Impairment In People Research Articles

Development and validation of predictive risk models for sight threatening diabetic retinopathy in patients with type 2 diabetes to be applied as triage tools in resource limited settings.

SummaryBackgroundDelayed diagnosis and treatment of sight threatening diabetic retinopathy (STDR) is a common cause of visual impairment in people with Type 2 diabetes. Therefore, systematic regular retinal screening is recommended, but global coverage of such services is challenging. We aimed to develop and validate predictive models for STDR to identify ‘at-risk’ population for retinal screening.MethodsModels were developed using datasets obtained from general practices in inner London, United Kingdom (UK) on adults with type 2 Diabetes during the period 2007–2017. Three models were developed using Cox regression and model performance was assessed using C statistic, calibration slope and observed to expected ratio measures. Models were externally validated in cohorts from Wales, UK and India.FindingsA total of 40,334 people were included in the model development phase of which 1427 (3·54%) people developed STDR. Age, gender, diabetes duration, antidiabetic medication history, glycated haemoglobin (HbA1c), and history of retinopathy were included as predictors in the Model 1, Model 2 excluded retinopathy status, and Model 3 further excluded HbA1c. All three models attained strong discrimination performance in the model development dataset with C statistics ranging from 0·778 to 0·832, and in the external validation datasets (C statistic 0·685 – 0·823) with calibration slopes closer to 1 following re-calibration of the baseline survival.InterpretationWe have developed new risk prediction equations to identify those at risk of STDR in people with type 2 diabetes in any resource-setting so that they can be screened and treated early. Future testing, and piloting is required before implementation.FundingThis study was funded by the GCRF UKRI (MR/P207881/1) and supported by the NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology.

Cognitive impairment in people with COVID-19 with mild-moderate symptoms in Ecuador

Cognitive impairment in people with COVID-19 with mild-moderate symptoms in Ecuador

¿Se Podrá Recomendar el Tratamiento con Litio Para el Deterioro Cognitivo Leve y la Demencia por Enfermedad de Alzheimer? Falta Evidencia Sobre su Eficacia y su Seguridad: Revisión Sistemática y Metanálisis

IntroductionAlzheimer's disease is the most prevalent neurodegenerative disease worldwide. Currently available treatments are scarce and have modest effects. Lithium has been shown to decrease cognitive impairment in people with bipolar affective disorder. However, studies evaluating lithium for cognitive impairment in Alzheimer's disease remain controversial. MethodsWe conducted a systematic search of the literature using PubMed, EMBASE, the Cochrane Library, LILACS, and Google Scholar between 30 April and 10 May 2021. Randomised controlled clinical trials (RCTs) conducted to evaluate the efficacy and safety of lithium as a treatment for cognitive impairment in people with dementia and mild cognitive impairment due to Alzheimer's disease were included. The primary outcome was the difference in cognitive functioning at the end of the study. Two authors selected the studies and extracted the data. We calculated the standardised mean differences (SMD) for continuous variables and the relative risk (RR) for dichotomous variables. Review Manager 5.4 software was used for data processing. Results2,078 reports were identified and 3 studies with data from 248 participants were included. A fourth report was included for safety analysis. Compared to placebo, no significant difference was found in the cognitive performance of patients with mild cognitive impairment or dementia due to Alzheimer's disease receiving lithium treatment (SMD=–0.39; 95%CI, –0.82 to 0.04; I2=53%; n=195). Also, significant differences were not found in the rate of discontinuation for any cause (RR=0.90; 95%CI, 0.46-1.78; I2=0%), and the rate of adverse effects between lithium and placebo (RR=1.29; 95%CI, 0.83-2.03; I2=0%). ConclusionsThe current evidence is insufficient to assume any effect of lithium as a treatment for cognitive impairment in Alzheimer's disease dementia. It is necessary to continue building better quality studies to justify the use of lithium in this population in clinical practice. Given the toxicity of lithium, adequate pre-selection of patients and close monitoring should be ensured.

Sagittal plane ankle kinetics are associated with dynamic hip range of motion and gait efficiency in women with hip osteoarthritis.

Loss of sagittal plane hip range of motion (ROM) is a commonly reported walking gait impairment in people with hip osteoarthritis (OA). The purpose of this study was to evaluate whether sagittal plane hip ROM reduction and the resulting altered sagittal plane ankle kinetics during gait influence the energy cost of walking in people with hip OA. We evaluated 24 women with unilateral hip OA (60 ± 9.1 years; 29.4 ± 6.1 kg/m2 ). Sagittal plane hip ROM and peak ankle dorsiflexion moment were assessed by instrumented gait analysis. We also used a portable metabolic system to measure the energy cost of walking. Pearson correlations and regression analyses were performed to test our hypotheses. We found that greater involved limb sagittal plane hip ROM was associated with a larger ankle peak dorsiflexion moment at push-off during gait (R = 0.50, p = 0.01). Greater involved limb peak ankle dorsiflexion moment at push-off was associated with a lower oxygen consumption during gait (R = -0.51, p = 0.01). Involved limb peak ankle dorsiflexion moment at push-off predicted 26% of the variance in O2 cost. Statement of Clinical Significance: Sagittal plane hip ROM was associated with peak ankle dorsiflexion moment at push-off during gait in women with hip OA. Moreover, peak ankle dorsiflexion moment at push-off was associated with the energy cost of walking. Therefore, modifying sagittal plane hip ROM and peak ankle dorsiflexion moment could be a possible rehabilitation strategy to improve gait efficiency in women with hip OA.

29. Increased micronuclei frequency and DNA methylation patterns associated with Down syndrome regression disorder

Down syndrome is associated with intellectual disability and physiological conditions, as well as an increased risk for developing behavioral disorders. A distinct pattern of profound behavioral deterioration in people with Down syndrome that differs from the clinical courses of autism spectrum disorder and/or Alzheimer-like dementia is termed “Down Syndrome Regression Disorder” (DSRD). We hypothesized that acquired somatic cell chromosomal instability and/or epigenetic alterations may contribute to the development of DSRD considering that: (1) DSRD does not typically occur until adolescence/early adulthood and might be associated with stressful events; and (2) increased frequencies of somatic cell chromosomal instability have been associated with stress and/or an aneuploidy chromosomal complement.

Factors associated with change over time in quality of life of people with dementia: longitudinal analyses from the MODEM cohort study

BackgroundResearch to date offers mixed evidence about the relationship between quality of life and severity of cognitive impairment in people with dementia. We aimed to investigate longitudinal changes in patient- and proxy-rated health-related quality of life (HRQL) by severity of dementia and explore factors associated with changes in HRQL over a one-year period. We used data from the MODEM longitudinal cohort study which recruited dyads of persons with clinically diagnosed dementia and their principal carer and interviewed them face-to-face at baseline and again 1 year later.MethodsQuota sampling was used to generate balanced numbers (target n = 100 for each severity level) of people with mild cognitive impairment (20+ on the standardised Mini-Mental State Examination (sMMSE)), moderate cognitive impairment (score 10 to 19), and severe cognitive impairment (score 0 to 9). Persons with dementia without an identifiable family carer or other informant (e.g., a formal/professional/paid carer) were excluded from the study. Participants answered a series of questions measuring their HRQL: DEMQOL, DEMQOL-proxy, EQ-5D-3 L, EQ-5D-3L proxy. Multiple regression models were built to understand the effects of baseline demographics and dementia symptoms (cognitive impairment, neuropsychiatric symptoms) on change in HRQL over 1 year.ResultsTwo hundred and forty-three dyads of people with clinically diagnosed dementia and carers completed baseline and follow-up interviews. Most measures of HRQL remaining relatively stable between time-points, but one index of HRQL, EQ-5D proxy, significantly declined. Depending on the HRQL measure, different factors were associated with change in HRQL. The only factor consistently associated with decline in HRQL (when compared to improvement) was having a diagnosis of a non-Alzheimer’s dementia.ConclusionsDeterioration in HRQL is not an inevitable part of the dementia journey. However, people with non-Alzheimer’s dementias may be more susceptible to HRQL decline. This may indicate that those with non-Alzheimer’s dementia may benefit from specific support focussed on maintaining their quality of life.

028 Cladribine to halt deterioration in people with advanced multiple sclerosis (ChariotMS)

BackgroundDisease modifying treatments (DMTs) have transformed the management of people with MS (pwMS). However, patients with an EDSS>6.5 (pwAMS) are considered beyond DMT due to (i) focus on ambulation as outcome measure, (ii) assumption that in pwAMS inflammation plays no role, and(iii) disregard for potentially length-dependent neuro-axonal damage. Cladribine is a CNS penetrant, effective, convenient and relatively safe DMT. Cladribine effectively depletes B cell subsets, particularly memory B cells, a potential key mechanism of disease control in pwMS.AimsTo test the efficacy, safety and cost-effectiveness of cladribine tablets in pwAMS (EDSS 6.5–8.5), expand the mechanistic understanding of cladribine in pwAMS and provide evidence for NHS adoption.MethodsRandomised, double-blind, placebo-controlled phase IIb trial. The primary outcome measure is 9-hole peg test speed at 104 weeks vs baseline. To detect a 15% treatment effect in 9-HPT peg speed with 90% power at 5% significance and 20% drop-out we calculated a sample size of n=200 across 20 UK sites.ConclusionsChariotMS will be the first DMT-trial focussing on pwAMS. If successful, ChariotMS would expand the DMT landscape to include pwAMS and provide a platform for potential add-on therapies. ChariotMS is due to start recruitment nationwide from 1 Sep 2020.david.lieberman@nhs.net

Cut-off of the one-minute sit-to-stand test to detect functional impairment in people with chronic obstructive pulmonary disease

IntroductionThe 6-minute walking test (6MWT) is a widely used measure to assess functional status of people with chronic obstructive pulmonary disease (COPD). However, it requires a long hallway and might be time-consuming. Other simple measures might be useful as a first screening tool. We explored the predictive ability of the 1-minute sit-to-stand test (1-min STS) in discriminating people with COPD with or without functional impairment. MethodsA receiver operating characteristics (ROC) curve analysis was performed. We determined a threshold for the 1-min STS to identify functional impairment based on different cut-offs of the 6MWT (300, 350, 400 and 450 m). ResultsA total of 135 people with COPD were included. Except for the <450 m cut-off of the 6MWT, all other cut-offs identified 19.5 repetitions as the optimal cut-off point for the 1-min STS. All AUCs showed excellent discrimination (AUCs = 0.812–0.901). The best AUC (<300 m cut-off) had an outstanding discrimination (0.901; 95%CI: 0.84–0.96; other AUCs 0.812–0.836) between people with or without functional impairment, with 86% specificity and 83% sensitivity. ConclusionA cut-off of 19.5 repetitions in the 1-min STS discriminates accurately people with COPD with a functional impairment. Future studies may validate our treatable trait candidate in other samples and investigate its utility in predicting other meaningful outcomes.

Chronic Stroke Sensorimotor Impairment Is Related to Smaller Hippocampal Volumes: An ENIGMA Analysis.

BackgroundPersistent sensorimotor impairments after stroke can negatively impact quality of life. The hippocampus is vulnerable to poststroke secondary degeneration and is involved in sensorimotor behavior but has not been widely studied within the context of poststroke upper‐limb sensorimotor impairment. We investigated associations between non‐lesioned hippocampal volume and upper limb sensorimotor impairment in people with chronic stroke, hypothesizing that smaller ipsilesional hippocampal volumes would be associated with greater sensorimotor impairment.Methods and ResultsCross‐sectional T1‐weighted magnetic resonance images of the brain were pooled from 357 participants with chronic stroke from 18 research cohorts of the ENIGMA (Enhancing NeuoImaging Genetics through Meta‐Analysis) Stroke Recovery Working Group. Sensorimotor impairment was estimated from the FMA‐UE (Fugl‐Meyer Assessment of Upper Extremity). Robust mixed‐effects linear models were used to test associations between poststroke sensorimotor impairment and hippocampal volumes (ipsilesional and contralesional separately; Bonferroni‐corrected, P<0.025), controlling for age, sex, lesion volume, and lesioned hemisphere. In exploratory analyses, we tested for a sensorimotor impairment and sex interaction and relationships between lesion volume, sensorimotor damage, and hippocampal volume. Greater sensorimotor impairment was significantly associated with ipsilesional (P=0.005; β=0.16) but not contralesional (P=0.96; β=0.003) hippocampal volume, independent of lesion volume and other covariates (P=0.001; β=0.26). Women showed progressively worsening sensorimotor impairment with smaller ipsilesional (P=0.008; β=−0.26) and contralesional (P=0.006; β=−0.27) hippocampal volumes compared with men. Hippocampal volume was associated with lesion size (P<0.001; β=−0.21) and extent of sensorimotor damage (P=0.003; β=−0.15).ConclusionsThe present study identifies novel associations between chronic poststroke sensorimotor impairment and ipsilesional hippocampal volume that are not caused by lesion size and may be stronger in women.

Long COVID: systemic inflammation and obesity as therapeutic targets

Long COVID: systemic inflammation and obesity as therapeutic targets

Educational level and cognitive impairment in people living with HIV on antiretroviral treatment in Ecuador.

Educational level and cognitive impairment in people living with HIV on antiretroviral treatment in Ecuador.

Modern methods of surgical hearing prosthesis

Resume. In recent years, the number of patients with hearing impairments around the world is constantly increasing. The WHO estimates that the unresolved problem of hearing loss costs the world 980 billion US dollars annually. Currently, the number of children and adults with sensorineural hearing loss has increased significantly. The aim of the work is to investigate the consequences of hearing loss in humans, and to describe current surgical methods of solving the problem based on scientific analysis of modern literature. Materials and methods. A comprehensive search of relevant literature sources was conducted in December 2021 using such electronic databases as RubMed, EMBASE, MEDLINE, U.S. National Library of Medicine Clinical Trials, Research Gate and Cocharane Library. Results. Despite the high-tech diagnostic capabilities of modern medicine, the study of etiology, prevention and correction of various hearing impairments in people of all ages take a paramount role in the modern medical community. Hearing aids are not able to transmit the full range of the sound palette to a person who is hard of hearing. In the analysis of the studied literature, modern surgical methods of correction of hearing disorders are cochlear implantation, bone-conducting system of sound conduction and brain-stem implantation. Each method has advantages, indications and features of rehabilitation. Restoration of hearing for a deaf child / adult is the result of the teamwork of psychologists, audiologists, otosurgeons/neurosurgeons, anesthesiologists, engineers and rehabilitation specialists. Conclusion. Hearing plays one of the most important roles in the formation and development of any society, transfer of accumulated knowledge from generation to generation through the formation of speech and communication skills. For timely detection of hearing impairment, on-time correction and rehabilitation measures, pediatricians and family doctors must know how to correct hearing impairment, taking into account modern medical and digital technologies.

Analysis of the Relationship among Cognitive Impairment, Nutritional Indexes and the Clinical Course among COVID-19 Patients Discharged from Hospital-Preliminary Report.

Numerous data indicate the presence of cognitive impairment in people who have undergone COVID-19, often called COVID Fog (CF). This phenomenon persists even 6 months after infection, and its etiology and pathogenesis are not fully known. The aim of this article was to analyze the relationship among cognitive functioning, clinical data and nutrition indexes in patients discharged from the COVID-19 hospital of the Military Institute of Medicine, Warsaw, Poland. The sample comprised 17 individuals—10 women and 7 men, with ages of 65 ± 14 years. Cognitive impairment was measured with the use of the Montreal Cognitive Assessment (MoCA). The nutrition parameters included: hemoglobin, red blood cells, total cholesterol and its fractions, triglycerides, total protein, albumin, urea, creatinine, phosphates, calcium and sodium. The analysis showed that albumin concentration significantly correlated with the total MoCA score and especially with the short-term memory test score. Conversely, total cholesterol, and especially LDL concentrations, were highly and negatively associated with the MoCA score. In conclusion: markers of nutritional status are correlated with the severity of CF. Individuals with malnutrition or risk of malnutrition should be screened for CF. Further studies need to be performed in this area.

Interventions to improve gait in Parkinson's disease: a systematic review of randomized controlled trials and network meta-analysis.

Disabling gait symptoms, especially freezing of gait (FoG), represents a milestone in the progression of Parkinson's disease (PD). This systematic review and network meta-analysis assessed and ranked interventions according to their effectiveness in treating gait symptoms in people with PD across four different groups of gait measures. A systematic search was carried out across PubMed, EMBASE, PubMed Central (PMC), and Cochrane Central Library from January 2000 to April 2021. All interventions, or combinations, were included. The primary outcome was changes in objective gait measures, before and after intervention. Outcome measures in the included studies were stratified into four different types of gait outcome measures; dynamic gait, fitness, balance, and freezing of gait. For the statistical analysis, five direct head-to-head comparisons of interventions, as well as indirect comparisons were performed. Corresponding forest plots ranking the interventions were generated. The search returned 6288 articles. From these, 148 articles could be included. Of the four different groups of measurement, three were consistent, meaning that there was agreement between direct and indirect evidence. The groups with consistent evidence were dynamic gait, fitness, and freezing of gait. For dynamic gait measures, treatments with the largest observed effect were Aquatic Therapy with dual task exercising (SMD 1.99 [-1.00; 4.98]) and strength and balance training (SMD 1.95 [-0.20; 4.11]). For measures of fitness, treatments with the largest observed effects were aquatic therapy (SMD 3.41 [2.11; 4.71] and high-frequency repetitive transcranial magnetic stimulation (SMD 2.51 [1.48; 3.55]). For FoG measures, none of the included interventions yielded significant results. Some interventions can ameliorate gait impairment in people with PD. No recommendations on a superior intervention can be made. None of the studied interventions proved to be efficacious in the treatment of FoG. PROSPERO (registration ID CRD42021264076).

HIV-Associated Neurocognitive Disorder (HAND): Obstacles to Early Neuropsychological Diagnosis.

Despite the recent advances in HIV treatment, HIV-associated neurocognitive disorder (HAND) prevalence remains high, especially in the mild forms. Current recommendations endorse routine screening for HAND and early identification, but there are several obstacles in diagnosing and managing cognitive impairment in people living with HIV. The purpose of this review is to provide an overview of the concepts and diagnostic tools in the field of HAND and report on the strengths and limitations of currently available approaches.

Icariin alleviates uveitis by targeting peroxiredoxin 3 to modulate retinal microglia M1/M2 phenotypic polarization

Uveitis causes blindness and critical visual impairment in people of all ages, and retinal microglia participate in uveitis progression. Unfortunately, effective treatment is deficient. Icariin (ICA) is a bioactive monomer derived from Epimedium. However, the role of ICA in uveitis remains elusive. Our study indicated that ICA alleviated intraocular inflammation in vivo. Further results showed the proinflammatory M1 microglia could be transferred to anti-inflammatory M2 microglia by ICA in the retina and HMC3 cells. However, the direct pharmacological target of ICA is unknown, to this end, proteome microarrays and molecular simulations were used to identify the molecular targets of ICA. Data showed that ICA binds to peroxiredoxin-3 (PRDX3), increasing PRDX3 protein expression in both a time- and a concentration-dependent manner and promoting the subsequent elimination of H2O2. In addition, GPX4/SLC7A11/ACSL4 pathways were activated accompanied by PRDX3 activation. Functional tests demonstrated that ICA-derived protection is afforded through targeting PRDX3. First, ICA-shifted microglial M1/M2 phenotypic polarization was no longer detected by blocking PRDX3 both in vivo and in vitro. Next, ICA-activated GPX4/SLC7A11/ACSL4 pathways and downregulated H2O2 production were also reversed via inhibiting PRDX3 both in vivo and in vitro. Finally, ICA-elicited positive effects on intraocular inflammation were eliminated in PRDX3-deficient retina from experimental autoimmune uveitis (EAU) mice. Taking together, ICA-derived PRDX3 activation has therapeutic potential for uveitis, which might be associated with modulating microglial M1/M2 phenotypic polarization.

Disentangling self-reported fatigue, depression, and cognitive impairment in people with multiple sclerosis

BackgroundFatigue is a common problem among people with multiple sclerosis (MS) and can have a negative effect on mental, physical, and social function. Self-reported measures of MS fatigue are often operationalized as a multi-dimensional symptom. However, questions remain about how best to account for the multi-dimensional aspects of self-reported fatigue and whether these aspects are distinct entities. Thus, the purpose of this study was to explore the overlap and distinctions between self-reported measures of the severity and impact of fatigue, between mental and physical fatigue, and between mental fatigue, depressive symptoms, and cognitive impairment. MethodsAn observational study was conducted with 289 participants with MS . The questionnaires were the Unidimensional Fatigue Impact Scale (UFIS), the Chalder Fatigue Scale (CFS), the Fatigue Scale for Motor and Cognitive Functions (FSMC), the Multiple Sclerosis Neuropsychological Screening Questionnaire (MSNSQ), and the Quality of Life in Neurological Disorders short form for depression (Neuro-QoL). Spearman's correlation coefficient was used to examine the bivariate correlations between composite and subscale scores. Exploratory structural equation modeling (ESEM) was used to determine the factor structure under a pre-specified number of factors to retain in the modeling of multiple items across questionnaires and examine model fit. Subsequently for poor fitting models in an iterative procedure to determine a better fitting multidimensional model, we posited a bifactor confirmatory factor analysis model. ResultsThe bivariate correlation analysis revealed that subscales from the same questionnaire measuring different aspects of fatigue had the highest correlations (r = 0.61–0.68), subscales from different questionnaires measuring the same aspect of fatigue had the next highest correlations (r = 0.43–0.60), and subscales from different questionnaires measuring different aspects of fatigue had the lowest correlations (r = 0.34–0.40). Bifactor models with a general fatigue factor and subdomains pertaining to impact, severity, and mental and physical fatigue had relatively good model fits compared to models omitting the subdomains. However, an ESEM model using subscales from the CFS and FSMC fit poorly and did not adequately identify separate factors for mental and physical fatigue. An ESEM model with separate factors for self-reported mental fatigue, depressive symptoms, and cognitive impairment was a good fit. ConclusionsThe working study hypothesis that fatigue constructs would be moderately correlated yet distinct entities was generally supported by the results of the study. However, we found that our hypothesized separation into a latent dimension existed only when the items or subscales came from the same questionnaire, in which case their level of specificity in terms of target, action, context, and time elements for measuring fatigue were consistent. The implications for the principle of compatibility in measuring self-reported MS fatigue are discussed.

Peripheral inflammation and depressed mood independently predict neurocognitive worsening over 12 years

BackgroundNeurocognitive (NC) impairment in people with HIV (PWH) is associated with important adverse outcomes, but no markers exist to predict long-term NC decline. We evaluated depressed mood and markers of persistent inflammation, oxidative stress and altered amyloid processing (all common in PWH) as predictors of NC worsening over 12 years. MethodsPWH were enrolled and followed longitudinally in the CNS HIV Antiretroviral Effects Research (CHARTER) study at six US sites. At entry we quantified biomarkers in blood of inflammation: (interleukin-6 [IL-6], C-reactive protein [CRP], monocyte chemoattractant protein type 1 [MCP-1], D-dimer, soluble sCD14 (sCD14), soluble tumor necrosis factor receptor – type II [sTNFR-II], neopterin, and soluble CD40 ligand [sCD40L], oxidative stress (protein carbonyls, 8-oxo-2'-deoxyguanosine [8-oxo-dG]) and altered amyloid processing [amyloid beta (Aβ)-42, soluble amyloid precursor protein-α (sAPPα)] using commercial immunoassays. The Beck Depression Inventory-II (BDI-II) assessed depressed mood at entry. NC decline over 12 years was evaluated using the published and validated summary (global) regression-based change score (sRBCS). A factor analysis reduced dimensionality of the biomarkers. Univariable and multiple regression models tested the relationship between baseline predictors and the outcome of neurocognitive decline. ResultsParticipants were 191 PWH, 37 (19.4%) women, 46.6% African American, 43.5% non-Hispanic white, 8.83% Hispanic, 15.7% white, 1.6% other; at study entry mean (SD) age 43.6 (8.06) years, estimated duration of HIV infection (median, IQR) 9.82 [4.44, 14.5] years, nadir CD4 104/μL (19,205), current CD4 568/μL (356, 817), and 80.1% had plasma HIV RNA <50 c/mL. Participants were enrolled between 2003 and 2007; median (IQR) duration of follow-up 12.4 [9.69, 16.2] years. Three biomarker factors were identified: Factor (F)1 (IL-6, CRP), F2 (sTNFR-II, neopterin) and F3 (sCD40L, sAPPα). Participants with higher F1, reflecting worse systemic inflammation at baseline, and higher F3, had greater decline in global neurocognition (r ​= ​−0.168, p ​= ​0.0205 and r ​= ​−0.156, p ​= ​0.0309, respectively). Of the F1 components, higher CRP levels were associated with worse decline (r ​= ​−0.154, p ​= ​0.0332), while IL-6 did not (r ​= ​−0.109, p ​= ​0.135). NC change was not significantly related to F2, nor to demographics, nadir and current CD4, viral suppression or baseline NC comorbidity ratings. Individuals with worse depressed mood at entry also experienced more NC decline (r ​= ​−0.1734, p ​= ​0.0006). Together BDI-II (p ​= ​0.0290), F1 (p ​= ​0.0484) and F3 (p ​= ​0.0309) contributed independently to NC decline (p ​= ​0.0028); their interactions were not significant. Neither CRP nor IL-6 correlated significantly with depression. ConclusionsPWH with greater systemic inflammation and more depression at entry had greater NC decline over 12 years. Understanding the basis of this inflammatory state might be particularly important. These findings raise the possibility that targeted anti-inflammatory or antidepressant therapies may help prevent NC worsening in PWH with depression and inflammation.

Longitudinal tracking of axonal loss using diffusion magnetic resonance imaging in multiple sclerosis.

Axonal loss in the CNS is a key driver of progressive neurological impairments in people with multiple sclerosis. Currently, there are no established methods for tracking axonal loss clinically. This study aimed to determine the sensitivity of longitudinal diffusion MRI-derived fibre-specific measures of axonal loss in people with multiple sclerosis. Fibre measures were derived from diffusion MRI acquired as part of a standard radiological MRI protocol and were compared (i) to establish measures of neuro-axonal degeneration: brain parenchymal fraction and retinal nerve fibre layer thickness and (ii) between different disease stages: clinically isolated syndrome and early/late relapsing–remitting multiple sclerosis. Retrospectively identified data from 59 people with multiple sclerosis (18 clinically isolated syndrome, 22 early and 19 late relapsing–remitting) who underwent diffusion MRI as part of their routine clinical monitoring were collated and analysed. Twenty-six patients had 1-year and 14 patients had a 2-year follow-up. Brain parenchymal fraction was calculated from 3D MRI scans, and fibre-specific measures were calculated from diffusion MRI using multi-tissue constrained spherical deconvolution. At each study visit, patients underwent optical coherence tomography to determine retinal nerve fibre layer thickness, and standard neurological assessment expanded the disability status scale. We found a significant annual fibre-specific neuro-axonal degeneration (mean ± SD = −3.49 ± 3.32%, P < 0.001) that was ∼7 times larger than the annual change of brain parenchymal fraction (−0.53 ± 0.95%, P < 0.001), and more than four times larger than annual retinal nerve fibre layer thinning (−0.75 ± 2.50% P = 0.036). Only fibre-specific measures showed a significant difference in annual degeneration between the disease stages (P = 0.029). Reduced brain parenchymal fraction, retinal nerve fibre layer thickness and fibre-specific measures were moderately related to higher expanded disability status scale (rho = −0.368, rho = −0.408 and rho = −0.365, respectively). Fibre-specific measures can be measured from data collected within a standard radiological multiple sclerosis study and are substantially more sensitive to longitudinal change compared with brain atrophy and retinal nerve fibre layer thinning.

Cognitive consequences of COVID-19: results of a cohort study from South America.

Neurological and psychiatric manifestations associated with SARS-CoV-2 infection have been reported throughout the scientific literature. However, studies on post-COVID cognitive impairment in people with no previous cognitive complaint are scarce. We aim to investigate the impact of COVID-19 on cognitive functions in adults without cognitive complaints before infection and to study cognitive dysfunction according to disease severity and cognitive risk factors. Forty-five post-COVID-19 patients and forty-five controls underwent extensive neuropsychological evaluation, which assessed cognitive domains such as memory, language, attention, executive functions, and visuospatial skills, including psychiatric symptomatology scales. Data were collected on the severity of infection, premorbid medical conditions, and functionality for activities of daily living before and after COVID-19. Significant differences between groups were found in cognitive composites of memory (p=0.016, Cohen's d= 0.73), attention (p<0.001, Cohen's d=1.2), executive functions (p<0.001, Cohen's d=1.4), and language (p=0.002, Cohen's d=0.87). The change from premorbid to post-infection functioning was significantly different between severity groups (WHODAS, p=0.037). Self-reported anxiety was associated with the presence of cognitive dysfunction in COVID-19 subjects (p=0.043). Our results suggest that the presence of cognitive symptoms in post-COVID-19 patients may persist for months after disease remission and argue for the inclusion of cognitive assessment as a protocolized stage of the post-COVID examination. Screening measures may not be sufficient to detect cognitive dysfunction in post-COVID-19 patients.