Cognitive Impairment Score Research Articles

Post-acute sequelae of COVID-19 3 to 12 months after infection: Delta vs Omicron

ObjectivesStudies have shown temporal changes in post-acute sequelae of COVID-19 (PASC) prevalence for early SARS-CoV-2 variants, although often lacking controls. This prospective study assesses the prevalence of symptoms in Delta- and Omicron-infected cases up to 12 months compared with population controls. MethodsAdult participants filled out surveys every 3 months (T0-T12) between July 2021 and August 2023. Cases were recruited with a positive SARS-CoV-2 test during the Delta or Omicron domination. Population controls were randomly invited from the Dutch Personal Records Database. Participants indicated the presence of 13 PASC-associated symptoms, and severity scores of fatigue, cognitive impairment, dyspnea, and pain. PASC prevalence was defined as the excess prevalence of havingat least one PASC-associated symptom in cases compared with population controls. ResultsPASC prevalence was 34.3% at T3 and decreased to 21.7% at T12 for Delta and decreased from 18.7% at T3 to 16.7% at T12 for Omicron. At T12, the difference between Delta and Omicron was not significant. Delta cases generally had higher excess symptom scores for fatigue, dyspnea, and cognitive impairment than Omicron. ConclusionsIn the first 9 months after infection, PASC prevalence was higher for Delta than Omicron, but the difference reduced over time and approximated after 12 months.

Theta Burst Stimulation Protocols for Schizophrenia

To date, several theta burst stimulation (TBS) protocols, such as intermittent TBS (iTBS), have been proposed; however, previous systematic reviews have revealed inconsistent efficacy findings in individual TBS studies for schizophrenia. To examine which TBS protocols are associated with the most favorable and acceptable outcomes in adults with schizophrenia. The Cochrane Library, PubMed, and Embase databases were searched for studies published before May 22, 2024. The inclusion criteria were as follows: (1) published and unpublished randomized clinical trials (RCTs) of any TBS treatment and (2) RCTs including individuals with schizophrenia spectrum disorders, other psychotic disorders, or both. This study followed the Cochrane standards for data extraction and data quality assessment and used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline for reporting. The risk of bias of individual studies was assessed using the second version of the Cochrane risk of bias tool, and the Confidence in Network Meta-Analysis application was used to rate the certainty of evidence for meta-analysis results. At least 2 authors double-checked the literature search, data transfer accuracy, and calculations. The primary outcome of this study was improvement in scores related to negative symptoms. Our frequentist network meta-analysis used a random-effects model. The standardized mean difference (SMD) or odds ratio for continuous or dichotomous variables, respectively, was calculated with 95% CIs. A total of 30 RCTs of 9 TBS protocols, with 1424 participants, were included. Only iTBS over the left dorsolateral prefrontal cortex (L-DLPFC) was associated with reduced negative symptom scores (SMD, -0.89; 95% CI, -1.24 to -0.55), overall symptom scores (SMD, -0.81; 95% CI, -1.15 to -0.48), Positive and Negative Syndrome Scale general subscale scores (SMD, -0.57; 95% CI, -0.89 to -0.25), depressive symptom scores (SMD, -0.70; 95% CI, -1.04 to -0.37), and anxiety symptom scores (SMD, -0.58; 95% CI, -0.92 to -0.24) and improved overall cognitive impairment scores (SMD, -0.52; 95% CI, -0.89 to -0.15) compared with a sham. However, positive symptom score changes, all-cause discontinuation rate, discontinuation rate due to adverse events, headache incidence, and dizziness incidence did not significantly differ between any TBS protocols and sham. In this network meta-analysis, iTBS over the L-DLPFC was associated with improved scores for negative, depressive, anxiety, and cognitive symptoms in individuals with schizophrenia and was well tolerated by the participants. Other forms of TBS were not associated with benefit. Further research is needed to assess the potential role of TBS in the treatment of schizophrenia.

Effect of an Autotaxin Inhibitor, 2-(4-Chlorophenyl)-7-methyl-8-pentylimidazo[1,2-a] Pyrimidin-5(8H)-one (CBT-295), on Bile Duct Ligation-Induced Chronic Liver Disease and Associated Hepatic Encephalopathy in Rats.

The role of autotaxin (ATX)-lysophosphatidic acid (LPA) is yet to be explored in the context of liver cirrhosis and associated encephalopathy. Our objective of this study was to evaluate the role of an ATX inhibitor in biliary cirrhosis and associated hepatic encephalopathy in rats. The preliminary investigation revealed significant impairment in liver function, which eventually led to the development of hepatic encephalopathy. Interestingly, LPA levels were significantly increased in the plasma, liver, and brain of rats following bile duct ligation. Subsequently, we tested the efficacy of an ATX inhibitor, CBT-295, in bile duct-induced biliary cirrhosis and neuropsychiatric symptoms associated with hepatic encephalopathy. CBT-295 showed good oral bioavailability and favorable pharmacokinetic properties. CBT-295 exhibited a significant reduction in inflammatory cytokines like TGF-β, TNF-α, and IL-6 levels, also reduced bile duct proliferation marker CK-19, and lowered liver fibrosis, as evident from reduced collagen deposition. The reversal of liver fibrosis with CBT-295 led to a reduction in blood and brain ammonia levels. Furthermore, CBT-295 also reduced neuroinflammation induced by ammonia, which is characterized by a significant reduction in brain cytokine levels. It improved neuropsychiatric symptoms such as locomotor activities, cognitive impairment, and clinical grading scores associated with hepatic encephalopathy. The improvement in hepatic encephalopathy observed with the ATX inhibitor could be the result of its hepatoprotective action and its ability to attenuate neuroinflammation. Therefore, inhibition of ATX-LPA signaling can be a multifactorial approach for the treatment of chronic liver diseases.

Blood-based multivariate methylation risk score for cognitive impairment and dementia.

The established link between DNA methylation and pathophysiology of dementia, along with its potential role as a molecular mediator of lifestyle and environmental influences, positions blood-derived DNA methylation as a promising tool for early dementia risk detection. In conjunction with an extensive array of machine learning techniques, we employed whole blood genome-wide DNA methylation data as a surrogate for 14 modifiable and non-modifiable factors in the assessment of dementia risk in independent dementia cohorts. We established a multivariate methylation risk score (MMRS) for identifying mild cognitive impairment cross-sectionally, independent of age and sex (P=2.0×10-3). This score significantly predicted the prospective development of cognitive impairments in independent studies of Alzheimer's disease (hazard ratio for Rey's Auditory Verbal Learning Test (RAVLT)-Learning=2.47) and Parkinson's disease (hazard ratio for MCI/dementia=2.59). Our work shows the potential of employing blood-derived DNA methylation data in the assessment of dementia risk. We used whole blood DNA methylation as a surrogate for 14 dementia risk factors. Created a multivariate methylation risk score for predicting cognitive impairment. Emphasized the role of machine learning and omics data in predicting dementia. The score predicts cognitive impairment development at the population level.

Endocrine-Disrupting Chemicals Exposure and Neurocognitive Function in the General Population: A Community-Based Study.

Endocrine-disrupting chemicals (EDCs) are pervasive in everyday environments. The impacts of these chemicals, along with EDC-related lifestyle and dietary habits on neurocognitive function, are not well understood. The Chang Gung Community Medicine Research Center conducted a cross-sectional study involving 887 participants. From this initial cohort, 120 individuals were selected based on their EDC exposure scores for detailed analysis. Among these, 67 participants aged 55 years or older were further chosen to undergo cognitive impairment assessments using the Ascertain Dementia-8 (AD-8) questionnaire. These 67 older participants did not significantly differ in age, albuminuria, or estimated glomerular filtration rate compared to those with lower impairment scores. This study revealed that mono-(2-ethylhexyl) phthalate (MEHP) levels (8.511 vs. 6.432 µg/g creatinine, p = 0.038) were associated with greater risk of cognitive impairment (AD-8 ≥ 2). Statistical models adjusting for age, gender, and diabetes indicated that MEHP levels positively correlated with AD-8 scores, achieving statistical significance in more comprehensive models (β ± SE: 0.160 ± 0.076, p = 0.042). Logistic regression analysis underscored a significant positive association between high MEHP levels and higher AD-8 scores (odds ratio: 1.217, p = 0.006). Receiver operating characteristic curves highlighted the association of high MEHP levels and EDC exposure scores for significant cognitive impairment, with areas under the curve of 66.3% and 66.6%, respectively. Exposure to EDCs, specifically di-(2-ethylhexyl) phthalate, the precursor to MEHP, may be associated with neurocognitive impairment in middle-aged and older adults.

Translation and validation to the Arabic language version of the climate change anxiety scale (CCAS)

BackgroundThe Arab world is one of the global regions the most directly concerned by, and suffering from climate change’s adverse consequences. As such, there appears to be a strong need for an understanding of how Arab people may emotionally respond to climate change. Providing valid and reliable measures of climate change anxiety (CCA) can help gain a clear overview of the situation in Arab countries, and allow to intervene timely and effectively to mitigate any adverse effects on Arab people’s mental health. To this end, the present study sought to validate the Arabic language version of the Climate Change Anxiety Scale (CCAS) in a sample of native Arabic-speaking adults from the general population of Lebanon.MethodsThis study adopted a cross-sectional approach and enrolled 763 adults between July and September 2023.ResultsA confirmatory analysis of the one-factor model showed poor fit indices as follows: CFI = 0.90, GFI = 0.83, SRMR = 0.048 and RMSEA 0.131 [90% CI 0.123, 0.138). The two-factor model showed a satisfactory fit with a high CFI of and a GFI of 0.91 and a SRMR of 0.04 and RMSEA of 0.05 [90% CI 0.04, 0.06]. Both McDonald’s omega and Cronbach alpha values were high for the overall CCAS score (α = 0.96 and ω = 0.96) in the whole sample. Configural, metric and scalar invariance across gender was demonstrated. No significant difference was found between males and females in terms of total CCAS scores (24.53 ± 10.59 vs. 26.03 ± 11.17, t(761) = -1.82, p = .069). Higher CCA, functional impairment and cognitive impairment scores were significantly associated with higher depression, anxiety and stress.ConclusionThe reliability and validity of the CCAS in its Arabic version were proven. The availability of this self-report measure could offer a chance to assess CCA among Adults speaking Arabic, and to spread its future use for screening and research purposes.

Marital History and Cognition in a Chinese Longevity Cohort

Background: Marital factor has been associated with dementia and Alzheimer’s disease, but there is limited evidence on the impact of holistic marital history over time. Objective: This study aimed to examine association of marital history with cognition. Methods: The study included 24,596 dementia-free participants from the Chinese Longitudinal Healthy Longevity Study (CLHLS). Holistic marital history was collected at baseline, categorizing participants into five groups: widow-single, widow-remarried, divorce-single, divorce-remarried and married based on the first two marriages. Dementia was collected at follow-up through self-report or from a delegate if the participant was deceased. For 15,355 participants, the Chinese Mini-Mental Status Examination (CMMSE) was administered at both baseline and follow-ups. Cognitive impairment was defined as a follow-up CMMSE score below 18, and rate of cognitive change was calculated as the change in CMMSE score between consecutive visits divided by the duration. Results: Compared with married older adults, widow-single group had significantly higher risk of dementia (HR 1.28, 95% CI 1.05, 1.54), cognitive impairment (HR 1.31, 95% CI 1.17, 1.47) and significantly faster decline of MMSE score (β –0.09, 95% CI –0.17, –0.01). Meanwhile, widow-remarried group had significantly lower risk of dementia, cognitive impairment and slower MMSE score decline than widow-single group, although the differences were only significant among female but not male. Conclusions: In this prospective cohort, married older adults and those widowed but with a second marriage had significantly better cognition than widowed individuals who did not remarry.

TICS-M scores in an oldest-old normative cohort identified by computable phenotype

Objective: To (1) examine the distribution of Telephone Interview for Cognitive Status modified (TICS-m) scores in oldest-old individuals (age 85 and above) identified as cognitively healthy by a previously validated electronic health records-based computable phenotype (CP) and (2) to compare different cutoff scores for cognitive impairment in this population. Method: CP identified 24,024 persons, 470 were contacted and 252 consented and completed the assessment. Associations of TICS-m score with age, sex, and educational categories (<10 years, 11–15 years, and >16 years) were examined. The number of participants perceived as impaired was studied with commonly used cutoff scores (27–31). Results: TICS-m score ranged from 18 to 44 with a mean of 32.6 (SD = 4.7) in older adults aged 85–99 years old. A linear regression model including (range-restricted) age, education, and sex, showed beta estimates comparable to previous findings. Different cutoff scores (27 to 31) generated slightly lower MCI and dementia prevalence rates of participants meeting the criteria for the impairments than studies of younger elderly using traditional recruitment methods. Conclusions: The use of validated computable phenotype to identify a normative cohort generated a normative distribution for the TICS-m consistent with prior findings from more effortful approaches to cohort identification and established expected TICS-m performance in the oldest-old population.

A minimally Invasive Biomarker for Sensitive and Accurate Diagnosis of Parkinson's Disease.

ImportanceParkinson′s disease (PD), the second most common neurodegenerative disease, is pathologically characterized by intraneuronal deposition of misfolded alpha-synuclein aggregates (αSynD). αSynDseeding activities in CSF and skin samples have shown great promise in PD diagnosis, but they require invasive procedures. Sensitive and accurate αSynDseed amplification assay (αSyn-SAA) for more accessible and minimally invasive samples (such as blood and saliva) are urgently needed for PD pathological diagnosis in routine clinical practice.ObjectiveTo develop a sensitive and accurate αSyn-SAA biomarker using blood and saliva samples for sensitive, accurate and minimally invasive PD diagnosis.Design, Setting, and ParticipantsThis prospective diagnostic study evaluates serum and saliva samples collected from patients clinically diagnosed with PD or healthy controls (HC) without PD at an academic Parkinson′s and Movement Disorders Center from February 2020 to March 2024. Patients diagnosed with non-PD parkinsonism were excluded from this analysis. A total of 124 serum samples (82 PD and 42 HC) and 131 saliva samples (83 PD and 48 HC) were collected and examined by αSyn-SAA. Out of the 124 serum donors, a subset of 74 subjects (48 PD and 26 HC) also donated saliva samples during the same visits. PD patients with serum samples had a mean age of 69.21 years (range 44-88); HC subjects with serum samples had a mean age of 66.55 years (range 44-81); PD patients with saliva samples had a mean age of 69.58 years (range 49-87); HC subjects with saliva samples had a mean age of 64.71 years (range 30-81).Main Outcomes and MeasuresSerum and/or saliva αSynDseeding activities from PD and HC subjects were measured by αSyn-SAA using the Real-Time Quaking-Induced Conversion (RT-QuIC) platform. These PD patients had extensive clinical assessments including MDS-UPDRS. For a subset of PD and HC subjects whose serum and saliva samples were both collected during the same visits, the αSynDseeding activities in both samples from the same subjects were examined, and the diagnostic accuracies for PD based on the seeding activities in either sample alone or both samples together were compared.ResultsRT-QuIC analysis of αSynDseeding activities in the 124 serum samples revealed a sensitivity of 80.49%, a specificity of 90.48%, and an accuracy of 0.9006 (AUC of ROC, 95% CI, 0.8472-0.9539, p&lt;0.0001) for PD diagnosis. RT-QuIC analysis of αSynDseeding activity in 131 saliva samples revealed a sensitivity of 74.70%, a specificity of 97.92%, and an accuracy of 0.8966 (AUC of ROC, 95% CI, 0.8454-0.9478, p&lt;0.0001). When aSynDseeding activities in the paired serum-saliva samples from the subset of 48 PD and 26 HC subjects were considered together, sensitivity was 95.83%, specificity was 96.15%, and the accuracy was 0.98 (AUC of ROC, 95% CI, 0.96-1.00, p&lt;0.001), which are significantly better than when αSynDseeding activities in either serum or saliva were used alone. For the paired serum-saliva samples, when specificity was set at 100% by elevating the αSyn-SAA cutoff values, a sensitivity of 91.7% and an accuracy of 0.9457 were still attained. Detailed correlation analysis revealed that αSynDseeding activities in the serum of PD patients were correlated inversely with Montreal Cognitive Assessment (MoCA) score (p=0.04), positively with Hamilton Depression Rating Scale (HAM-D) (p=0.03), and weakly positively with PDQ-39 cognitive impairment score (p=0.07). Subgroup analysis revealed that the inverse correlation with MoCA was only seen in males (p=0.013) and weakly in the ≥70 age group (p=0.07), and that the positive correlation with HAM-D was only seen in females (p=0.04) and in the &lt;70 age group (p=0.01). In contrast, αSynDseeding activities in the saliva of PD patients were inversely correlated with age at diagnosis (p=0.02) and the REM sleep behavior disorder (RBD) status (p=0.04), but subgroup analysis showed that the inverse correlation with age at diagnosis was only seen in males (p=0.04) and in the &lt;70 age group (p=0.01).Conclusion and RelevanceOur data show that concurrent RT-QuIC assay of αSynDseeding activities in both serum and saliva can achieve high diagnostic accuracies comparable to that of CSF αSyn-SAA, suggesting that αSynDseeding activities in serum and saliva together can potentially be used as a valuable biomarker for highly sensitive, accurate, and minimally invasive diagnosis of PD in routine clinical practice. αSynDseeding activities in serum and saliva of PD patients correlate differentially with some clinical characteristics and in an age and sex-dependent manner.

Association of objective sleep duration with cognition and brain aging biomarkers in older adults.

The neuropathological mechanisms underlying the association between sleep duration and mild cognitive impairment remain poorly understood. This population-based study included 2032 dementia-free people (age ≥ 60 years; 55.1% women) derived from participants in the Multimodal Interventions to Delay Dementia and Disability in Rural China; of these, data were available in 841 participants for Alzheimer's plasma biomarkers (e.g. amyloid-β, total tau and neurofilament light chain), 1044 for serum microvascular biomarkers (e.g. soluble adhesion molecules) and 834 for brain MRI biomarkers (e.g. whiter matter, grey matter, hippocampus, lacunes, enlarged perivascular spaces and white matter hyperintensity WMH). We used electrocardiogram-based cardiopulmonary coupling analysis to measure sleep duration, a neuropsychological test battery to assess cognitive function and the Petersen's criteria to define mild cognitive impairment. Data were analysed with multivariable logistic and general linear models. In the total sample (n = 2032), 510 participants were defined with mild cognitive impairment, including 438 with amnestic mild cognitive impairment and 72 with non-amnestic mild cognitive impairment. Long sleep duration (>8 versus 6-8 h) was significantly associated with increased likelihoods of mild cognitive impairment and non-amnestic mild cognitive impairment and lower scores in global cognition, verbal fluency, attention and executive function (Bonferroni-corrected P < 0.05). In the subsamples, long sleep duration was associated with higher plasma amyloid-β40 and total tau, a lower amyloid-β42/amyloid-β40 ratio and smaller grey matter volume (Bonferroni-corrected P < 0.05). Sleep duration was not significantly associated with serum-soluble adhesion molecules, white matter hyperintensity volume, global enlarged perivascular spaces and lacunes (P > 0.05). Alzheimer's and neurodegenerative pathologies may represent common pathways linking long sleep duration with mild cognitive impairment and low cognition in older adults.

Development and Validation of a Risk Score for Mild Cognitive Impairment in Individuals with Type 2 Diabetes in China: A Practical Cognitive Prescreening Tool.

Numerous evidence suggests that diabetes increases the risk of cognitive impairment. This study aimed to develop and validate a multivariable risk score model to identify mild cognitive impairment (MCI) in patients with type 2 diabetes mellitus (T2DM). This cross-sectional study included 1256 inpatients (age: 57.5 ± 11.2 years) with T2DM in a tertiary care hospital in China. MCI was diagnosed according to the criteria recommended by the National Institute on Aging-Alzheimer's Association Workgroup, and a MoCA score of 19-25 indicated MCI. Participants were randomly allocated into the derivation and validation sets at 7:3 ratio. Logistic regression models were used to identify predictors for MCI in the derivation set. A scoring system based on the predictors' beta coefficient was developed. Predictive ability of the risk score was tested by discrimination and calibration methods. Totally 880 (285 with MCI, 32.4%) and 376 (167 with MCI, 33.8%) patients were allocated in the derivation and validation set, respectively. Age, education, HbA1c, self-reported history of severe hypoglycemia, and microvascular disease were identified as predictors for MCI and constituted the risk score. The AUCs (95% CI) of the risk score were 0.751 (0.717, 0.784) in derivation set and 0.776 (0.727, 0.824) in validation set. The risk score showed good apparent calibration of observed and predicted MCI probabilities and was capable of stratifying individuals into 3 risk categories by two cut-off points (low risk: ≤ 3, medium risk: 4-13, and high risk ≥ 14). The risk score based on age, education, HbA1c, self-reported history of severe hypoglycemia, and microvascular disease can effectively assess MCI risk in adults with T2DM at different age. It can serve as a practical prescreening tool for early detection of MCI in daily diabetes care.

Discontinuity of deep medullary veins in SWI is associated with deep white matter hyperintensity volume and cognitive impairment in cerebral small vessel disease

BackgroundDiscontinuation of the deep medullary veins (DMVs) may be an early imaging marker for identifying cognitive impairment caused by cerebral small vessel disease (CSVD). However, this method lacks mechanistic exploration. We aimed to investigate whether the DMV score is related to CSVD imaging markers and cognitive impairment in patients with CSVD. MethodsThis retrospective study included patients with CSVD who completed DMV score and cognition (e.g., MMSE, MoCA) assessments, and underwent MRI scanning (T2-FLAIR for white matter hyperintensities (WMH) volume, T1-weighted MRI for brain parenchymal fractions (BPF) analysis, and SWI for assessment of DMV score). The CSVD imaging markers were quantitatively assessed using the AccuBrain® system. We assessed the diagnostic value of neuroimaging biomarkers for detecting CSVD-related cognitive impairment. In addition, we explored the relationship between the DMV score, CSVD imaging markers, and cognition using mediation analysis. ResultsNinety-four patients with CSVD were divided into a cognitive impairment group (n = 39) and a non-cognitive impairment group (n = 55). Higher DMV scores, larger WMH volumes, and smaller BPF were observed in the cognitive impairment group than those in the non-cognitive impairment group. Receiver operating characteristics (ROC) analysis revealed that the discovery value of the integration of patient age, BPF, whole WMH volume, and DMV score for cognitive impairment was 0.742, with a sensitivity and specificity of 79.5 % and 61.5 %, respectively. Mediation analysis showed mediation by WMH and BPF in the relationship between DMV score and cognitive impairment (all P < 0.05). LimitationsThis study did not evaluate the DMV score in subregions according to DMV anatomy. ConclusionsThe DMV score is significantly associated with cognitive impairment in patients with CSVD, and this association is mediated through WMH and BPF.

Systemic inflammatory response index and monocyte-to-high density lipoprotein ratio- new biomarkers remarking the inflammation in primary sarcopenia: The SIMPS study.

To investigate the relationship of sarcopenia with systemic inflammation response index (SIRI), monocyte to high-density lipoprotein ratio (MHR) and platelet parameters in geriatric patients. We designed across-sectional retrospective study in patients presented to ageriatric outpatient clinic for the first time. The diagnosis of sarcopenia was made in accordance with the EWGSOP2 criteria. SIRI, MHR, mean platelet volume /Platelet count (MPV/Plt), platelet distribution width /Platelet (PDW/Plt), platelet/lymphocyte ratio (PLR) were calculated from fasting blood test results at the time of admission. Among 262 patients, 79 patients (30.1%) with sarcopenia had significantly higher frequencies of delirium, hypothyroidism, chronic kidney disease and probable depression (p=0.010; p=0.018; p=0.034; p<0.001). Malnutrition scores and cognitive impairment scores were significantly lower in sarcopenic group (p<0.001 for both). Patients with sarcopenia had significantly higher MHR, SIRI and C-reactive protein values than patients without sarcopenia (p<0.001; p=0.001 and p=0.006, respectively). No significant difference was found between the groups in terms of MPV/Plt, PDW/Plt, PLR (p=0.605; p=0.920; p=0.510). Area under the curve for MHR was 0.675 (95% CI: 0.604-0.746, p0.99. The finding of higher MHR and SIRI in geriatric sarcopenia patients supports low-grade chronic inflammation in the pathophysiology of sarcopenia. These non-invasive, cost-effective and simple parameters based on traditional peripheral blood cell counts may be warning signs for sarcopenia in the geriatric population (Tab. 3, Fig. 1, Ref. 25). Text in PDF www.elis.sk Keywords: primary sarcopenia, inflammation, systemic inflammation response index, monocyte/high-density lipoprotein ratio, platelet parameters.

Evaluation of the Relationship between Cognitive Impairment and Atria Score Systems in Patients with Atrial Fibrillation.

Atrial fibrillation (AF) is the main arrhythmia associated with thromboembolic complications and cognitive impairment. In this study, we aimed to evaluate the relationship between cognitive impairment and different scoring systems developed for AF to improve the medical follow-up of cognitive impairment. Between January 2019 and December 2020, 124 patients between the age of 30 and 80 years, diagnosed with AF for at least 5 years and complaining about memory impairment during cardiological follow-up, were included in the study. The patients were divided into two groups based on their cognitive status as assessed by the Mini-Mental State Examination group 1 consisted of 52 patients with cognitive impairment and group 2 comprised 72 patients without cognitive impairment. The ATRIA bleeding score had a positive moderate correlation (r = 0.454, P < 0.001), the ATRIA stroke score had a strong correlation (r = 0.738, P < 0.001), and the SAMe-TT2R2 score had a strong correlation (r = 0.688, P < 0.001) with cognitive impairment. However, CHADS2 and CHA2DS2VASc scores were not statistically correlated with cognitive impairment. According to the receiver operating characteristic (ROC) curve, the area under the curve (AUC) of the ATRIA bleeding score was 0.761 with a 95% confidence interval (CI) of 0.678-0.844 and P < 0.001; also, for the ATRIA stroke score, AUC was 0.930 with a 95% CI of 0.886-0.974 and P < 0.001. In addition, for the SAMe-TT2R2 score, AUC was 0.895 with a 95% CI of 0.838-0.952 and P < 0.001. In the pairwise comparison of AUC on ROC curves, the ATRIA stroke score and the SAMe-TT2R2 score were statistically similar (P = 0.324). ATRIA bleeding, ATRIA stroke, and SAMe-TT2R2 scores were greater than CHADS2 stroke score (P: 0.0004, P < 0.0001, and P < 0.0001, respectively), but CHA2DS2-VASc and CHADS2 stroke scores were statistically similar (P: 0.402). Both ATRIA stroke and SAMe-TT2R2 scoring systems can provide a better correlation than CHADS2 and CHA2DS2-VASc scores in patients with AF to evaluate their cognitive status. These two scores can be more useful to monitor the patients with AF for medical follow-up of cognitive status.

Efficiency evaluation of the Neuromidin in the treatment of pain of the patients with discogenic lumbosacral radiculopathy: results of a multicenter post-registration prospective open comparative trial

Evaluation of the effect of Neuromidine on the dynamics of pain syndrome in the treatment of patients with discogenic lumbosacral radiculopathy. Patients with a confirmed diagnosis of discogenic lumbosacral radiculopathy no more than one year old and moderate intensity of pain syndrome on a visual analog scale were included in the main group (OH, n=62, age - 53.1±15.6 yrs) and the comparison group (HS, n=40, age - 53.7±12.9 yrs). OG patients received Neuromidine (15 mg/1 mL 1 once a day IM for 10 days, then 20 mg 3 times a day for 8 weeks) in addition to the standard drug therapy, HS patients received only standard drug therapy. The duration of the study was 8 weeks. The degree of decrease in the intensity and dynamics of pain syndrome, activity and frequency of pain in the lumbar spine, changes in the level of physical activity, and the severity of emotional disorders were evaluated. The level of inflammatory markers in the blood and the dynamics of monosynaptic spinal H-reflex parameters were evaluated. Before the study, there were no statistically significant differences there were no results of clinical and laboratory-instrumental examination between groups. After 8 weeks, the reduction of pain by VAS in the main group was statistically significant in contrast to the comparison group (p=0.0001). In the main group there was a statistically significant increase in the mean cognitive impairment score (p=0.0029), as well as an improvement in psycho-emotional state with a significant decrease in GAD-7 (p=0.0002) and PHQ-9 (p=0.0096). After 8 weeks of therapy, IL-6 level in the main group was statistically significantly lower (p=0.0027) than in the comparison group. The results of H-reflex study revealed an increase in its amplitude and some shortening of latency at the end of Neuromidine therapy. The drug had no undesirable side effects and was well tolerated. Administration of Neuromidine 15 mg/1 ml once a day intramuscularly for 10 days followed by 20 mg 3 times a day for 8 weeks has an effective analgesic effect as adjuvant therapy in patients with discogenic lumbosacral radiculopathy. The inclusion of Neuromidine in the complex treatment of patients with pain syndrome in discogenic radiculopathy is superior in efficacy to standard drug therapy.

NEIGHBORHOOD DISADVANTAGE, IMAGING BIOMARKERS OF ALZHEIMER’S DISEASE, AND COGNITION IN DIVERSE OLDER ADULTS

Abstract Neuroimaging biomarkers of Alzheimer’s disease (AD) are well-validated in White populations. However, it remains unclear how these biomarkers are associated with cognition in non-White populations disproportionately affected by systemic socioeconomic discrimination. We investigated whether neighborhood disadvantage modifies associations of neuroimaging biomarkers with cognition in a diverse cohort of 198 adults ≥50 years, 50% of whom are Black. Outcomes included cognitive impairment and neuropsychological test scores. Predictors were indices of neurodegeneration, vascular damage, and brain amyloid burden, quantified using MR-based measures of cortical thickness and white matter hyperintensities (WMH) and [11C]PiB PET, respectively. We measured neighborhood disadvantage using area deprivation index (ADI), a composite measurement of socioeconomic conditions in a census tract. In linear models, higher ADI, neurodegeneration, and WMH were separately associated with worse cognition. We found an ADI*neurodegeneration interaction on delayed recall memory (p=0.08). Neurodegeneration-positive participants had worse story delayed recall compared to neurodegeneration-negative regardless of ADI (β=-1.57, p=0.01). In neurodegeneration-negative participants, higher ADI is associated with worse delayed recall (β=-0.04, p=0.004): those with a high ADI exhibited low delayed recall, comparable to neurodegeneration-positive participants. ADI was not associated with cognition in neurodegeneration-positive participants. WMH and ADI interacted in models of impairment, visual memory, and visual copy (interaction p’s&amp;lt; 0.10). In those with high ADI, greater WMH was associated with worse cognition (β=-0.30, p=0.02) while participants with low ADI scored well regardless of WMH volume. Taken together, the relationship between neuroimaging biomarkers and cognition differs by neighborhood socioeconomic conditions, highlighting the need for clinical strategies that acknowledge structural disadvantage.

Cognitive impairment experienced by Chinese breast cancer survivors

To identify cognitive function in Chinese breast cancer survivors. Research questions were: is cognitive function was associated with breast cancer and/or chemotherapy treatment and/or psychological functioning:? and did women with breast cancer experience more cognitive and psychological issues than age-matched women without cancer? Breast cancer survivors with chemotherapy (n = 106, mean age = 50.2 ± 9.5), breast cancer survivors without chemotherapy (n = 100, mean age = 50.5 ± 10.0) and matched healthy controls (n = 96, mean age = 47.9 ± 9.1) completed a battery of cognitive and psychosocial functioning. Demographic characteristics were also collected. The Perceived Cognitive Impairment score for cancer groups was significantly higher than for the healthy group (p = 0.04), but not between the cancer groups. Processing speed was significantly slower in the cancer groups than in the healthy group (both p < 0.001), but not between the cancer groups. Age, living status and education were significantly associated with the FACT-Cog (all p < 0.05). The correlations between the FACT-Cog score and BSI score were strong (r = 0.60 p < 0.01), and between the HADS anxiety and depression scales were strong (r = 0.53 and 0.50, p < 0.01) but correlations were weaker between performance based cognitive tests and measures of psychological functioning. Breast cancer groups indicated more cognitive impairment and reduced psychological functioning compared to the healthy group. However, there was no differences between the breast cancer groups. Chinese breast cancer survivors experienced excess cognitive impairment not associated with usual ageing. Assessment and intervention to address cognitive impairment should be made available to breast cancer survivors.

Subjective cognitive impairment score associate with regional amyloid burden and brain atrophy in subjective cognitive decline subjects

AbstractBackgroundSubjective cognitive decline (SCD) is now regarded as the first preclinical stage of Alzheimer’s disease (AD) spectrum disorders. It is important to predict which patients would progress to dementia, and screening tools might be helpful. In this study, we aimed to investigate the possible correlations between AD biomarkers‐regional amyloid burden and volume changes‐and Korean Dementia Screening Questionnaire‐Cognition (KDSQ‐C) score in SCD.MethodThis study analyzed SCD data from prospective population cohort study from July 2018 to December 2020. Brain magnetic resonance imaging (MRI) volumetry, visual and standardized uptake value ratio (SUVR) analysis of 18F‐Florbetaben brain amyloid Positron Emission Tomography (PET) were performed. Demographics, physical data, social and physiological functions were also obtained.KDSQ‐C was administered to SCD subjects as part of the clinical evaluation at the 36 month follow‐up visit. KDSQ‐C included 15 questions that assess 3 dimensions: memory impairment (items 1‐5), other cognitive impairments including language impairments (items 6‐10), and the ability to perform complex tasks in daily life (items 11‐15).ResultPrevalence of subjective cognitive impairment (KDSQ‐C ≧6) among 86 subjects was 73.3%.. No significant difference was observed between groups in terms of demographic characteristics including age, sex and APOE Ɛ4 status and neuropsychological test. However, regional SUVR (amygdala, inferior temporal gyrus and precuneus) and global SUVR were significantly higher in subjectively cognitive impaired group(p&lt;0.05). There were no brain volume differences between groups.For volumetry and KDSQ‐C correlation analysis, partial correlation analysis controlled for age, sex and APOE Ɛ4 status showed significant negative correlation between left entorhinal cortex, right hippocampal volume and KDSQ‐C (r = ‐0.230, p = 0.046; r = ‐0.226, p = 0.049). Similar association was also found between KDSQ‐C memory domain score and brain volume.ConclusionKDSQ‐C can be a useful tool for screening SCD patients at a higher risk with higher amyloid deposition and brain atrophy.This study was supported by a grant from the Ministry of Health and Welfare, HI18C0530

Neurocognitive Outcomes over the First 3 Months after Chimeric Antigen Receptor T-Cell (CAR T) Therapy: Preliminary Findings from a Longitudinal Study

Introduction People treated with systemic therapies for cancer may exhibit changes in neurocognitive functioning over time, affecting domains such as memory, processing speed, and executive functioning. There is a need for prospective data regarding neurocognitive outcomes among patients treated with Chimeric Antigen Receptor T-Cell (CAR T) therapy. The purpose of this study was to investigate the trajectory of neurocognitive performance and self-reported cognitive functioning over the first 3 months of CAR T therapy. Methods As part of a larger cohort study of patients treated with CAR T, neurocognitive outcomes were assessed prior to starting CAR T and again at 1- and 3- months post-CAR T. Neurocognitive performance was measured using standardized neuropsychological tests including measures of verbal memory (Hopkins Verbal Learning Test-Revised (HVLT-R) - immediate recall, delayed recall, retention), processing speed (Trail-making Test - Part A (TMT-A)) and executive functioning (Trail-making Test Part B (TMT-B), Controlled Oral Word Association Test (COWAT)). Raw test scores were converted to z-scores (Mean 0, SD 1) based on norms adjusted for age, sex, and education, where applicable. Impairment on individual tests was defined by a z score ≤ -1.64. Participants were categorized as showing overall impairment if they had at least two tests with a z-score of ≤ -1.5 or a z-score ≤ -2.0 on one test. Self-reported cognitive functioning was measured using the Functional Assessment of Cancer Therapy - Cognition, Perceived Cognitive Impairment score (FACT-Cog3 PCI) and the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire C-30, Cognitive Functioning scale (EORTC QLQ-C30 CF). Demographic and clinical data were collected through self-report and patient records. Frequencies of impairment were determined at each time point, with clinically significant changes on individual test scores in the first month determined based on z-score changes of ≥1.0 or minimal clinically important differences for self-report questionnaires. Linear mixed models were generated to estimate the trajectory of neurocognitive performance and self-reported cognitive functioning over time from baseline to 3 months. Results Neurocognitive outcomes were available for 37 participants at baseline, with follow-up data available for 29 patients at 1 month and 17 patients at 3 months. Participants were 54% male, had a mean age 58.4 years (sd 11.3) and a mean 15.5 years (sd 3.2) education. All patients had a diagnosis of non-Hodgkin lymphoma (53% diffuse large B-cell lymphoma (DLBCL), 31% transformed DLBCL from follicular lymphoma). Immune effector cell-associated neurotoxicity syndrome (ICANS) affected 32% of patients (5% Grade 4, 3% Grade 3, 8% Grade 2, 16% Grade 1). Cytokine release syndrome (CRS) affected 97% of patients (3% Grade 3, 76% Grade 2, 19% Grade 1). Frequency of overall impairment at each time point was 10/37 (27%) at baseline, 12/29 (41.4%) at 1 month, and 3/17 (17.6%) at 3 months. At each time point, impairment was most common on tests of executive functioning and memory. Based on individual test score changes between baseline and 1 month, rates of decline on individual tests of neurocognitive performance ranged from 11.5% (TMT-A) to 34.6% (COWAT). Decline on self-reported cognitive functioning was observed for 14.3% (FACT-Cog PCI) and 28.6% (EORTC QLQ-C30 CF) of participants. Based on mixed models (Table 1), there was a statistically significant decline in estimated mean z-scores on a test of executive function (COWAT: -0.52, 95% CI -0.89-(-0.16), p=0.007) at 1-month compared to baseline. At three months, there was a statistically significant improvement in estimated mean z-scores on memory (HVLT-R immediate recall: 0.56, 95% CI 0.11-1.01, p=0.017) and executive functioning (TMT-B: 0.87, 95% CI 0.17-1.57, p=0.019; COWAT: 0.68, 95% CI 0.19-1.16, p=0.009) compared to baseline. Conclusions Impairment is present in a subgroup of patients prior to starting CAR T therapy. Patients may demonstrate declines on performance-based measures and report worsening cognitive symptoms in the first month after CAR T therapy, but also improved performance in some domains by three months. Enrollment and long-term follow-up of patients in this study is ongoing. Future analyses will explore differences in trajectories among subgroups, such as those who have experienced ICANS and CRS.

TANGO: a placebo-controlled randomized phase 2 study of efficacy and safety of the anti-tau monoclonal antibody gosuranemab in early Alzheimer’s disease

In Alzheimer’s disease, the spread of aberrantly phosphorylated tau is an important criterion in the Braak staging of disease severity and correlates with disease symptomatology. Here, we report the results of TANGO (NCT03352557), a randomized, double-blind, placebo-controlled, parallel-group and multiple-dose long-term trial of gosuranemab—a monoclonal antibody to N-terminal tau—in patients with early Alzheimer’s disease. The primary objective was to assess the safety and tolerability of gosuranemab compared to placebo. The secondary objectives were to assess the efficacy of multiple doses of gosuranemab in slowing cognitive and functional impairment (using the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) scores at week 78) and evaluate the immunogenicity of gosuranemab (using the incidence of anti-gosuranemab antibody responses). Participants were randomized (n = 654); received (n = 650) low-dose (125 mg once every 4 weeks (q4w), n = 58; 375 mg q12w, n = 58), intermediate-dose (600 mg q4w, n = 106) or high-dose (2,000 mg q4w, n = 214) gosuranemab or placebo (q4w, n = 214) intravenously for 78 weeks; and assigned to cerebrospinal fluid (n = 327) and/or tau positron emission tomography (n = 357) biomarker substudies. Gosuranemab had an acceptable safety profile and was generally well tolerated (incidence of serious adverse events: placebo, 12.1%; low dose, 10.3%; intermediate dose, 12.3%; high dose, 11.7%). The incidence of treatment-emergent gosuranemab antibody responses was low at all time points. No significant effects were identified in cognitive and functional tests as no dose resulted in a favorable change from the baseline CDR-SB score at week 78 compared to placebo control (adjusted mean change: placebo, 1.85; low dose, 2.20; intermediate dose, 2.24; high dose, 1.85). At week 76, all doses caused significant (P < 0.0001) reductions in the cerebrospinal fluid levels of unbound N-terminal tau compared to placebo.