Moderate Cognitive Impairment Research Articles

The effects of rehabilitation potential on activities of daily living in patients with stroke in Taiwan: a prospective longitudinal study.

This study aimed to explore the effect of three-dimensional rehabilitation potential on the activity of daily living (ADL) among patients with stroke in rehabilitation wards. Prospective longitudinal study. Two rehabilitation wards situated within a nationally recognized referral centre in Northern Taiwan, followed by subsequent discharge. A total of 101 participants were admitted due to either a primary or recurring incident of infarction or haemorrhagic stroke, subsequently being transferred to the rehabilitation ward of a medical centre. Not applicable. Rehabilitation potential included biological (swallowing ability, muscle power, and urinary incontinence), psychological (rehabilitation motivation and cognitive function), and social (social support) dimensions. The rehabilitation treatment outcome was activities of daily living measured using the Barthel Index. Time-variant variables, including swallowing ability, rehabilitation motivation, social support, and ADL, were collected at the time of transfer to the rehabilitation ward, 1-3 days before discharge, and 1 month after discharge. The results of the generalized estimating equations model revealed that poor swallowing ability, lower muscle power, and urinary incontinence in the biological dimension, along with lower rehabilitation motivation and moderate cognitive impairment in the psychological dimension, are significant indicators of rehabilitation potential among stroke patients. When the different dimensional rehabilitation potential was considered overall, both biological and psychological indicators can still predict ADL outcomes during and after inpatient rehabilitation therapy. Of these indicators, swallowing ability and rehabilitation motivation were positively correlated with ADL over time. Further, increased rehabilitation motivation enhanced the protective effect of swallowing ability on ADL. Important indicators of rehabilitation potential, which can predict ADL outcomes, were identified for stroke patients in the rehabilitation ward. Policymakers can design appropriate intervention plans to enhance the rehabilitation potential and improve the effectiveness of inpatient rehabilitation treatment for stroke patients.

Non-motor symptoms in patients with Spinocerebellar ataxia type 12.

Spinocerebellar ataxia type 12 (SCA12) is a rare autosomal dominant neurodegenerative disorder caused by abnormal CAG repeat expansion in the PPP2R2B gene. This disease is classically characterized by action tremor, dysarthria, ataxia, and hyperreflexia. There are limited reports regarding the non-motor symptoms in patients with SCA 12. We investigated the frequency and factors associated with the selected non-motor symptoms in patients with SCA 12. Genetically diagnosed (CAG repeats > 43) and symptomatic cases of SCA 12 were included in the study. Motor severity was assessed using the Scale for the Assessment and Rating of Ataxia (SARA) and The Essential Tremor Rating Assessment Scale (TETRAS). Non-motor symptoms such as depression, autonomic function, and cognition were assessed using the Hamilton Depression Rating Scale (HAM-D), the Scales for Outcomes in Parkinson's Disease-Autonomic Dysfunction (SCOPA-AUT), and the Montreal Cognitive Assessment (MoCA), respectively. The mean age of the cohort with 34 SCA12 patients was 64.87 years (standard deviation 6.844). In this study, 21 patients (61.76%) had either mild or moderate cognitive impairment, almost equally frequent in early and advanced cases. Similarly a number of patients demonstrated evidence of moderate and severe depression. The SARA score was strongly associated with the MoCA score, and CAG repeat length could independently predict the MoCA score in this cohort. Autonomic symptoms were commonly present, with the majority of the patients experiencing urinary symptoms. Non-motor symptoms are common in SCA12 patients, even in the early stages of the condition. Timely detection and treatment of these symptoms may improve the therapeutic outcome and quality of life for SCA12 patients. The diverse symptoms of SCA12 perhaps indicate a widespread neurodegeneration beyond the cerebellum or its direct connections.

Mild to moderate cognitive impairment does not bias the Geriatric Depression Scale in a large US sample of older adults.

The Geriatric Depression Scale (GDS) is widely used to screen for depression in clinical practice and to assess symptoms of depression in research about older adults. To determine whether the 15-item GDS can be used in adults with dementia, this study investigated whether item- or test-level bias in the GDS-15 is associated with the respondent's level of cognitive impairment. Using a large U.S. sample of 24,674 adults, we first conducted sample matching procedures between the five groups defined by CDR® Dementia Staging Instrument scores to control for potential confounding effects of common demographic variables. Then, we employed confirmatory factor analysis (for single-group and configural-invariance models only) and item response theory models to test potential differential item/test functioning effects associated with the GDS-15 across the five CDR groups. Practical consequences of the identified biases were quantified using sample-based Cohen's d effect sizes and misclassification rates. In general, people with higher CDR scores were older and had fewer years of education. In comparison to the normal cognition group (CDR-0), negligible biases in GDS-15 scores were found for the groups with questionable, mild, or moderate cognitive impairment (CDR-0.5/1/2). For individuals with severe cognitive impairment (CDR-3), their responses were inconsistent with the normal cognition group and their depression scores were significantly biased with a small-to-medium effect size. The GDS-15 can be used to assess depression in individuals with mild or moderate cognitive impairment, but not in individuals with severe cognitive impairment.

Possibilities of using innovative non-drug technologies in the rehabilitation of patients with early post-stroke cognitive impairment

BACKGROUND: One of the leading factors complicating social adaptation after ischemic stroke is cognitive and motor impairment. AIM: This study aimed to evaluate the effect of rehabilitation using virtual reality technologies and the influence of the main clinical and functional parameters on virtual reality (VR) therapy in patients with different degrees of cognitive decline in the acute period of ischemic stroke. MATERIALS AND METHODS: This study examined 170 patients diagnosed with ischemic stroke with cognitive decline according to the Montreal Cognitive Assessment. Depending on the volume of therapy, the patients were divided into two groups: group 1 included 120 patients who received additional therapy using VR technologies (62 patients with moderate cognitive impairment, 58 patients with dementia), and group 2 consisted of 50 patients who received only basic therapy and standard methods of early rehabilitation. In group 1, on days 4–5 following basic therapy, rehabilitation using VR was performed. The Barthel Index (BI) scale, Rankin Scale (mRS), and National Institute of Health Stroke Scale (NIHSS) were used to examine cognitive and functional status, and tests were performed to assess cognitive functions, as well as neuroimaging scales ASPECTS, STRIVE, and MTA. The effectiveness of rehabilitation (ΔRE) was measured by the indicator of changes in the parameters of the VR system before and after treatment. RESULTS: A more significant improvement of the patient’s independence and regression of perceptual and executive functions was demonstrated in group 1 than in the control group. In patients with MCI, significant improvement was observed in all cognitive and functional parameters except semantic information processing, attention, and constructive praxis. In patients with dementia, improvement was noted in NIHSS, speech and amnestic disorders. In group 1, ΔRE was found to be associated with the parameters of perception, attention, semantic information processing, IQCODE, and NIHSS and the presence of hypertension and repeated stroke. In patients with MCI, ΔRE was correlated with lesion size, attention level, BI, mRS, and NIHSS and with age, sex, degree of IQCODE and STRIVE, semantic aphasia, and perceptual impairment in patients with dementia. CONCLUSION: The present study revealed a polymorphism of factors influencing the effectiveness of VR therapy in patients with varying degrees of cognitive decline. Modern approaches to VR rehabilitation of patients with post-stroke cognitive impairment require the development of individual methods of rehabilitation using immersion environment focused on the structure, etiology, and severity of cognitive deficit considering the degree of the patient’s functional state.

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.

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.

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.

A 3 month nutrition and exercise program improved hallux strength among senior daycare center users in Korea: a cluster randomized controlled trial.

With a growing aging population, the focus on the health and well-being of older adults, especially in preventing falls, becomes crucial. This 3 month study, initiated in July 2022, aimed to assess the impact of a nutrition and exercise program in senior daycare centers in Chuncheon, South Korea. A 3 month study, beginning in July 2022, included 204 older adults from 10 senior daycare centers in Chuncheon, South Korea. Randomly assigned to intervention or control groups, the intervention involved nutrition, daily toe exercises, or both. Control centers received interventions post-measurements. Pre- and post-intervention analyses used paired t-tests and multiple linear regression, assessing metrics like toe grip strength for significance. While 204 were initially enrolled, the analysis included 151 participants due to dropouts. Participants, with a mean age of 83.3 years (43.1% aged ≥ 85 years), exhibited mild to moderate cognitive impairment and multiple chronic illnesses. Health data indicated that 37.3% were obese, and the average BMI was 24.0 kg/m2. Both the intervention and control groups showed significant improvements in toe grip strength post-intervention. Specifically, the exercise-only and combined exercise-nutrition groups demonstrated significant differences in hallux strength compared to the control group after adjusting for age and gender. The study showed that a basic nutrition and exercise program increased toe strength in older adults with chronic diseases, including mild cognitive impairments. This intervention holds potential to prevent muscle strength decline and reduce fall risks in older individuals. As the first of its kind in Korean senior daycare centers, it emphasizes the need for future research and standardized programs for senior daycare users.

Preventing medication errors in patients with decompensated heart failure and cognitive impairment following hospital discharge, in Saudi Arabia

Abstract Background Heart failure (HF) is a progressive health challenge, with an increased prevalence of 30% in older adults. It is estimated that approximately 50% of patients with HF have a degree of cognitive impairment, affecting adherence to self-care and medication taking. Therefore, medication errors are becoming a global health challenge and account was estimated at 44.4% in Saudi Arabia. Purpose To explore the perspectives of patients with cognitive impairment and their caregivers on the pre-discharge medication education received. Methods A qualitative study, using semi-structured interviews. 7 dyads were recruited from a Cardiac center in Saudi Arabia The purposive sample was selected of patients who are identified as having cognitive impairment, as assessed by Montreal Cognitive Assessment scale (MoCA). Caregivers were nominated by the respective patient. Interviews were audio recorded, transcribed in Arabic, and translated into English. Transcripts were checked for authenticity. Data were analysis using thematic analysis. Results Most patients identified as male (n=5), including both patients with mild cognitive impairment (n=4) and moderate cognitive impairment (n=3). Four major themes were identified Complexity of Medication Management: Patients and caregivers struggle with the multifaceted nature of medication regimens, indicating a need for simplified schedules and clear instructions. Importance of Clear Communication and Education: There’s a critical need for comprehensive, understandable information about the indications and side effects of the medications. This should be tailored to individual learning preferences. Crucial Role of Caregiver Support: Caregivers have an important role in ensuring medication adherence. Some highlighted the benefit of being included in educational interventions. Challenges with Post-Discharge Support: All participants expressed a sense of abandonment post-discharge, with difficulties in accessing follow-up. Conclusion The study highlights the need for simplified medication regimens, enhanced communication, and comprehensive education for heart failure patients with cognitive impairment and their caregivers. Addressing these interconnected challenges through a multifaceted approach is crucial for improving medication management, adherence, and overall patient outcomes.

Psychosocial Factors Associated With Long-Term Cognitive Impairment Among COVID-19 Survivors: A Cross-Sectional Study.

COVID-19 survivors complained of the experience of cognitive impairments, which also called "brain fog" even recovered. The study aimed to describe long-term cognitive change and determine psychosocial factors in COVID-19 survivors. A cross-sectional study was recruited 285 participants from February 2020 to April 2020 in 17 hospitals in Sichuan Province. Cognitive function, variables indicative of the virus infection itself, and psychosocial variables were collected by telephone interview. Univariate logistic regression and Lasso logistic regression models were used for variable selection which plugged into a multiple logistics model. Overall prevalence of moderate or severe cognitive impairment was 6.3%. Logistic regression showed that sex, religion, smoking status, occupation, self-perceived severity of illness, sleep quality, perceived mental distress after COVID-19, perceived discrimination from relatives and friends, and suffered abuse were associated with cognitive impairment. The long-term consequences of cognitive function are related to multiple domains, in which psychosocial factors should be taken into consideration.

Risk of behavioral disturbances in pediatric patients with epilepsy and mild to moderate cognitive impairment: A cross-sectional study.

The aim of the study was to assess whether children and adolescents with epilepsy are at higher risk of behavioral disturbances when they have concomitant cognitive disturbances. Behavioral scores were generated using the Child Behavior Checklist (CBCL). Cognitive evaluation was applied by using different age appropriate versions of the Wechsler Intelligence Scale. CBCL scores (total, externalizing, internalizing) were compared between patients with and without intellectual disability (IQ score < 70 and ≥70, respectively). 144 (10.2 mean age, 6.0-17.9 range) patients were recruited for the study. Patients with mild to moderate intellectual disability (full-scale intelligence quotient (FSIQ) < 70) were not at higher risk of behavioral disturbances (total CBCL score ≥ 63) than patients without cognitive impairment. The mean total CBCL score was 62.0 ± 10.6 (range 42.0-83.5, 95% CI 57.9-62.0) and 59.3 ± 10.3 (range 38.0-80.0, CI 57.4-61.2) for patients with FSIQ < 70 and ≥70, respectively. There was no correlation between FSIQ and total CBCL scores. These findings were true for all IQ subcategories. Behavioral disturbances among children and adolescents with epilepsy occur despite the presence or absence of intellectual dysfunction with respect to full-scale IQ.

Multimorbidity and associated informal care receiving characteristics for US older adults: a latent class analysis

BackgroundOlder adults with varying patterns of multimorbidity may require distinct types of care and rely on informal caregiving to meet their care needs. This study aims to identify groups of older adults with distinct, empirically-determined multimorbidity patterns and compare characteristics of informal care received among estimated classes.MethodsData are from the 2011 National Health and Aging Trends Study (NHATS). Ten chronic conditions were included to estimate multimorbidity patterns among 7532 individuals using latent class analysis. Multinomial logistic regression model was estimated to examine the association between sociodemographic characteristics, health status and lifestyle variables, care-receiving characteristics and latent class membership.ResultsA four-class solution identified the following multimorbidity groups: some somatic conditions with moderate cognitive impairment (30%), cardiometabolic (25%), musculoskeletal (24%), and multisystem (21%). Compared with those who reported receiving no help, care recipients who received help with household activities only (OR = 1.44, 95% CI 1.05–1.98), mobility but not self-care (OR = 1.63, 95% CI 1.05–2.53), or self-care but not mobility (OR = 2.07, 95% CI 1.29–3.31) had greater likelihood of being in the multisystem group versus the some-somatic group. Having more caregivers was associated with higher odds of being in the multisystem group compared with the some-somatic group (OR = 1.09, 95% CI 1.00-1.18), whereas receiving help from paid helpers was associated with lower odds of being in the multisystem group (OR = 0.36, 95% CI 0.19–0.77).ConclusionsResults highlighted different care needs among persons with distinct combinations of multimorbidity, in particular the wide range of informal needs among older adults with multisystem multimorbidity. Policies and interventions should recognize the differential care needs associated with multimorbidity patterns to better provide person-centered care.

Multi-colour reflective metagrating with neutral transparency for augmented reality.

This paper presents the design and experimental validation of an all-dielectric and transparent metagrating-based metalens. Leveraging multiple guided mode resonances simultaneously, the metagrating enables the generation of two or more spectrally narrow reflection peaks. These peaks are achieved through the precise engineering of guided mode resonances, allowing for the reflection of a comb of vibrant and saturated colours. In addition to the investigation of underlying mechanisms, we introduce an analytical numerical method that facilitates rapid engineering of the spectral positions of the reflection peak comb. Experimental validation is provided for a bichromatic sample. Such metagrating can be promising for augmented reality systems, supporting individuals with mild to moderate cognitive impairments by delivering visual and textual stimuli that can improve indoor navigation, home safety, communication, and decision-making.

PSEUDOBULBAR AFFECT AND COGNITIVE DECLINE POST SEVERE TRAUMATIC BRAIN INJURY: A CASE REPORT

Introduction: Pseudobulbar affect is described as episodes of laughing or crying that occur suddenly and uncontrollably without appropriate stimulation. Pseudobulbar affect is often preceded by various neurological disorders, one of which is a history of severe head injury. Case Report: Female, 21 years old, experienced sudden frequent laughing for no apparent reason and could not be controlled. This has been happening after she suffered a severe head injury, which was a subarachnoid hemorrhage, about two years ago. She was diagnosed with pseudobulbar affect according to Cummings criteria and confirmed by Center for Neurologic Study – Lability Scale (CNS-LS) questionnaire with a score of 19. The patient also complained of forgetting things, therefore a cognitive function was examined with Indonesian Version of the Montreal Cognitive Assessment (MoCA-Ina) with a score of 14 which indicated moderate cognitive impairment. Discussion: Pseudobulbar affect post traumatic brain injury is suspected to be caused by decreased inhibition of sensory cortex transmission to the motor cortex and limbic system leading to disturbances in the cerebellum and decreased threshold for emotional expression. Pseudobulbar affect may coexist with impaired cognitive function due to the intersection of the anatomical structure of cognitive function with pathways that regulate emotion. Conclusion: Pseudobulbar affect with cognitive impairment creates a burden and interferes the patient’s quality of life. It is necessary for health workers to be able to identify the clinical manifestations of pseudobulbar affect as a complication after traumatic brain injury, therefore optimal management for the patients can be achieved.

IMPAIRED GAIT AND BALANCE DISORDERS AS RISK MARKERS FOR FALLS IN CHRONIC CEREBRAL ISCHEMIA

The main clinical syndromes of chronic cerebral ischemia (CCI) are impaired gait and balance disorders, which increase risks for falls. The objective of the study is to analyze correlation between impaired gait and postural instability to determine risk markers for falls in CCI patients. Materials and Methods. We examined 104 CCI patients (15 men and 89 women, median age 70 (63; 76) years). The patients did not have significant functional limitations in daily life (modified Rankin scale, 0–2 points). Thirteen patients (13 %) had a history of acute cerebrovascular accidents, thirty-seven patients (36 %) had a history of falls. Moderate cognitive impairment was detected in 53 patients (51 %). Impaired gait and balance disorders were assessed according to Tinetti test, Berg balance scale, and stabilometric platform. Statistica 13.0, SPSS 22 was used for statistical data processing. Results. According to the Tinetti test, impaired gait was detected in 101 patients (97 %), balance disorders were found in 32 patients (31 %). According to the Berg balance scale, most patients had a low risk for falls. Stabilometry showed a decrease in the limits of stability, mainly forward. Discriminant analysis revealed that significant predictors of falls in CCI patients are the “forward” limit of stability (&lt;59 points), female gender, age (&gt;67 y.o.), depression (&gt;9 points, HADS), sway index (eyes closed) in the clinical test for sensory integration and balance (&gt;0.855), balance score for the Tinetti test (&lt;15 points), and a history of acute cerebrovascular accident. Conclusion. Stabilometry along with clinical assessment can improve the effectiveness of determining the risk group for falls in CCI patients.

Genetic Testing for Global Developmental Delay in Early Childhood

Global developmental delay (GDD) is characterized by a complex etiology, diverse phenotypes, and high individual heterogeneity, presenting challenges for early clinical etiologic diagnosis. Cognitive impairment is the core symptom, and despite the pivotal role of genetic factors in GDD development, the understanding of them remains limited. To assess the utility of genetic detection in patients with GDD and to examine the potential molecular pathogenesis of GDD to identify targets for early intervention. This multicenter, prospective cohort study enrolled patients aged 12 to 60 months with GDD from 6 centers in China from July 4, 2020, to August 31, 2023. Participants underwent trio whole exome sequencing (trio-WES) coupled with copy number variation sequencing (CNV-seq). Bioinformatics analysis was used to unravel pathogenesis and identify therapeutic targets. The main outcomes of this study involved enhancing the rate of positive genetic diagnosis for GDD, broadening the scope of genetic testing indications, and investigating the underlying pathogenesis. The classification of children into levels of cognitive impairment was based on the developmental quotient assessed using the Gesell scale. The study encompassed 434 patients with GDD (262 [60%] male; mean [SD] age, 25.75 [13.24] months) with diverse degrees of cognitive impairment: mild (98 [23%]), moderate (141 [32%]), severe (122 [28%]), and profound (73 [17%]). The combined use of trio-WES and CNV-seq resulted in a 61% positive detection rate. Craniofacial abnormalities (odds ratio [OR], 2.27; 95% CI, 1.45-3.56), moderate or severe cognitive impairment (OR, 1.69; 95% CI, 1.05-2.70), and age between 12 and 24 months (OR, 1.57; 95% CI, 1.05-2.35) were associated with a higher risk of carrying genetic variants. Additionally, bioinformatics analysis suggested that genetic variants may induce alterations in brain development and function, which may give rise to cognitive impairment. Moreover, an association was found between the dopaminergic pathway and cognitive impairment. In this cohort study of patients with GDD, combining trio-WES with CNV-seq was a demonstrable, instrumental strategy for advancing the diagnosis of GDD. The close association among genetic variations, brain development, and clinical phenotypes contributed valuable insights into the pathogenesis of GDD. Notably, the dopaminergic pathway emerged as a promising focal point for potential targets in future precision medical interventions for GDD.

Neurocognitive testing to predict ICANS post-CAR T.

e19003 Background: Since the approvals of chimeric antigen receptor T-cell (CAR T) therapy in acute lymphoblastic leukemia (ALL), non-Hodgkin lymphoma (NHL), and multiple myeloma (MM), it has been increasingly offered in centers nationwide. Immune effector cell-associated neurotoxicity syndrome (ICANS) poses a potentially fatal risk with CAR-T. Identifying patients at risk of having high grade ICANS is a thus a priority. Scoring systems such as the EASIX scores have accounted for disease and comorbidity factors but haven’t addressed neurocognitive function. The St. Louis University Mental Status (SLUMS) Exam and the Montreal Cognitive Assessment (MoCA) have not been examined for validity and reliability in this population, so we performed a retrospective review of CAR T patients at the University of Kansas Medical Center to identify if incidence or severity of ICANS could be correlated with neurocognitive testing performed in the pre-infusion period. Methods: Patients receiving CAR T targeting CD19 or BCMA between December 2017 and December 2023 were included. Neurocognitive testing was performed by trained onco-psychology, neurology, or hematology-oncology staff. The SLUMS exam is an 11 question exam scored on a 30 point scale to predict normal neurocognitive function (27-30 points), mild neurocognitive disorders (21-26 points), and dementia (0-20 points). The MoCA is an 11 question exam scored on a 30 point scale to predict normal cognition (26-30 points), mild cognitive impairment (18-25 points), moderate cognitive impairment (10-17 points), and severe cognitive impairment (&lt;10 points). Incidence of ICANS and severity of ICANS were compared between patients who had any detected cognitive dysfunction and those who had none, as well as between the tiered result system unique to each test. Results: We included 360 patients in this analysis, (257 NHL, 84 MM and 19 ALL) leading to comparisons of 276 CD19-directed CAR T patients and 84 BCMA-directed CAR T patients. In CD19-directed patients, there were no differences in ICANS incidence according to the SLUMS scores. There was a significant increase in ICANS incidence for patients who had a positive MoCA exam, p=0.006. Additionally, ICANS incidence was correlated with more severe MoCA results, p=0.01. No differences in ICANS severity were observed using any neurocognitive test. In BCMA-directed patients, no differences in ICANS were observed using the SLUMS or MoCA. Conclusions: Our results suggest that while the SLUMS exam does not predict ICANS, the MoCA may independently predict incidence of ICANS. Patients with a higher score correlating with normal cognition are less likely to develop ICANS and may be appropriate for outpatient therapy. For those with lower scores correlating with more severe neurocognitive disorders, inpatient monitoring and early intervention will continue to be important.

Analysis of the Relationship between Moderate Cognitive Impairments and Changes in Synchronization between Photostimulation and Brain Activity

Analysis of the Relationship between Moderate Cognitive Impairments and Changes in Synchronization between Photostimulation and Brain Activity

The effect of anticholinergic drugs on cognition of patients with Parkinson’s disease: a cohort study from the Egyptian population

ABSTRACT Background Cognitive dysfunction is a non-motor manifestation of Parkinson’s disease (PD). We aimed to determine the frequency and patterns of cognitive dysfunction in treated patients with PD and their predictors. Research design and methods This study included 80 patients (male = 48; female = 32) and 30 healthy individuals. They underwent neuropsychiatric evaluations. Measurements included Beck’s depression inventory – II (BDI-II), mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA). Results Patients had mean age of 55.56 ± 9.06 yrs, duration of PD of 4.86 ± 2.71 yrs and Hoehn and Yahr Scoring of 2.19 ± 0.89. They were on levodopa/carbidopa therapy and adjuvant therapy with benztropine mesylate, an anticholinergic drug, (n = 51) or amantadine sulfate, a dopaminergic drug, (n = 29). Sixteen (20%) had moderate depressive symptoms. Mild and moderate cognitive impairments were reported in 38.8% and 28.8% (by MMSE) and 46.3% and 31.3% (by MoCA). Patients had lower global cognitive scoring (p = 0.0001) and scorings of different cognitive functions (naming, attention, language, abstraction, memory and orientation) than controls. Patients treated with benztropine had lower cognition than with amantadine. Correlation analyses showed that lower cognition was only associated with chronic PD and its treatment (p = 0.0001). Conclusions Cognitive dysfunction is common with PD (77.5%) particularly with anticholinergic drugs. De-prescription of anticholinergics is recommended for patients with PD.

A randomized, controlled clinical trial demonstrates improved owner-assessed cognitive function in senior dogs receiving a senolytic and NAD+ precursor combination

Age-related decline in mobility and cognition are associated with cellular senescence and NAD + depletion in dogs and people. A combination of a novel NAD + precursor and senolytic, LY-D6/2, was examined in this randomized controlled trial. Seventy dogs with mild to moderate cognitive impairment were enrolled and allocated into placebo, low or full dose groups. Primary outcomes were change in cognitive impairment measured with the owner-reported Canine Cognitive Dysfunction Rating (CCDR) scale and change in activity measured with physical activity monitors. Fifty-nine dogs completed evaluations at the 3-month primary endpoint, and 51 reached the 6-month secondary endpoint. There was a significant difference in CCDR score across treatment groups from baseline to the primary endpoint (p = 0.02) with the largest decrease in the full dose group. No difference was detected between groups using in house cognitive testing. There were no significant differences between groups in changes in measured activity. The proportion of dogs that improved in frailty and owner-reported activity levels and happiness was higher in the full dose group than other groups, however this difference was not significant. Adverse events occurred equally across groups. All groups showed improvement in cognition, frailty, and activity suggesting placebo effect and benefits of trial participation. We conclude that LY-D6/2 improves owner-assessed cognitive function over a 3-month period and may have broader, but more subtle effects on frailty, activity and happiness as reported by owners.