirm lower performance in terms of long-term verbal memory and word fluency compared to controls, as well as depressive symptoms in IIH patients. Significant improvement after short-term normalization of intracranial pressure by means of CSF drainage was seen only for word fluency. This indicates that short-term normalization of CSF pressure is not sufficient to normalize observed neurocognitive deficits.

Increased Blood-Brain Barrier Permeability and Cognitive Impairment in Patients With ESKD

Background and AimsChronic kidney disease (CKD) is associated with an increased risk of cognitive impairment. This cognitive impairment is associated with an increased permeability of blood-brain barrier (BBB) in rodents with CKD, linked to activation of aryl hydrocarbon receptor (AhR) by indoxyl sulphate (IS). The objective of BREIN study is to confirm the increased BBB permeability in humans with CKD. MethodThe BREIN comparative study (NCT04328415) prospectively included patients with end-stage kidney disease (ESKD), and healthy volunteers (Ctrl) matched in age, sex, and educational level to a patient. In all participants, BBB permeability was quantified by brain 99mTc-DTPA SPECT/CT as percentage of injected activity (%IA). A battery of neuro-cognitive tests was performed, serum uremic toxins accumulation and AhR activation were assessed. ResultsFifteen ESKD patients and 14 healthy volunteers were analysed. ESKD patients had higher BBB permeability compared to controls: 0.29±0.07 vs. 0.14±0.06 %IA, p=0.002. ESKD patients displayed lower MoCA score: 22.0±5.0 vs. 27.3 ± 2.8, p=0.008, impaired short-term memory (doors test): 12.5±3.4 vs. 16.5±3.4, p=0.005, higher Beck depression score 8.1±9.1 vs. 2.7±3.4, p=0.046, and slightly more daily cognitive complaints: 42.5±29.3 vs. 29.8±14.0 p=0.060. ESKD patients displayed higher IS levels (86.1±48.4 vs. 3.2±1.7 μmol/L, p=0.001) and AhR activating potential (37.7±17.8% vs. 24.7±10.4%, p=0.027). BBB permeability was inversely correlated with MoCA score (r=-0.60, 95%CI [-0.772; -0.339], p=0.001) in the overall population. ConclusionESKD patients display an increased BBB permeability compared to matched healthy volunteers. Association with uremic toxins and cognitive impairment needs to be assessed in larger cohorts of patients.

Persistent organic pollutants and cognitive decline among middle-aged or older adults in the Hispanic Community Health Study/Study of Latinos

Persistent organic pollutants may negatively impact cognition; however, associations between persistent organic pollutants and changes in cognition among United States Hispanic/Latino adults have not been investigated. Herein, we examined the associations between 33 persistent organic pollutants and cognitive changes among 1837 Hispanic/Latino adults. At baseline (2008–2011; Visit 1), participants provided biospecimens in which we measured levels of 5 persistent pesticides or pesticide metabolites, 4 polybrominated diphenyl ethers and 2,2’,4,4’,5,5’-hexabromobiphenyl, and 24 polychlorinated biphenyls. At Visit 1 and again at Visit 2 (2015–2018), a battery of neurocognitive tests was administered which included the Brief-Spanish English Verbal Learning Test, Word Fluency Test, and Digit Symbol Substitution Test. To estimate the adjusted associations between changes in cognition and each POP, we used linear regression for survey data. Each doubling in plasma levels of polychlorinated biphenyls 146, 178, 194, 199/206, and 209 was associated with steeper declines in global cognition (βs range:-0.053 to −0.061) with stronger associations for the Brief-Spanish English Verbal Learning Test. Persistent organic pollutants, in particular polychlorinated biphenyls, were associated with declines in cognition over 7 years and may be a concern for Hispanic/Latino adults.

QOL-24. TREATMENT- AND TIME-RELATED IMPACT ON LONG-TERM NEUROCOGNITIVE OUTCOMES IN ADULT SURVIVORS OF A PEDIATRIC BRAIN TUMOR

Abstract Treatment for pediatric brain tumors has been associated with the risk of developing long-term neurocognitive impairment. However, it is not well understood which neurocognitive profiles exist within this population. We investigated neurocognitive functioning (NF) in survivors in early adulthood and aimed to assess the impact of radiotherapy dose (RTD) and time since treatment (TxT) on NF. Forty-six survivors of pediatric brain tumors (mean age 23.99±4.71, mean age at diagnosis 9.29±4.54) performed an extensive neurocognitive test battery resulting in intelligence (n=5), memory (n=2), and language (n=3) scores. NF in long-term survivors was compared to sex-, age-, and education-matched controls, and between the different treatment strategies (surgery-only n=19, chemotherapy n=8, radiotherapy n=11, or chemo-radiotherapy n=8). Furthermore, relation between max-RTD (range 40.28 – 61.61 Gy) as well as TxT and NF was assessed. Three ANCOVA models were tested, and false discovery rate (FDR) was applied. For all scales and domain scores, survivors scored lower compared to controls. Scores were significant lower on full scale intelligence (pfdr&amp;lt; 0.001), verbal comprehension (pfdr&amp;lt; 0.001), working memory (pfdr= 0.003), perceptual reasoning (pfdr&amp;lt; 0.001), processing speed (pfdr&amp;lt; 0.001), spoken word comprehension (pfdr= 0.001), and semantic word generation (pfdr= 0.036) compared to controls. NF was not significantly different between the different treatments, nor did the association with max-RTD reach significance. TxT was associated with verbal comprehension and spoken word comprehension; albeit significance was not retained after FDR correction. In this study, the overall survivor cohort scored lower on multiple cognitive outcomes. More detailed analysis of various risk factors might further elucidate the different neurocognitive profiles for this population. Furthermore, more detailed analysis of RTD distributions and affected brain structures may provide greater insight on the impact of radiotherapy on NF.

A transdiagnostic examination of cognitive heterogeneity in children and adolescents with neurodevelopmental disorders

ABSTRACT Children and adolescents with neurodevelopmental disorders demonstrate extensive cognitive heterogeneity that is not adequately captured by traditional diagnostic systems, emphasizing the need for alternative assessment and classification techniques. Using a transdiagnostic approach, a retrospective cohort study of cognitive functioning was conducted using a large heterogenous sample (n = 1529) of children and adolescents 7 to 18 years of age with neurodevelopmental disorders. Measures of short-term memory, verbal ability, and reasoning were administered to participants with attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), comorbid ADHD/ASD, and participants without neurodevelopmental disorders (non-NDD) using a 12-task, web-based neurocognitive testing battery. Unsupervised machine learning techniques were used to create a self-organizing map, an artificial neural network, in conjunction with k-means clustering to identify data-driven subgroups. The study aims were to: 1) identify cognitive profiles in the sample using a data-driven approach, and 2) determine their correspondence with traditional diagnostic statuses. Six clusters representing different cognitive profiles were identified, including participants with varying forms of cognitive impairment. Diagnostic status did not correspond with cluster-membership, providing evidence for the application of transdiagnostic approaches to understanding cognitive heterogeneity in children and adolescents with neurodevelopmental disorders. Additionally, the findings suggest that many typically developing participants may have undiagnosed learning difficulties, emphasizing the need for accessible cognitive assessment tools in school-based settings.

Neurocognitive Impairment among HIV-Infected Participants on Methadone for IV-Heroin use in Yunnan, China Relates to AIDS Status and Depression Severity, not Patterns of Substance use

We used a comprehensive and culturally normed battery of Neurocognitive (NC) tests to evaluate NC impairment (NCI) in 406 adults with prior IV heroin use who were in a government-supervised methadone maintenance program in Yunnan province, China. Participants included 202 without HIV infection, 57 with AIDS, and 147 HIV+ without AIDS (“nonAIDS group”). The AIDS group had higher proportions of individuals with global NCI (38.6%) relative to nonAIDS (15.7%) and HIV- participants (17.3%; ps &lt; 0.01). The AIDS group performed worse than the non AIDS group globally (&lt; 0.001), and in the domains of executive functioning (ps = 0.001), learning (ps = 0.035), and speeded information processing (ps = 0.0002). Despite the lack of difference in prevalence of NCI between non AIDS and HIV- groups, the non AIDS group showed impairment in memory and complex motor domains relative to the HIV- group (p = 0.03). In People With HIV (PWH), NCI was associated with more severe depression symptoms and HIV disease characteristics (duration of illness, CD4 nadir, AIDS status). Nearly all participants were HCV infected. Alcohol use disorder diagnoses, non-invasive indications of liver fibrosis, and characteristics of prior heroin use were not associated with NCI. PWH with NCI had worse daily functioning, as indexed by unemployment (ps = 0.016) and reported increased cognitive difficulties in daily life (ps = 0.016). These results highlight the importance of early HIV diagnosis and treatment to avoid HIV disease progression, particularly among IV drug users, with the goal of protecting NC abilities, everyday functioning, and life quality in infected individuals.

Bringing the field into the lab: a novel virtual reality outdoor march simulator for evaluating cognitive and physical performance

Soldiers, athletes, and rescue personnel must often maintain cognitive focus while performing intense, prolonged, and physically demanding activities. The simultaneous activation of cognitive and physical functions can disrupt their performance reciprocally. In the current study, we developed and demonstrated the feasibility of a virtual reality (VR)-based experimental protocol that enables rigorous exploration of the effects of prolonged physical and cognitive efforts. A battery of established neurocognitive tests was used to compare novel cognitive tasks to simulated loaded marches. We simulated a 10-km loaded march in our virtual reality environment, with or without integrated cognitive tasks (VR-COG). During three experimental visits, participants were evaluated pre- and post-activity, including the Color Trail Test (CTT), the Synthetic Work Environment (SYNWIN) battery for assessing multitasking, and physical tests (i.e., time to exhaustion). Results show that Strong or moderate correlations (r ≥ 0.58, p ≤ 0.05) were found between VR-COG scores and scores on the cognitive tests. Both the SYNWIN and CTT showed no condition effects but significant time effects, indicating better performance in the post-activity assessment than in the pre-activity assessment. This novel protocol can contribute to our understanding of physical-cognitive interactions, since virtual environments are ideal for studying high performance professional activity in realistic but controlled settings.

#1086 Blood-brain barrier permeability in patients with end-stage kidney disease: results from the BREIN study

Abstract Background and Aims Chronic kidney disease (CKD) is associated with an increased risk of cognitive impairment. In several models of CKD in rodents, we highlighted that CKD was associated with cognitive impairment and increased blood-brain barrier (BBB) permeability, quantified using 99mTc-DTPA scintigraphy imaging (SPECT/CT). BBB permeability was both correlated with cognitive impairment and with indoxyl sulfate (IS) levels. Inactivation of Aryl Hydrocarbon Receptor (AhR), receptor of the IS, protected the CKD mouse from the IS-induced BBB permeability. The objective of the BREIN study is to confirm the existence of an increased BBB permeability in humans with CKD. Method The prospective cohort study BREIN (NCT04328415) prospectively included patients with end-stage kidney disease (ESKD), and healthy volunteers (Ctrl) matched in age (±5 years), gender, and educational level to a patient. In patients and volunteers, BBB permeability was quantified by brain 99mTc-DTPA SPECT/CT performed by a senior nuclear physician and as percentage of injected activity (%IA). A battery of neuro-cognitive tests was performed, serum uremic toxins accumulation and AhR activation were assessed in all participants. Results 15 ESKD patients and 14 healthy volunteers were included. In ESKD patients had higher BBB permeability compared to controls: 0.29 0.07 vs. 0.14 0.06%IA, p &amp;lt; 0.0001. ESKD patients displayed lower MoCA score: 22.0 ± 5.0 vs. 27.3 ± 2.8, p = 0.008, impaired short-term memory (doors test): 12.5 ± 3.4 vs. 16.5 ± 3.4, p = 0.009, higher Beck depression score 8.1 ± 9.1 vs. 2.7 ± 3.4, p = 0.046, and slightly more daily cognitive complaints: 42.5 ± 29.3 vs. 29.8 ± 14.0 p = 0.153. ESKD patients displayed higher IS levels (2.8 ± 2.3 mmol/L vs. 0.9 ± 0.7 mmol/L, p = 0.006) and AhR activation (37.5 ± 17.8% vs. 24.7 ± 10.4%, p = 0.027). In ESKD patients, no significant correlation was found between BBB permeability and scores in cognitive tests, or serum uremic toxins levels. Conclusion This study confirms that ESKD patients display an increased BBB permeability compared to matched healthy volunteers, as well as cognitive and impairment. Association with uremic toxins and cognitive impairment needs to be assessed in larger cohorts.

Relationship of physical activity and cognitive functioning among breast cancer survivors: a cross-sectional analysis.

Cancer related cognitive decline is a common long-term side effect of cancer and its treatments among breast cancer survivors. Physical activity is a modifiable risk factor related to cognitive decline. However, existing research lacks consensus regarding the relationship between cognition and exercise as well as the impact of cancer treatments on this relationship. Baseline data from an ongoing randomized clinical trial was utilized to examine the relationship between self-reported and objectively measured cognition with physical activity. Exploratory analyses examined cancer treatments as potential moderators. Breast cancer survivors (N = 253) completed a battery of neurocognitive tests, the PROMIS Cognitive abilities questionnaire, medical charts abstracted for treatment information, and wore an ActiGraph accelerometer at the waist for 7 days. Data were analyzed using multiple linear regression models. Participants were on average 58.5 (SD = 8.88) years old, diagnosed 3 years prior to enrollment (SD = 1.27) with 57% treated with chemotherapy and 80% receiving hormone therapy at baseline. Better self-reported cognitive ability was significantly associated with greater min of moderate to vigorous physical activity (MVPA; β = 0.070, se = 0.028, p = 0.012). There were no significant associations with any objectively measured cognitive domains. Time since diagnosis (years) was a significant moderator of MVPA and Processing Speed (β = -0.103, se = 0.043, p = 0.017). Treatment with chemotherapy and/or hormones did not significantly moderate the relationship between MVPA and any of the cognitive measures or domains. Findings suggest that physical activity is related to self-reported cognition but not objectively measured cognition. Greater physical activity was associated with faster processing speed in participants closer in time to their cancer diagnosis. These results emphasize the need for more research to understand when cancer survivors may benefit from physical activity and what aspects of cognition may be improved.

Abstract PO2-19-01: A Single-Arm Prospective Study of the Neurocognitive Changes Occurring in Breast Cancer Patients on Aromatase Inhibitors. Is There a Difference Between Objective and Perceived Neurocognition?

Abstract Background: Estrogen (ER) and Progesterone (PR) receptors are rich in regions of the brain involved in cognitive functions, like the hippocampus and cerebral cortex. Animal models have shown that estradiol regulates neurocognition and plays an important role in the normal brain development. Hormone positive (HR+) breast cancers (BC) comprise 70% of the disease and the standard of care in the post-menopausal group is the use of Aromatase Inhibitors (AI) for at least 5 years. While “chemo brain” is a well-recognized term, neurocognitive changes from estrogen inhibition by AI have not been clearly defined. As neurocognition is multi-faceted, information on specific aspects affected by AI use is unclear. We hope to answer this through our trial. Design: The study is a single arm, self-controlled prospective observational cohort study in which, post-menopausal BC patients who are to be started on AIs will undergo a battery of neurocognitive tests just before starting AI, at 6 months and at 12 months after being on AI. The changes at 6 and 12 months will be compared to baseline. The tests will involve objective [Hopkins verbal learning test revised (HVLT), Controlled Oral Word Association Test from Multilingual Aphasia Examination, Trial Making Test A and B, and Recall and Recognition of Word List encoded from the HVLT] and subjective/patient-reported [The Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog)] components. Tests for anxiety [Generalized Anxiety Disorder (GAD)–7], depression [Patient Health Questionnaire (PHQ)-9] and working memory (Working Memory Tasks from the Wechsler Adult Intelligence Scale) will also be assessed. While the objective tests involve providing patients with specific instructions and asking them to complete the tasks, the FACT Cog questionnaire uses a self-reported 37-item questionnaire enabling assessment of their perceived symptoms. The tests have been summarized in the table. Eligibility criteria: ER/PR+ post-menopausal BC and DCIS patients who are English speaking and are planning to start AIs will be included. Patients who have received hormonal therapy or chemotherapy in the past, those who are scheduled to receive chemotherapy, those who have undergone Whole brain Radiation therapy (RT), those with a premenopausal status, and those having comorbid conditions that could affect cognitive functioning (like any form of dementia or brain metastasis) will be excluded. Specific aims: Our aim is to see if there are progressive neurocognitive changes compared to an age-appropriate baseline and to see if changes to both objective and perceived cognitive changes occur over the course of AI use, in post-menopausal HR+ BC patients. Statistical methods: The T-test and McNemer test will be used. The normal values provided from the test may be used as a standard to justify normal or abnormal values from the collected data. Therefore, a percentage of normal (or abnormal) subjects in each time point can be derived and compared using the McNemar's test. Present accrual and target accrual: 4 patients have been accrued as of June 2023 with a target accrual of 80 patients [80% power to detect a significant change, at a p of 0.05]. Contact information for people with a specific interest in the trial: Dr Abirami Sivapiragasam (abisiva2019@yahoo.com), Dr Sam Benjamin (benjamis@upstate.edu), Dr Prashanth Ashok Kumar (ashokkup@upstate.edu), Amy Bubb (bubbam@upstate.edu). Summary of the neurocognitive tests employed in the trial. Citation Format: Prashanth Ashok Kumar, Erinn McDowell, Amy Bubb, Danning Huang, Susan Sperry, Sam Benjamin, Abirami Sivapiragasam. A Single-Arm Prospective Study of the Neurocognitive Changes Occurring in Breast Cancer Patients on Aromatase Inhibitors. Is There a Difference Between Objective and Perceived Neurocognition? [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-19-01.

Long-term neurocognitive, psychosocial, and physical outcomes after prenatal exposure to radiotherapy: a multicentre cohort study of the International Network on Cancer, Infertility, and Pregnancy

The main data available on the safety of radiation during pregnancy originate from animal studies and from studies of survivors of atomic or nuclear disasters. The effect of radiotherapy to treat maternal cancer on fetal development is uncertain. This report presents a unique cohort and aims to determine the long-term neurocognitive, psychosocial and physical outcomes of offspring of mothers treated with radiotherapy during pregnancy. In this international, multicentre, mixed retrospective-prospective cohort study, we recruited participants between Aug 5, 2006, and Aug 24, 2023, aged between 1·5 and 46 years, at three referral centres in Belgium, the Netherlands, and the USA. Participants were eligible if they were born from mothers treated with radiotherapy during pregnancy. Fetal radiation doses were obtained from medical records and participants were followed up at predefined ages (1·5, 3, 6, 9, 12, 15, and 18 years) and 5-yearly in adulthood, based on age at enrolment, using a neurocognitive test battery (measuring intelligence, attention, and memory), parent-reported executive function and psychosocial questionnaires, and a medical assessment. Results were compared with test-specific normative data. Linear regression models investigated associations between radiotherapy factors (fetal radiation dose, gestational age at the start and end of radiotherapy, and radiotherapy duration) and outcomes. 68 maternal cases of radiotherapy during pregnancy were registered by the three participating centres, of which 61 resulted in a livebirth and were therefore eligible to participate in the child follow-up study. After excluding those who did not give consent, 43 participants born from 42 mothers treated with radiotherapy during pregnancy were included in the study (median age at first assessment 3 years [IQR 2-11]; median age at last assessment 12 years [9-18]; median number of assessments two [1-4]). 18 (42%) of the included participants were female and 25 (58%) male, and 37 (86%) were of White ethnicity. Mean neurocognitive outcomes of the entire cohort were within normal ranges. No associations were found with fetal radiation dose or timing of radiotherapy during pregnancy. Six (16%) of 38 participants with neurocognitive outcomes scored lower than one SD on at least one neurocognitive outcome, three (7%) reported chronic medical conditions (spasmophilia, spastic diplegia, and IgG deficiency), and three (7%) were diagnosed with attention-deficit hyperactivity disorder (of whom two scored lower on attention). Of ten (23%) participants with lower neurocognitive score(s), a chronic medical condition, or attention-deficit hyperactivity disorder, eight were born preterm. The remaining 33 (77%) participants showed no neurocognitive, psychosocial, or chronic physical problems. We show on average normal neurocognitive, psychosocial, and physical outcomes after prenatal exposure to radiotherapy. Differences in outcomes could not be explained by exposure to radiotherapy during pregnancy. These results suggest that extra-abdomino-pelvic radiotherapy exposure during pregnancy in general does not adversely affect outcomes of liveborn children. Further research with a larger sample is necessary to confirm these findings. Kom Op Tegen Kanker, KWF Kankerbestrijding, Stichting Tegen Kanker, Research Foundation Flanders.

A preliminary study on the neurocognitive deficits associated with loneliness in young adults.

The experience of loneliness is universal and may have an adverse effect on neurocognitive functioning even at a younger age. Using a comprehensive neurocognitive functioning test (NCFT) battery, we examined the possible negative effects of loneliness on neurocognitive functioning in young adults. The high-loneliness and low-loneliness groups were screened using the UCLA Loneliness Scale v. 3, and measures pertaining to the domains of intelligence, attention, memory, executive function, and psychomotor functioning were tested and compared. As depression and anxiety were significantly higher in the high-loneliness group, an analysis of covariance was conducted. As a result, the high-loneliness group showed significantly poor performance on measures of executive function and attention prior to controlling for depression and anxiety, and executive function retained its significance even after controlling for these variables. Additional analysis showed that depression and anxiety did not significantly mediate the relationship between loneliness and neurocognitive functioning. Such results suggest that loneliness is likely to negatively affect executive functioning and attention in early adulthood and then progressively spread to other domains of cognitive functioning, as reported in the older adult population. The limitations and implications of the present study were considered and addressed.