Global Impairment Research Articles

Selective Motor Control is a Clinical Correlate of Brain Motor Tract Impairment in Children with Spastic Bilateral Cerebral Palsy.

Selective voluntary motor control is an important factor influencing gross motor function, interjoint coordination, and the outcome of hamstring-lengthening surgery in spastic cerebral palsy. Using DTI, we investigated whether selective voluntary motor control would show strong correlations with WM motor tract microstructure and whether selective voluntary motor control is more sensitive to global WM impairment than gross motor function. Children with spastic bilateral cerebral palsy born preterm and typically developing children were recruited. The Selective Control Assessment of the Lower Extremity (SCALE) and Gross Motor Function Measure (GMFM) were assessed in participants with cerebral palsy. Participants underwent brain MR imaging to collect DWI data. Tract-Based Spatial Statistics was used to analyze the WM for between-group differences and correlations with SCALE and GMFM. ROI analyses compared motor regions. Twelve children with cerebral palsy (mean age, 11.5 years) and 12 typically developing children (mean age, 10.3 years) participated. Altered DTI outcomes were found throughout the whole brain for the cerebral palsy group. SCALE, developed to evaluate selective voluntary motor control in cerebral palsy, showed significant positive correlations with fractional anisotropy in more WM voxels throughout the whole brain and for motor regions, including the corticospinal tract and corpus callosum, compared with GMFM. A significant negative correlation between radial diffusivity and SCALE, but not GMFM, was found within the corpus callosum. SCALE was a more sensitive clinical correlate of motor and whole-brain WM tract impairment in children with spastic bilateral cerebral palsy, suggesting greater anisotropy and myelination in these regions for those with higher selective voluntary motor control.

Screening for cognitive impairment among patients with work-related stress complaints in Denmark: validation and evaluation of objective and self-report tools.

ObjectiveMany patients with work-related stress display cognitive impairment that may hamper recovery. We examined objective and subjective tools for screening of cognitive impairment in this patient group.MethodsPatients were assessed with Danish versions of the objective Screen for Cognitive Impairment in Psychiatry (SCIP-D), standardized neuropsychological tests that tapped into the same cognitive domains, the self-assessed Cognitive Failure Questionnaire (CFQ), and several additional scales of symptom severity and psychosocial status. Concurrent validity of the SCIP-D and CFQ was assessed by calculation of Pearson’s correlation coefficients between the objective and subjective tools and the scores on more conventional standardized neuropsychological tests. Decision validity was assessed with logistic receiver-operating-characteristic analyses using a cut-score approach to the objective and the subjective test results to predict impairment detected by the standardized tests. Cognitive norms were established through the data of 79 healthy controls. SCIP-D scores were compared between patients and healthy controls with independent t-tests.ResultsWe included 82 patients with work-related stress. The SCIP-D total scores were strongly associated with standardized neuropsychological tests (r=0.76, P<0.001). The self-assessed CFQ was not associated with either measure of objective cognitive functioning (r≤0.12, P≥0.30). The optimal SCIP-D total-score cut of ≤72 identified 43.2% of the patients with global objective cognitive impairment. The patients performed mildly-to.moderately lower than the healthy controls on the SCIP-D total score (Cohen’s d=0.39) and the subtests for working memory (d=0.39) and processing speed (d=0.61).ConclusionThe SCIP-D is a valid screening tool sensitive to objective performance-based cognitive impairment among patients with work-related stress.

Association Between the Prognostic Nutritional Index and Cognitive Function Among Older Adults in the United States: A Population-Based Study.

Nutritional status has been recognized as an important factor influencing cognitive function-related diseases, but few comprehensive nutrition indicators are available to assess the risk of cognitive decline. This study aimed to investigate the relationship between the prognostic nutritional index (PNI) and cognitive function in an elderly population, and the differences in nutrient intake between different levels of nutritional risk. Based on cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014, we included 2,564 older participants. The lower quartile of each of the four cognitive tests was considered to have cognitive function impairment (CFI). Binary and multivariate logistic regression models were used to estimate the relationship between the PNI and the odds ratio of CFI. After adjustment for confounding variables, we found that the odds of CFI were significantly lower for participants with normal PNI levels than for those with low PNI levels. In a comparison of global cognitive impairment scores, participants with a normal PNI had lower ratios of poor cognitive performance than those with a low PNI. By comparing the nutrient intake at different PNI levels, we found a reduction in the intake of protein, dietary fiber, total saturated fatty acids, and multiple micronutrients in the low PNI group. Our study shows that the PNI can be a good predictor of the odds of CFI in the elderly population and that it is a convenient indicator of reduced intake of nutrients which may be important to brain health.

The impact of common genetic variants in cognitive decline in the first seven years of Parkinson’s disease: A longitudinal observational study

IntroductionCognitive impairment is a common feature of Parkinson’s disease and is a significant determinant of patients’ quality of life and dependence. The pattern and progression of cognitive symptoms vary greatly between individuals, and genetic biomarkers may help to predict the severity and trajectory of cognitive impairment in groups of patients. MethodsThe study included 171 patients from a longitudinal population-based incident Parkinson’s disease study from South Western Norway. All participants were followed from the time of diagnosis for up to seven years, undertaking repeated batteries of clinical and neuropsychological tests, measuring global cognitive impairment, executive function, attention, verbal learning and memory, and visuospatial skills. We used linear mixed regression analyses to explore associations between the function in specific cognitive domains over time and common genetic variants in APOE, MAPT, COMT and BDNF. ResultsThe COMT158Val/Val allele wasassociatedwith faster decline in executive function (p = 0.028), verbal learning and memory (p = 0.029), and visuospatial skills (p = 0.027). The BDNF, MAPT and APOE genotypes were not significantly associated with longitudinal changes in individual cognitive domains, however carriers of the APOE-ε4 allele were shown to be at increased risk of mild cognitive impairment and dementia within the study period (OR3.03; p = 0.006). ConclusionsThis population-based study of newly diagnosed patients provides new evidence that COMTVal158Met effects cognitive outcomes limited to discrete domains and APOE-ε4 status predicts a poor overall cognitive prognosis. Together, these data contribute to our understanding of the biology underlying the heterogeneity observed in the progression of PD.

Evidence for a pervasive autobiographical memory impairment in Logopenic Progressive Aphasia

Although characterized primarily as a language disorder, mounting evidence indicates episodic amnesia in Logopenic Progressive Aphasia (LPA). Whether such memory disturbances extend to information encoded pre-disease onset remains unclear. To address this question, we examined autobiographical memory in 10 LPA patients, contrasted with 18 typical amnestic Alzheimer's disease and 16 healthy Control participants. A validated assessment, the Autobiographical Interview, was employed to explore autobiographical memory performance across the lifespan under free and probed recall conditions. Relative to Controls, LPA patients showed global impairments across all time periods for free recall, scoring at the same level as disease-matched cases of Alzheimer's disease. Importantly, these retrieval deficits persisted in LPA, even when structured probing was provided, and could not be explained by overall level of language disruption or amount of information generated during autobiographical narration. Autobiographical memory impairments in LPA related to gray matter intensity decrease in predominantly posterior parietal brain regions implicated in memory retrieval. Together, our results suggest that episodic memory disturbances may be an under-appreciated clinical feature of LPA.

Tablet-Based Cognitive Impairment Screening for Adults With HIV Seeking Clinical Care: Observational Study.

BackgroundNeurological complications including cognitive impairment persist among people with HIV on antiretrovirals; however, cognitive screening is not routinely conducted in HIV clinics.ObjectiveOur objective for this study was 3-fold: (1) to determine the feasibility of implementing an iPad-based cognitive impairment screener among adults seeking HIV care, (2) to examine the psychometric properties of the tool, and (3) to examine predictors of cognitive impairment using the tool.MethodsA convenience sample of participants completed Brain Baseline Assessment of Cognition and Everyday Functioning (BRACE), which included (1) Trail Making Test Part A, measuring psychomotor speed; (2) Trail Making Test Part B, measuring set-shifting; (3) Stroop Color, measuring processing speed; and (4) the Visual–Spatial Learning Test. Global neuropsychological function was estimated as mean T score performance on the 4 outcomes. Impairment on each test or for the global mean was defined as a T score ≤40. Subgroups of participants repeated the tests 4 weeks or >6 months after completing the first test to evaluate intraperson test–retest reliability and practice effects (improvements in performance due to repeated test exposure). An additional subgroup completed a lengthier cognitive battery concurrently to assess validity. Relevant factors were abstracted from electronic medical records to examine predictors of global neuropsychological function.ResultsThe study population consisted of 404 people with HIV (age: mean 53.6 years; race: 332/404, 82% Black; 34/404, 8% White, 10/404, 2% American Indian/Alaskan Native; 28/404, 7% other and 230/404, 58% male; 174/404, 42% female) of whom 99% (402/404) were on antiretroviral therapy. Participants completed BRACE in a mean of 12 minutes (SD 3.2), and impairment was demonstrated by 34% (136/404) on Trail Making Test A, 44% (177/404) on Trail Making Test B, 40% (161/404) on Stroop Color, and 17% (67/404) on Visual-Spatial Learning Test. Global impairment was demonstrated by 103 out of 404 (25%). Test–retest reliability for the subset of participants (n=26) repeating the measure at 4 weeks was 0.81 and for the subset of participants (n=67) repeating the measure almost 1 year later (days: median 294, IQR 50) was 0.63. There were no significant practice effects at either time point (P=.20 and P=.68, respectively). With respect for validity, the correlation between global impairment on the lengthier cognitive battery and BRACE was 0.63 (n=61; P<.001), with 84% sensitivity and 94% specificity to impairment on the lengthier cognitive battery.ConclusionsWe were able to successfully implement BRACE and estimate cognitive impairment burden in the context of routine clinic care. BRACE was also shown to have good psychometric properties. This easy-to-use tool in clinical settings may facilitate the care needs of people with HIV as cognitive impairment continues to remain a concern in people with HIV.

Impact of epicardial adipose tissue on cardiovascular haemodynamics, metabolic profile, and prognosis in heart failure.

We evaluated the impact of echocardiographic epicardial adipose tissue (EAT) on cardiovascular haemodynamics, metabolic profile and prognosis in heart failure (HF) using combined cardiopulmonary-echocardiography exercise stress. We analysed EAT thickness of HF patients with reduced (HFrEF, n=205) and preserved (HFpEF, n=188) ejection fraction, including 44 controls. HFpEF patients displayed the highest EAT, while HFrEF patients had lower values than controls. EAT showed an inverse correlation with natriuretic peptides, troponin T and C-reactive protein in HFrEF, while having a direct association with troponin T and C-reactive protein in HFpEF. EAT was independently associated with peak oxygen consumption (VO2 ) and peripheral extraction (AVO2 diff), regardless of body mass index. EAT was inversely correlated with peak VO2 and AVO2 diff in HFpEF, while a direct association was observed in HFrEF, where lower EAT values were associated with worse left ventricular systolic dysfunction. In HFpEF, increased EAT was related to right ventriculo-arterial (tricuspid annular plane systolic excursion/systolic pulmonary artery pressure) uncoupling. After 21 months of follow-up, 146 HF hospitalizations and 34 cardiovascular deaths were recorded in the HF population. Cox multivariable analysis supported an independent differential role of EAT in HF cohorts (interaction P=0.01): higher risk of adverse events for increasing EAT in HFpEF [hazard ratio (HR) 1.12, 95% confidence interval (CI) 1.04-1.37] and for decreasing EAT in HFrEF (HR 0.75, 95% CI 0.54-0.91). In HFpEF, EAT accumulation is associated with worse haemodynamic and metabolic profile, also affecting survival. Conversely, lower EAT values imply higher left ventricular dysfunction, global functional impairment and adverse prognosis in HFrEF.

Dengzhanxixin Injection Ameliorates Cognitive Impairment Through a Neuroprotective Mechanism Based on Mitochondrial Preservation in Patients With Acute Ischemic Stroke.

Acute ischemic stroke (AIS) is a global health burden and cognitive impairment is one of its most serious complication. Adequate interventions for AIS may have the potential to improve cognitive outcomes. In the present study, we selected Erigeron breviscapus (Vaniot) Hand.-Mazz. injection (Dengzhanxixin injection, DZXI), a widely used Chinese herbal injection, in contrast to edaravone as the positive control drug to test its potential to ameliorates neurological and cognitive impairments caused by AIS. We performed a 2-week randomized trial with these two drugs in AIS patients presenting mild to moderate cognitive impairments. Neuropsychological tests and MRI examinations showed that DZXI attenuated the neurological and cognitive impairments of patients and protected the grey matter in specific regions from ischemic damage. Notably, DZXI exerted better effects than edaravone in some neuropsychological tests, probably due to the protective effect of DZXI on grey matter. To explore the therapeutic mechanisms, we carried out an experiment with a middle cerebral artery occlusion rat model. We found that DZXI decreased the infarct volume and increased the survival of neuronal cells in the ischemic penumbra; furthermore, DZXI modulated the mitochondrial respiratory chain process and preserved the mitochondrial structure in the brain tissue. Overall, our data suggested that the administration of DZXI is effective at ameliorating neurological and cognitive impairments in AIS, and the underlying mechanisms are related to the protective effects of DZXI on cerebral neurons and neuronal mitochondria.

A-78 Interdisciplinary Consultation in a Case of Herpes Simplex Encephalitis with Unique Neuropsychiatric Symptoms

Abstract Objective Herpes simplex encephalitis (HSE) is a rare neurological condition (~2–4 per million) marked by brain inflammation caused by herpes simplex virus (HSV). HSE is associated with both cognitive and neuropsychiatric symptoms, particularly memory and executive dysfunction. We present the case of a 63-year-old, right-handed, St. Lucian female who completed serial neuropsychological evaluations (NPE). Method The patient presented with a six-day history (per collateral) of fever, confusion, and nausea. The patient denied cognitive changes. Magnetic Resonance Imaging (MRI) revealed leptomeningeal enhancement in the right sylvian fissure, multiple right temporal sulci, and inferior right frontal lobe (Figure 1). There was no indication of seizures. Cerebrospinal fluid analysis was positive for HSV-1. A two-week course of intravenous acyclovir was initiated on hospital day three. Results (Table 1). Initial NPE results (day five) revealed global cognitive impairment with sparing of auditory attention; exam was limited secondary to significant fatigue. Following completion of antivirals, subsequent NPE (day 17) revealed similar findings, despite improved alertness; left neglect (Figure 2) and significant anosagnosia (i.e., lack of disease awareness) and anosodiaphoria (i.e., indifference reaction to neurological deficits) were noted. Two-month outpatient follow-up NPE revealed marginal improvement in aspects of language and learning, but continued memory impairment, dense anosagnosia, and anosodiaphoria. Conclusion In this case, the patient presented with salient neuropsychiatric sequelae of HSE that have not been commonly associated with this condition in the extant literature. Her denial of cognitive symptoms may have initially confounded the differential diagnosis, emphasizing the importance of multi-specialty collaboration. Limitations of available normative data also complicated examination.

A-81 Neuropsychological Profile of Child with Spinocerebellar Ataxia, Type 29

Abstract Objective Spinocerebellar ataxia 29 (SCA29) is a rare autosomal dominant disorder resulting in infantile-onset hypertonia, gross motor delay and cognitive impairment. SCA29 causes cerebellar dysfunction and atrophy manifested by poor hand coordination, instability of gait, impaired articulation, poor hand-eye coordination, language delay, and a wide legged, unsteady walk. Slow improvement across childhood is common, but the limited available research suggests significant clinical heterogeneity among individuals diagnosed with SCA29. We report the case of a six-year-old first grade girl to highlight the cognitive profile of SCA29 and determine its consistency with the literature. Methods Full neuropsychological evaluation was conducted, including examination of overall cognitive ability, academic achievement, and behavior. Results The patient demonstrated delayed cognitive and motor skills, slow processing, reduced reading fluency, and weak reading comprehension. Impaired verbal comprehension and limited fund of knowledge was seen. Working memory and visual spatial ability were relative individual strengths, though normatively weak. Untimed and non-motor academic skills were well below peers. Performances met criteria for ADHD and Language Disorder. Conclusion Six-year-old girl with SCA29 with expected motor difficulties including gross motor delay, hypotonia, ataxia, poor ocular fixation evidenced global impairments with expected weakness with verbal comprehension and receptive language skills. This is consistent with the findings in the SCA29 literature. Comorbid diagnoses of ADHD and Language Disorder were present. Given clinical heterogeneity, this case serves to expand existing knowledge on case variability, and adds the consideration of wider comorbidities in this rare condition.

Neuropsychological Phenotypes in Pediatric Temporal Lobe Epilepsy

Adults with temporal lobe epilepsy (TLE) have been found to have a fairly characteristic pattern of neuropsychological performance, but there is considerably less research and more variability in findings with children. Because the cognitive domains included in most studies with children have been limited, the current study attempted to better characterize the cognitive phenotype of children with TLE using a broader neuropsychological battery. The study included 59 children with TLE (59% male) age 7 to 16 (M = 12.67; SD = 3.12) who underwent comprehensive neuropsychological evaluation. Patient results were grouped into cognitive domains (reasoning, language, visuoperceptual, verbal memory, executive function, and motor function) based upon their test performance. These factor scores were subjected to Ward's hierarchical clustering method with squared Euclidean distance. Cluster analysis revealed three distinct cognitive profiles: (1) normal functioning (20% of sample); (2) delayed verbal memory and motor weaknesses (61% of the sample); and (3) global impairment (19% of the sample). Cluster 3 had longer epilepsy duration and a higher incidence of hippocampal sclerosis (HS) compared to Cluster 1 (p < .05). There were no significant differences among the three cluster groups on demographic characteristics or remaining clinical characteristics. Children with TLE present with distinct cognitive phenotypes ranging from average performance to global impairment. Results partially support previous hypotheses highlighting the cumulative neurobiological burden on the developing brain in the context of chronic epilepsy and provide a preliminary framework for the cognitive domains most vulnerable to the TLE disease process.

Associations of fat mass and muscle function but not lean mass with cognitive impairment: The Yishun Study.

BackgroundSarcopenia and obesity are reportedly associated with risk of cognitive decline, and sarcopenic obesity (SO) heightens the risk, but the evidence is sparse and inconclusive. This study aimed to examine the association between SO and cognitive impairment.MethodsA total of 542 community-dwelling adults aged between 21 and 90 years were recruited. All participants were assessed for body composition (dual X-ray absorptiometry), handgrip strength (HGS), gait speed (GS), and cognitive function (Repeatable Battery for the Assessment of Neuropsychological Status). Sarcopenia was defined by the presence of low appendicular lean mass index (ALMI) and low HGS or low GS according to the 2019 Asian Working Group for Sarcopenia criteria, and obesity was defined based on the upper two quintiles of fat mass index (FMI).ResultsSarcopenia alone or in combination with obesity were not significantly associated with cognitive impairment after controlling for confounding variables. Obesity on its own was significantly associated with greater odds of impaired attention (OR: 2.05, 95%CI 1.12–3.82). Low ALMI was not associated, but low HGS, slow GS, and high FMI were individually associated with cognitive impairment: low HGS and immediate memory (OR: 1.91, 95% CI 1.04–3.49); low GS and immediate memory (OR: 2.17, 95% CI 1.26–3.72); high FMI and attention (OR: 2.06, 95% CI 1.22–3.51). Co-occurring high FMI with either low HGS or slow GS exacerbated the observed odds of global and domain-specific (attention, visuospatial) cognitive impairment.ConclusionsLean mass is not relevant, whereas muscle strength and physical performance or adiposity are relevant in defining sarcopenia or sarcopenic obesity in terms of their cognitive impacts.

Determining minimally clinically important differences for outcome measures in patients with chronic motor deficits secondary to traumatic brain injury

ABSTRACT Objective To determine minimally clinically important differences (MCIDs) for Disability Rating Scale (DRS), Fugl-Meyer Upper Extremity Subscale (FM-UE), Fugl-Meyer Lower Extremity Subscale (FM-LE), and Fugl-Meyer Motor Scale (FMMS) in patients with chronic motor deficits secondary to traumatic brain injury (TBI). Methods Retrospective analysis from the 1-year, double-blind, randomized, surgical sham-controlled, Phase 2 STEMTRA trial (NCT02416492), in which patients with chronic motor deficits secondary to TBI (N = 61) underwent intracerebral stereotactic implantation of modified bone marrow-derived mesenchymal stromal (SB623) cells. MCIDs for DRS, FM-UE, FM-LE, and FMMS were triangulated with distribution-based, anchor-based, and Delphi panel estimates. Results Triangulated MCIDs were: 1) −1.5 points for the Disability Rating Scale; 2) 6.2 points for the Fugl-Meyer Upper Extremity Subscale; 3) 3.2 points for the Fugl-Meyer Lower Extremity Subscale; and 4) 8.4 points for the Fugl-Meyer Motor Scale. Conclusions For the first time in the setting of patients with chronic motor deficits secondary to TBI, this study reports triangulated MCIDs for: 1) DRS, a measure of global outcome; and 2) Fugl-Meyer Scales, measures of motor impairment. These findings guide the use of DRS and Fugl-Meyer Scales in the assessment of global disability outcome and motor impairment in future TBI clinical trials.

Pain experience and social support of endometriosis patients during the COVID-19 pandemic in Germany - results of a web-based cross-sectional survey.

BackgroundEndometriosis is a chronic pain condition in premenopausal women. Pain is mainly characterized by pain intensity and may induce disability in all areas of daily life. Nevertheless, pain is influenced by emotional and social factors as well. Social distancing measures or quarantine, as reaction to rapidly rising infections with the COVID-19 virus due to the SARS-CoV-2 pandemic, were implemented across Europe to prevent the spread of the virus and social distancing measures were imposed by the German government by beginning of March 2020 with initiation of the lockdown by the end of March 2020. The objective of this study was to assess, how social distancing measures during the lockdown impacted the various aspects of pain perception in a group of chronic pain patients, such as women suffering from endometriosis.MethodsBetween 6th to 27th April 2020, an online questionnaire was activated at internet platforms of endometriosis patients support groups. Participants were asked retrospectively at one time point about their visual pain intensity measured by the visual analogue scale (VAS) and pain disability via pain disability index (PDI) prior to initiation of social distancing measures in Germany (VASP, PDIP), as well as the pain intensity and pain disability since implementation of social distancing measures (VASI, PDII). Differences of VAS and PDI previous and after implementation of social distancing measures were displayed as ΔVAS and ΔPDI. Pain experience and social support were assessed by a 5-point Likert scale.Results285 participants completed at least one question regarding pain intensity, disability, pain experience or social support. Dysmenorrhea, the symptom with the highest level of pain assessed by VAS, decreased significantly during the SARS-CoV-2 pandemic compared to the time period prior to social isolation (45.30% respondents experienced improvemenet vs 40.50% who experienced worsening; p = 0.025). The global physical impairment improved significantly (improvement of pain induced disability in 48.20% vs 40.90% with worsening of pain symptoms; p = 0.032) after the implementation of social distancing measures. Pain experience was negatively affected by social distancing measures, since frequency of pain awareness increased in 43.6% (p<0.001) of participants and 30.0% (p<0.001) more participants experienced pain as a threat. Verbalization of pain experience was reduced in 36.6% (p = 0.001) of participants and 14.6% (p = 0.91), 21.9% (p<0.001) and 31.5% (p<0.001) of participants reported less social support from their partner, family and friends.ConclusionsPhysical pain and disability on one hand and emotional and social pain experience on the other were differentially affected by the emerged emotional, social and health care constraints related to the SARS-CoV-2 pandemic.

Global functional impairment in head and neck cancer survivors after completing radiotherapy treatment

Purpose Improvements in diagnosis and treatment of head and neck cancer (HNC) patients have resulted in improved long-term survival rates. However, a variety of symptoms and comorbidities, often secondary to the cancer and its treatments, are experienced by a relevant number of survivors. So, the aim of this study was to determine the global functional impairment in HNC survivors 1 year after radiotherapy treatment. Materials and methods A descriptive case-control study was performed. HNC survivors were recruited from San Cecilio Clinical University Hospital in Granada. The main variables included were functionality and quality of life. Results 30 HNC survivors were included in our study. Significant differences were found in the WHO-DAS 2.0 test, with a worse score in the HNC group in most subscales (p < 0.05), and poorer scores in the COMP test, performance (p < 0.001) and satisfaction (p < 0.001). Significant differences were also found in most QLQ-30 subscales (p < 0.05) and the QLQ-H&N35. In regard to the EQ-5D, significant differences were found between groups, with worse results in the HNC group (p < 0.05). Conclusion HNC survivors presented a poorer global function and a worse quality of life and health status 1 year after the radiotherapy treatment. Moreover, a good correlation was found between functionality and quality of life outcomes. IMPLICATIONS FOR REHABILITATION A worse quality of life and health status are shown in head and neck survivors 1 year after radiotherapy. Global functionality is related to quality of life outcomes in head and neck cancer survivors. There is a need to recognise the need for and to provide longer term rehabilitation.

One-carbon metabolism and global DNA methylation in mothers of individuals with Down syndrome.

Down syndrome (DS) is the most common chromosomal disorder, resulting from the failure of normal chromosome 21 segregation. Studies have suggested that impairments within the one-carbon metabolic pathway can be of relevance for the global genome instability observed in mothers of individuals with DS. Based on the association between global DNA hypomethylation, genome instability, and impairments within the one-carbon metabolic pathway, the present studyaimedto identify possible predictors, within the one-carbon metabolism, of global DNA methylation, measured by methylation patterns of LINE-1 and Alu repetitive sequences, in mothers of individuals with DS and mothers of individuals without the syndrome. In addition, we investigated one-carbon genetic polymorphisms and metabolites as maternal predisposing factors for the occurrence of trisomy 21 in children. Eighty-three samples of mothers of children with DS with karyotypically confirmed free trisomy 21 (case group) and 84 of mothers who had at least one child without DS or any other aneuploidy were included in the study. Pyrosequencing assays were performed to access global methylation. The results showed that group affiliation (case or control), betaine-homocysteine methyltransferase (BHMT) G742A and transcobalamin 2 (TCN2) C776G polymorphisms, and folate concentration were identified as predictors of global Alu DNA methylation values. In addition, thymidylate synthase (TYMS) 28-bp repeats 2R/3R or 3R/3R genotypes are independent maternal predisposing factors for having a child with DS. This study adds evidence that supports the association of impairments in the one-carbon metabolism, global DNA methylation, and the possibility of having a child with DS.

The influence of language comprehension proficiency on assessment of global cognitive impairment following Acquired Brain Injury: A comparison between MMSE, MoCA and CASP batteries

Language disorders are among the primary obstacles in care and rehabilitation process following acquired brain injuries (ABI). While early cognitive screening is considered critical for sketching a reliable picture of patients’ residual abilities and devising efficient therapeutic plans, it has been shown that commonly-used screening tools—which strongly rely on verbal materials—might be inappropriate when used with ABI patients. This study aimed at testing the robustness and validity of the Cognitive Assessment for Stroke Patients (CASP) battery—devised to minimize the use of verbal materials—and two gold-standards in clinical practice—i.e. Mini Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA)—in presence of language comprehension difficulties. Forty-two ABI patients took part in the study. Half of the cohort was classified as aphasic. Participants underwent neuropsychological assessment including MMSE, MoCA and CASP, and completed the Token test to estimate language comprehension proficiency. The influence of linguistic ability on the outcomes of the screening tools was investigated. Regression analyses highlighted that, in aphasic patients, MMSE and MoCA scores proved to be significantly and remarkably determined by patients’ proficiency in linguistic comprehension, while the outcome of the CASP battery was not significantly affected by language comprehension impairments.

The Impact of Vascular Risk Factors on Post-stroke Cognitive Impairment: The Nor-COAST Study.

Introduction: Post-stroke cognitive impairment (PSCI) is common, but evidence on the impact of vascular risk factors is lacking. We explored the association between pre-stroke vascular risk factors and PSCI and studied the course of PSCI.Materials and Methods: Vascular risk factors were collected at baseline in stroke survivors (n = 635). Cognitive assessments of attention, executive function, memory, language, and the Montreal Cognitive Assessment (MoCA) were performed at 3 and/or 18 months post-stroke. Stroke severity was assessed with the National Institutes of Health Stroke Scale (NIHSS). PSCI was measured with global z; MoCA z-score; and z-score of the four assessed cognitive domains. Mixed-effect linear regression was applied with global z, MoCA z-score, and z-scores of the cognitive domains as dependent variables. Independent variables were the vascular risk factors (hypertension, hypercholesterolemia, smoking, diabetes mellitus, atrial fibrillation, coronary heart disease, previous stroke), time, and the interaction between these. The analyses were adjusted for age, education, and sex. There were between 5 and 25% missing data for the variables for PSCI.Results: Mean age was 71.6 years (SD 11.7); 42% were females; and the mean NIHSS score at admittance was 3.8 (SD 4.8). Regardless of vascular risk factors, global z, MoCA, and all the assessed cognitive domains were impaired at 3 and 18 months, with MoCA being the most severely impaired. Atrial fibrillation (AF) was associated with poorer language at 18 months and coronary heart disease (CHD) with poorer MoCA at 18 months (LR = 12.80, p = 0.002, and LR = 8.32, p = 0.004, respectively). Previous stroke was associated with poorer global z and attention at 3 and 18 months (LR = 15.46, p < 0.001, and LR = 16.20, p < 0.001). In patients without AF, attention improved from 3 to 18 months, and in patients without CHD, executive function improved from 3 to 18 months (LR = 10.42, p < 0.001, and LR = 9.33, p = 0.009, respectively).Discussion: Our findings indicate that a focal stroke lesion might be related to pathophysiological processes leading to global cognitive impairment. The poorer prognosis of PSCI in patients with vascular risk factors emphasizes the need for further research on complex vascular risk factor interventions to prevent PSCI.

Association between Veterans Aging Cohort Study (VACS) index and neurocognitive function among people living with HIV\u2013a cross sectional study in coastal South India

BackgroundHIV is an infectious disease affecting 36.7 million people worldwide. In recent times, Antiretroviral Therapy (ART) has become accessible to the majority of People Living with HIV (PLHIV) and this has transformed the course of infection to one that is chronic, characterized by fewer diseases pathognomonic of AIDS. In view of this, there is a pressing need for better markers, apart from the routine HIV indicators, to detect comorbidities such as Neurocognitive Impairment (NCI). The aim of this study was to find out the association between Veterans Aging Cohort Study (VACS) index and Neurocognitive function in HIV positive patients.MethodsIn our study, we included 97 HIV positive patients and their Neurocognitive function was assessed using a combination of Montreal Cognitive Assessment and Grooved Pegboard Test, while VACS index was calculated using the most recent laboratory values. Binomial Logistics Regression analyses, adjusting for potential confounding variables, was performed to determine the association between VACS score and Neurocognitive Impairment.ResultsWe found that a higher VACS Index was associated with global and domain-wise Neurocognitive impairment (p < 0.01), specifically in the domains of attention (p < 0.01) and fine motor skills (p = 0.01). Our study also showed that among all the VACS components, older age (p = 0.02) and lower hemoglobin (p < 0.01) values were associated with global NCI. After plotting an ROC curve, a VACS cut-off score of 11.00 was identified as it had good sensitivity (87.0%) and specificity (71.4%) in identifying Global NCI.ConclusionOur findings extend prior research on the use of VACS Index to predict global and domain-wise NCI in HIV-positive patients. However, further research with more comprehensive neurocognitive testing is required in our setting before VACS Index can be used as a tool to screen for neurocognitive dysfunction among PLHIV.

Cognitive impairment burden in older and younger adults across the kidney transplant care continuum.

Younger kidney transplant (KT) candidates and recipients may have cognitive impairment due to chronic diseases and reliance on dialysis. To quantify cognitive impairment burden by age across the KT care continuum, we leveraged a two-center cohort study of 3854 KT candidates at evaluation, 1114 recipients at admission, and 405 recipients at 1-year post-KT with measured global cognitive performance (3MS) or executive function (Trail Making Test). We also estimated burden of severe cognitive impairment that affects functional dependence (activities of daily living [ADL]<6 or instrumental activities of daily living [IADL]<8). Among KT candidates, global cognitive impairment (18-34 years: 11.1%; 35-49 years: 14.0%; 50-64 years: 19.5%; ≥65 years: 22.0%) and severe cognitive impairment burden (18-34 years: 1.1%; 35-49 years: 3.0%; 50-64 years: 6.2%; ≥65 years: 7.7%) increased linearly with age. Among KT recipients at admission, global cognitive impairment (18-34 years: 9.1%; 35-49 years: 6.1%; 50-64 years: 9.3%; ≥65 years: 15.7%) and severe cognitive impairment burden (18-34 years: 1.4%; 35-49 years: 1.4%; 50-64 years: 2.2%; ≥65 years: 4.6%) was lower. Despite lowest burden of cognitive impairment among KT recipients at 1-year post-KT across all ages (18-34 years: 1.7%; 35-49 years: 3.4%; 50-64 years: 4.3%; ≥65 years: 6.5%), many still exhibited severe cognitive impairment (18-34 years: .0%; 35-49 years: 1.9%; 50-64 years: 2.4%; ≥65 years: 3.5%). Findings were consistent for executive function impairment. While cognitive impairment increases with age, younger KT candidates have a high burden comparable to community-dwelling older adults, with some potentially suffering from severe forms. Transplant centers should consider routinely screening patients during clinical care encounters regardless of age.