Lower glomerular filtration rate after mild stroke induces cognitive impairment by causing endothelial dysfunction.

The incidence of post stroke cognitive impairment (PSCI) is high in patients with mild stroke (MIS), and the risk factors and mechanism are uncertain. Increased cystatin C (CysC) levels after stroke may reflect lower glomerular filtration rate (GFR) and renal impairment. Previous studies have suggested endothelial dysfunction (ED) is closely related to renal impairment and cognitive impairment, respectively. We aimed to observe whether lower GFR estimated by CysC after MIS leaded to a high incidence of PSCI, and the role of ED in this process. 256 patients were enrolled in this prospective observational study. Renal function was assessed using GFR estimated by serum CysC. Endothelial function was evaluated by reactive hyperemia index (RHI) which calculated automatically by peripheral arterial tonometry (PAT). The cognitive function at baseline and 3 months was evaluated by MoCA score, and MoCA score ≤ 26 indicates the presence of PSCI. Spearman correlation analysis and linear regression were conducted to explore the factors affecting ED. Univariate and multivariate analysis was used to identify the independent risk factors of PSCI. The receiver operating characteristic (ROC) curve was applied to explore the optimal cutoff value of the independent risk factors levels for predicting PSCI. A total of 141 patients (55.1%) suffered from ED. Multiple linear regression analysis showed that there was a strong linear correlation between eGFRcys and RHI (p < 0.001). At the three-month follow-up, a total of 150 (58.6%) patients had been diagnosed with PSCI. Multivariate logistic regression analysis showed that RHI was an independent factor affecting the occurrence of PSCI (p < 0.05). ROC curve showed that the area under the curve was 0.724, and the optimal cut-off value of RHI was 1.655, with the sensitivity and specificity for PSCI were 72.7% and 73.6%, respectively. The lower eGFRcys level after MIS was significantly associated with ED, and ED may mediate the higher incidence of PSCI at 3 months after MIS.

Functional network disorganization and cognitive decline following fractionated whole-brain radiation in mice.

Cognitive dysfunction following radiotherapy (RT) is one of the most common complications associated with RT delivered to the brain, but the precise mechanisms behind this dysfunction are not well understood, and to date, there are no preventative measures or effective treatments. To improve patient outcomes, a better understanding of the effects of radiation on the brain's functional systems is required. Functional magnetic resonance imaging (fMRI) has shown promise in this regard, however, compared to neural activity, hemodynamic measures of brain function are slow and indirect. Understanding how RT acutely and chronically affects functional brain organization requires more direct examination of temporally evolving neural dynamics as they relate to cerebral hemodynamics for bridging with human studies. In order to adequately study the underlying mechanisms of RT-induced cognitive dysfunction, the development of clinically mimetic RT protocols in animal models is needed. To address these challenges, we developed a fractionated whole-brain RT protocol (3Gy/day for 10 days) and applied longitudinal wide field optical imaging (WFOI) of neural and hemodynamic brain activity at 1, 2, and 3 months post RT. At each time point, mice were subject to repeated behavioral testing across a variety of sensorimotor and cognitive domains. Disruptions in cortical neuronal and hemodynamic activity observed 1 month post RT were significantly worsened by 3 months. While broad changes were observed in functional brain organization post RT, brain regions most impacted by RT occurred within those overlapping with the mouse default mode network and other association areas similar to prior reports in human subjects. Further, significant cognitive deficits were observed following tests of novel object investigation and responses to auditory and contextual cues after fear conditioning. Our results fill a much-needed gap in understanding the effects of whole-brain RT on systems level brain organization and how RT affects neuronal versus hemodynamic signaling in the cortex. Having established a clinically-relevant injury model, future studies can examine therapeutic interventions designed to reduce neuroinflammation-based injury following RT. Given the overlap of sequelae that occur following RT with and without chemotherapy, these tools can also be easily incorporated to examine chemotherapy-related cognitive impairment.

Inhibiting CSF1R alleviates cerebrovascular white matter disease and cognitive impairment.

White matter abnormalities, related to poor cerebral perfusion, are a core feature of small vessel cerebrovascular disease, and critical determinants of vascular cognitive impairment and dementia. Despite this importance there is a lack of treatment options. Proliferation of microglia producing an expanded, reactive population and associated neuroinflammatory alterations have been implicated in the onset and progression of cerebrovascular white matter disease, in patients and in animal models, suggesting that targeting microglial proliferation may exert protection. Colony-stimulating factor-1 receptor (CSF1R) is a key regulator of microglial proliferation. We found that the expression of CSF1R/Csf1r and other markers indicative of increased microglial abundance are significantly elevated in damaged white matter in human cerebrovascular disease and in a clinically relevant mouse model of chronic cerebral hypoperfusion and vascular cognitive impairment. Using the mouse model, we investigated long-term pharmacological CSF1R inhibition, via GW2580, and demonstrated that the expansion of microglial numbers in chronic hypoperfused white matter is prevented. Transcriptomic analysis of hypoperfused white matter tissue showed enrichment of microglial and inflammatory gene sets, including phagocytic genes that were the predominant expression modules modified by CSF1R inhibition. Further, CSF1R inhibition attenuated hypoperfusion-induced white matter pathology and rescued spatial learning impairments and to a lesser extent cognitive flexibility. Overall, this work suggests that inhibition of CSF1R and microglial proliferation mediates protection against chronic cerebrovascular white matter pathology and cognitive deficits. Our study nominates CSF1R as a target for the treatment of vascular cognitive disorders with broader implications for treatment of other chronic white matter diseases.

J147 affects cognition and anxiety after surgery in Zucker rats.

Vulnerable patients are at risk for neuroinflammation-mediated post-operative complications, including depression (POD) and cognitive dysfunction (POCD). Zucker rats, expressing multiple risk factors for post-operative complications in humans, may provide a clinically relevant model to study pathophysiology and explore potential interventions. J147, a newly developed anti-dementia drug, was shown to prevent POCD in young healthy rats, and improved early post-surgical recovery in Zucker rats. Aim of the present study was to investigate POCD and the therapeutic potential of J147 in male Zucker rats. Risk factors in the Zucker rat strain were evaluated by comparison with lean littermates. Zucker rats were subjected to major abdominal surgery. Acute J147 treatment was provided by a single iv injection (10 mg/kg) at the start of surgery, while chronic J147 treatment was provided in the food (aimed at 30 mg/kg/day), starting one week before surgery and up to end of protocol. Effects on behavior were assessed, and plasma, urine and brain tissue were collected and processed for immunohistochemistry and molecular analyses. Indeed, Zucker rats displayed increased risk factors for POCD, including obesity, high plasma triglycerides, low grade systemic inflammation, impaired spatial learning and decreased neurogenesis. Surgery in Zucker rats reduced exploration and increased anxiety in the Open Field test, impaired short-term spatial memory, induced a shift in circadian rhythm and increased plasma neutrophil gelatinase-associated lipocalin (NGAL), microglia activity in the CA1 and blood brain barrier leakage. Chronic, but not acute J147 treatment reduced anxiety in the Open Field test and protected against the spatial memory decline. Moreover, chronic J147 increased glucose sensitivity. Acute J147 treatment improved long-term spatial memory and reversed the circadian rhythm shift. No anti-inflammatory effects were seen for J147. Although Zucker rats displayed risk factors, surgery did not induce extensive POCD. However, increased anxiety may indicate POD. Treatment with J147 showed positive effects on behavioral and metabolic parameters, but did not affect (neuro)inflammation. The mixed effect of acute and chronic treatment may suggest a combination for optimal treatment.

Downregulation of the glucose transporter GLUT 1 in the cerebral microvasculature contributes to postoperative neurocognitive disorders in aged mice.

INTRODUCTION: Glucose transporter 1 (GLUT1) is essential for glucose transport into the brain and is predominantly expressed in the cerebral microvasculature. Downregulation of GLUT1 precedes the development of cognitive impairment in neurodegenerative conditions. Surgical trauma induces blood-brain barrier (BBB) disruption, neuroinflammation, neuronal mitochondria dysfunction, and acute cognitive impairment. We hypothesized that surgery reduces the expression of GLUT1 in the BBB that in turn disrupts its integrity and contributes to metabolic dysregulation in the brain that culminates in postoperative cognitive impairment. METHODOLOGY: Using an abdominal surgery model in aged WT mice, we assessed the perioperative changes in cognitive performance, tight junction proteins expression, GLUT1 expression, and the associated metabolic effects in the hippocampus. Thereafter, we evaluated the effects of these parameters in aged mice with conditional overexpression of GLUT1, and then again in aged mice with conditional overexpression of GLUT1 with or without prior exposure to the GLUT1 inhibitor ST-31. RESULTS: We showed a significant decline in cognitive performance, along with GLUT1 reduction and diminished glucose metabolism, especially in the ATP level in the postoperative mice compared with controls. Overexpression of GLUT1 expression alleviated postoperative cognitive decline and improved metabolic profiles, especially in adenosine, but did not directly restore ATP generation to control levels. GLUT1 inhibition ameliorated the postoperative beneficial effects of GLUT1 overexpression. CONCLUSIONS: Surgery-induced GLUT1 reduction significantly contributes to postoperative cognitive deficits in aged mice by affecting glucose metabolism in the brain. It indicates the potential of targeting GLUT1 to ameliorate perioperative neurocognitive disorders.

Associations Between Parity and Cognition: Race/Ethnic Differences.

BACKGROUND: Race/ethnicity is associated with differences in reproductive history and cognition individually, yet it remains an understudied factor in the relationship between parity and later-life cognition. OBJECTIVE: To evaluate if the association between parity and cognition differs between racial/ethnic groups. METHODS: Participants included 778 older, postmenopausal women from the Health and Nutrition Examination Survey (Latina: n = 178, Non-Latino Black [NLB]: n = 169, Non-Latino White [NLW]: n = 431) who self-reported at least one birth. Cognitive outcomes included working memory, learning memory, and verbal fluency. Covariates included age, education, cardiovascular and other reproductive health factors, adult socioeconomic status (SES) and depressive symptoms. We fit a series of linear models to examine a) whether parity was associated with cognitive functioning, b) if this association varied by race/ethnicity through parity by race/ethnicity interactions, and c) individual parity with cognition associations stratified by race/ethnicity. RESULTS: In the full sample, parity was significantly negatively associated with Digit Symbol Substitution Test (DSST) performance (b = -0.70, p = 0.024) but not Animal Fluency or word-list learning and memory. Tests of race/ethnicity-by-parity interactions were not statistically significant (ps > 0.05). However, stratified analyses by race/ethnicity showed a differential effect of parity on DSST performance, such that parity was significantly negatively associated with DSST performance (b = -1.66, p = 0.007) among Latinas but not in NLWs (b = -0.16, p = 0.74) or NLBs (b = -0.81, p = 0.191). CONCLUSION: Among Latina, but not NLB or NLW women, greater parity was associated with worse processing speed/executive functioning later in life. Further research is needed to understand the mechanisms driving racial/ethnic differences.

Social cognitive deficit is associated with visuomotor coordination impairment and dopamine transporter availability in euthymic bipolar disorder.

BACKGROUND: Extensive evidence has suggested functional connections between co-occurring visuomotor and social cognitive deficits in neuropsychiatric disorders; however, such association has not been studied in bipolar disorder (BD). We aimed to investigate the relationship between visuomotor coordination and social cognition in the euthymic stage of BD (euBD). Given the shared neurobiological underpinnings involving the dopaminergic system and corticostriatal circuitry, we hypothesized a positive correlation between social cognition and visuomotor coordination in euBD patients. METHODS: 40 euBD patients and 59 healthy control (HC) participants underwent evaluation of social (Diagnostic Analysis of Nonverbal Accuracy 2-Taiwan version (DANVA-2-TW)), non-social cognitive function and visuomotor coordination. A subgroup of participants completed single-photon emission computed tomography for striatal dopamine transporter (DAT) availability assessment. RESULTS: EuBD patients showed impaired nonverbal emotion recognition (ps ≤ 0.033) and poorer visuomotor coordination (ps < 0.003) compared to HC, with a positive correlation between these two abilities (r = 0.55, p < 0.01). However, after considering potential confounding factors, instead of visuomotor coordination, striatal DAT availability was a unique predictor of emotion recognition accuracy in euBD (beta = 0.33, p = 0.001). CONCLUSION: Our study result supported a functional association between social cognition and visuomotor coordination in euBD, with striatal dopaminergic dysfunction emerged as a crucial contributing factor in their interrelation.

A bibliometric analysis of cerebral microbleeds and cognitive impairment.

BACKGROUND AND OBJECTIVES: Cerebral microbleeds (CMBs) are imaging markers for small cerebral vascular diseases, which can accumulate and impact the corresponding brain networks. CMBs can affect cognitive function, including executive function, information processing speed, and visuospatial memory. Bibliometrics is a scientific and innovative method that can analyze and visualize the scientific field quantitatively. In this study, we aimed to use bibliometric analysis to demonstrate the relationship and mechanisms between CMBs and cognitive impairment. Furthermore, we reviewed the relationship between CMBs and different cognitive disorders. The use of bibliometrics can help further clarify this relationship. METHODS: We retrieved articles on CMBs and cognitive impairment from the Web of Science Core Collection. The keywords (such as stroke, dementia, and cerebral amyloid angiopathy), authors, countries, institutions and journals, in the field were visually analyzed using VOSviewer software and bibliometric websites. RESULTS: This bibliometric analysis reveals the related trends of CMBs in the field of cognitive impairment. CMBs, along with other small vascular lesions, constitute the basis of cognitive impairment, and studying CMBs is essential to understand the mechanisms underlying cognitive impairment. CONCLUSION: This bibliometric analysis reveals a strong link between CMBs and cognitive impairment-related diseases and that specific brain networks were affected by CMBs. This provides further insights into the possible mechanisms and causes of CMBs and cognitive impairment. The direct and indirect damage (such as oxidative stress and neuroinflammation) to the brain caused by CMBs, destruction of the frontal-subcortical circuits, elevated Cystatin C levels, and iron deposition are involved in the occurrence and development of cognitive impairment. CMBs may be a potential marker for detecting, quantifying, and predicting cognitive impairment.

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.

BACKGROUND: 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. METHODS: 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. RESULTS: At V1, a history of cancer (6.4%) versus no history of cancer (93.6%) was associated with higher WF scores (ß = 0.14, SE = 0.06; p = 0.03) and global cognition (ß = 0.09, SE = 0.04; p = 0.04). Among women, a history of cervical cancer predicted decreases in SEVLT-Recall scores (ß = -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 (ß = 0.29, SE = 0.12; p = 0.02) and predicted increases in SEVLT-Sum (ß = 0.46, SE = 0.22; p = 0.04) from V1 to V2. CONCLUSION: 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.

Cognitive function after carotid endarterectomy in asymptomatic patients.

Asymptomatic carotid stenosis has been shown to be associated with progressive neurocognitive decline, but the effects of carotid endarterectomy (CEA) on this are not well defined. Due to the wide heterogeneity of studies and lack of standardization in cognitive function tests and study design, there is mounting scientific evidence to support the notion that CEA is effective in reversing or slowing neurocognitive decline; however, definitive conclusions are difficult to make. Further, while the association between ACS and cognitive decline has been well document, a direct etiological role has not been established. More research is required to elucidate the relationship between asymptomatic carotid stenosis and the benefit of carotid endarterectomy and its potential protective effects regarding cognitive decline. This article aims to review current evidence in preoperative and postoperative cognitive function in asymptomatic patients with carotid stenosis undergoing CEA.

Cognitive impairment after cancer treatment: mechanisms, clinical characterization, and management.

Cognitive impairment is a debilitating side effect experienced by patients with cancer treated with systemically administered anticancer therapies. With around 19.3 million new cases of cancer worldwide in 2020 and the five year survival rate growing from 50% in 1970 to 67% in 2013, an urgent need exists to understand enduring side effects with severe implications for quality of life. Whereas cognitive impairment associated with chemotherapy is recognized in patients with breast cancer, researchers have started to identify cognitive impairment associated with other treatments such as immune, endocrine, and targeted therapies only recently. The underlying mechanisms are diverse and therapy specific, so further evaluation is needed to develop effective therapeutic interventions. Drug and non-drug management strategies are emerging that target mechanistic pathways or the cognitive deficits themselves, but they need to be rigorously evaluated. Clinically, consistent use of objective diagnostic tools is necessary for accurate diagnosis and clinical characterization of cognitive impairment in patients treated with anticancer therapies. This should be supplemented with clinical guidelines that could be implemented in daily practice. This review summarizes the recent advances in the mechanisms, clinical characterization, and novel management strategies of cognitive impairment associated with treatment of non-central nervous system cancers.

Asymptomatic carotid stenosis and cognitive impairment.

INTRODUCTION: The aim of this review was to assess the evidence supporting an association between asymptomatic carotid stenosis (ACS) with impaired cognitive function due to chronic cerebral hypoperfusion and/or silent cerebral embolization. EVIDENCE ACQUISITION: PubMed/Medline, Embase and the Cochrane databases were searched up to December 1, 2022 to identify studies focusing on the association between ACS and cognitive function, as well as the mechanisms involved. EVIDENCE SYNTHESIS: A total of 49 studies were identified. The evidence supports an association between ACS and progressive cognitive deterioration. The mechanisms involved in the cognitive decline associated with ACS include cerebral hypoperfusion and silent cerebral embolization. Irrespective of the mechanism involved, severe ACS is associated with a progressive decline in several aspects of cognitive function, including global cognition, memory and executive function. CONCLUSIONS: Patients with ACS are at increased risk of developing a progressive decline in their cognitive function. The evidence from the present systematic review suggests that it may be inappropriate to consider ACS patients developing cognitive dysfunction as "asymptomatic". Besides stroke, myocardial infarction and death rates, future studies should include evaluation of cognitive function as part of their outcomes.

Safety and Tolerability of High-Resolution Esophageal Manometry in Children and Adults.

INTRODUCTION: While high-resolution manometry (HRM) is widely accepted as a safe procedure, no study has assessed the safety profile of HRM in clinical practice. This study aimed to determine the safety and tolerability of HRM and to investigate potential determinants of intolerability. METHODS: We obtained HRM procedure reports, demographics, and clinical data (2005-2022) at a tertiary center using electronic chart review. Our primary outcome was HRM tolerability. Multivariable regression was performed to identify associations between the outcome and covariates including age, sex, race, and comorbidities. RESULTS: A total of 5,107 patients (60.3% female) were included. Of them, 5,050 patients (98.9%) tolerated HRM well and 57 patients (1.1%) did not. Age had a statistically significant effect on tolerance: those younger than 18 years had more than a 5-fold increase in not tolerating HRM compared with those aged 18-79 years (5.77% vs 0.99%; odds ratio [OR] = 5.44, 95% confidence interval [CI] 1.60-18.45; P = 0.007), and those aged 80 years or older were also more likely to terminate HRM (2.43% vs 0.99%; OR = 2.56, 95% CI 1.13-5.76; P = 0.024). While prior foregut surgery had a significant effect on tolerance (OR = 8.06, 95% CI 2.29-28.39; P = 0.001), other factors of race, sex, body mass index, and psychological or cognitive disorders had no significant impact. No serious complications were identified. DISCUSSION: HRM is safe and well-tolerated with approximately 1 in every 100 patients being unable to tolerate HRM. Intolerance was more commonly seen in children and seniors due to minor symptoms of discomfort without serious complications. These data points are crucial to counsel patients in whom HRM is being considered.

Predictors of early postoperative cognitive dysfunction in middle-aged patients undergoing cardiac surgery: retrospective observational study.

PURPOSE: This study aimed to identify the incidence and risk factors of early post-operative cognitive dysfunction (POCD) in middle-aged patients undergoing cardiac surgery. METHODS: Data were examined retrospectively from 71 patients aged 46-64 years who underwent elective cardiac surgery. Magnetic resonance imaging (MRI) and MR angiography were obtained preoperatively to assess prior cerebral infarctions, carotid artery stenosis, and intracranial arterial stenosis. Patients also completed six neuropsychological tests of memory, attention, and executive function before and after surgery. Mild cognitive impairment (MCI) was defined as performance 1.5 standard deviations (SD) below the population means on any neurocognitive battery, whereas POCD was defined as a decrease of 1 SD population means on at least two in the test battery. Patient characteristics were analyzed using univariate analysis, and independent predictors were analyzed using multivariate logistic regression analysis. RESULTS: After surgery, 25 patients (35%) were assessed with POCD. Patients with POCD had significantly higher rates of preoperative MCI and cerebral infarcts on MRI. Multivariate logistic regression analysis identified preoperative MCI and cerebral infarctions detected by MRI as a predictor of POCD. CONCLUSION: More than one-third of middle-aged patients undergoing cardiac surgery developed POCD. Our findings suggested preoperative MCI and infarcts detected by MRI were risk factors for POCD in these middle-aged patients.

Interventions promoting cognitive function in patients experiencing cancer related cognitive impairment: A systematic review.

OBJECTIVE: To examine the effect of interventions used to enhance cognitive function in patients experiencing cancer-related cognitive impairment. METHODS: Studies including adults with a non-metastatic cancer who have received chemotherapy as part of their treatment and who have undergone interventions targeting cancer-related cognitive impairment were included. Studies involving patients with metastatic cancer and pre-existing cognitive deficits were excluded. Academic Search Complete, CINAHL Plus with full text, MEDLINE, Education Full Text, PsycARTICLES, PsycINFO, and ERIC were searched for studies published between January 2011 and September 2022. Data extraction and quality appraisal were conducted by two authors and cross-checked by the review team. Quality appraisal was conducted using 12 items from the Mixed Methods Appraisal Tool. Findings were presented narratively without meta-analysis. RESULTS: Thirty-one studies were included. Interventions were categorised as integrative/complementary, cognitive behavioural therapy and compensatory strategies, exercise, psychoeducational/psychosocial, brain-training, and pharmacological. Over 100 instruments were identified, including the Functional Assessment of Cancer Therapy-Cognitive, Trail Making Tests-A and B, and instruments measuring secondary outcomes, including depression. Instruments often measured attention and concentration, language, memory, executive function, and/or patient-reported outcomes. Improvements were reported, with most studies measuring some or various aspects of cognitive functioning and very few studies measuring all domains of cognitive functioning, making it difficult to draw definitive conclusions about effectiveness. CONCLUSIONS: Various interventions are available to treat cancer-related cognitive impairment. Outcome measurement was inconsistent and future research should prioritise using standardised measures. Current evidence, whilst not being definitive, suggests that certain interventions show greater promise than others, including cognitive behavioural therapy and brain training.

Binary classification threatens the validity of cognitive impairment detection.

OBJECTIVE: Neuropsychological literature reports varying prevalence of cognitive impairment within patient populations, despite assessment with standardized neuropsychological tests. Within the domain of oncology, the International Cognition and Cancer Task Force (ICCTF) proposed standard cutoff points to harmonize the operationalization of cognitive impairment. We evaluated how this binary classification affects agreement between two highly comparable test batteries. METHOD: Two hundred non-central nervous system (non-CNS) cancer patients who finished treatment (56% females; median age 53 yrs) completed traditional tests and their online equivalents in a counterbalanced design. Following ICCTF standards, impairment was defined as a score of ≥ 1.5 standard deviations (SDs) below normative means on two tests and/or ≥ 2 SDs below normative means on one test. Agreement of classification between traditional and online assessment was evaluated using Cohen's κ. Additional Monte Carlo simulations were conducted to demonstrate how different cutoff points and test characteristics affect agreement. RESULTS: The correlation between total scores of traditional and online assessment was .78. Proportions of impaired patients did not differ between assessment methods: 40% using traditional tests and 38% using online equivalents, χ²(1) = .17, p < .68. Nevertheless, within-person agreement in impairment classification between traditional and online assessment was merely fair (K = .35). Monte Carlo simulations showed similarly low agreement scores (K = .41 for 1.5 SD; K = .33 for 2 SD criterion). CONCLUSIONS: Our results show that binary classification can lead to a situation where two highly similar batteries fail to identify the same individuals as impaired. Additional simulations suggest that within-person agreement between assessment methods using binary classification is inherently low. Modern statistical tools may help to improve validity of impairment detection. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Self-perceived cognitive function and neuropsychological performance in women with fibromyalgia

BACKGROUND: Cognitive dysfunction is a common complain in patients with fibromyalgia (FM). Aim: To assess the perceived cognitive function and cognitive performance in women with FM. MATERIAL AND METHODS: Cross-sectional study including 100 women with FM (FMG) and 100 healthy controls (CG). Self-perceived cognitive functioning was evaluated using the Functional Assessment of Cancer Therapy Cognition scale (FACT-Cogv3). The neuropsychological performance was assessed with the Trail Making Test (TMT-A, TMT-B), Digit Span test (DS), Barcelona test (DS-F/B) and the Frontal Assessment Battery (FAB-E), Spanish version test. Results: The mean scores of all cognitive self-perception factors and all neuropsychological tests were lower in the FMG (p < 0.001). Over 90% of the FMG took longer than the population mean (P50) to complete the TMT-A and TMT-B tests, while in the CG, 1/3 took longer than the P50 in both tests. The minimum expected scores for the DS-F and DS-B tests were not achieved by 40 and 9% of FMG participants, respectively. According to FAB-E, 54% and 24% of FMG were categorized as fronto-subcortical deficit and fronto-subcortical dementia, respectively. CONCLUSIONS: Women with FM have a higher perception of cognitive dysfunction and lower cognitive performance in objective tests than healthy women. More research is needed to explore the clinical, psychosocial, and sociodemographic characteristics that predispose to cognitive deficits in this group of patients.

ANTECEDENTESA: La disfunción cognitiva es una queja común en pacientes con fibromialgia (FM). Objetivo: Investigar la función cognitiva percibida y el desempeño cognitivo en mujeres chilenas con FM. MATERIAL Y MÉTODOS: Estudio transversal incluyendo a 100 mujeres con FM (GFM) y 100 mujeres como controles sanos (GC). El funcionamiento cognitivo autopercibido se evaluó mediante la prueba Functional Assessment of Cancer Therapy Cognition scale (FACT-Cogv3). El rendimiento neuropsicológico se evaluó mediante las pruebas Trail Making Test (TMT-A, TMT-B) y Digit Span test (DS), Barcelona test (DS-F/B) y la prueba Frontal Assessment Battery, versión española (FAB-E). RESULTADOS: Las puntuaciones medias de todos los factores de autopercepción cognitiva y todas las pruebas neuropsicológicas fueron significativamente menores en el GFM. Para TMT-A y TMT-B, más del 90% del GFM tardó más que la media poblacional (P50) para completar las pruebas, mientras que en el GC aproximadamente 1/3 requirió más tiempo que el P50 en ambas pruebas. Un 40 y 9% del GFM no obtuvo la puntuación mínima esperada para las pruebas DS-F y DS-B, respectivamente. Según FAB-E, el 54% y 24% del GFM se clasificó como déficit fronto-subcortical y demencia fronto-subcortical, respectivamente. Conclusiones: Las mujeres con FM tienen una mayor percepción de disfunción cognitiva y menor rendimiento cognitivo en pruebas objetivas que mujeres sanas. Se necesita más investigación para explorar las características clínicas, psicosociales y sociodemográficas que predisponen a los déficits cognitivos en este grupo de pacientes.

Multitargeting the Action of 5-HT6 Serotonin Receptor Ligands by Additional Modulation of Kinases in the Search for a New Therapy for Alzheimer's Disease: Can It Work from a Molecular Point of View?

In view of the unsatisfactory treatment of cognitive disorders, in particular Alzheimer's disease (AD), the aim of this review was to perform a computer-aided analysis of the state of the art that will help in the search for innovative polypharmacology-based therapeutic approaches to fight against AD. Apart from 20-year unrenewed cholinesterase- or NMDA-based AD therapy, the hope of effectively treating Alzheimer's disease has been placed on serotonin 5-HT6 receptor (5-HT6R), due to its proven, both for agonists and antagonists, beneficial procognitive effects in animal models; however, research into this treatment has so far not been successfully translated to human patients. Recent lines of evidence strongly emphasize the role of kinases, in particular microtubule affinity-regulating kinase 4 (MARK4), Rho-associated coiled-coil-containing protein kinase I/II (ROCKI/II) and cyclin-dependent kinase 5 (CDK5) in the etiology of AD, pointing to the therapeutic potential of their inhibitors not only against the symptoms, but also the causes of this disease. Thus, finding a drug that acts simultaneously on both 5-HT6R and one of those kinases will provide a potential breakthrough in AD treatment. The pharmacophore- and docking-based comprehensive literature analysis performed herein serves to answer the question of whether the design of these kind of dual agents is possible, and the conclusions turned out to be highly promising.