Frontal Assessment Battery Research Articles

Protocol for Safety and Efficacy of MLC901 (NeuroAiD II) in Patients With Moderate Traumatic Brain Injury: A Randomized Double-Blind Placebo-Controlled Trial (ANDROMEDA).

Traumatic brain injury (TBI) remains a leading cause of death and disability, affecting approximately 69 million individuals each year worldwide. A significant portion of TBI research has focused on treatments for neuroprotection and/or neurorecovery, with most failing to transition to successful clinical applications despite promising animal/in vitro study results. MLC901 (NeuroAiD II), with origins from a traditional Chinese medicine, has been shown to exhibit both neuroprotective and neuroregenerative properties in in vitro and animal studies for stroke and TBI. Clinical trials have demonstrated its safety with significant improvements in some functional outcome and cognitive domain measures. To determine the efficacy and safety of MLC901 (NeuroAiD II) vs placebo in adult patients with moderate TBI. This is a multicenter randomized double-blind placebo-controlled trial that aims to enroll 120 adult patients with moderate TBI receiving standard of care in 2 arms: MLC901 vs placebo for a treatment period of 6 months with a further follow-up of 3 months. The total duration of the study is 9 months. The primary end point is Glasgow Outcome Scale Extended (GOS-E) at 6 months. Other assessments include mortality at 6 months, GOS-E, Glasgow Coma Scale, Montreal Cognitive Assessment Filipino Version, Frontal Assessment Battery Conflicting Instructions and Go-No-Go, Rivermead Post-Concussion Symptom Questionnaire, Barthel Index, Hospital Anxiety and Depression Scale, and Health related Quality of life (EQ-5D) at 1, 3, 6, and 9 months. Cerebral swelling at baseline and at 1 and 2 weeks will also be documented. Adverse events and drug compliance will also be monitored. We expect to find a significant improvement in functional and cognitive outcomes in patients who were given MLC901. Previous studies on the effect of MLC901 in adult patients with moderate TBI showed positive results; However, these studies are limited by the small number of patients. This study will establish a more definitive role of MLC901 in improving functional and cognitive outcomes in patients with moderate TBI.

Cognition in older offenders in North Rhine-Westphalia: A comparison of prisoners and patients in forensic psychiatry hospitals

The number of elderly delinquent individuals living in prisons and forensic hospitals is increasing. For both settings, complex needs have been described for the elderly related to age-related changes and frequent somatic disorders as well as mental disorders, primarily depressive symptoms.. One of the biggest challenges are cognitive impairments which have been described for both groups, probably not least due to frequent risk factors (e.g., substance abuse, depressive symptoms). Given that the group of forensic patients has a manifest mental illness, which is usually treated with psychopharmaceuticals, the question arises as to what extent cognitive deficits are more frequent here. For both groups, the detection of cognitive deficits with regard to therapy and release planning is of relevance. In sum, studies on cognitive function in both populations are rare, and the results are hard to compare due to different instruments to assess cognition.Sociodemographic, health-, and incarceration-related data were collected as well as neuropsychological functions using established instruments to evaluate global cognitive functioning (Mini-Mental State Examination [MMSE], DemTect), executive function (Frontal Assessment Battery [FAB], and Trail Making Test [TMT]).In the final sample, 57 prisoners and 34 forensic inpatients from North Rhine Westphalia, Germany being 60 years and older were included. The groups were comparable in age (prisoners: M = 66.5 years, SD ± 5.3; forensic inpatients: M = 66.8 years, SD ± 7.5) and education (prisoners: M = 11.47, SD ± 2.91; forensic inpatients: M = 11.39, SD ± 3.64), but the offenders in forensic psychiatry had spent significantly more time in the correctional setting than prisoners (prisoners: M = 8.6, SD ± 10.8; forensic inpatients: M = 15.6 years, SD ± 11.9). In both groups cognitive deficits were frequent. Depending on the tests and population, between 42% and 64% showed impairments in global cognition, and between 22% and 70% were classified with impaired executive functioning. We found no significant differences in global cognition or executive functions assessed with the TMT between the two groups. However, forensic inpatients were significantly more impaired in the FAB compared to the prisoners.The results emphasize the high frequency of cognitive dysfunction in both settings and a possibly higher frequency of “frontal” dysfunction in forensic inpatients, and, thus, indicate the relevance of routine neuropsychological diagnostic and treatment procedures in these settings.

Effects of Nordic walking in Alzheimer’s disease: A single-blind randomized controlled clinical trial

Non-pharmacological approaches, including exercise programs, have been proposed to improve cognitive function and behavioral symptoms, such as depression, agitation, or aggression, in the management of patients with Alzheimer's disease (AD). Indeed, physical inactivity is one of the main modifiable risk factors in patients with AD, as well as in the development of cardiovascular diseases and related pathologies.Although Nordic Walking (NW), a particular type of aerobic exercise, is known to benefit the health of aging populations, there is little evidence that patients with AD may benefit from this non-pharmacological treatment. In this context, we performed a pilot study in 30 patients with mild/moderate AD to evaluate whether NW influences different cognitive domains, including executive functions, visual-spatial abilities, and verbal episodic memory. To this aim, 15 patients (Control group, CG) underwent reality orientation therapy, music therapy, motor, proprioceptive and postural rehabilitation, and 15 patients (experimental group, EG) in addition to the activities performed by the CG also had the NW with a frequency of twice a week. Neuropsychological assessments and evaluations of daily activities and quality of life were performed at baseline and after 24 weeks. Twenty-two patients, including 13 in the CG and nine in the EG completed the activity program after 24 weeks. The EG showed a significant improvement in the Frontal Assessment Battery, Rey's auditory Verbal Learning Test Delayed Recall, Raven's Colored Progressive Matrices, and completion time for the Stroop Word-Color Interference test, compared to the CG. NW was able to improve cognitive domains like visual-spatial reasoning abilities, verbal episodic memory, selective attention, and processing speed in AD patients. These results, if confirmed by further studies with a larger number of patients and a longer training period, may prospect NW as a safe and likely useful strategy to slow down cognitive impairment in mild/moderate AD.

Comparative analysis of the impact of selected anesthesia methods on the cognitive function of patients undergoing ophthalmic surgery

Background: Anesthesiologists should not only save patient’s life as a process, but also enable the patient to recover his/her social life after surgery, given increased longevity, high social activity throughout life, and increased use of technical equipment in everyday life. Purpose: To assess central nervous system (CNS) changes in patients undergoing penetrating keratoplasty in order to optimize the choice of anesthesia technique, while taking into account the impact of general anesthesia on postoperative cognitive functions. Material and Methods: We employed neuropsychological tests such as Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB) and Luria’s test to examine the cognitive function of patients before surgery and 6 hours, 24 hours, 7 days and 21 days after surgery. Results: On the basis of comparative analysis of the impact of selected anesthesia methods on cognitive function of patients undergoing surgery (penetrating keratoplasty), we concluded that a combination of regional anesthesia (pterygopalatine fossa blockade), dexmedetomidine infusion (0.3 µg/kg) and general analgesia (maintenance in an oxygen/sevoflurane mixture) with exclusion of Sibazon 0.5% had the shortest and the least profound impact on the cognitive function. Conclusion: On the basis of comparative analysis of the impact of selected anesthesia methods on cognitive function of patients undergoing penetrating keratoplasty, we concluded that a combination of regional anesthesia (pterygopalatine fossa blockade), dexmedetomidine infusion (0.3 µg/kg) and general analgesia (maintenance in an oxygen/sevoflurane mixture) with removal of Sibazon 0.5% from premedication and presence of a reduced amount of fentanyl used during anesthesia had the shortest (with a mean duration of a day) and the least profound impact on cognitive state in patients undergoing ophthalmic surgery.

Association Between Neuropsychological Functions and Activities of Daily Living in People with Mild Cognitive Impairment

ABSTRACT Objective The aim of this study was to explore the relationship between performance in neurocognitive variables and daily functioning (basic or b- and instrumental or i-ADL) in people with mild cognitive impairment (MCI). Methods A sample of 157 participants with MCI (73.65 ± 7.58 years) completed a battery of tests for assessing ADL and cognitive functions. t-test, Pearson’s correlation and multiple linear regression (backward stepwise selection) were used for data analyses. Results Significant correlations were found between b- and i-ADL, and several neuropsychological tests (p < .01). Multivariate analysis showed that difficulties in Blessed Rating Scales (BLS) explained 33.2% of the variation in b-ADL and that this variation rises to 42.9% when BLS is associated with Frontal Assessment Battery Flexibility, Trail Making Test A (TMT-A) and BLS Personality. For i-ADL, BLS and Dementia Rating Scale Total (DRS-T) explained 47.7% of the variation and the inclusion in the model of BLS, DRS-IP (Initiation/Perseveration), TMT-A and BLS Personality explained 53.5% of this variation. Executive functions explained 24.8% of the variation in i-ADL. Conclusions Cognitive functions are related to i- and b-ADL in people with MCI. The general indicators and those that assess executive functions and verbal- or visual-spatial memory should be considered to predict i-ADL.

Serum neurofilament light chain in patients with epilepsy and cognitive impairment.

The neurofilament light chain (NfL) is receiving increased attention as a biomarker of neurological diseases, as NfL concentration elevated in the blood and cerebrospinal fluid after neuronal damage. However, few studies have addressed NfL in epilepsy. We aimed to investigate the alteration of serum NfL in adult patients with epilepsy, and the association between this biomarker and cognitive impairment. A total of 38 consecutive patients with epilepsy and 24 controls underwent cross-sectional measurement of serum NfL levels and cognitive testing using the Mini-Mental State Examination (MMSE), the Japanese version of the Montreal Cognitive Assessment (MoCA-J), the Frontal Assessment Battery (FAB), the Trail-Making Test, and the Stroop Color-Word Test. Statistical analysis was performed with Student's t-test to compare serum NfL levels between the epilepsy group and the control group, and with Spearman's correlation and age-corrected partial correlation analyses to evaluate the association between serum NfL level and cognitive impairment in epilepst patients. There was no difference in serum NfL levels between the epilepsy and control groups (epilepsy [mean ± SD]: 17.3 ± 13.9 pg/mL; control: 17.7 ± 11.5 pg/mL; p = .92); however, the MoCA-J scores were lower in the epilepsy group (26.6 ± 3.1 vs. 28.1 ± 1.6; p = .03). The age-corrected partial correlation analysis showed a correlation between serum NfL level and cognitive test scores in the epilepsy group (MMSE: rs = -.63, p < .01; MoCA-J: rs = -.54, p < .01; FAB: rs = -.68, p < .01), whereas serum NfL levels were correlated exclusively with MMSE scores in the control group (rs = .44, p = .04). In adult epilepsy patients, the serum NfL level was not significantly elevated, but was correlated with cognitive test scores. Our findings suggest that serum NfL concentration could be an indicator of cognitive function in epilepsy patients.

Клинические и нейрофизиологические корреляты когнитивных нарушений у пациентов с атеросклеротическим поражением сонных артерий

INTRODUCTION: Cognitive disorders often do not come to the fore in the interpretation of clinical manifestations in hemodynamically significant stenoses of brachiocephalic arteries. In this regard, the objectification of cognitive disorders based on a battery of tests, as well as of their neurophysiological correlates, is an important task of both angiology and neurology. Endogenous evoked potential P300 is a frequently used neurophysiological phenomenon characterizing the psychophysiological functions of perception, attention, and thinking. AIM: To study the dynamics of cognitive functions and their neurophysiological correlates in patients with hemodynamically significant carotid artery stenosis before and after carotid endarterectomy. MATERIALS AND METHODS: An open prospective study included 60 patients divided to two groups. Group A included 30 ‘symptomatic’ patients with a hemodynamically significant lesion (stenosis) of the internal carotid artery and a history of acute cerebrovascular accident. Group B included 30 ‘asymptomatic patients’ without a history of cerebrovascular events. Within the study, before surgery for carotid stenosis and 6 months after, the following parameters were assessed: cognitive status (according to the MMSE, FAB, MoCA, NIHSS scales), and also clinical and neurophysiological correlates of cognitive functions (P300 evoked potential). RESULTS: In the group of patients with neurological disorders (group A), a reliably greater number of errors (p = 0.048), as well as a decrease in the amplitude (p = 0.006) and increase in latency (p = 0.022) of P2 component of P300 cognitive evoked potential were determined. Based on the parameters of P300 event-related potential, a logit regression model was created that permitted to classify patients to the above-mentioned groups. The cluster analysis of dynamics of cognitive functions was additionally performed before and after surgery. In cluster 1, there were 45% of symptomatic patients, 55% of asymptomatic ones, in cluster 2 — 58% and 32%, respectively, no reliable differences were found (chi-square 0.58; p = 0.445). Cluster 1 was characterized by initially higher level of test performance with some increase in this parameter after surgery; Cluster 2 was characterized by a lower level of these parameters, with the greatest differences found in frontal assessment battery (FAB) characteristics. Reliable differences in the level of P300 were found only after surgery: the greatest differences were recorded in the amplitude of P2, P3, N2 components. CONCLUSION: The factor of cognitive impairment is a separate phenomenon, not closely related to focal neurological syndrome in patients with carotid atherosclerosis. An objective neurophysiological criterion for cognitive impairment in these patients is the endogenous evoked potential P300. With this, the greatest differences between the neurophysiological correlates of cognitive disorders are determined 6 months after the operation for carotid stenosis.

Long-term changes in cognitive status of patients with type 2 diabetes mellitus after coronary artery bypass graft surgery

Aim. To study long-term changes (5 to 7 years after coronary artery bypass graft (CABG) surgery) in cognitive status of patients with type 2 diabetes.Materials and Methods. The study included 47 male patients admitted to the Research Institute for Complex Issues of Cardiovascular Diseases for the CABG surgery. Criteria of inclusion were signed informed consent, age from 40 to 75 years, male gender, planned on-pump CABG surgery, and right-handedness. Criteria of exclusion were brain pathology at multislice computed tomography, chronic cerebral ischemia grade II-IV, Beck Depression Inventory score &gt; 16 points, the Mini-Mental State Examination (MMSE) score &lt; 24 points and the Frontal Assessment Battery score &lt; 11 points, arrhythmia, class IIB-IV chronic heart failure stage IIB, chronic obstructive pulmonary disease, cancer, and past medical history of brain injury or stroke. Pre-operative examination of patients classified them into two groups: with (n = 21) and without (n = 26) type 2 diabetes mellitus (DM).Results. 5-7 years after CABG surgery, patients with type 2 DM had a cognitive decline according to MMSE scale as compared to the preoperative level (28,0 [27,0; 29,0] and 27,0 [26,0; 28,0], p = 0.04). In keeping with these findings, odds ratio (OR) of mild cognitive impairment (MCI) in patients with type 2 DM was 1.92 (95% CI = 1.09- 3.37, p = 0.02). Psychomotor and executive functions were reduced in patients with type 2 DM both at baseline and in particular 5-7 years after CABG (p ≤ 0.05). The correlation between glycated hemoglobin (HbA1c) and cognitive parameters were found only in patients with type 2 DM. Higher HbA1c level was also associated with deteriorated executive functions and short-term memory.Conclusion. 5−7 years after CABG surgery, patients with type 2 DM suffer from a cognitive decline and reduced psychomotor and executive functions.

Clinimetrics and feasibility of the Italian version of the Frontal Assessment Battery (FAB) in non-demented Parkinson's disease patients.

This study aimed at assessing the cross-sectional and longitudinal clinimetrics and feasibility of the Frontal Assessment Battery (FAB) in non-demented Parkinson's disease (PD) patients. N = 109 PD patients underwent the FAB and the Montreal Cognitive Assessment (MoCA). A subsample of patients further underwent a thorough motor, functional and behavioral evaluation (the last including measures of anxiety, depression and apathy). A further subsample was administered a second-level cognitive battery tapping on attention, executive functioning, language, memory, praxis and visuo-spatial abilities. The following properties of the FAB were tested: (1) concurrent validity and diagnostics against the MoCA; (2) convergent validity against the second-level cognitive battery; (4) association with motor, functional and behavioral measures; (5) capability to discriminate patients from healthy controls (HCs; N = 96); (6) assessing its test-retest reliability, susceptibility to practice effects and predictive validity against the MoCA, as well as deriving reliable change indices (RCIs) for it, at a ≈ 6-month interval, within a subsample of patients (N = 33). The FAB predicted MoCA scores at both T0 and T1, converged with the vast majority of second-level cognitive measures and was associated with functional independence and apathy. It accurately identified cognitive impairment (i.e., a below-cut-off MoCA score) in patients, also discriminating patients from HCs. The FAB was reliable at retest and free of practice effects; RCIs were derived according to a standardized regression-based approach. The FAB is a clinimetrically sound and feasible screener for detecting dysexecutive-based cognitive impairment in non-demented PD patients.

Plasma Soluble ST2 Levels Are Higher in Neurodegenerative Disorders and Associated with Poorer Cognition.

Suppressor of tumorgenicity 2 (ST2) is highly expressed in brain tissue and is a receptor for interleukin 33 (IL-33). ST2 exists in two forms, a transmembrane receptor (ST2L) and a soluble decoy receptor (sST2). IL-33 binds to ST2L, triggering downstream signaling pathways involved in amyloid plaque clearance. Conversely, sST2 binds competitively to IL-33, attenuating its neuroprotective effects. High sST2 levels have been reported in mild cognitive impairment (MCI) and Alzheimer's disease (AD), suggesting that the IL-33/ST2 signaling pathway may be implicated in neurodegenerative diseases. To investigate plasma sST2 levels in controls and patients with MCI, AD, frontotemporal dementia (FTD), and Parkinson's disease (PD). Plasma sST2 levels were measured using ELISA in 397 subjects (91 HC, 46 MCI, 38 AD, 28 FTD, and 194 PD). Cerebrospinal fluid (CSF) levels of sST2 were measured in 22 subjects. Relationship between sST2 and clinical outcomes were analyzed. Plasma sST2 levels were increased across all disease groups compared to controls, with highest levels seen in FTD followed by AD and PD. Dementia patients with higher sST2 had lower cross-sectional cognitive scores in Frontal Assessment Battery and Digit Span Backward. At baseline, PD-MCI patients had higher sST2, associated with worse attention. In the longitudinal PD cohort, higher sST2 significantly associated with decline in global cognition and visuospatial domains. Plasma sST2 levels correlated with CSF sST2 levels. Plasma sST2 is raised across neurodegenerative diseases and is associated with poorer cognition. Higher baseline sST2 is a potential biomarker of disease severity in neurodegeneration.

Rapid eye movement sleep behavior disorder is associated with decreased quality of life and stigma in people with Parkinson’s disease

Individuals with Parkinson's disease (PD) may present with rapid eye movement sleep behavior disorder (RBD). We therefore investigated the association between RBD and quality of life (QOL) in people with PD. Individuals with PD and a Mini-Mental State Examination score ≥ 24 were divided into two groups using the RBD screening questionnaire (RBDSQ): those with an RBDSQ score ≥ 5 were assigned to the "probable RBD" (pRBD) group, and those with a score < 5 to the "non-pRBD" group. Participants were then evaluated for motor symptoms (Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III and modified Hoehn and Yahr Scale), cognitive functions (Montreal Cognitive Assessment and Frontal Assessment Battery [FAB]), anhedonia (Snaith-Hamilton Pleasure Scale), and QOL (Parkinson's Disease Questionnaire [PDQ]-39 total and subscores for mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication, and bodily discomfort). Each measure was compared between the two groups (Mann-Whitney U test/χ2 test). Multiple regression analyses were performed to identify factors contributing to the total score and the subscore of the stigma domain of the PDQ-39. Ninety-three individuals with PD were recruited (mean ± standard deviation age, 67.0 ± 10.6years). The pRBD group exhibited a longer disease duration (P = 0.006), worse FAB (P = 0.015) and PDQ-39 total (P = 0.032) scores. RBDSQ scores correlated with higher scores in the PDQ-39 stigma domain (B = 2.44, P = 0.033). RBD is associated with worse QOL andstigma in people with PD. The RBDSQ is a useful tool for the prediction of such disturbances in QOL.

Prediction of postoperative cognitive dysfunction in patients with coronary artery disease after on­pump coronary artery bypass grafting

Coronary artery disease is the most common cause of death world­wide. On­pump coronary artery bypass grafting and cardioplegia remains the gold standard for the treatment of multivessel coronary disease. However, this method of surgical treatment has a number of perioperative complications, the most common of which is post­operative cognitive dysfunction (POCD).Aim. To develop a mathematical model for predicting the binary outcome "presence/absence of POCD deterioration" using Mini­Mental State Examination (MMSE) and Frontal Assessment Battery (FAB) for timely prevention of cognitive impairment in the early postoperative period.Material and methods. The study included 180 patients with coronary artery disease with stable angina who underwent on­pump coronary artery bypass grafting. The patients’ age [Me (Q25­-Q75)] was 62 [56­-67] years. After the operation, all patients were divided into 2 groups: 108 patients without POCD and 72 patients with cognitive deficit of various severity. The study was conducted in three stages: stage I — 2 days before surgery; stage II — during the operation; stage III — 7 days after the operation. Assessment of cognitive status using FAB, MMSE tests was carried out at stages I and III. At the second stage, biochemical parameters were assessed: in arterial blood — lactate and hemoglobin levels, in venous blood — pH, partial pressure of carbon dioxide (pCO2, mm Hg) and partial pressure of oxygen (pO2, mm Hg), as well as the duration of operation, cardiopulmonary bypass and myocardial anoxia. Discriminant analysis was used to develop a mathematical model for predicting a binary outcome.Results. Two groups of the most informative indicators were identified that were included in prediction algorithms for binary outcomes "presence/absence of negative dynamics of POCD" for MMSE and FAB. Group 1 included perioperative MMSE values, atrial fibrillation before surgery, cardiopulmonary bypass time and pO2. Group 2 included cardiopulmonary bypass time and intraoperative venous pH. Conclusion. Mathematical models have been developed for predicting the binary outcome "presence/absence of POCD deterioration" ac­cording to the MMSE and FAB cognitive tests, which make it possible to assess the possibility of postoperative cognitive dysfunction. The proposed algorithms are implemented using spreadsheets and a computer program.

Association between Cognitive Impairment and Hippocampal Subfield Volumes in Multiple System Atrophy.

This study aimed to explore morphological changes of hippocampal subfields in patients with multiple system atrophy (MSA) with and without cognitive impairment using FreeSurfer-automated segmentation of hippocampal subfield techniques and their relationship with cognitive function. We enrolled 75 patients with MSA classified as cognitively impaired MSA (MSA-CI, n = 40) and cognitively preserved MSA (MSA-CP, n = 35), as well as 68 healthy controls. All participants underwent three-dimensional volume T1-weighted magnetic resonance imaging. The hippocampal subfield volume was measured using FreeSurfer version 7.2 and compared among groups. Regression analyses were performed between the hippocampal subfield volumes and cognitive variables. Compared with healthy controls, the volume of the right cornu ammonis (CA) 2/3 was significantly lower in the MSA-CI group (P=0.029) and that of the left fimbria was significantly higher in the MSA-CP group (P=0.046). Results of linear regression analysis showed that the right CA2/3 volume was significantly correlated with the Frontal Assessment Battery score in patients with MSA (adjusted R 2 = 0.282, β = 0.227, and P=0.041). The hippocampal subfield volume decreased in patients with MSA-CI, even at the early disease stages. Specific structural changes in the hippocampus might be associated with cognitive deficits in MSA.

Cognitive impairment in obese patients: a pilot study. Correction possibilities

Obesity is a risk factor for cognitive impairment (CI) that has a significant impact on quality of life in patients. Objective. To study the frequency and nature of CI in obese patients. Subjects and methods. The study involved 51 obese patients and 28 healthy normal-weighted volunteers matched for age, gender, and level of education. Cognitive functions were assessed using the MoCa test and the Frontal Assessment Battery (FAB) scale. Results. The median MoCA scores were 28 (27; 29) in the normal weight group and 25 (25; 27) in obese patients; the differences between the groups were statistically significant (p &lt; 0.05). The median total FAB score in both groups was 18 (17; 18) and had no significant differences (p &gt; 0.05). Conclusion. The findings may suggest that the carbohydrate metabolism is associated with the risk of CI in obese patients, since obesity is related to a number of metabolic and hemodynamic disorders. The MoCa test proved to be a more sensitive cognitive screening test for mild CI in obese patients. Phytopreparations "Femo-Klim" and "Nervo-Vit" can be recommended for women with estrogen deficiency and obesity, as they contribute to the normalization of estrogen levels and weight loss, as well as contribute to the improvement of cognitive functions and psychological state. The drug "Eromax" is recommended for the correction of obesity and cognitive disorders in men associated with low testosterone levels.

Serum levels of IL-6 are associated with cognitive impairment in the salus in apulia population-based study

Growing evidence suggests that inflammation contributes to brain aging and neurodegeneration. This study investigates the relationship between global cognitive as well executive function and the inflammatory markers IL-6, CRP, and TNF-α in a population-based study of older adults. A population-based sample, of older people in Southern Italy, was enrolled. We measured serum levels of IL-6, CRP, and TNF-α. We also administered two neuropsychological tests: Mini-Mental State Examination and Frontal Assessment Battery. Rank-based regression models were performed to investigate the relationship between inflammatory markers and cognitive functions, including major demographic and clinical confounders for adjustment. The sample consisted of 1929 subjects aged between 65 and 95 years. Multivariate linear regression analysis revealed that higher serum levels of IL-6 were associated with lower MMSE and FAB scores even after adjustment for demographic data and cardiovascular risk factors. No significant associations were found between cognitive functioning and serum levels of CRP and TNF-α. Our results suggest that higher levels of IL-6 were associated with cognitive impairment in an older adult population of Southern Italy.

Serum inflammatory cytokines levels and the correlation analyses in Parkinson's disease.

Objective: To investigate the serum levels of inflammatory cytokines and the correlations with Parkinson's disease (PD) clinical symptoms. Methods: Serum levels of the cytokines, including IL-6, IL-8, and TNF-α, were measured in 273 PD patients and 91 healthy controls (HCs). The clinical manifestations of PD were assessed with nine different scales to evaluate the cognitive function, non-motor symptoms, motor symptoms, and disease severity. The differences in these inflammatory indicators were examined between PD patients and HCs, and the correlations of these inflammatory indicators with clinical variables were analyzed in PD patients. Results: Serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in PD patients were higher than those in HCs, but serum interleukin-8 (IL-8) level was not significantly different from that in HCs. In PD patients, serum IL-6 level was positively correlated with age of onset, the Hamilton Depression Scale (HAMD), and the Non-Motor Symptom Scale (NMSS), UPDRS part I, part II, and part III, but it was inversely correlated with the Frontal Assessment Battery (FAB) and the Montreal Cognitive Assessment (MoCA) scores. Serum TNF-α level was positively correlated with age of onset and H&Y stage in PD patients (p = .037), but negatively correlated with FAB scores in PD patients (p = .010). However, no associations were found between all the clinical variables and the serum IL-8 level. The forward binary logistic regression model revealed that serum IL-6 level was associated with MoCA (p = .023) and UPDRS I scores (p = .023), but no associations was found with the remaining factors. The ROC curve of TNF-α for the diagnosis of PD showed the area under the curve (AUC) was .719 (p < .05, 95% CI: .655-.784), and the critical value of TNF-α was 5.380pg/ml, with a diagnostic sensitivity of 76.0% and a specificity of 59.3%. Conclusion: Our results suggest increased serum levels of IL-6 and TNF-α in PD, we further found that IL-6 level was associated with non-motor symptoms and cognitive dysfunction, and IL-6 may play a role in the pathophysiology of non-motor symptoms in PD. At the same time, we also propose that TNF-α has a good diagnostic value for PD despite its irrelevance to clinical symptoms.

The Effects of SARS-CoV-2 Infection on the Cognitive Functioning of Patients with Pre-Existing Dementia.

Cognitive postscripts of COVID-19, codenamed as 'cognitive COVID' or 'brain fog,' characterized by multidomain cognitive impairments, are now being reckoned as the most devastating sequelae of COVID-19. However, the impact on the already demented brain has not been studied. We aimed to assess the cognitive functioning and neuroimaging following SARS-CoV-2 infection in patients with pre-existing dementia. Fourteen COVID-19 survivors with pre-existing dementia (four with Alzheimer's disease, five with vascular dementia, three with Parkinson's disease dementia, and two with the behavioral variant of frontotemporal dementia) were recruited. All these patients had detailed cognitive and neuroimaging evaluations within three months before suffering from COVID-19 and one year later. Of the 14 patients, ten required hospitalization. All developed or increased white matter hyperintensities that mimicked multiple sclerosis and small vessel disease. There was a significant increase in fatigue (p = 0.001) and depression (p = 0.016) scores following COVID-19. The mean Frontal Assessment Battery (p < 0.001) and Addenbrooke's Cognitive Examination (p = 0.001) scores also significantly worsened. The rapid progression of dementia, the addition of further impairments/deterioration of cognitive abilities, and the increase or new appearance of white matter lesion burden suggest that previously compromised brains have little defense to withstand a new insult (i.e., 'second hit' like infection/dysregulated immune response, and inflammation). 'Brain fog' is an ambiguous terminology without specific attribution to the spectrum of post-COVID-19 cognitive sequelae. We propose a new codename, i.e. 'FADE-IN MEMORY' (i.e., Fatigue, decreased Fluency, Attention deficit, Depression, Executive dysfunction, slowed INformation processing speed, and subcortical MEMORY impairment).

White and gray matter alterations in de novo PD patients: which matter most?

This paper aimed to identify white matter (WM) and gray matter (GM) abnormalities in a sample of early PD patients, and their correlations with motor and non-motor symptom severity. We enrolled 62 de novo PD patients and 31 healthy subjects. Disease severity and non-motor symptom burden were assessed by the Unified Parkinson's Disease Rating Scale part III and the Non-Motor Symptoms Scale, respectively. Cognitive performance was assessed using Montreal Cognitive Assessment and Frontal Assessment Battery. All subjects underwent a 3-Tesla MRI protocol. MRI analyses included tract-based spatial statistics, cortical thickness, and subcortical and cerebellar volumetry. In comparison to control subjects, PD patients exhibited lower fractional anisotropy and higher mean, axial, and radial diffusivity in most WM bundles, including corticospinal tracts, the internal and external capsule, the anterior and posterior thalamic radiations, the genu and body of the corpus callosum, cerebellar peduncles, and superior and inferior longitudinal and fronto-occipital fasciculi. Correlations between Montreal Cognitive Assessment scores and fractional anisotropy values in the right posterior thalamic radiation, left superior corona radiata, right inferior-fronto-occipital fasciculus, left inferior longitudinal fasciculus, bilateral anterior thalamic radiations, and bilateral superior longitudinal fasciculi were found. Smaller cerebellar volumes in early PD patients in the left and right crus I were also found. No GM changes were present in subcortical or cortical regions. The combined evaluation of WM and GM in the same patient sample demonstrates that WM microstructural abnormalities precede GM structural changes in early PD patients.

Abstract WP112: Iodine-123-iomazenil Spect Revealed Recovery Of Neuronal Viability In Association With Improvement Of Cognitive Dysfunction After Revascularization In Moyamoya Disease

Background: Recent studies indicate 123I-iomazenil (123I-IMZ) SPECT could demonstrate a neuronal viability. Although cognitive dysfunction has been recognized as an important issue in adult moyamoya disease (MMD), standard neuroradiological methods to define such condition are not established. Aim: Relationship between cognitive function and 123I-IMZ SPECT before and after revascularization in MMD was firstly examined. Method: Fifteen patients whose cerebrovascular reactivities (CVRs) were decreased only on the treatment sides were studied. Cognitive function was examined using mini-mental scale examination (MMSE, cutoff 27) and frontal assessment battery (FAB, cutoff 16) before and 6 months after surgery. 123I-IMZ and 123I-iodoamphetamine SPECT with acetazolamide challenge were performed at the same timings. Radioreactivities of 123I-IMZ SPECT at the regions with decreased CVR were investigated using affected-to-contralateral side ratio (ACR). Results: Eleven patients showed normal cognitive dysfunction before surgery (MMSE 29.5, FAB 18). In their preoperative 123I-IMZ SPECT, there were no regions with decreased uptakes (ACR 0.97). The cognitive functions and 123I-IMZ SPECT were not worsened after surgery (MMSE 29.9, FAB 18, ACR 0.99). By contrast, preoperative images of four patients with cognitive dysfunction (MMSE 23.8, FAB 14) showed decrease of 123I-IMZ uptakes, and the preoperative ACRs (0.82) were significantly lower than those of the normal group. Cognitive functions and 123I-IMZ uptakes of these four patients tended to ameliorate after revascularization (MMSE 27.5, FAB 15.5, ACR 0.92). Conclusion: Cognitive functions of MMD patients were associated with 123I-IMZ uptakes, and could improve after surgery with recoveries of neuronal viabilities.

Executive dysfunctions in patients recovering from Covid-19

Background COVID-19 is recognized as a multi-organ disease that can affect many organs either during the acute stage of infection or even after recovery. These are part of the post COVID-19 syndrome. Neuropsychiatric symptoms such as cognitive impairments are part of them and include memory difficulties, executive functions impairments, and trouble focusing. However cognitive profile in these patients is still not precise and underlying mechanisms are still unclear. Besides, most studies were performed in western or Asian countries. Almost no studies were performed in African or Arab countries. The aim of our study was to assess neuropsychiatric and cognitive disorders in Tunisian patients who recovered from Covid-19. Method A cross-sectional survey was conducted during the months of May and June 2021, including patients one month after discharge from the pneumology ward in Mongi Slim Hospital in Marsa Tunisia. They all were hospitalized there for COVID-19 infection. Socio-demographic and clinical data were collected from medical records and through interviewing patients directly. To assess cognitive impairment, we used: Mini Mental State (MMS), Frontal Assessment Battery (FAB), Trail Making Test (TMT), and the maze task. Anxiety and depressive symptoms were also screened using the Hospital Anxiety and Depression. Results Twenty patients were included in the study, with 65% males. There were 14 patients with at least one cognitive dysfunction, which represents 70% of the sample. Three patients had less than the cut off score on the MMS and 8 patients on the FAB (showing respectively memory and executive impairment). On the TMT and the maze task, respectively 5 and 9 patients had abnormal timing scores. Conclusion Patients hospitalized with COVID-19 may show cognitive impairment shortly after discharge. Memory and executive functions are the most affected domains. For better management of these patients, screening for cognitive disorders in post COVID is vividly recommended. Long term studies are needed to check whether these impairments remain after the early phase.