Severe Cognitive Impairment Research Articles

Association between widowhood and cognitive function among Chinese older adults with hearing impairment: the moderating effect of social support and participation

BackgroundOlder adults with hearing impairments are vulnerable to cognitive impairment. Although previous reports suggest a correlation between widowhood and cognitive impairment, further investigation is needed to elucidate the effect of widowhood on cognitive function and the moderating effects of social support and participation on widowhood-related cognitive impairment in this vulnerable demographic.MethodsThe study’s data were sourced from the nationally representative Chinese Longitudinal Healthy Longevity Survey (CLHLS) for the years 2011, 2014, and 2018. Multiple linear regression was used to analyze the association between widowhood and cognitive function among older adults. Multivariate logistic regression examined the effect of widowhood on the likelihood of experiencing various levels of cognitive impairment in older adults with hearing impairments. A moderating effect model explored the roles of social support and participation in mitigating widowhood-related cognitive impairment.ResultsThe cognitive function of older adults with hearing impairment was found to be lower than that of those without hearing impairment. Widowhood was significantly negatively correlated with Mini-Mental State Examination (MMSE) scores in older adults, both with (Coef. = -0.898) and without (Coef.: = -0.680) hearing impairments. A stronger association was observed between widowhood and declining cognitive function among older adults with hearing impairment. Specifically, widowhood may be more likely to significantly increase the likelihood of moderate and severe cognitive impairment (RRR = 1.326, 1.538) among older adults with hearing impairments. Social support and social participation significantly moderated the cognitive impairment associated with widowhood among hearing-impaired older adults. These forms of support and engagement are buffers against the risk of widowhood-related cognitive impairment among this demographic.ConclusionsOur findings indicate that widowhood is significantly associated with cognitive impairment in older adults with hearing impairment. Social support and participation help mitigate this risk. Strategies should prioritize early screening, specialized cognitive rehabilitation, comprehensive care, and enhancing social support and participation to maintain cognitive health in this vulnerable population following widowhood.

Ex vivo disease modelling of Rett syndrome: the transcriptomic and metabolomic implications of direct neuronal conversion.

Rett syndrome (RTT) is a rare neurodevelopmental disorder that primarily affects females and is characterized by a period of normal development followed by severe cognitive, motor, and communication impairment. The syndrome is predominantly caused by mutations in the MECP2. This study aimed to use comprehensive multi-omic analysis to identify the molecular and metabolic alterations associated with Rett syndrome. Transcriptomic and metabolomic profiling was performed using neuron-like cells derived from the fibroblasts of 3 Rett syndrome patients with different MECP2 mutations (R168X, P152R, and R133C) and 1 healthy control. Differential gene expression, alternative splicing events, and metabolite changes were analyzed to identify the key pathways and processes affected in patients with Rett syndrome. Transcriptomic analysis showed there was significant down-regulation of genes associated with the extracellular matrix (ECM) and cytoskeletal components, which was particularly notable in patient P3 (R133C mutation), who had non-random X chromosome inactivation. Additionally, significant changes in microtubule-related gene expression and alternative splicing events were observed, especially in patient P2 (P152R mutation). Metabolomic profiling showed that there were alterations in metabolic pathways, particularly up-regulation of ketone body synthesis and degradation pathways, in addition to an increase in free fatty acid levels. Integrated analysis highlighted the interplay between structural gene down-regulation and metabolic shifts, underscoring the adaptive responses to cellular stress in Rett neurons. The present findings provide valuable insights into the molecular and metabolic landscape of Rett syndrome, emphasizing the importance of combining omic data to enlighten the molecular pathophysiology of this syndrome.

Intracerebroventricular Enzyme Replacement Therapy in Patients with Neuropathic Form of Mucopolysaccharidosis Type II: to Help Practicing Physician

Mucopolysaccharidosis type II (Hunter syndrome, MPS II) is a rare hereditary disease from the group of hereditary metabolic diseases. There are neuropathic and non-neuropathic forms of this disease. The neuropathic form is most common and leads to severe cognitive impairment and progressive damage of central nervous system. Nowadays, early diagnosis and timely initiation of pathogenetic therapy in patients with orphan diseases is the crucial problem of modern pediatrics. Intracerebroventricular administration of idursulfase beta is one of the promising treatment options in patients with neuropathic form of MPS II as it prevents severe complications development. The study of new pathogenetic therapy methods for rare hereditary diseases will help doctors of pediatric specialties to route patient correctly in timely manner to receive all the necessary treatment.

High-dose chemotherapy for patients with stage III breast cancer with homologous recombination deficiency: a discrete choice experiment among healthcare providers.

High-dose chemotherapy with autologous stem cell rescue (HDCT) is currently under investigation as a potential therapy for patients with stage III HER2-negative breast cancer with homologous recombination deficiency (HRD). In addition to survival, the impact on short- and long-term side effects might influence the uptake of HDCT by healthcare professionals. As part of the SUBITO trial, we investigated healthcare professionals' treatment (outcome) preferences for patients with HRD stage III HER2-negative breast cancer and established how healthcare professionals make trade-offs between these treatment outcomes. We conducted a discrete choice experiment in which healthcare professionals were asked to choose repeatedly between scenarios with two treatment options (HDCT or standard of care (SOC)) that varied in outcome with respect to 10-year overall survival (OS), short-term toxicity, long-term cognitive impairment, and premature menopause. We analysed treatment preferences, relative importance, and trade-offs using a multinomial logistic model. Thirty-five of the 151 dedicated breast cancer professionals with extensive experience in treating breast cancer patients completed the survey. The 10-year OS and long-term cognitive impairment were the most important attributes. The results indicate a requirement of 10.4% and 25.1% absolute additional improvement in the 10-year survival rate to justify accepting moderate or severe long-term cognitive impairment as a trade-off, respectively. Therefore, we found in our dataset that healthcare professionals expected a large improvement in 10-year OS to accept moderate to severe cognitive impairment. This information calls for further research into chemotherapy-related cognitive impairment, shared decision-making, and treatment preferences for patients with stage III breast cancer.

Assessment of mood after severe acquired brain injury: Interviews with UK clinical psychologists and medical professionals

Objective Mood assessment is challenging when people have cognitive and receptive communication impairments after severe brain injury. This study explored how UK-based medical and psychology professionals working with people with severe cognitive and communication impairments after brain injury assess mood in this population. Design Following their participation in an online survey, professionals were invited to participate in individual semi-structured interviews. Interviews were analysed using thematic analysis to label explicit data (semantic themes) and implicit data (latent themes). Participants Twenty-three clinical psychologists and nine medical professionals participated in online or in-person interviews. Results Both groups explicitly reported using a combination of collateral information, history, observations, and patient interviews when assessing mood in this population. Medical professionals did not routinely use standardised measures and clinical psychologists often adjusted them when they used them. The respondents discussed difficulties conceptualising depression after brain injury, the experience needed by the assessor, and the need for an individualised approach for this population. Clinical psychologists discussed the pressures of working in healthcare systems and medical professionals discussed how symptoms may influence prescription choices. Seven latent themes were labelled which highlighted additional challenges and complexities experienced by those assessing mood, beyond the actual assessment process itself. Conclusions No ‘gold standard’ approach to assessing mood in those with cognitive and communication difficulties after severe brain injury was identified. There was overlap in assessment approaches but no clear consensus. Interviewees felt that mood assessment must be approached differently in this population and that self-report measures are not useful.

The Association Between Distinct Delusional Ideations and Depressive Symptoms in Alzheimer's Disease: A Re-Analysis of CATIE-AD.

Delusional ideations, one of neuropsychiatric symptoms (NPSs), are frequently shown in the long-term progression of Alzheimer's disease (AD), and comorbid with other NPSs including depression or agitation. Despite various types of delusional ideations, the comorbidity between each delusional ideation and depressive symptoms has not been discussed. The present cross-sectional study is aimed at testing the hypothetical mechanism of comorbid pattern in AD. Among 421 patients with AD, we analyzed the dataset of the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease to compare age, sex, racial type, Mini-Mental State Examination (MMSE) scores, and Neuropsychiatric Inventory (NPI) depression score of between the presence and absence of each delusional ideation (delusion of persecution, theft, jealousy, abandonment, phantom boarder, Capgras syndrome, misidentification of place, or television sign). Next, with the stratification based on MMSE score of < or > = 15 points, we further explored association between delusional ideation and depressive symptom that was found significances in the primary analysis. Among eight subtypes of delusional ideations, depression score was higher in those with persecution delusion or Capgras syndrome. Moreover, the Capgras syndrome was associated with presence of depression in severer global cognitive impairment status. As comorbid NPSs of delusional ideation in AD, depressive severity is associated with specific delusional subtype: persecution delusion and Capgras syndrome. Capgras syndrome may be attributable to severe cognitive impairment in addition to depressive symptom. The consideration of pathogenetic differences in the distinct delusional ideations may be helpful for clinicians to select the treatment strategy.

Exploring the relationship between lipid metabolism and cognition in individuals living with stable-phase Schizophrenia: a small cross-sectional study using Olink proteomics analysis

BackgroundCognitive impairment is a core symptom of schizophrenia. Metabolic abnormalities impact cognition, and although the influence of blood lipids on cognition has been documented, it remains unclear. We conducted a small cross-sectional study to investigate the relationship between blood lipids and cognition in patients with stable-phase schizophrenia. Using Olink proteomics, we explored the potential mechanisms through which blood lipids might affect cognition from an inflammatory perspective.MethodsA total of 107 patients with stable-phase schizophrenia and cognitive impairment were strictly included. Comprehensive data collection included basic patient information, blood glucose, blood lipids, and body mass index. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) and the MATRICS Consensus Cognitive Battery (MCCB). After controlling for confounding factors, we identified differential metabolic indicators between patients with mild and severe cognitive impairment and conducted correlation and regression analyses. Furthermore, we matched two small sample groups of patients with lipid metabolism abnormalities and used Olink proteomics to analyze inflammation-related differential proteins, aiming to further explore the association between lipid metabolism abnormalities and cognition.ResultsThe proportion of patients with severe cognitive impairment (SCI) was 34.58%. Compared to patients with mild cognitive impairment (MCI), those with SCI performed worse in the Attention/Alertness (t = 2.668, p = 0.009) and Working Memory (t = 2.496, p = 0.014) cognitive dimensions. Blood lipid metabolism indicators were correlated with cognitive function, specifically showing that higher levels of TG (r = -0.447, p < 0.001), TC (r = -0.307, p = 0.002), and LDL-C (r = -0.607, p < 0.001) were associated with poorer overall cognitive function. Further regression analysis indicated that TG (OR = 5.578, P = 0.003) and LDL-C (OR = 5.425, P = 0.001) may be risk factors for exacerbating cognitive impairment in individuals with stable-phase schizophrenia. Proteomics analysis revealed that, compared to individuals with stable-phase schizophrenia and normal lipid metabolism, those with hyperlipidemia had elevated levels of 10 inflammatory proteins and decreased levels of 2 inflammatory proteins in plasma, with these changes correlating with cognitive function. The differential proteins were primarily involved in pathways such as cytokine-cytokine receptor interaction, chemokine signaling pathway, and IL-17 signaling pathway.ConclusionBlood lipids are associated with cognitive function in individuals with stable-phase schizophrenia, with higher levels of TG, TC, and LDL-C correlating with poorer overall cognitive performance. TG and LDL-C may be risk factors for exacerbating cognitive impairment in these patients. From an inflammatory perspective, lipid metabolism abnormalities might influence cognition by activating or downregulating related proteins, or through pathways such as cytokine-cytokine receptor interaction, chemokine signaling pathway, and IL-17 signaling pathway.

Investigating the Impact of IL-6 and CXCL8 on Neurodegeneration and Cognitive Decline in Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder primarily affecting the elderly, characterized by severe cognitive impairment and memory loss. Emerging evidence suggests that neuroinflammation plays a significant role in AD pathogenesis, with cytokines like interleukin-6 (IL-6) and C-X-C motif chemokine ligand 8 (CXCL8) contributing to the disease progression. We utilized GEO datasets to identify IL-6 and CXCL8 as pivotal inflammatory markers in AD. In vitro experiments were conducted using SK-N-BE(2)-M17 and THP-1 cell lines treated with IL-6 and CXCL8 to model AD. Additionally, in vivo tests on Amyloid Precursor Protein/Presenilin 1 (APP/PS1) AD mouse models were performed to assess the impact of these cytokines on cognitive functions and brain pathology. The results indicated a significant decrease in cell viability, increased apoptosis, and elevated inflammatory factor secretion following IL-6 and CXCL8 treatment in vitro. In vivo, AD mouse models treated with these cytokines exhibited exacerbated emotional distress, decreased social interaction, impaired cognitive functions, and increased amyloid protein deposition in neural tissues. The study highlights the detrimental effects of IL-6 and CXCL8 on neuronal health and cognitive functions in AD. These findings suggest that targeting these cytokines could offer potential therapeutic interventions for improving patient outcomes in Alzheimer's disease.

Dysphagia in primary progressive aphasia: Clinical predictors and neuroanatomical basis.

Dysphagia is an important feature of neurodegenerative diseases and potentially life-threatening in primary progressive aphasia (PPA) but remains poorly characterized in these syndromes. We hypothesized that dysphagia would be more prevalent in nonfluent/agrammatic variant (nfv)PPA than other PPA syndromes, predicted by accompanying motor features, and associated with atrophy affecting regions implicated in swallowing control. In a retrospective case-control study at our tertiary referral centre, we recruited 56 patients with PPA (21 nfvPPA, 22 semantic variant [sv]PPA, 13 logopenic variant [lv]PPA). Using a pro forma based on caregiver surveys and clinical records, we documented dysphagia (present/absent) and associated, potentially predictive clinical, cognitive, and behavioural features. These were used to train a machine learning model. Patients' brain magnetic resonance imaging scans were assessed using voxel-based morphometry and region-of-interest analyses comparing differential atrophy profiles associated with dysphagia presence/absence. Dysphagia was significantly more prevalent in nfvPPA (43% vs. 5% svPPA and no lvPPA). The machine learning model revealed a hierarchy of features predicting dysphagia in the nfvPPA group, with excellent classification accuracy (90.5%, 95% confidence interval = 77.9-100); the strongest predictor was orofacial apraxia, followed by older age, parkinsonism, more severe behavioural disturbance, and more severe cognitive impairment. Significant grey matter atrophy correlates of dysphagia in nfvPPA were identified in left middle frontal, right superior frontal, and right supramarginal gyri and right caudate. Dysphagia is a common feature of nfvPPA, linked to underlying corticosubcortical network dysfunction. Clinicians should anticipate this symptom particularly in the context of other motor features and more severe disease.

Intensity-dependence of auditory-evoked potentials might present an early surrogate marker for post-stroke depression

ObjectivePost-stroke depression (PSD) is a common stroke complication, associated with severe physical and cognitive impairment. Low central serotonergic tone, associated with depression, inversely correlates with the intensity-dependence of auditory-evoked potentials (IDAP). Aim of this study was to investigate IDAP’s usability as early surrogate marker for PSD development by assessing the correlation between IDAP early after stroke and the occurrence of PSD from 4 weeks after stroke. MethodsWe assessed auditory-evoked potentials (AEP) and depressive symptoms using the Montgomery-Åsberg Depression Rating Scale (MADRS) at day 1 – 3 and > 30 after stroke onset. IDAP was calculated as the linear slope of the N1-P2 amplitude/stimulus intensity function (ASF). Results37 patients completed the study. We diagnosed 7 patients with PSD, defined as MADRS-score≥ 7 at follow-up. The PSD group showed significantly steeper ASF slopes at admission compared with the non-depressed group (p = 0.007). We also found a positive correlation between ASF slopes on first and MADRS-scores on last measurement point for all stroke patients as a group (p = 0.007). ConclusionsThe study findings support the hypothesis that IDAP can predict the development of depressive symptoms following stroke and may therefore serve as an early surrogate marker for PSD. SignificanceThis is the first longitudinal study to assess the relationship between IDAP and PSD.

The effects of a cognitive training program on individuals with moderate to severe cognitive impairment: A program evaluation study

The effects of a cognitive training program on individuals with moderate to severe cognitive impairment: A program evaluation study

Current Trends of Exercise Programs for Improving Cognitive Function in Older Adults

PURPOSE: Limited studies have analyzed exercise protocols for cognitive improvement in older adults. Therefore, we closely examined the composition, content, and operation methods of these exercise programs to identify current trends.METHODS: We searched the Web of Science, PubMed, and Google Scholar databases for studies published between 2019 and 2024. The search terms used included “older adults”, “cognitive function”, “mild cognitive impairment”, “dementia”, “exercise”, “physical activity”, and other related terms, in both Korean and English.RESULTS: Aerobic exercises primarily comprised step-based exercises (walking and stepping) and dance routines, typically lasting 15-60 minutes per session, 1-3 times per week for 6-24 weeks, regardless of the individual’s cognitive level. Assistant instructors often participated, and in cases of severe cognitive impairment, patients’ caregivers also participated. Resistance exercises were most often performed using body weight and elastic bands, along with other tools and equipment, such as balls, water bottles, or specialized equipment. The exercises commonly involved 8-12 repetitions, 2-3 sets, with 1-minute rest between sets. Several programs included functional exercises to improve daily living performance. Other activities that were incorporated into the exercise programs included exergames and balance, mind-body, peripheral, and eye exercises.CONCLUSIONS: Recent cognitive exercise programs for older adults typically last three months and use a variety of tools or digital technologies within the scope of older adult exercise guidelines. Exercises for people with severe cognitive impairment tend to be more individualized, gradual, and flexible in their approach.

Fragilidad del adulto mayor con enfermedad renal crónica. Un estudio observacional de centro único

Introduction: Frailty in the elderly (AM) increases morbidity and mortality. This condition is highly prevalent in Chronic Kidney Disease (CKD) and, together with frailty, greatly affects physical, cognitive, and emotional capacity. The study aimed to determine frailty in older adults with CKD in a reference center in Cuenca-Ecuador. Methods: The present observational study was conducted at the “José Carrasco Arteaga” Hospital from September 2020 to April 2021. Older adults with a diagnosis of CKD were included; patients with disabilities, severe cognitive impairment, and those with palliative care were excluded. The direct source variables are demographic, clinical, physical activity, functional capacity, mood, mental state, and frailty. The sample was probabilistic. The Chi2 test is used to compare percentages. Results: 79 cases are analyzed. The MA had 38% frailty, 36.7% were pre-frail, and 25.3% were robust. A more significant proportion of 'young' AM was observed in patients classified as robust. A more substantial proportion of robust patients were receiving clinical treatment, while patients in the hemodialysis program were classified as frail. The most significant proportion of robust patients had mild degrees of renal failure, while frail patients were classified as CKD grades 4 and 5. Physical activity was active primarily in robust patients and mostly passive in patients with frailty. Conclusion: Conclusion: there is a high prevalence of frailty in this population group, especially in women and those between 75 and 85 years old. The results suggest that CKD in older adults is associated with a higher risk of frailty, dependence, and comorbidities, which underlines the importance of implementing multidisciplinary and personalized interventions to improve the quality of life and prognosis of these patients.

Loss of Smek1 Induces Tauopathy and Triggers Neurodegeneration by Regulating Microtubule Stability.

Suppressor of Mek1 (Smek1) is a regulatory subunit of protein phosphatase 4. Genome-wide association studies have shown the protective effect of SMEK1 in Alzheimer's disease (AD). However, the physiological and pathological roles of Smek1 in AD and other tauopathies are largely unclear. Here, the role of Smek1 in preventing neurodegeneration is investigated in tauopathy. Smek1 is downregulated in the aged human brain. Through single-cell sequencing, a novel neuronal cluster is identified that possesses neurodegenerative characteristics in Smek1-/- mice. Smek1 deficiency caused markedly more severe motor and cognitive impairments in mice, as well as neuronal loss, gliosis, and tau hyperphosphorylation at major glycogen synthase kinase 3β (Gsk3β) sites. Protein-protein interaction analysis revealed that the Ran-binding domain (RanBD) in the N-terminus of Smek1 facilitated binding with kinesin family member 2A (Kif2a). Depletion of Smek1 resulted in cytoplasmic aggregation of Kif2a, axon outgrowth defects, and impaired mitochondrial axonal trafficking. Downregulation of Kif2a markedly attenuated tau hyperphosphorylation and axon outgrowth defects in shSmek1 cells. For the first time, this study demonstrates that Smek1 deficiency progressively induces neurodegeneration by exacerbating tau pathology and mitochondrial dysfunction in an age-dependent manner.

Severe Cognitive Impairment in Trauma-Affected Refugees-Exploring the Impact of Traumatic Brain Injury.

Background/Objectives: This study explores the relationship between cognitive performance measured by the Symbol Digit Modality Test (SDMT) and the severity of self-reported head injury, traumatic brain injury (TBI), post-traumatic stress disorder (PTSD), depression, pain, and psychosocial dysfunction in a population of trauma-affected refugees. Refugees, especially those who have been subjected to torture, often face various difficulties, such as PTSD, depression and somatic disturbances (e.g., pain), which can significantly impact their day-to-day functioning. Methods: Participants included 141 adult refugees (38% women) with a mean age of 45.4 years (SD = 9.4) and 9.7 years (SD = 4.9) of education who were referred for treatment of post-traumatic distress to DIGNITY, Danish Institute Against Torture. Participants completed standardized self-report measures of PTSD, anxiety, depression, pain, and health-related disability and measures of trauma history, physical injuries including head injury and loss of consciousness, and the SDMT, a quick standardized performance-based measure of cognitive impairment. Results: Eighty-eight percent of participants evidenced signs of substantial cognitive impairment as indexed by lower SDMT scores. Those with a self-reported history of TBI, marked by loss of consciousness, exhibited lower SDMT scores and higher health-related disabilities. Severity of PTSD, depression, anxiety, and pain were highly correlated with lower SDMT scores. TBI history was not significantly associated with the severity of PTSD, depression, anxiety, or pain, suggesting a complex interplay among these factors. Conclusions: Cognitive impairments are prevalent in trauma-affected refugees, interacting with symptoms of post-traumatic stress and pain, likely explaining the high disability levels in this population. Further research should employ a broader range of cognitive measures and detailed investigations of head injury/TBI experiences to investigate their impact on overall functioning, treatment response, and longer-term outcomes. This study adds to a small but growing body of studies documenting cognitive impairments in trauma-affected refugees, highlighting the importance of addressing cognitive impairments in treatment for trauma-affected refugees, particularly those with histories of torture and TBI. Clinicians working with trauma-affected refugees should consider the assessment of cognitive difficulties as part of comprehensive care planning.

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.