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International Journal of Molecular... Nov 2023Autism spectrum disorder (ASD) is a neurodevelopmental disability and recent evidence suggests that autistic adults are more likely to develop Alzheimer's disease (Alz)...
Autism spectrum disorder (ASD) is a neurodevelopmental disability and recent evidence suggests that autistic adults are more likely to develop Alzheimer's disease (Alz) and other dementias compared to neurotypical (NT) adults. The ε4-allele of the Apolipoprotein E () gene is the strongest genetic risk factor for Alz and negatively impacts cognition in middle-aged and older (MA+) adults. This study aimed to determine the impact of the ε4-allele on verbal learning and memory in MA+ autistic adults (ages 40-71 years) compared to matched NT adults. Using the Auditory Verbal Learning Test (AVLT), we found that ε4 carriers performed worse on short-term memory and verbal learning across diagnosis groups, but there was no interaction with diagnosis. In exploratory analyses within sex and diagnosis groups, only autistic men carrying ε4 showed worse verbal learning ( = 0.02), compared to autistic men who were not carriers. Finally, the ε4-allele did not significantly affect long-term memory in this sample. These findings replicate previous work indicating that the ε4-allele negatively impacts short-term memory and verbal learning in MA+ adults and presents new preliminary findings that MA+ autistic men may be vulnerable to the effects of ε4 on verbal learning. Future work with a larger sample is needed to determine if autistic women may also be vulnerable.
Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Alleles; Alzheimer Disease; Apolipoprotein E4; Apolipoproteins E; Autism Spectrum Disorder; Autistic Disorder; Genotype; Neuropsychological Tests; Verbal Learning
PubMed: 37958971
DOI: 10.3390/ijms242115988 -
Schizophrenia Research. Cognition Sep 2023In the general population, repeated cognitive testing produces learning effects with potential for improved test performance. It is currently unclear whether the same...
OBJECTIVE
In the general population, repeated cognitive testing produces learning effects with potential for improved test performance. It is currently unclear whether the same effect of repeated cognitive testing on cognition pertains to people living with schizophrenia, a condition often associated with significant cognitive impairments. This study aims to evaluate learning ability in people with schizophrenia and-considering the evidence that antipsychotic medication can additionally impair cognitive performance-explore the potential impact of anticholinergic burden on verbal and visual learning.
METHOD
The study included 86 patients with schizophrenia, treated with clozapine, who had persisting negative symptoms. They were assessed at baseline, weeks 8, 24 and 52 using Positive and Negative Syndrome Scale, Hopkins Verbal Learning Test-Revised (HVLT-R) and Brief Visuospatial Memory Test-R (BVMT-R).
RESULTS
There were no significant improvements in verbal or visual learning across all measurements. Neither the clozapine/norclozapine ratio nor anticholinergic cognitive burden significantly predicted participants' total learning. Premorbid IQ was significantly associated with verbal learning on the HVLT-R.
CONCLUSIONS
These findings advance our understanding of cognitive performance in people with schizophrenia and demonstrate limited learning performance in individuals with treatment-refractory schizophrenia.
PubMed: 37006704
DOI: 10.1016/j.scog.2023.100283 -
JAMA Network Open Jul 2023Although professional soccer players appear to be at higher risk of neurodegenerative disease, the reason remains unknown.
IMPORTANCE
Although professional soccer players appear to be at higher risk of neurodegenerative disease, the reason remains unknown.
OBJECTIVE
To examine whether heading frequency is associated with risk of cognitive impairment in retired professional soccer players.
DESIGN, SETTING, AND PARTICIPANTS
A UK nationwide cross-sectional study was conducted between August 15, 2020, and December 31, 2021, in 459 retired male professional soccer players older than 45 years and registered with the Professional Footballers' Association or a League Club Players' Association.
EXPOSURE
Data on heading frequency in 3 bands-0 to 5, 6 to 15, and more than 15 times per match or training session and other soccer-specific risk factors, such as player position and concussion-were collected through a self-reported questionnaire.
MAIN OUTCOMES AND MEASURES
Cognitive impairment was defined using the Telephone Interview for Cognitive Status-modified as scores of less than or equal to 21. Hopkins Verbal Learning Test, verbal fluency, and independent activities of daily living were also assessed. Test Your Memory and physician-diagnosed dementia/Alzheimer disease were self-reported via the questionnaire. Adjusted odds ratios (AORs) with 95% CIs were calculated.
RESULTS
Of 468 retired male professional soccer players who completed questionnaires (mean [SD] age, 63.68 [10.48]; body mass index, 27.22 [2.89]), 459 reported heading frequency: 114 headed 0 to 5 times, 185 headed 6 to 15 times, 160 headed more than 15 times per match, and 125 headed 0 to 5 times, 174 headed 6 to 15 times, and 160 headed more than 15 times per training session during their careers. The prevalence of cognitive impairment was 9.78% (0-5 times), 14.78% (6-15 times), and 15.20% (>15 times) per match (P = .51). Compared with players reporting 0 to 5 headers per match, the AORs were 2.71 (95% CI, 0.89-8.25) for players reporting 6 to 15 headers per match and 3.53 (95% CI, 1.13-11.04) for players reporting more than 15 headers per match (P = .03 for trend). Corresponding AORs for heading frequency per training session were 2.38 (95% CI, 0.82-6.95) for those reporting 6 to 15, and 3.40 (95% CI, 1.13-10.23) for those reporting more than 15 in comparison with those who reported 0 to 5 (P = .03 for trend). Concussion involving memory loss was also associated with a greater risk of cognitive impairment (AOR, 3.16; 95% CI, 1.08-9.22). Similar results were observed with other cognitive tests and self-reported physician-diagnosed dementia/Alzheimer disease.
CONCLUSIONS AND RELEVANCE
The findings of this study suggest that repetitive heading during a professional soccer career is associated with an increased risk of cognitive impairment in later life. Further study is needed to establish the upper threshold for heading frequency to mitigate this risk.
Topics: Humans; Male; Middle Aged; Soccer; Alzheimer Disease; Neurodegenerative Diseases; Cross-Sectional Studies; Activities of Daily Living; Brain Concussion; Cognitive Dysfunction
PubMed: 37459095
DOI: 10.1001/jamanetworkopen.2023.23822 -
Pain and Therapy Aug 2023This review is made up of two parts; the first part discussing intellectual disability (ID) in general, while the second part covers the pain associated with... (Review)
Review
This review is made up of two parts; the first part discussing intellectual disability (ID) in general, while the second part covers the pain associated with intellectual disability and the challenges and practical tips for the management of pain associated with (ID). Intellectual disability is characterized by deficits in general mental abilities, such as reasoning, problem solving, planning, abstract thinking, judgment, academic learning, and learning from experience. ID is a disorder with no definite cause but has multiple risk factors, including genetic, medical, and acquired. Vulnerable populations such as individuals with intellectual disability may experience more pain than the general population due to additional comorbidities and secondary conditions, or at least the same frequency of pain as in the general population. Pain in patients with ID remains largely unrecognized and untreated due to barriers to verbal and non-verbal communication. It is important to identify patients at risk to promptly prevent or minimize those risk factors. As pain is multifactorial, thus, a multimodal approach using both pharmacotherapy and non-pharmacological management is often the most beneficial. Parents and caregivers should be oriented to this disorder, given adequate training and education, and be actively involved with the treatment program. Significant work to create new pain assessment tools to improve pain practices for individuals with ID has taken place, including neuroimaging and electrophysiological studies. Recent advances in technology-based interventions such as virtual reality and artificial intelligence are rapidly growing to help give patients with ID promising results to develop pain coping skills with effective reduction of pain and anxiety. Therefore, this narrative review highlights the different aspects regarding the current status of the pain associated with intellectual disability, with more emphasis on the recent pieces of evidence for the assessment and management of pain among populations with intellectual disability.
PubMed: 37284926
DOI: 10.1007/s40122-023-00526-w -
Cerebral Cortex (New York, N.Y. : 1991) May 2024Sleep supports memory consolidation via the reactivation of newly formed memory traces. One way to investigate memory reactivation in sleep is by exposing the sleeping...
Sleep supports memory consolidation via the reactivation of newly formed memory traces. One way to investigate memory reactivation in sleep is by exposing the sleeping brain to auditory retrieval cues; a paradigm known as targeted memory reactivation. To what extent the acoustic properties of memory cues influence the effectiveness of targeted memory reactivation, however, has received limited attention. We addressed this question by exploring how verbal and non-verbal memory cues affect oscillatory activity linked to memory reactivation in sleep. Fifty-one healthy male adults learned to associate visual stimuli with spoken words (verbal cues) and environmental sounds (non-verbal cues). Subsets of the verbal and non-verbal memory cues were then replayed during sleep. The voice of the verbal cues was either matched or mismatched to learning. Memory cues (relative to unheard control cues) prompted an increase in theta/alpha and spindle power, which have been heavily implicated in sleep-associated memory processing. Moreover, verbal memory cues were associated with a stronger increase in spindle power than non-verbal memory cues. There were no significant differences between the matched and mismatched verbal cues. Our findings suggest that verbal memory cues may be most effective for triggering memory reactivation in sleep, as indicated by an amplified spindle response.
Topics: Humans; Male; Cues; Young Adult; Sleep; Adult; Mental Recall; Electroencephalography; Memory Consolidation; Acoustic Stimulation; Brain; Photic Stimulation; Brain Waves
PubMed: 38745557
DOI: 10.1093/cercor/bhae183 -
Journal of Education & Teaching in... Apr 2024The target audiences for this team-based learning (TBL) activity are resident physicians and medical students.
AUDIENCE
The target audiences for this team-based learning (TBL) activity are resident physicians and medical students.
INTRODUCTION
According to the Centers for Disease Control and Prevention (CDC), nearly half of the adults in the United States have hypertension,1 which is a leading cause of cardiovascular disease and premature death.2 In extreme cases, patients may present in hypertensive emergencies, defined as an acute, marked elevation of systolic blood pressure >180mmHg or diastolic blood pressure >120mmHg with evidence of organ dysfunction.3,4 Patients presenting to the emergency department (ED) with symptoms of hypertensive emergencies must be promptly diagnosed and treated to prevent further morbidity and mortality. This TBL utilizes four clinical cases to educate resident physicians and medical students not only on the recognition of hypertensive emergencies, but also on the workup, management, and disposition of patients who present to the ED with hypertension.
EDUCATIONAL OBJECTIVES
By the end of this TBL session, learners should be able to: 1) define features of asymptomatic hypertension versus hypertensive emergency, 2) discuss which patients with elevated blood pressure may require further diagnostic workup and intervention, 3) identify a differential diagnosis for patients presenting with elevated blood pressures, 4) recognize the features of different types of end-organ damage, 5) review an algorithm for the pharmacologic management of hypertensive emergencies, 6) indicate dosing and routes of various anti-hypertensive medications, 7) choose the appropriate treatment for a patient who is hypertensive and presenting with flash pulmonary edema, 8) identify an aortic dissection on computed tomography (CT), 9) choose the appropriate treatment for a patient who is hypertensive and presenting with an aortic dissection, 10) identify intracranial hemorrhage on CT, 11) choose the appropriate treatment for a patient who is hypertensive and presenting with an intracranial hemorrhage, and 12) describe the intervention for warfarin reversal.
EDUCATIONAL METHODS
This is a classic TBL that includes an individual readiness assessment test (iRAT), a multiple-choice group readiness assessment test (gRAT), and a group application exercise (GAE).
RESEARCH METHODS
Learners and instructors were given the opportunity to provide verbal feedback after completion of the TBL. Learners included senior medical students and first-, second-, and third-year emergency-medicine residents. Learners were specifically asked if they felt the cases were educational, relevant, and useful to their training.
RESULTS
Six resident physicians and three medical students volunteered their verbal feedback, and agreed when they were specifically asked if the cases were educational, relevant, and useful to their training. The same learners also agreed when asked if they felt the TBL was a more enjoyable activity than a direct lecture to refresh their knowledge and skills. One instructor observed that interns and medical students were generally able to reach a correct diagnosis; however, they seemed to struggle more with describing appropriate pharmacologic interventions when compared to more senior learners.
DISCUSSION
Hypertension is a common complaint and incidental finding in patients presenting to the ED. Given its non-specific value, it can be a difficult topic for the novice healthcare provider to master. The differential diagnosis for a patient presenting with hypertension is vast, ranging from benign to emergent, and can sometimes necessitate minimal to substantial workups. Thus, this TBL is a useful, relevant, and effective exercise for residents-in-training to review and understand the management of hypertension.
TOPICS
Hypertension, hypertensive emergency, asymptomatic hypertension, flash pulmonary edema, aortic dissection, intracranial hemorrhage, warfarin reversal, team-based learning.
PubMed: 38707946
DOI: 10.21980/J8BP90 -
Neurology(R) Neuroimmunology &... Jan 2024Identifying optimal methods for evaluation and monitoring of cognitive outcomes in AE is important for clinical care and research. This scoping review aimed to evaluate... (Review)
Review
BACKGROUND AND OBJECTIVES
Identifying optimal methods for evaluation and monitoring of cognitive outcomes in AE is important for clinical care and research. This scoping review aimed to evaluate neuropsychological tests (NPT) that are most frequently impaired in AE cohorts to provide recommendations for a standardized NPT battery for AE outcome.
METHODS
PubMed search for studies examining NPT in patients with AE was conducted on June 9, 2023. Studies were screened for inclusion/exclusion criteria as follows: at least 1 NPT, individual NPT test scores with comparison with healthy controls or normative data and neural-IgG status, total sample size ≥5, and English manuscript available.
RESULTS
The search yielded 5,393 studies, of which 3,359 were screened, 107 were full text reviewed, and 32 met inclusion/exclusion criteria, anti-NMDA-R (k = 18), anti-LGI1 (k = 10), anti-GABA-R (k = 2), anti-GAD-65 (k = 4), and anti-CASPR2 (k = 3). The cognitive domains most frequently impaired were visual and verbal episodic memory, attention/working memory, processing speed, and aspects of executive functions.
DISCUSSION
Given the dearth of literature examining NPT in AE in combination with small sample sizes and methodological differences, more research in this area is needed. However, we provide recommendations for a test battery to be used in future studies, with the aim of standardizing research in this area. Based on the available literature, we recommend the use of comprehensive NPT batteries, spanning all cognitive domains. The highest yield measures may include the tests of (1) visual and verbal learning/memory, (2) basic and sustained attention, (3) processing speed, and (4) executive functions.
Topics: Humans; Cognition Disorders; Cognition; Neuropsychological Tests; Autoimmune Diseases of the Nervous System
PubMed: 37949665
DOI: 10.1212/NXI.0000000000200179 -
Translational Psychiatry Oct 2023Cognitive impairment is a core feature of schizophrenia, which is aggravated by antipsychotics-induced metabolic disturbance and lacks effective pharmacologic treatments... (Randomized Controlled Trial)
Randomized Controlled Trial
Cognitive impairment is a core feature of schizophrenia, which is aggravated by antipsychotics-induced metabolic disturbance and lacks effective pharmacologic treatments in clinical practice. Our previous study demonstrated the efficiency of metformin in alleviating metabolic disturbance following antipsychotic administration. Here we report that metformin could ameliorate cognitive impairment and improve functional connectivity (FC) in prefrontal regions. This is an open-labeled, evaluator-blinded study. Clinically stable patients with schizophrenia were randomly assigned to receive antipsychotics plus metformin (N = 48) or antipsychotics alone (N = 24) for 24 weeks. The improvement in cognition was assessed by the MATRICS Consensus Cognitive Battery (MCCB). Its association with metabolic measurements, and voxel-wise whole-brain FC with dorsolateral prefrontal cortex (DLPFC) subregions as seeds were evaluated. When compared to the antipsychotics alone group, the addition of metformin resulted in significantly greater improvements in the MCCB composite score, speed of processing, working memory, verbal learning, and visual learning. A significant time × group interaction effect of increased FC between DLPFC and the anterior cingulate cortex (ACC)/middle cingulate cortex (MCC), and between DLPFC subregions were observed after metformin treatment, which was positively correlated with MCCB cognitive performance. Furthermore, the FC between left DLPFC A9/46d to right ACC/MCC significantly mediated metformin-induced speed of processing improvement; the FC between left A46 to right ACC significantly mediated metformin-induced verbal learning improvement. Collectively, these findings demonstrate that metformin can improve cognitive impairments in schizophrenia patients and is partly related to the FC changes in the DLPFC. Trial Registration: The trial was registered with ClinicalTrials.gov (NCT03271866). The full trial protocol is provided in Supplementary Material.
Topics: Humans; Schizophrenia; Dorsolateral Prefrontal Cortex; Magnetic Resonance Imaging; Cognitive Dysfunction; Cognition; Antipsychotic Agents; Prefrontal Cortex
PubMed: 37821461
DOI: 10.1038/s41398-023-02616-x -
Research Square Jan 2024Urine albumin, high in kidney disease, predicts cardiovascular incidents and CNS white matter hyperintensity (WMH) burdens. Serum albumin - a more general biomarker...
Urine albumin, high in kidney disease, predicts cardiovascular incidents and CNS white matter hyperintensity (WMH) burdens. Serum albumin - a more general biomarker which can be low in several disorders - including kidney and liver disease, malnutrition, and inflammation - also predicts cardiovascular events and is associated with cognitive impairment in several clinical populations; relations between serum albumin and WMH prevalence, however, have rarely been evaluated. In a sample of 160 individuals with alcohol use disorder (AUD), 142 infected with HIV, and 102 healthy controls, the hypothesis was tested that lower serum albumin levels would predict larger WMH volumes and worse cognitive performance irrespective of diagnosis. After considering traditional cardiovascular risk factors (e.g., age, sex, body mass index (BMI), nicotine use, hypertension, diabetes) and study-relevant variables (i.e., primary diagnoses, race, socioeconomic status, hepatitis C virus status), serum albumin survived false discovery rate (FDR)-correction in contributing variance to larger periventricular but not deep WMH volumes. This relationship was salient in the AUD and HIV groups, but not the control group. In secondary analyses, serum albumin and periventricular WMH along with age, sex, diagnoses, BMI, and hypertension were considered for hierarchical contribution to variance in performance in 4 cognitive domains. Albumin survived FDR-correction for significantly contributing to visual and verbal learning and memory performance after accounting for diagnosis. Relations between albumin and markers of liver integrity [e.g., aspartate transaminase (AST)] and blood status (e.g., hemoglobin, red blood cell count, red cell distribution width) suggest that in this sample, albumin reflects both liver dysfunction and hematological abnormalities. The current results suggest that albumin, a simple serum biomarker available in most clinical settings, can predict variance in periventricular WMH volumes and performance in visual and verbal learning and memory cognitive domains. Whether serum albumin contributes mechanistically to periventricular WMH prevalence will require additional investigation.
PubMed: 38260299
DOI: 10.21203/rs.3.rs-3822513/v1 -
JAMA Network Open Nov 2023Blood-based biomarkers associated with increased risk of Alzheimer disease (AD) are understudied in people living with and without HIV, particularly women.
IMPORTANCE
Blood-based biomarkers associated with increased risk of Alzheimer disease (AD) are understudied in people living with and without HIV, particularly women.
OBJECTIVE
To determine whether baseline or 1-year changes in plasma amyloid-β40 (Aβ40), Aβ42, ratio of Aβ42 to Aβ40, total tau (t-tau), phosphorylated tau 231 (p-tau231), glial fibrillary acidic protein (GFAP), and/or neurofilament light chain (NFL) are associated with neuropsychological performance (NP) among women living with HIV (WLWH) and women living without HIV (WLWOH).
DESIGN, SETTING, AND PARTICIPANTS
This longitudinal, prospective, cohort study with 1-year repeated clinical measures (NP only measured once) and biospecimen collection occurred between 2017 and 2019. Participants were women aged 40 years or older from 10 clinical research sites in cities across the US that were part of the Women's Interagency HIV Study. Data analysis was conducted from April to December 2022.
EXPOSURE
Laboratory-confirmed HIV status and AD biomarkers.
MAIN OUTCOMES AND MEASURES
Sociodemographically adjusted NP T-scores (attention and working memory, executive function, processing speed, memory, learning, verbal fluency, motor function, and global performance) were the primary outcomes. Baseline and 1-year fasting plasma Aβ40, Aβ42, t-tau, p-tau231, GFAP, and NFL levels were measured and analyzed using multivariable linear regression.
RESULTS
The study consisted of 307 participants (294 aged ≥50 years [96%]; 164 African American or Black women [53%]; 214 women with a high school education or higher [70%]; 238 women who were current or former smokers [78%]; and 236 women [77%] who were overweight or obese [body mass index >25]) including 209 WLWH and 98 WLWOH. Compared with WLWOH at baseline, WLWH performed worse on learning (mean [SD] T-score 47.8 [11.3] vs 51.4 [10.5]), memory (mean [SD] T-score 48.3 [11.6] vs 52.4 [10.2]), verbal fluency (mean [SD] T-score 48.3 [9.8] vs 50.7 [8.5]), and global (mean [SD] T-score 49.2 [6.8] vs 51.1 [5.9]) NP assessments. Baseline median Aβ40, GFAP, and NFL levels were higher among WLWH vs WLWOH. There were no differences in 1-year biomarker change by HIV serostatus. Lower learning, memory, and motor NP were associated with 1-year Aβ40 increase; lower learning and motor with Aβ42 increase; lower motor with p-tau231 increase; and lower processing speed, verbal fluency and motor with NFL increase in the entire sample. Among WLWH, a 1-year increase in Aβ40 from baseline to follow-up was associated with worse learning, memory, and global NP; a 1-year increase in t-tau with worse executive function; and a 1-year increase in NFL with worse processing speed. Among WLWOH, a 1-year increase in Aβ40 and Aβ42 were associated with poorer memory performance and NFL was associated with poorer motor performance.
CONCLUSIONS AND RELEVANCE
These findings suggest that increases in certain plasma AD biomarkers are associated with NP in WLWH and WLWOH and may be associated with later onset of AD, and measuring these biomarkers could be a pivotal advancement in monitoring aging brain health and development of AD among women with and without HIV.
Topics: Female; Humans; Male; Alzheimer Disease; Cohort Studies; Prospective Studies; Biomarkers; HIV Infections
PubMed: 38019518
DOI: 10.1001/jamanetworkopen.2023.44194