Cognition In People Research Articles

Study development and protocol for a cohort study examining the impact of baseline social cognition on response to treatment for people living with post-traumatic stress disorder

ABSTRACT Background: Social cognitive impairments, specifically in facial emotion processing and mental state attribution, are common in post-traumatic stress disorder. However few studies so far have examined whether social cognitive ability impacts on PTSD recovery. Objective: To examine whether baseline social cognitive abilities are associated with treatment outcomes following trauma-focused therapy for PTSD. Method: This is a cohort study that will relate treatment outcomes post-discharge to baseline measures of social cognition (five tasks: Emotion Odd-One-Out Task (Oddity), Reading the Mind in the Eyes Task (RMET), Social Shapes Test (SST), Spontaneous Theory of Mind Protocol (STOMP), and Reflective Functioning Questionnaire (RFQ-8)) in people starting a course of psychological therapy for PTSD (target N = 60). The primary outcome will be pre- to post-treatment change in PTSD symptom severity (assessed using the PTSD Checklist for DSM-5). Secondary outcomes include functional impairment (assessed using the Work and Social Adjustment Scale), drop-out rate, and analyses differentiating participants with DSM-5 PTSD and ICD-11 PTSD and CPTSD. Regression models will be used to examine associations between baseline social cognitive performance and outcome measures while adjusting for potential confounders. Two pilot studies informed the development of our study protocol. The first involved qualitative analysis of interviews with nine participants with lived experience of mental health problems to inform our research questions and study protocol. The second involved trialling social cognitive tasks on 20 non-clinical participants to refine our test battery. Discussion: This study will address a gap in the literature about whether abilities in social cognition in people living with PTSD are associated with treatment-related recovery. HIGHLIGHTS Impairments in social cognition are recognised in people with PTSD. Few studies have examined whether social cognitive ability is associated with recovery from PTSD. We present a study protocol, developed after pilot testing, to address this question.

Affective Empathy, Theory of Mind and Social Functioning in Patients With Focal Epilepsy.

ObjectiveSocial cognition comprises basic and more complex functions, such as theory of mind (ToM) and affective empathy. Although everyday social interactions may be impaired if such higher-order social cognitive functions are compromised, associations between social functioning and social cognition in people with focal epilepsy (PWFE) are still poorly understood. We used a novel, naturalistic approach to investigate ToM in PWFE by applying the Movie for the Assessment of Social Cognition (MASC). Furthermore, we studied affective empathy, the relationship between social cognitive parameters and measures of social functioning, as well as between epilepsy focus and ToM.MethodsThirty patients with either temporal (TLE) or frontal lobe epilepsy (FLE) were compared to 29 healthy control subjects (HC). In addition to the MASC, we applied questionnaire measures assessing empathy and everyday social functioning.ResultsPWFE, especially with FLE, performed significantly worse than HC on the MASC. Perceived social integration and social activities, but not affective empathy, were reduced in PWFE. Regression analyses revealed associations between perceived social integration, clinical group status, affective empathy and ToM.ConclusionPWFE displayed ToM deficits during a naturalistic task, whereas affective empathy was unimpaired. FLE may be associated with especially compromised ToM performance. Social cognition and social functioning appear to be interrelated in PWFE, whose self-perceived levels of social integration and social activities are lower than those of HC. More research into the association between social cognition and social functioning in PWFE is needed, in order to develop tailored intervention programs for these patients.

Effects of cognitive interventions on quality of life among adults with mild cognitive impairment: A systematic review and meta-analysis of randomised controlled trials

BackgroundThere is considerable research exploring the impact of cognitive interventions on cognition in people with mild cognitive impairment (MCI). However, the impact on quality of life (QOL) is not routinely reported. As QOL is a key predictor of health outcomes, it is important to determine the evidence supporting cognitive interventions for improving QOL in people with MCI. ObjectiveTo evaluate the evidence on the effectiveness of cognitive interventions for improving QOL among people with MCI. DesignSystematic review and meta-analysis. MethodsA systematic database search was conducted from inception to December 11, 2021, using four databases. Quality assessment was conducted, and data on the characteristics of the studies and the effects on QOL were extracted. Subgroup analyses and meta-regression were conducted to elucidate the effects of potential moderator variables on QOL measures. ResultsOf the 1550 records initially identified, 17 studies met the criteria for the final meta-analysis. The findings revealed that cognitive interventions produced moderate gains in overall QOL compared to the control group at the posttest (standardized mean difference (SMD): 0.53, 95% confidence interval (CI): [0.23, 0.84]), but no statistically significant differences were found at the end of follow-up (SMD: 0.40, 95% CI: [−0.15,0.94]). Furthermore, the effects of cognitive interventions were moderated by intervention duration, session duration, and study location. However, intervention types, session frequency, intervention components, control condition, total number of sessions, types of QOL measures, and responders to QOL-AD had no statistically significant effects on QOL outcome. ConclusionsCognitive interventions have positive effects on QOL among adults with MCI. However, the high heterogeneity of the included studies calls for more well-designed cognitive intervention trials to examine the association between QOL and relevant moderators.

Systematic review and meta-analysis of randomization controlled and nonrandomized controlled studies on nurse-led nonpharmacological interventions to improve cognition in people with dementia.

To evaluate nurse-led nonpharmacological interventions for improving cognition in people with dementia. Starting in 2006, donepezil was administered worldwide to improve cognition; however, its side effects limited its therapeutic value for long-term use, prompting a need for nonpharmacological interventions to improve cognition. Nurse-led nonpharmacological interventions are especially important because they are effective in terms of resources and costs, reduce patient latency and improve patient safety and satisfaction. A systematic review was identified by searching 10 electronic databases. The search period was between 1 January 2007, and 30 September 2021. Languages were limited to English and Korean. The inclusion criteria were studies of nurse-led interventions that evaluated cognition using validated instruments. The exclusion criteria were qualitative research, scale development studies, abstracts and grey literature. Quality appraisal of research was conducted using the Risk of Bias in Nonrandomized Studies of Interventions for quasi-experimental studies and the Risk of Bias 2.0 for randomised controlled studies. This study was conducted in accordance with PRISMA reporting guideline (AppendixS1). The search protocol was registered in the PROSPERO (CRD 42021229358). A total of 24 studies were included in the systematic review, and 15 studies were included in the meta-analysis. Meta-analysis included 8 RCT and 7 quasi-experimental studies. The studies (11 quasi-experimental studies and 9 randomised controlled studies) demonstrated low to moderate quality of evidence for improving the cognition of people with dementia. The meta-analysis showed that nurse-led single nonpharmacological interventions more effectively improved cognition than complex interventions in people with dementia. Nurse-led nonpharmacological interventions were effective for improving cognition in people with dementia. Nurses are qualified professionals with expertise in providing nonpharmacological interventions to improve cognition in people with dementia. Nurse-led nonpharmacological interventions for this purpose should be developed in future research.

Computerised cognitive training tools and online nutritional group counselling for people with mild cognitive impairment: study protocol of a completely digital, randomised, controlled trial

IntroductionPeople with mild cognitive impairment (MCI) are at increased risk of decreasing cognitive functioning. Computerised cognitive training (CCT) and nutrition have been shown to improve the cognitive capacities of people...

Plain language summary of the effects of iclepertin (BI 425809) on cognition in patients with schizophrenia

What is this summary about? This is a summary of an article originally published in Lancet Psychiatry. Many people affected by schizophrenia have difficulties with cognition (thinking), known as cognitive impairment. Cognitive impairment includes a decline in a person’s memory and their ability to learn new things and carry out everyday tasks. However, there are currently no approved drugs to treat cognitive impairment associated with schizophrenia. What were the results? In this study, a drug called iclepertin (originally called BI 425809) was tested to find out whether it could improve cognition in people with schizophrenia. A total of 509 participants took one of four different doses of iclepertin or placebo once a day for 12 weeks. Iclepertin improved cognition when compared with placebo and showed no serious side effects. What do the results of the study mean? These results mean that iclepertin might be an effective treatment for cognitive impairment associated with schizophrenia. These results will need to be confirmed in larger studies. ClinicalTrials.gov NCT number: NCT02832037

The Weekly Calendar Planning Activity to Assess Functional Cognition in Parkinson Disease.

The Weekly Calendar Planning Activity (WCPA) may improve understanding of functional cognition in people with Parkinson disease (PwPD) without dementia. We aimed to determine if WCPA performance (a) discriminates between PwPD with and without cognitive impairment and healthy controls and (b) correlates with other indicators of cognition and daily function. This was a cross-sectional study. Parkinson disease (PD) participants without dementia were divided into normal cognition (PD-NC, n = 25) and possible mild cognitive impairment (PD-MCI, n = 21) groups. Their WCPA performance was compared with that of a normative sample (n = 196) and correlated with neuropsychological test performance and self-reported cognition and participation. Both the PD-MCI and PD-NC groups had impaired WCPA performance. WCPA performance correlated with executive function, processing speed, and self-reported cognition and participation. The WCPA can detect functional cognitive deficits in PwPD without dementia and can inform occupational therapy interventions to support functional cognition, occupational performance, and participation in this population.

Leisure Time Physical Activities' Association With Cognition and Dementia: A 19 Years' Life Course Study.

IntroductionCognitive impairment is one of the main disabilities in dementia. Physical activity (PA) has been suggested as protective for dementia. However, the findings are disparate in studies, and the question of whether this is because of reverse causality is still open. We aimed to explore the association of PA with cognition in people who later developed dementia compared to those who did not.MethodSince 2001, 11,512 (55% women) participants over the age of 50 years had taken at least one cognitive test in the Tromsø Study. Of these, 1,123 (58% women) later developed dementia. The cases were extracted from hospital journals and entered into an endpoint registry. Leisure time PA (LTPA) was self-reported. Multilevel mixed-effects linear regression was used to address whether LTPA was associated with cognition, stratified by those later developing dementia, and dementia-free in a separate analysis.ResultsLeisure time PA was associated with scores in cognitive tests that were 55% (z-score 0.14) higher in those who did not develop dementia. For those in a preclinical phase of dementia, there was no association with LTPA on global cognitive scores. However, in a multifactorial test on processing speed and memory, women had a positive association with processing speed and memory.ConclusionLeisure time PA had a positive association with global cognition function only for those who did not develop dementia. In women who were developing dementia, LTPA had a positive association with processing speed and memory, while in men, there were no such associations.

Cancer-related cognitive impairment in patients with newly diagnosed aggressive lymphoma undergoing standard chemotherapy: a longitudinal feasibility study

PurposeCancer-related cognitive impairment (CRCI) is a recognised adverse consequence of cancer and its treatment. This study assessed the feasibility of collecting longitudinal data on cognition in patients with newly diagnosed, aggressive lymphoma undergoing standard therapy with curative intent via self-report, neuropsychological assessment, peripheral markers of inflammation, and neuroimaging. An exploration and description of patterns of cancer-related cognitive impairment over the course of treatment and recovery was also undertaken and will be reported separately.MethodsEligible participants completed repeated measures of cognition including self-report and neuropsychological assessment, and correlates of cognition including blood cell–based inflammatory markers, and neuroimaging at three pre-specified timepoints, time 1 (T1) — pre-treatment (treatment naïve), time 2 (T2) — mid-treatment, and time 3 (T3) — 6 to 8 weeks post-completion of treatment.Results30/33 eligible patients (91%, 95% CI: 76%, 97%) were recruited over 10 months. The recruitment rate was 3 patients/month (95% CI: 2.0, 4.3 patients/month). Reasons for declining included feeling overwhelmed and rapid treatment commencement. Mean age was 57 years (SD = 17 years) and 16/30 (53%) were male. Most patients (20/30, 67%) had diffuse large B cell lymphoma or Hodgkin lymphoma (4/30, 13%). The neuroimaging sub-study was optional, 11/30 participants (37%) were eligible to take part, and all agreed. The remaining 19 participants were ineligible as their diagnostic PET/CT scan was completed prior. Retention and compliance with all assessments were 89 to 100% at all timepoints. Only one participant was withdrawn due to disease progression.ConclusionsFindings from this study including excellent recruitment, retention, and compliance rates demonstrate it is feasible to longitudinally assess cognition in people with newly diagnosed aggressive lymphoma during their initial treatment and recovery to inform the development of future research to improve patient experiences and cognitive outcomes.Trial registration.Australian New Zealand Clinical Trials Registry ACTRN12619001649101.

Top-Down Influence Leads to a Reduced Sense of Body Ownership in Individuals With Depersonalization Tendencies: A Focus on Full Body Illusion.

Sense of body ownership, that is, the feeling that “my body belongs to me,” has been examined by both the rubber hand illusion (RHI) and full body illusion (FBI). In a study that examined the relationship between RHI and depersonalization, a symptom in which people experience a lower sense of body ownership, people with a high depersonalization tendency experienced RHI through the bottom-up process of visual-tactile integration. Why is it that people with depersonalization feel a lower sense of body ownership over their bodies? Case studies of depersonalization suggest that the top-down cognition in people with depersonalization may make them less likely to feel a sense of body ownership. However, the top-down influence on the sense of body ownership in depersonalization has not yet been experimentally demonstrated. By incorporating top-down manipulation (e.g., instructing participants to regard a fake body as their own) into the FBI procedure, we aimed to clarify the cause of the reduced sense of body ownership in people with a high depersonalization tendency. The FBI procedure was conducted in a virtual reality environment using an avatar as a fake body. The avatar was presented from a third-person perspective, and visual-tactile stimuli were presented to create an illusion. To examine the degree of illusion, we measured the skin conductance responses to the fear stimulus presented after the visual-tactile stimuli presentation. The degree of depersonalization was measured using the Japanese version of the Cambridge Depersonalization Scale. To manipulate the top-down influence, we provided self-association instructions before the presentation of the visual-tactile stimuli. We predicted that the higher the degree of depersonalization, the lower the degree of illusion in the self-association instruction. The results showed that participants with a higher depersonalization tendency had a lower degree of illusion (rho = −0.424, p = 0.035) in the self-association condition. This indicates that in people with a high depersonalization tendency, top-down cognition of the body as their own leads to a decrease in the sense of body ownership.

Neuropathic pain correlates with worsening cognition in people with human immunodeficiency virus.

Neuropathic pain and cognitive impairment are among the HIV-related conditions that have most stubbornly resisted amelioration by virally suppressive antiretroviral therapy. Overlaps between the regional brain substrates and mechanisms of neuropathic pain and cognitive disorders are increasingly recognized, yet no studies have examined the longitudinal relationship between these two disorders. Participants in the prospective, observational CNS HIV AntiRetroviral Therapy Effects Research (CHARTER) cohort underwent standardized clinical evaluations for clinical examination findings of distal sensory polyneuropathy, reporting distal neuropathic pain and neurocognitive performance at study entry (baseline) and an average of 12 years later. Change in neuropathic pain and neuropathy status from baseline to follow-up was by self-report and repeat examination, and change in neurocognitive performance was assessed using a previously published summary regression-based change score. Relationships between incident or worsened neuropathic pain and neurocognitive change were evaluated using uni- and multivariable regressions, including age at baseline and other relevant covariates. Participants were 385 people with HIV, 91 (23.6%) females, mean ± standard deviation (SD) age at baseline 43.5 (7.81) years, ethnicity 44.9% African American, 10.6% Hispanic, 42.6% non-Hispanic white and 1.82% other. Baseline median (interquartile range) nadir CD4 was 175 (34 309) cells/µl and current CD4 was 454 (279 639). Incident or worsened distal neuropathic pain occurred in 98 (25.5%) over the follow-up period. People with HIV with incident or worsened distal neuropathic pain had significantly worsened neurocognitive performance at follow-up compared to those without incident or worsened distal neuropathic pain (summary regression-based change score mean ± SD -0.408 ± 0.700 versus -0.228 ± 0.613; P = 0.0158). This effect remained significant when considering viral suppression on antiretroviral therapy, incident diabetes and other covariates as predictors. Overall neurocognitive change related to neuropathic pain was driven primarily by changes in the domains of executive function and speed of information processing. Those with incident distal neuropathy signs did not have neurocognitive worsening, nor did individuals who used opioid analgesics or other pain-modulating drugs such as amitriptyline. Worsened neurocognitive performance in people with HIV was associated with worsened neuropathic pain but not with changes in physical signs of neuropathy, and this was not attributable to therapies for pain or depression or to differences in viral suppression. This finding implies that incident or worsened pain may signal increased risk for neurocognitive impairment, and deserves more investigation, particularly if better pain management might stabilize or improve neurocognitive performance.

Weight-loss induced by carbohydrate restriction does not negatively affect health-related quality of life and cognition in people with type 2 diabetes: A randomised controlled trial

We evaluated the effect of weight loss induced by dietary carbohydrate restriction on health-related quality of life (HRQoL) and cognition in type 2 diabetes (T2D). In this randomised parallel trial, 72 adults with T2D and overweight/obesity (mean±SD, HbA1c: 57±8mmol/mol and BMI: 33±5kg/m2) were randomly assigned to a carbohydrate-reduced high-protein diet (CRHP: C30E%-P30E%-F40E%) or conventional diabetes diet (CD: C50E%-P17E%-F33E%) for 6 weeks, targeting a 6% weight loss. HRQoL was assessed from the short form 36 (SF-36) questionnaire, including physical and mental component summary (PCS and MCS) scores; global cognition, verbal memory, attention and psychomotor speed, and executive function were assessed from a neuropsychological test battery. Both diet groups achieved a 5.8kg weight loss and improved PCS (median [25th;75th percentiles], CD: 2.7 [1.1; 4.2] vs. CRHP: 2.1 [0.7; 3.7]), with no difference between diets. The CRHP diet resulted in a clinically relevant improvement of MCS, albeit non-significantly different compared with the change after the CD diet (2.0 [-0.7; 4.8], p=0.15). Global cognition, attention, and verbal memory were unaffected by the CRHP diet, which selectively worsened the Symbol Digit Modality Test assessing psychomotor speed when compared with the CD diet (-4.1 [-7.2;-1.1], p<0.01). Physical health improved by weight loss independently of macronutrient distribution, while mental health and cognition may be affected by the amount of carbohydrate, protein and fat in the diet. Collectively, our data suggest that weight loss through moderate carbohydrate restriction has no clinically important impact on HRQoL and global cognition in patients with T2D. Registered under ClinicalTrials.gov Identifier no. NCT03814694.

Characterization of Mild and Moderate Dysarthria in Parkinson's Disease: Behavioral Measures and Neural Correlates.

PurposeAlterations in speech and voice are among the most common symptoms in Parkinson’s disease (PD), often resulting in motor speech disorders such as hypokinetic dysarthria. We investigated dysarthria, verbal fluency, executive functions, and global cognitive function in relation to structural and resting-state brain changes in people with PD.MethodsParticipants with mild-moderate PD (n = 83) were recruited within a randomized controlled trial and divided into groups with varying degrees of dysarthria: no dysarthria (noDPD), mild dysarthria (mildDPD), moderate dysarthria (modDPD), and also combined mildDPD and modDPD into one group (totDPD). Voice sound level and dysphonia, verbal fluency, motor symptoms, executive functions, disease severity, global cognition, and neuroimaging were compared between groups. Gray matter volume and intensity of spontaneous brain activity were analyzed. Additionally, regressions between behavioral and neuroimaging data were performed.ResultsThe groups differed significantly in mean voice sound level, dysphonia, and motor symptom severity. Comparing different severity levels of dysarthria to noDPD, groups differed focally in resting-state activity, but not in brain structure. In totDPD, lower scores on semantic verbal fluency, a composite score of executive functions, and global cognition correlated with lower superior temporal gyrus volume.ConclusionThis study shows that severity of dysarthria may be related to underlying structural and resting-state brain alterations in PD as well as behavioral changes. Further, the superior temporal gyrus may play an important role in executive functions, language, and global cognition in people with PD and dysarthria.

Effects of Socioeconomic Status in Cognition of People with Schizophrenia: Results From a Latin American Collaboration Network with 1175 Subjects - CORRIGENDUM.

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Immersive Technology for Cognitive-Motor Training in Parkinson's Disease.

Background: Parkinson’s disease (PD) is a neurodegenerative disease in which the progressive loss of dopaminergic neurons (DA) leads to initially sporadic and eventually widespread damage of the nervous system resulting in significant musculoskeletal and cognitive deterioration. Loss of motor function alongside increasing cognitive impairment is part of the natural disease progression. Gait is often considered an automatic activity; however, walking is the result of a delicate balance of multiple systems which maintain the body’s center of mass over an ever-changing base of support. It is a complex motor behavior that requires components of attention and memory to prevent falls and injury. In addition, evidence points to the critical role of salient visual information to gait adaptability. There is a growing understanding that treatment for PD needs to address movement as it occurs naturally and walking needs to be practiced in more complex environments than traditional therapy has provided.MethodsIn this single-blinded randomized-controlled pilot study, an immersive treadmill training was piloted to determine feasibility and preliminary efficacy on gait and cognition in people with PD. Eighteen participants with Hoehn and Yahr stages I-III PD were randomized to either an intervention or a waitlist control group. Following baseline data collection, the intervention group trained for 30 min, three times/week for 4 weeks on a split belt treadmill combined with a first-person immersive video game targeting visuospatial skills and working memory. Assessment was repeated after 4 weeks of training for the experimental group and 1-month after baseline for the control group. Primary motor outcomes were captured with the APDM Opal sensors during 6 MWT, TUG, and TUG Cognitive. Secondary outcomes of cognition were measured with the Montreal Cognitive Assessment (MoCA), Verbal Fluency (Fruit, Vegetable, and Animal) and the Symbol Digit Modality Test (SDMT). Within subject differences were calculated using the Wilcoxon Signed Ranked Test and between subject comparisons were analyzed using the Mann Whitney U-test.ResultsThis novel treadmill training program was well-tolerated with all participants in the intervention group completing 4 weeks of training three times a week without any adverse effects. After immersive cognitive motor training, the experimental group made clinically relevant improvements in gait speed and walking distance during the 6 MWT while members of the control group showed no change or decreased gait speed and walking distance over the 1-month trial. In addition, the experimental group demonstrated significant improvement for the TUG Cognitive (p = 0.05) and those changes were greater than the control group (between group p = 0.040). The experimental group also improved scores on MoCA (p = 0.007) and SDMT (p = 0.01) cognitive outcome measures while the control group did not.ConclusionThe use of immersive gaming technology to engage specific areas of cognition related to gait is feasible in PD. The treadmill training program paired with a customized interactive video game improved walking velocity in addition to non-significant but consistent improvements in other gait measures and cognitive performance in participants with early to mid-stage PD.

Association between aerobic fitness and the functional connectome in patients with schizophrenia

BackgroundSchizophrenia is accompanied by widespread alterations in static functional connectivity associated with symptom severity and cognitive deficits. Improvements in aerobic fitness have been demonstrated to ameliorate symptomatology and cognition in people with schizophrenia, but the intermediary role of macroscale connectivity patterns remains unknown.ObjectiveTherefore, we aim to explore the relation between aerobic fitness and the functional connectome in individuals with schizophrenia. Further, we investigate clinical and cognitive relevance of the identified fitness-connectivity links.MethodsPatients diagnosed with schizophrenia were included in this cross-sectional resting-state fMRI analysis. Multilevel Bayesian partial correlations between aerobic fitness and functional connections across the whole brain as well as between static functional connectivity patterns and clinical and cognitive outcome were performed. Preliminary causal inferences were enabled based on mediation analyses.ResultsStatic functional connectivity between the subcortical nuclei and the cerebellum as well as between temporal seeds mediated the attenuating relation between aerobic fitness and total symptom severity. Functional connections between cerebellar seeds affected the positive link between aerobic fitness and global cognition, while the functional interplay between central and limbic seeds drove the beneficial association between aerobic fitness and emotion recognition.ConclusionThe current study provides first insights into the interactions between aerobic fitness, the functional connectome and clinical and cognitive outcome in people with schizophrenia, but causal interpretations are preliminary. Further interventional aerobic exercise studies are needed to replicate the current findings and to enable conclusive causal inferences.Trial registrationThe study which the manuscript is based on is registered in the International Clinical Trials Database (ClinicalTrials.gov identifier [NCT number]: NCT03466112) and in the German Clinical Trials Register (DRKS-ID: DRKS00009804).

Relationships Among Phantom Limb Pain, Peripheral Sensations, and Cognition in People with Lower-Limb Loss

ABSTRACT Introduction After amputation, altered sensory input leads to cortical reorganization that partly explains phantom limb pain (PLP). However, many factors impact the PLP phenomenon, and modern conceptualizations of chronic pain including PLP integrate both peripheral inputs and central interpretation. Clinicians without functional MRI could benefit from clinical measures related to PLP to assess clinical presentations. The purpose of this pilot study was to identify peripheral sensation and cognition measures related to PLP to inform outcome measure selection in future PLP research. Methods This cross-sectional analysis included people with PLP of any age, sex, and amputation cause or level. Assessments included patient-reported residual limb pain and PLP using the Prosthesis Evaluation Questionnaire, peripheral sensation measures (light touch, temperature, vibration, two-point discrimination), and cognition measures (laterality recognition, trail making, clock drawing). Unadjusted Spearman ρ coefficients were reported. Results Eleven volunteers (48.5 ± 13.2 years) with lower-limb amputations (seven transtibial) of various causes (nine medical) participated. More severe PLP symptoms were associated with impaired peripheral sensation (light touch, ρ = 0.514; temperature, ρ = 0.756) and poorer cognition (laterality recognition, ρ = 0.524; trail making, ρ = 0.565). Residual limb pain was not correlated with cognition measures (ρ &lt; 0.4). Conclusions This pilot study identified clinical measures assessing cognition and peripheral sensation impairments associated with worse PLP symptoms. Phantom limb pain was related to temperature and light touch sensation measures, but two-point discrimination was not associated with PLP consistent with past research. Laterality recognition was associated with PLP per prior research, and the association of PLP with the Trail Making Test in this pilot study suggests that the Trail Making Test may be an additional cognition measure potentially useful in future clinical research to document the PLP experience.

Associations of L-Ferritin and Tim-1 with frailty measures in people with HIV: a cross-sectional and longitudinal study

BackgroundPeople with HIV are at high risk of frailty. Iron transport is key to energy production and is dysregulated by HIV and inflammation. We previously linked higher cerebrospinal fluid levels of the iron transporter heavy-chain-ferritin (Fth1) to better cognition in people with HIV. Here, we evaluated whether higher levels of serum Fth1 and light-chain-ferritin (Ftl), and lower levels of urine T-cell immunoglobulin-and-mucin domain (Tim)-1 (Fth1 receptor) are associated with better frailty measures in people with HIV. MethodsSerum Fth1, Ftl, inflammation markers (IL-6, sTNFR2), and urine Tim-1 were quantified by ELISA in 324 AIDS Clinical Trials Group Study A5322 enrollees at entry. Prefrailty and frailty were assessed using Fried's criteria. Relationships among baseline biomarker concentrations, HIV clinical variables and demographic variables were tested using Pearson's χ2 test, non-parametric tests for trend, or Spearman's correlations. Multivariable regression models evaluated cross-sectional and longitudinal Fth1, Ftl, and Tim-1 associations with prefrail and frail status, average 4-metre walk time, and grip strength in all people with HIV and by sex. FindingsAt study entry, 127 (40%) of 321 participants were prefrail and 15 (4%) of 321 were frail (mean age 52 years [SD 7·3]]; 61 (19%) of 321 were female and 260 (81%) of 321 were male; and 306 (96%) of 319 were virally suppressed). Serum Fth1 was correlated with Ftl (rho 0·14; p<0·01), but not to urine Tim-1. In univariate analyses, Tim-1 was higher (ptrend=0·06) and Ftl lower (ptrend=0·02) across non-frail, prefrail, and frail groups. Higher Tim-1 was associated with prefrailty (odds ratio [OR] 1·5; p<0·01) and combined prefrailty and frailty (OR 2·3; p=0·01) versus non-frail people with HIV. Higher Ftl was associated with faster 4 m walk time (β –0·045; p<0·01), lower odds of weak grip (OR 0·49; p<0·01), and less frailty, particularly in female participants (OR 0·28; p=0·03). In multivariable-adjusted analyses, higher Ftl was associated with faster 4 m walk time and better grip strength (both p<0·05), reduced odds of combined prefrailty and frailty versus non-frailty (adjusted OR 0·56 in all people with HIV and 0·29 in female participants, both p<0·05 for levels greater than or equal to the median versus less than the median) and lower odds of weak grip (OR 0·50; p<0·05). Ftl concentrations in the highest versus lowest quartile were associated with lower odds of slow 4 m walk time in female participants (OR 0·060; p<0·05). Higher Tim-1 was associated with combined prefrailty and frailty versus non-frailty (OR 2·6; p<0·05). Serum Fth1 was not associated with frailty measures. InterpretationIncreased urine Tim-1 is a marker of risk for prefrailty and frailty in people with HIV. Higher serum Ftl is associated with preserved motor function and less prefrailty or frailty, particularly in female individuals. Future studies will explore causal pathways. FundingNational Institutes of Health grant (to AK): 5R03 MH123291-02; National Institute of Allergy and Infectious Diseases, National Institute of Mental Health, National Institute on Aging, and National Institute of Diabetes and Digestive and Kidney Diseases.

Investigating repetitive transcranial magnetic stimulation on cannabis use and cognition in people with schizophrenia

Cannabis use disorder (CUD) occurs at high rates in schizophrenia, which negatively impacts its clinical prognosis. These patients have greater difficulty quitting cannabis which may reflect putative deficits in the dorsolateral prefrontal cortex (DLPFC), a potential target for treatment development. We examined the effects of active versus sham high-frequency (20-Hz) repetitive transcranial magnetic stimulation (rTMS) on cannabis use in outpatients with schizophrenia and CUD. Secondary outcomes included cannabis craving/withdrawal, psychiatric symptoms, cognition and tobacco use. Twenty-four outpatients with schizophrenia and CUD were enrolled in a preliminary double-blind, sham-controlled randomized trial. Nineteen participants were randomized to receive active (n = 9) or sham (n = 10) rTMS (20-Hz) applied bilaterally to the DLPFC 5x/week for 4 weeks. Cannabis use was monitored twice weekly. A cognitive battery was administered pre- and post-treatment. rTMS was safe and well-tolerated with high treatment retention (~90%). Contrast estimates suggested greater reduction in self-reported cannabis use (measured in grams/day) in the active versus sham group (Estimate = 0.33, p = 0.21; Cohen’s d = 0.72), suggesting a clinically relevant effect of rTMS. A trend toward greater reduction in craving (Estimate = 3.92, p = 0.06), and significant reductions in PANSS positive (Estimate = 2.42, p = 0.02) and total (Estimate = 5.03, p = 0.02) symptom scores were found in the active versus sham group. Active rTMS also improved attention (Estimate = 6.58, p < 0.05), and suppressed increased tobacco use that was associated with cannabis reductions (Treatment x Time: p = 0.01). Our preliminary findings suggest that rTMS to the DLPFC is safe and potentially efficacious for treating CUD in schizophrenia.

Childhood Maltreatment, Educational Attainment, and IQ: Findings From a Multicentric Case-control Study of First-episode Psychosis (EU-GEI).

Evidence suggests that childhood maltreatment (ie, childhood abuse and childhood neglect) affects educational attainment and cognition. However, the association between childhood maltreatment and Intelligence Quotient (IQ) seems stronger among controls compared to people with psychosis. We hypothesised that: the association between childhood maltreatment and poor cognition would be stronger among community controls than among people with first-episode of psychosis (FEP); compared to abuse, neglect would show stronger associations with educational attainment and cognition; the association between childhood maltreatment and IQ would be partially accounted for by other risk factors; and the association between childhood maltreatment, educational attainment, and IQ would be stronger among patients with affective psychoses compared to those with nonaffective psychoses. 829 patients with FEP and 1283 community controls from 16 EU-GEI sites were assessed for child maltreatment, education attainment, and IQ. In both the FEP and control group, childhood maltreatment was associated with lower educational attainment. The association between childhood maltreatment and lower IQ was robust to adjustment for confounders only among controls. Whereas childhood neglect was consistently associated with lower attainment and IQ in both groups, childhood abuse was associated with IQ only in controls. Among both patients with affective and nonaffective psychoses, negative associations between childhood maltreatment and educational attainment were observed, but the crude association with IQ was only evident in affective psychoses. Our findings underscore the role of childhood maltreatment in shaping academic outcomes and cognition of people with FEP as well as controls.