Severe Cognitive Impairment Research Articles

Effects of voluntary, involuntary exercise and sertraline on anxiety, social and cognitive behavior in female rat model of post-traumatic stress disorder

Post-traumatic stress disorder (PTSD) is considered as a complex syndrome comprising extremely severe anxiety levels, social-interpersonal dysfunction, and cognitive impairment that may be based on severe traumatic events. Although PTSD is more prevalent in females than in males, most preclinical studies have been carried out in males. The present study investigated the effects of voluntary and involuntary exercise, as well as sertraline on behavioral deficits in a female nonhuman animal model of PTSD using the single-prolonged stress (SPS) paradigm. Female adult rats were exposed to SPS protocol (2-hour restrain, 20-minute forced swimming, 15-minute rest, and 2–3 minute diethyl ether exposure) and were then kept undisturbed. Following a 7-day undisturbed period, animals were subjected to a 10 min restraint (re-stress). SPS rats were treated with voluntary wheel running or moderate treadmill exercise (5 days/week) and/or the administration of sertraline (10 mg/kg/day) for four consecutive weeks. Behavioral assessments were conducted using the Elevated Plus Maze (EPM) test for anxiety, the Three-Chamber Social Test (3-CST) for social interaction, and the Morris Water Maze (MWM) test for spatial memory. Involuntary exercise combined with sertraline significantly increased time spent in the open arms of the EPM test (P < 0.001), and interaction with new rats in 3-CST (P < 0.001) compared to SPS rats. The voluntary exercise plus sertraline group showed a significant increase in entries into the training platform during the probe phase of the MWM test (P < 0.001) compared to SPS rats. Overall, sertraline combined with involuntary exercise was more effective than voluntary exercise plus sertraline in enhancing social interaction and reducing anxiety in the SPS model of PTSD. Conversely, voluntary exercise combined with sertraline provided greater benefits for spatial memory enhancement in female rats.

Physical activity modifies cognitive impairment-associated mortality risks among chronic kidney disease

BackgroundOlder chronic kidney disease (CKD) patients frequently face unrecognized cognitive impairment and excess mortality. Physical activity (PA) reduces cognitive decline but whether PA modifies cognitive impairment-associated mortality remains unknown. MethodsFrom 2005 to 2011, 30,561 older Taiwanese CKD patients were enrolled. Patients were divided into intact cognition (≥8 scores), mild (6–7 scores), and severe (≤5 scores) cognitive impairment groups by the Short Portable Mental Status Questionnaire (SPMSQ), and were also categorized into high-PA (≥60 min/week of moderate-intensity PA), low-PA (20–60 min/week) or inactive (<20 min/week) groups. Cox regression was conducted to evaluate the individual and joint associations of cognitive impairment and PA on all-cause and cardiovascular mortality. ResultsAfter a median follow-up of 4.52 years, the all-cause mortality were higher in CKD patients with severe (multivariable-adjusted hazard ratio [aHR] 2.31; 95% confidence interval [CI] 2.05–2.60) and mild (aHR 1.74; CI 1.51–1.99) cognitive impairment than cognitively intact ones. Remarkably, decreased PA amount interacted and amplified the cognitive impairment-associated mortality risks. Notably, the high-PA status linked to lower overall mortality risks both in mild (aHR 0.65; CI 0.45–0.93) and severe (aHR 0.73; CI 0.54–0.99) cognitively-impaired patients as compared to inactivity. Survival tree analysis indicated the least mortality in those with high PA and >8 SPMSQ scores. Similar associations were found in the cardiovascular mortality. LimitationsResidual confounding and single ethnicity. ConclusionsCognitive impairment defined by SPMSQ was progressively associated with higher mortality among elderly CKD. Higher PA linked to lower cognitive impairment-associated death risks, and could be promoted for longevity benefits.

Cognitive Impairment Features in Patients With Multiple Sclerosis

Introduction: Multiple sclerosis (MS) is an inflammatory and demyelinating disease of the central nervous system accompanied by neurodegeneration contributing to cognitive dysfunction. Cognitive impairment occurs in 40%-65% of patients with MS and can manifest even in the early stages of the disease.Objective: To evaluate cognitive dysfunction features in patients with MS.Materials and methods: The study included patients with MS (n=30; age, 40.8±9.74 years; disease duration, 9.67±6.96 years; Expanded Disability Status Scale [EDSS] score, 4.76±2.11) and healthy individuals (n=30; age, 40.3±12.24 years). Cognitive impairment was assessed using the Montreal Cognitive Assessment Scale (MoCA) and the Paced Auditory Serial Addition Test (PASAT).Results: Cognitive impairment in the group of MS patients was found in 73.3% of the cases. The mean MoCA, PASAT-3, and PASAT-2 scores of MS patients were 13.56%, 24.31%, and 29.48% lower than those in the control group, respectively. In women, the cognitive level in MS patients remains higher than in men. Analysis of the PASAT-3 and PASAT-2 results in MS patients did not reveal any statistically significant differences between the groups of patients aged 18-35 years and those aged 36-44 years and the groups of patients aged 18-35 years and those aged 45-59 years. The results of the MoCA and hearing tests in patients with higher and secondary education were not statistically significant. We found an inverse relationship between EDSS and PASAT-2 (R= −0.49; P&lt; .05), EDSS and PASAT-3 (R= −0.37; P&lt; .05). The most severe cognitive impairment was observed with high EDSS (7.5-9).Conclusions: We have identified features of cognitive functions in MS. Follow-up and therapy of MS patients require cognitive dysfunction assessment using appropriate scales.

Long term functioning with poor neurologic outcome after cardiac arrest

AimAround six percent of comatose patients after cardiac arrest have a Cerebral Performance Categories score of three (CPC3) at six months after the arrest, classified as severe neurological disability. There is limited knowledge regarding the likelihood of further recovery in the cognitive, emotional, and quality of life domains. We aimed to estimate the probability of recovery towards independency. MethodsFrom a prospective Registry on comatose cardiac arrest patients admitted between 2013 and 2017 in two Dutch hospitals, we included patients with a CPC3 at six months after cardiac arrest. We followed patients up to November 2023. The primary outcome measure was the CPC score at time of follow up. Secondary outcomes were scores on questionnaires on cognition, mood, and quality of life according to the minimal dataset of acquired brain injury. ResultsIn our cohort of 667 patients, 29 (4.3%) had a CPC3 score at six months (median age 68 years, 83% male). At a median time of eight years after cardiac arrest, sixteen patients had died. Twelve of thirteen alive patients still had a CPC3 score (92%) and one a CPC2 (8%). Seven patients agreed with further interviewing, one showed independency in activities of daily living (14%). Six patients (86%) reported limitations due to physical and one (14%) due to emotional problems. All had severe cognitive impairment. Six (86%) missed cognitive rehabilitation. ConclusionOur study shows that while the probability of recovery towards independence for patients with severe neurological disability at six months after cardiac arrest is limited, most long-term survivors are satisfied with their quality of life.

Pros and Cons of APOE4 Homozygosity and Effects on Neuroplasticity, Malnutrition, and Infections in Early Life Adversity, Alzheimer's Disease, and Alzheimer's Prevention.

Fortea et al.'s. (2024) recent data analysis elegantly calls attention to familial late-onset Alzheimer's disease (AD) with APOE4 homozygosity. The article by Grant (2024) reviews the factors associated with AD, particularly the APOE genotype and lifestyle, and the broad implications for prevention, both for individuals with the lifestyles associated with living in resource-rich countries and for those enduring environmental adversity in poverty settings, including high exposure to enteric pathogens and precarious access to healthcare. Grant discusses the issue of APOE genotype and its implications for the benefits of lifestyle modifications. This review highlights that bearing APOE4 could constitute an evolutionary benefit in coping with heavy enteric infections and malnutrition early in life in the critical formative first two years of brain development. However, the critical issue may be that this genotype could be a health concern under shifts in lifestyle and unhealthy diets during aging, leading to severe cognitive impairments and increased risk of AD. This commentary supports the discussions of Grant and the benefits of improving lifestyle for decreasing the risks for AD while providing further understanding and modelling of the early life benefits of APOE4 amidst adversity. This attention to the pathophysiology of AD should help further elucidate these critical, newly appreciated pathogenic pathways for developing approaches to the prevention and management in the context of the APOE genetic variations associated with AD.

Hospital referrals, exclusions from hospital care, and deaths among long-term care residents in the Community of Madrid during the March–April 2020 COVID-19 epidemic period: a multivariate time series analysis

BackgroundFrom March 7 to April 7, 2020, the Community of Madrid (CoM), Spain, issued interventions in response to the COVID-19 epidemic, including hospital referral triage protocols for long-term care facility (LTCF) residents (March 18–25). Those with moderate to severe physical disability and cognitive impairment were excluded from hospital referral. This research assesses changes in the association between daily hospital referrals and the deaths of LTCF residents attributable to the triage protocols.MethodsDaily hospital referrals and all-cause mortality from January to June 2020 among LTCF residents and the CoM population aged 65 + were obtained. Significant changes in LTCF resident daily hospital referrals time series, and in-LTCF and in-hospital daily deaths, were examined with tests for breaks and regimes in time series. Multivariate time series analyses were conducted to test changes in the associations between LTCF resident hospital referrals with daily deaths in-hospital and in-LTCF, and in the CoM population aged 65 + when the triage protocols were implemented.ResultsAmong LTCF residents, hospital referrals declined sharply from March 6 to March 23, 2020. Increases in LTCF residents' daily deaths occurred from March 7 to April 1, followed by a decrease reaching pre-epidemic levels after April 28. The daily ratio of in-hospital deaths to in-LTCF deaths reached its lowest values from March 9 to April 19, 2020. The four versions of the triage protocol, published from March 18 to March 25 had no impact on further changes in the association of hospital referrals with daily deaths of LTCF residents in-hospital or in-LTCF.ConclusionsWhile LTCF residents’ deaths increased, hospital referrals of LTCF residents decreased with the introduction of the CoM governmental interventions on March 7. They were implemented before the enactment of the triage protocols, protecting hospitals from collapse while overlooking the need for standards of care within LTCFs. The CoM triage protocols sanctioned the existing restrictions on hospital referrals of LTCF residents.

Association of EEG and cognitive impairment in overweight and non-overweight patients with schizophrenia

ObjectiveSchizophrenia (SCZ) is a globally prevalent, severe chronic mental disorder, with cognitive dysfunction being one of its core symptoms. Notably, overweight is exceedingly common among individuals with SCZ, and overweight can also impact cognitive function. Therefore, the relationship between overweight and cognition in SCZ is a clinical issue that is in need of research attention. MethodsThis study enrolled 77 patients with SCZ, including 36 overweight and 41 non-overweight patients. The Positive and Negative Syndrome Scale (PANSS) was used to assess symptom severity, while cognitive functions were evaluated using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Electroencephalography (EEG) testing was performed, with power spectral analysis conducted across various frequency bands (δ, θ, α, β, low γ, and high γ). ResultsCompared to non-overweight SCZ patients, those overweight exhibited significantly lower RBANS total and index scores in immediate memory, visuospatial/constructional abilities, and delayed memory. EEG spectral analysis revealed that overweight SCZ patients demonstrated significantly lower oscillation power ratios in the β, low γ, and high γ frequency bands compared to their non-overweight counterparts. Correlation analyses indicated a significant positive relationship between β wave activity and RBANS total scores among overweight SCZ patients, suggesting that reduced β power correlates with more severe cognitive dysfunction. ConclusionOur findings indicate that overweight SCZ patients experience more severe cognitive impairments in a resting state than those who are not overweight, with significant differences in EEG spectrum observed in the β and γ frequency bands. Additionally, our study establishes a correlation between various EEG spectrum dimensions and cognition. This research highlights the effects of overweight on cognition in individuals with SCZ. Additionally, employing EEG technology to study cognitive function in overweight SCZ patients can offer valuable electrophysiological insights.

Endothelium-related biomarkers and cognitive decline in prevalent hemodialysis patients: A prospective cohort study.

Cognitive decline is prevalent in maintenance hemodialysis patients. The blood-brain barrier has been implicated in cognitive decline. In this prospective cohort study, we investigated the associations between endothelium-related biomarkers and steeper cognitive decline in this population. Cognitive function was assessed using the Portuguese-adapted Cambridge Cognitive Examination (CAMCOG) with items of the Mini-Mental State Examination (MMSE). Endothelium-related biomarkers included syndecan-1, ICAM-1, VCAM-1 and angiopoietin-2 (AGPT2). Patients were followed up for 4 years, and cognitive assessments were repeated. Multinomial regression analyses were performed to evaluate associations between biomarkers and cognitive decline. A total of 216 patients completed the test battery at baseline. After 4 years, 102 patients had follow-up data. There was a significant decrease in cognitive function according to the CAMCOG and MMSE scores: a change of -0.39 (95% CI -0.27 to -0.51) and -0.51 (95% CI -0.27 to -0.76) standard deviation (SD) of the baseline scores. Additionally, executive function but not memory significantly decreased. Syndecan-1 level was independently associated with steeper cognitive decline; each increase in the SD of the syndecan-1 level was associated with a decrease in the CAMCOG of 0.20 (95% CI 0.07-0.33) SD from baseline. Syndecan-1 was associated with a steeper decline in MMSE score (β 0.54, 95% CI 0.28-0.81) and executive function (β 0.17, 95% CI 0.02-0.32). Syndecan-1 predicted severe cognitive impairment with an area under the curve for receiver operating characteristic curves of 0.75 (95% CI 0.64-0.83). Our findings highlight the potential of syndecan-1, a biomarker of endothelium glycocalyx derangement, as a predictor of steeper cognitive decline in prevalent hemodialysis patients.

Characterizing dog cognitive aging using spontaneous problem-solving measures: development of a battery of tests from the Dog Aging Project.

Companion dogs are a valuable model for aging research, including studies of cognitive decline and dementia. With advanced age, some dogs spontaneously develop cognitive impairments and neuropathology resembling features of Alzheimer's disease. These processes have been studied extensively in laboratory beagles, but the cognitive assays used in that context-which rely on time-consuming operant procedures-are not easily scalable to large samples of community-dwelling companion dogs. We developed a battery of five short-form tasks targeting three aspects of cognition that are impaired in Alzheimer's disease: spatial memory, executive functions, and social cognition. In Experiment 1, we tested a cross-sectional sample of dogs (N = 123) and estimated associations between age and task performance. Older dogs scored lower on measures of spatial learning, memory, and response flexibility, and spent less time near, but more time gazing at, the experimenter. We found no differences in associations between age and performance across dogs of different body masses, a proxy for expected lifespan. In Experiment 2, we demonstrated the feasibility of these measures in clinical settings (N = 35). Dogs meeting clinical criteria for moderate or severe cognitive impairment scored lower, on average, than dogs characterized as mildly impaired and healthy agers, although these distributions overlapped. However, few dogs in our study cohort met the criteria for moderate or severe impairment. The measures presented here show promise for deployment in large-scale longitudinal studies of companion dogs, such as the Dog Aging Project.

Prevalence of Mild and Severe Cognitive Impairment in World Trade Center Exposed Fire Department of the City of New York (FDNY) and General Emergency Responders.

The emergency personnel who responded to the World Trade Center (WTC) attacks endured severe occupational exposures, yet the prevalence of cognitive impairment remains unknown among WTC-exposed-FDNY-responders. The present study screened for mild and severe cognitive impairment in WTC-exposed FDNY responders using objective tests, compared prevalence rates to a cohort of non-FDNY WTC-exposed responders, and descriptively to meta-analytic estimates of MCI from global, community, and clinical populations. A sample of WTC-exposed-FDNY responders (n = 343) was recruited to complete an extensive battery of cognitive, psychological, and physical tests. The prevalences of domain-specific impairments were estimated based on the results of norm-referenced tests, and the Montreal Cognitive Assessment (MoCA), Jak/Bondi criteria, Petersen criteria, and the National Institute on Aging and Alzheimer's Association (NIA-AA) criteria were used to diagnose MCI. NIA-AA criteria were also used to diagnose severe cognitive impairment. Generalized linear models were used to compare prevalence estimates of cognitive impairment to a large sample of WTC-exposed-non-FDNY responders from the General Responder Cohort (GRC; n = 7102) who completed the MoCA during a similar time frame. Among FDNY responders under 65 years, the unadjusted prevalence of MCI varied from 52.57% to 71.37% depending on the operational definition of MCI, apart from using a conservative cut-off applied to MoCA total scores (18 < MoCA < 23), which yielded a markedly lower crude prevalence (24.31%) compared to alternative criteria. The prevalence of MCI was higher among WTC-exposed-FDNY-responders, compared to WTC-exposed-non-FDNY-GRC-responders (adjusted RR = 1.53, 95% C.I. = [1.24, 1.88], p < .001) and meta-analytic estimates from different global, community, and clinical populations. Following NIA-AA diagnostic guidelines, 4.96% of WTC-exposed-FDNY-responders met the criteria for severe impairments (95% CI = [2.91% to 7.82%]), a prevalence that remained largely unchanged after excluding responders over the age of 65 years. There is a high prevalence of mild and severe cognitive impairment among WTC-responders highlighting the putative role of occupational/environmental and disaster-related exposures in the etiology of accelerated cognitive decline.

Using an Empathetic Approach to Explore Technology Readiness and Needs for Digital Services to Assist People with Dementia.

This qualitative study investigates technology readiness, i.e., self-management, social support, and digital health literacy, in people with dementia (PwD). PwD are difficult to recruit; therefore, we used an empathic approach to recruit and conduct interviews. The interviews with seven participants with dementia and two informal caregivers, guided by the READHY framework, reveal nuanced insights into their experiences. Participants demonstrate varying degrees of self-management, with informal caregivers playing pivotal roles in facilitating activities and supporting overall well-being. Cognitive challenges, such as concentration and communication difficulties, are prevalent, highlighting the importance of robust support systems. Internal and external support networks significantly influence social integration, yet societal misconceptions impede inclusion, exacerbating feelings of isolation for both participants and caregivers. Limited interaction with technology is observed, primarily reliant on caregivers for assistance. Technology may hold potential for enhancing independence and alleviating caregiver burden. As an empathetic approach eased recruitment and communication with PwD, we recommend using this approach for future studies to include participants who otherwise would not be recruited. Given that the number of participants in this study is limited to only seven PwD with moderate to severe cognitive impairment, further investigation using mixed methods, including the READHY framework, and a larger number of participants is needed to examine the generalizability of the findings.

Delayed Post-hypoxic Leukoencephalopathy after Carbon Monoxide Intoxication Improved by High-dose Steroid Treatment

Delayed post-hypoxic leukoencephalopathy (DHPL) is a demyelinating syndrome characterized by acute onset of neuropsychiatric symptoms within days to weeks following apparent recovery from coma after a period of prolonged cerebral hypo-oxygenation. The majority of DPHL cases are associated with carbon monoxide intoxication. There is no specific treatment, and the prognosis is usually poor. However, we present a case of DHPL patient with akinetic mutism, parkinsonism, stool and urine incontinence, and severe cognitive impairment improved after treatment with high-dose steroid therapy.

Anxiety disorders in schizophrenia - the importance of differentiation and targeted treatment a case report and literature review

Schizophrenia is a chronic mental disorder characterized by severe cognitive and behavioral impairments. It often coexists with multiple and complex anxiety symptoms that exacerbate the clinical challenges associated with schizophrenia. This case report presents the history of a 32-year-old woman with a final diagnosis of both paranoid schizophrenia and mixed anxiety disorders. The patient presented with persistent auditory pseudohallucinations, severe anxiety together with occasional panic attacks, which were treated with a variety of antipsychotics. Treatment adjustments were necessitated by the emergence of side effects, including neutropenia, motor disturbances and the observation of major anxiety symptoms, including panic disorder. Ultimately, the successful use of quetiapine in monotherapy was achieved. This case study emphasizes the need for comprehensive treatment strategies to address the complex interplay of psychotic and anxiety symptoms. Increased clinical awareness and targeted treatment of comorbid anxiety can significantly improve the quality of life of patients with schizophrenia.

Calcium homeostasis restoration in pyramidal neurons through micrometer-scale wireless electrical stimulation in spinal cord injured mice

Spinal Cord Injury (SCI) is a significant neurological disorder that can result in severe motor and cognitive impairments. Neuronal regeneration and functional recovery are critical aspects of SCI treatment, with calcium signaling being a crucial indicator of neuronal excitability. In this study, we utilized a murine model to investigate the effects of targeted wireless electrical stimulation (ES) on neuronal activity following SCI. After establishing a complete SCI model in normal mice, flexible electrodes were implanted, and targeted wireless ES was administered to the injury site. We employed fiber-optic photometric in vivo calcium imaging to monitor calcium signals in pyramidal neurons within the CA3 region of the hippocampus and the M1 region of the primary motor cortex. The experimental results demonstrated a significant reduction in calcium signals in CA3 and M1 pyramidal neurons following SCI (reduced by 76 % and 59 %, in peak respectively). However, the application of targeted wireless ES led to a marked increase in calcium signals in these neurons (increased by 118 % and 69 %, in peak respectively), indicating a recovery of calcium activity. These observations suggest that wireless ES has a positive modulatory effect on the excitability of pyramidal neurons post-SCI. Understanding these mechanisms is crucial for developing therapeutic strategies aimed at enhancing neuronal recovery and functional restoration following spinal cord injuries.

A prospective cohort study on cognitive and psychological outcomes in COVID-19 ICU survivors at 3 months of follow up.

The Outcomes - Short and Long term in ICU patient with COVID-19 "OUTSTRIP COVID-19" study was initiated to assess overall mortality, physical and psychiatric co-morbidities, reduction in lung function, and the ability to return to work post-ICU discharge with a follow-up period of 2 years in COVID-19 patients admitted to ICUs in Qatar. This paper focuses on the prevalence of cognitive impairment, depression, anxiety, and stress at baseline and 3 months after ICU discharge. This prospective cohort study included 100 ICU survivors reviewed at baseline within 7 weeks of ICU discharge, with a 3-month follow-up. Demographics, clinical characteristics, and relevant medical history were collected at baseline. Cognitive outcomes were assessed using the Montreal Cognitive Assessment-Basic (MoCA-B) tool, while psychological outcomes were evaluated using the Depression Anxiety and Stress Scale-21 (DASS-21). At baseline, 72% of ICU survivors exhibited mild cognitive impairment, which significantly improved to 56% at 3 months. However, severe cognitive impairment persisted in 20% of survivors at 3 months.For psychological outcomes, the mean depression score remained below 9 (5.64 ± 6.90) at both time points, with no significant change. At baseline, 25% of survivors had clinical depression, which reduced to 16% at 3 months.The mean anxiety score at baseline (9.35 ± 8.50) significantly decreased to 6.51 ± 7.74 (p = 0.002) at 3 months. Anxiety was not reported by 48% of survivors at baseline and this increased to 66% at 3 months. Severe to extremely severe anxiety decreased from 19% to 12% during the same period.The mean stress score at baseline (8.34 ± 8.07) did not significantly change at 3 months. At baseline, 18% experienced stress, which decreased to 12% at 3 months, with 5.3% facing severe to extremely severe stress. COVID-19 ICU survivors experience significant cognitive impairment, anxiety, and stress. While cognitive impairment and anxiety showed improvements at 3 months, depression and stress remained unchanged. These outcomes strongly emphasize the requirement for thorough post-ICU care and comprehensive mental health assistance for individuals recovering from COVID-19. Customized interventions and additional research endeavors are crucial to effectively manage the cognitive and psychological consequences faced by these patients. The exploration of telemonitoring and innovative approaches can offer avenues to enhance the overall quality of life for survivors. Further investigation should encompass extended timeframes to analyze prolonged effects and consider the broader socioeconomic impact.

Biomarkers in Alzheimer’s disease progression: a longitudinal cohort study of NPTX2, GRIA1, and GRIA4

Early diagnosis and intervention are vital for slowing Alzheimer’s disease progression and improving the quality of life in older people. Mild cognitive impairment, an early stage of Alzheimer’s disease, offers a key opportunity for research and intervention. However, current diagnostic methods are typically applied after significant symptoms appear, limiting the effectiveness of early intervention. The data of middle-aged and older individuals collected from the publicly available NCBI datasets GSE5281 and GSE1297 were included in this longitudinal cohort study. The cognitive status changes in participants over time were assessed using standard cognitive assessment tools, such as the Mini-Mental State Examination, along with mild cognitive impairment-specific tools. There was a significant negative correlation between Mini-Mental State Examination scores and the expression levels of neuronal pentraxin 2, glutamate receptor ionotropic AMPA 1 and 4. These results suggest that higher expression levels of these genes are associated with more severe cognitive impairment, highlighting their potential as biomarkers for the early detection of mild cognitive impairment. This study provides new insights into the molecular mechanisms underlying cognitive decline in older people and suggests directions for future research.

Brain age prediction using interpretable multi-feature-based convolutional neural network in mild traumatic brain injury

BackgroundConvolutional neural network (CNN) can capture the structural features changes of brain aging based on MRI, thus predict brain age in healthy individuals accurately. However, most studies use single feature to predict brain age in healthy individuals, ignoring adding information from multiple sources and the changes in brain aging patterns after mild traumatic brain injury (mTBI) were still unclear. MethodsHere, we leveraged the structural data from a large, heterogeneous dataset (N = 1464) to implement an interpretable 3D combined CNN model for brain-age prediction. In addition, we also built an atlas-based occlusion analysis scheme with a fine-grained human Brainnetome Atlas to reveal the age-sstratified contributed brain regions for brain-age prediction in healthy controls (HCs) and mTBI patients. The correlations between brain predicted age gaps (brain-PAG) following mTBI and individual's cognitive impairment, as well as the level of plasma neurofilament light were also examined. ResultsOur model utilized multiple 3D features derived from T1w data as inputs, and reduced the mean absolute error (MAE) of age prediction to 3.08 years and improved Pearson's r to 0.97 on 154 HCs. The strong generalizability of our model was also validated across different centers. Regions contributing the most significantly to brain age prediction were the caudate and thalamus for HCs and patients with mTBI, and the contributive regions were mostly located in the subcortical areas throughout the adult lifespan. The left hemisphere was confirmed to contribute more in brain age prediction throughout the adult lifespan. Our research showed that brain-PAG in mTBI patients was significantly higher than that in HCs in both acute and chronic phases. The increased brain-PAG in mTBI patients was also highly correlated with cognitive impairment and a higher level of plasma neurofilament light, a marker of neurodegeneration. The higher brain-PAG and its correlation with severe cognitive impairment showed a longitudinal and persistent nature in patients with follow-up examinations. ConclusionWe proposed an interpretable deep learning framework on a relatively large dataset to accurately predict brain age in both healthy individuals and mTBI patients. The interpretable analysis revealed that the caudate and thalamus became the most contributive role across the adult lifespan in both HCs and patients with mTBI. The left hemisphere contributed significantly to brain age prediction may enlighten us to be concerned about the lateralization of brain abnormality in neurological diseases in the future. The proposed interpretable deep learning framework might also provide hope for testing the performance of related drugs and treatments in the future.

Remotely-delivered exercise training program for improving physical and cognitive functions among older adults with multiple sclerosis: Protocol for an NIH stage-I randomized controlled trial

BackgroundOlder adults with multiple sclerosis (MS) present with low physical activity participation, cognitive and ambulatory dysfunctions, and compromised quality of life (QOL). ObjectiveWe propose a NIH Stage-I, randomized controlled trial (RCT) that examines the feasibility and efficacy of a 16-week theory-based, remotely-delivered, exercise training program for improving cognitive and physical functions in older adults with MS who have moderate mobility disability without severe cognitive impairment. MethodsThis Stage-I study utilizes a parallel-group RCT design. Participants (N = 50; age ≥ 50 years) will be randomly assigned into exercise training (combined aerobic and resistance exercise) or active control (flexibility and stretching) conditions. The conditions will be undertaken within a participant's home/community over a 16-week period, and monitored remotely and supported by Zoom-based chats guided by social cognitive theory (SCT) via a behavioral coach. Participants will receive training manuals and equipment, one-on-one behavioral coaching, action-planning calendars, self-monitoring logs, and SCT-based newsletters. The primary outcomes include feasibility (e.g., recruitment and retention rates), exercise behavior and physical activity; other outcomes include physical function (lower-extremity function, mobility, walking), cognition (processing speed, learning and memory, executive function), MS symptoms, QOL, and vascular function. We will collect outcome data at baseline (Week 0), post-intervention (Week 16), and follow-up (Week-32). Data analysis will follow intent-to-treat principles using linear mixed-effects models. DiscussionThis Stage-I trial adopts an innovative approach for exercise training via telerehabilitation and is convenient and accessible for older adults with MS. If successful, the study will provide foundations for future research using remotely-delivered exercise intervention for managing the consequences of aging with MS.Trial Registration Number:NCT05930821

Antipsychotic use in a large community sample of patients with delusional disorder

BackgroundTo examine clinical and sociodemographic differences between patients with delusional disorder; with and without diagnoses of an additional severe mental disorder (SMD) or cognitive impairment. MethodsPopulation-based study including all individuals diagnosed with DD between 2005 and 2021 from a large catchment area in Madrid, Spain. Sociodemographic and clinical characteristics and the antipsychotic prescription patterns of the study population was described. Patients were divided into (i) patients with DD and no additional diagnosis of SMD or cognitive impairment (DD group), (ii) patients with DD and a diagnosis of an additional SMD (DD-SMD group), and (iii) patients with DD and cognitive impairment (DD-CI group). ResultsOf 1109 patients with a DD diagnosis (62.5 % female), 131 (11.8 %) patients were diagnosed with an additional SMD, and 69 (6.2 %) were diagnosed with cognitive impairment. DD-SMD patients were on average 10 years younger and had longer time between first mental healthcare contact and DD disorder than DD patients. DD-CI patients were on average 10 years older and had a higher proportion of females. Paliperidone (21.9 %) and aripiprazole (20.6 %) were the modal antipsychotic drugs chosen overall. DD-SMD patients were more likely to receive paliperidone and to be prescribed long-acting injectable medication; DD-CI were more likely to receive risperidone or quetiapine; and DD patients were more likely to receive olanzapine. ConclusionsSociodemographic and clinical characteristics and choice of antipsychotic drug and delivery method for individuals with DD vary based on its comorbidity.

Assessing pain in older people with normal, mildly impaired or severely impaired cognition.

Pain is a relatively common experience among older people, but unrelieved pain has significant functional, cognitive and emotional consequences for this population. A comprehensive and accurate pain assessment is essential for effective pain management. Self-report tools are suitable to assess pain in older people with normal or mildly impaired cognition, while observational tools are suitable for use with those with significant cognitive impairment or communication difficulties. However, pain assessment in older people can be challenging. The use of one tool on its own is rarely sufficient and it is crucial to involve family carers in assessment of pain in older people with severe cognitive impairment. This article discusses different tools and strategies, including the benefits and limitations, for assessing pain in older people.