bluuebunny/crossref_metadata_2025_split huggingface dataset:
SEMA4D blocking antibody, pepinemab, is a novel potential treatment for neurodegenerative disease: Clinical proof of concept in Phase 2 HD study supports ongoing clinical development in Phase 1/2 AD study
Authors: Fisher Terrence L , Evans Elizabeth E , Boise Megan , Foster Amber , Mishra Vikas , Mallow Crystal L , Smith Ernest S , Leonard John E , Feigin Andrew , Siemers Eric , Walters Kimberly , Sheldon Elizabeth , Turner Scott , Farlow Martin R. , Zauderer Maurice 
Published: June 2023

AbstractBackgroundPepinemab (VX15/2503) is a humanized IgG4 monoclonal antibody that blocks the binding of semaphorin 4D (SEMA4D) to its plexin receptors. SEMA4D is upregulated in neurons in response to stress and triggers activation of plexin‐positive astrocytes with concomitant loss of normal astrocyte functions. Drivers of glial cell activation may represent important novel targets to modify progression of neurodegenerative pathology. Blocking antibody to SEMA4D has been shown to reduce neurodegenerative processes in preclinical models, including Huntington’s disease (HD) and Alzheimer’s disease (AD). SIGNAL‐HD (NCT02481674), a completed Phase 2 trial, provided clinical rationale for the ongoing Phase 1/2 SIGNAL‐AD study (NCT04381468).MethodThe SIGNAL‐HD study included 301 subjects with late prodromal (LP) and early manifest (EM) HD. Subjects were treated with monthly infusions of pepinemab for at least 18 months and evaluated for safety and a variety of clinical parameters including cognition (HD‐CAB). Imaging endpoints included structural MRI to assess brain atrophy and FDG‐PET to assess brain metabolism. The SIGNAL‐AD study plans to include 40 subjects with early AD treated for approximately 1 year, with objectives including safety, change in brain metabolism via FDG‐PET, and clinical endpoints including cognition.ResultIn SIGNAL‐HD, pepinemab was well‐tolerated and was shown to cross the BBB to engage its target. Co‐primary efficacy outcome measures did not achieve statistical significance in this study, however, positive trends in the direction of pepinemab benefit were observed and analysis of secondary and exploratory endpoints was therefore pursued. In 179 EM subjects, a treatment benefit was observed in 6/6 components of the HD‐CAB cognitive assessment battery, with a significant treatment effect on HD‐CAB composite score (p = 0.007). Further changes in prespecified exploratory imaging endpoints suggest that pepinemab treatment reduced brain atrophy (volumetric MRI) and slowed or reversed decline in metabolic activity in 26/26 brain regions, with 15/26 regions showing a significant positive treatment effect (p≤0.05) by FDG‐PET imaging.ConclusionSIGNAL‐HD showed a favorable safety profile and positive trends in cognition and imaging endpoints that encourage continued development in both HD and AD. The Phase 1b/2a study in AD (SIGNAL‐AD), is currently enrolling and initial safety review is planned for end of February.
Understanding differences in antidepressant use patterns among african american and white volunteers with dementia
Authors: Leoutsakos Jeannie‐Marie S , Rebok George , Thorpe Roland J. , Xue Qian‐Li 
Published: June 2023

AbstractBackgroundOlder African Americans are less likely to use antidepressants than Older White Americans. These findings are based on cross‐sectional studies or studies with limited followup periods; less is known about patterns of use (initiation, augmentation, switching, discontinuation) over many years. We describe antidepressant use patterns over 5 or more years in a large prospective sample of US volunteers with dementia.MethodOur sample was 12,627 white and 1,617 African American volunteers (mean: 75.2; SD 10.5) followed approximately yearly at Alzheimer Disease Research Centers 2005‐2020. We used Webplots to visualize antidepressant use patterns over time, and will explore predictors of these patterns.ResultAt their first visit, 413 (21.6%) of African Americans and 5,634 (36.0%) of White Americans were using antidepressants. Among African Americans, 78 (9.3%), 33 (6.6%), and 11 (3.5%) initiated antidepressant use at visits 2,3, and 4, respectively; among White Americans 807 (13.4%), 409 (10.9%), and 211 (9.2%). Among African Americans using antidepressants, 38 (23%), 49 (9.8%), and 30 (9.4%) discontinued antidepressant use at visits 2,3, and 4 respectively; whereas among White Americans, 683 (18.7%), 419 (16.3%), and 302 (16.9%). Among African Americans using antidepressants, 37 (14.5%), 20 (12.5%), and 8 (9.1%) changed their regimen at visits 2,3, and 4 respectively; whereas among White Americans, 526 (14.4%), 239 (10.9%), and 135 (9.7%).ConclusionCompared to white volunteers, African American voluntee had lower rates of antidepressant use at baseline and lower rates of initiation at subsequent visits. Rates of discontinuation were higher among African Americans at study visit 2, but lower at later visits. Rates of regimen change were similar by race. Differences in patterns of medication use over time speak to potential equity issues that cannot be observed with cross‐sectional study designs. Further, in order to understand whether these medications are helpful in participants with dementia, it is first important to understand differences in who uses these medications, and which factors predict regimen changes and discontinuation.
Multi‐faceted frail older adults and chronic diseases
Authors: Lee Jiyeon , Park Ji‐Hyuk 
Published: June 2023

AbstractBackgroundThe older adults who are in the middle of health and disability are called frail older adults because they are vulnerable to disability. Although the relationship between chronic diseases and frailty has been reported through a number of previous studies, the latest studies examining the prevalence of frailty based on multifaceted factors are limited.MethodIn this study, data from the 5th Survey of Living Conditions of Older adults study conducted in 2020 was selected. Data of the older adults over 65 (N = 10,097) were used for the analyses. Using the Comprehensive Korean Frailty Instrument (CKFI), participants were classified into robust, pre‐frail, and frail groups. Binominal logistic regression was used. Analysis was performed using SPSS 25. Three models were set. In Model 1, cutoff was set to 7 points to examine the possibility of chronic diseases in the frail group compared to the robust and pre‐frail groups. In Model 2, cutoff was set to 5 to examine the possibility of chronic diseases in the pre‐frail and frail groups compared to the robust group. In Model 3, except for the frail group, the possibility that the pre‐frail group has chronic diseases compared to the robust group was examined.ResultThe prevalence of robust, pre‐frail and frail group was found to be 26.59%, 27.65%, 45.76% respectively (Table 1). For all models, the probability according to the Likelihood Ratio statistic value was less than 0.01. The p‐value was less than 0.01.According to z‐statistics of Model 1, it was confirmed that Rheumatoid Arthritis/Osteoarthritis (16.17), hypertension (13.54), diabetes (13.14), lumbago (11.75), stroke (11.96) and osteoporosis (OST) (10.92) affect frailty (Table 2). The z‐statistics of Model 2 confirmed that RHE (12.45), DIA (10.82), high blood pressure (10.62), and LUM (10.15) had the effect of pre‐frail and frail groups (Table 3). In Model 3, there were no results with z‐statistics more than 10. Though the model was significant, the explanatory power was low (Table 4).ConclusionWe found that there was a significant correlation between multifaceted frailty and chronic diseases. In the future, it is necessary to examine the causal relationship between multifaceted frailty and chronic diseases through longitudinal studies.
Cognitive impairment and depressive symptoms in severe COVID‐19 elderly survivors: Preliminary results from 1‐year follow‐up assessment
Authors: Ribeiro José Pedro , Martins Sónia , Ferreira Ana Rita , Fontes Liliana , Fernandes Joana , Vieira Tatiana , Reis Nuno P , Braga António P , Coimbra Isabel , Paiva José Artur , Fernandes Lia 
Published: June 2023

AbstractBackgroundStudies have pointed towards the presence of neuropsychiatric sequelae after COVID‐19 infection, yet in the midst of the biggest health threat of this generation there are relatively few long‐term studies which have endeavored to identify such complications, known to have a negative impact on quality of life. In this context, this study aims to identify cognitive impairment (CI) and depressive symptoms in severe COVID‐19 elderly survivors, 1‐year after hospital discharge and also to analyse the association between CI and depressive symptoms.MethodThis study is part of the longitudinal MAPA project still ongoing at a University Hospital in Porto, Portugal. Patients with >60 y.o., admitted into Intensive Care Medicine Department (ICMD), due to COVID‐19 (1st wave), were included. Exclusion criteria were: ICMD length of stay ≤24h, terminal illness, major auditory loss or inability to communicate at the follow‐up assessment. Participants were evaluated 1‐year after hospital discharge, with a research protocol, which includes Patient Health Questionnaire (PHQ‐9; depressive symptoms) and Six Item Cognitive Impairment Test (6CIT; CI).ResultThirty‐eight patients were included (median age = 71years). Mostly were male (66%), married (66%) and with low education (58% = 0‐4years). About 53% had previous psychiatric history (none had clinical registry of CI or dementia). Most patients (71%) needed deep sedation and invasive mechanical ventilation (71%). CI and depressive symptoms were observed in 18.4% of the sample, for both. Patients with depression had more CI (42.9%vs12.9%), however this difference was not statistically significant.ConclusionThese findings showed that an important proportion of severe COVID‐19 elderly survivors suffers from depressive symptoms and CI, 1‐year post‐discharge, which are in line with other studies. These results underline the need to better clarify the long‐term relationship between depression and CI in severe COVID‐19 survivors.
Cognitive impairment and COVID‐19 in an urban indigenous community from Amazonas
Authors: Bezerra Camila Carlos , Toledo Noeli N , Duarte Vanessa Vasconcellos , Sampaio Rebeca Lima , Brucki Sonia Maria Dozzi , Souza‐Talarico Juliana Nery 
Published: June 2023

AbstractBackgroundLike all minority groups worldwide, indigenous populations were most impacted by the COVID‐19 pandemic, especially in low‐middle income countries (LMICs). However, little is known about the relationship between previous COVID‐19 and cognitive performance. This study aimed to identify the prevalence of cognitive impairment and its relationship with previous COVID‐19 in indigenous mid‐aged and older adults.MethodsUsing a cross‐section approach, 134 indigenous people, 50 years and older, from an urban dwelling community located in Manaus, Amazonas, Brazil, were evaluated for cognitive impairment and previous covid‐19 disease. Cognitive impairment (CI) was based on consensus diagnostic guided by the following criteria: 1) scores on Mini‐Mental State Examination (MMSE) ≤ 14 for illiterate subjects and ≤ 19 for literate subjects (mean minus two standard deviations); 2) scores ≤ 8 on verbal fluency or ≤ 7 on delayed recall on the Brief Battery for Cognitive Screening. All those tests and criteria were already used in Brazil’s previously indigenous community and population with a low‐education level.Results30.6% of the urban indigenous community met the criteria for cognitive impairment, among them 48.8% tested positive for COVID‐19 since the pandemic has started. Logistic regression show that low education increases the changes of cognitive impairment (OD = 0.839; 95% CI = 0.748 – 0.942; p = 0.003) while previous COVID‐19 did not (OD = 0.495; 95% CI = 0.224 – 1.094; p = 0.082).ConclusionThe prevalence of cognitive impairment in an urban community of Brazilian indigenous people increased in older adults with lower education levels regardless of previous COVID‐19.
Magnetoencephalography(MEG) spectral signature of cognitive impairment ‐ A perspective on pathophysiological changes with blood pressure
Authors: Srivastava Pallavi , Proskovec Amy L , Rossetti Heidi , Yu Fang F. , Berry Jarett D , Maldjian Joseph , Davenport Elizabeth M 
Published: June 2023

AbstractBackgroundSpectral ratios (e.g., resting‐state EEG alpha/theta power ratio), which index rhythmic brain activity, have been shown to distinguish early‐onset AD from healthy controls. Magnetoencephalographic (MEG) brain imaging offers advantages over EEG through its unique combination of excellent temporal as well as spatial precision for detecting brain activity. The purpose of this study is to compare MEG spectral activity in cognitively impaired and healthy controls with changes in systolic blood pressure (sbp), specifically focused in the frontal lobe as this region is known to be susceptible to hypertension related white matter degradation.MethodsSixteen cognitively impaired, including 13 possible and 3 probable mild cognitive impairment (MCI), (mean age 65.6 years, males/females: 5/11, Whites/Blacks: 11/5) and sixteen age, sex, and race matched healthy controls (mean age 62.4 years, males/females: 4/12, Whites/Blacks: 11/5) were recruited from an ongoing multiethnic community‐based study to complete six minutes of resting‐state MEG along with a T1w brain MRI. All MEG data underwent standard preprocessing. Resultant whole‐brain maps of spectral activity were filtered into six canonical frequency bands, including delta (2‐4 Hz), theta (5‐7 Hz), alpha (8‐12 Hz), beta (15‐29 Hz), gamma (30‐59 Hz) and high gamma (60‐90 Hz). Relative mean power of each frequency band, and spectral ratios of alpha/theta, beta/delta as well as a spectral slowing index [(alpha+beta+gamma)/(delta+theta)] were computed.ResultMean sbp was 135 mm Hg for both groups. Generalized linear regression models showed cognitive impairment was negatively associated with spectral ratios beta/delta and spectral slowing index. We also found a significant positive association between spectral ratios (beta/delta β = ‐0.0115, p = 0.0015; spectral slowing index β = ‐0.0125, p = 0.0144) and interaction of systolic blood pressure with cognitive impairment. Results are summarized in tables 1‐2.ConclusionLower spectral ratios have previously been demonstrated in individuals with AD. Somewhat surprisingly, our findings indicate that lower blood pressure is associated with lower values on these MEG metrics in cognitively impaired individuals. Interestingly, overtreatment of hypertension in elderly with MCI has been associated with greater cognitive decline. Thus, these results will be examined in a larger cohort and the analysis will be expanded to include anti‐hypertensive medication data to potentially explain the above findings.
Analysis of epigenetic mediators for the effect of Polyunsaturated fatty acids Omega6/3 ratio on cognitive function and progression to dementia
Authors: Andrade Victor 
Published: June 2023

AbstractBackgroundPrevious research reported the association between circulating Omega‐3 polyunsaturated fatty acids (PUFA) in blood and the risk of dementia and Alzheimer’s disease (AD). However, a large intervention study supplementing Omega‐3 reported that this supplementation has only a marginal effect on improvement of cognitive performance after the supplementation. Since PUFA metabolism shared the processing enzymes, we explored whether the relationship between two main families of PUFA, i.e., Omega‐3 and Omega‐6, might associate with cognitive performance. Hence, we observed that the ratio Omega‐6/Omega‐3 in blood is associated with cognitive decline and dementia. To follow up on this finding, we sought to explore whether modulation of immune response and inflammation may underlie these effects.MethodThree independent cohort were used for this study: i) the observational memory‐clinic‐based cohort DELCODE (n = 1036); ii) the primary care‐derived cohort AgeCoDe (n = 1252); iii) the Multidomain Alzheimer Preventive Trial (MAPT study) cohort (n = 1679). Omega‐3 and PUFA levels were quantified specifically in plasma from each cohort. COX regressions and linear mixed models were applied to evaluate PUFA ratio effect on cognitive performance and progression to dementia. Genomic and epigenomic modulators for the observed effects were further explored using the previously published tool (MetaMeth). Results were confirmed using our pipeline for epigenome‐wide association study (EWAS).ResultOmega‐6/Omega‐3 ratio is associated with cognitive performance and risk of progressing to AD in DELCODE and AgeCoDe. In MAPT, the improvement of this ratio is associated with improvement on cognitive performance. Moreover, levels of Omega‐3 in blood modulate methylation of genes coding for key enzymes of PUFA metabolism. Our data showed that the biological effect for some genetic susceptibility signals for AD is mediated by changes in DNA methylation, including immune‐related genes like MS4A and TREM2.ConclusionOur data suggests that balance between PUFA is relevant on cognitive decline and dementia. In addition, the genetic effect of risk variants located at the AD risk loci containing the MS4A gene cluster and TREM2 are mediated by changes in methylation. To provide a connection between PUFA and neuroinflammation in the context of AD, we are currently exploring the effect of PUFA levels on DNA methylation at MS4A and TREM2 loci.
A study protocol on teaching english to people with mild cognitive impairment with the use of songs
Authors: Makri Marina , Christakidou Alexandra , Tsolaki Magda 
Published: June 2023

AbstractBackgroundPeople with Mild Cognitive Impairment (MCI) need to improve their cognitive functions in order to avoid the deterioration of their condition. Cognitive abilities can be improved by learning a foreign language. Due to the cognitive deficits of MCI people, conventional methods that teaching English cannot have significant results. The use of songs in teaching English is proved to be a promising method for more effective acquisition of the language while also improving cognitive functions and symptoms of depression and anxiety.MethodThis learning method had been designed by combining elements from four methodologies in language learning “Communicative Language Teaching”, “Natural Approach”, “(De) suggestopedia” and “Neurolinguistic Programming (NLP)”. The intervention of this study involves a randomized controlled trial design with two arms (an intervention arm and a control group) over a nine‐month period and will be provided twice a week. Participants will be people with MCI aged 60‐85 years, of both genders. A sample size of 90 participants is targeted based on expected neuropsychological test performance, and drop‐out rates. Interventions will be provided by trained staff with a control group not receiving any intervention but continuing life as usual. Assessments will be done at baseline, and nine months, and include neuropsychological tests to measure for changes in cognition. Secondary outcome measures will include mood changes in anxiety, depression and quality of life. All efficacy statistical analysis will be carried out on an intention to treat basis. Primary and secondary outcomes will be modeled using the linear mixed model for repeated measurements and further analysis will be undertaken.ResultThis study protocol is implementing by Greek Association of ALzheimer Disease and Related Disorders and the final results will be announced soon.ConclusionThis will be the first study to implement and assess this intervention in a randomized controlled trial. We expect that this study protocol could prevent cognitive decline, decrease symptoms of depression and anxiety and significantly impact quality of life and the wellbeing of people with MCI.
Ethics and the predictive turn in Alzheimer’s
Authors: Stümpel Johanne , Snijders Katharina Elisabeth , Boada Mercè , Frisoni Giovanni B , Marquié Marta , Ribaldi Federica , Rostamzadeh Ayda , Schmitz‐Luhn Björn , Schwegler Carolin , Jessen Frank , Woopen Christiane 
Published: June 2023

AbstractBackgroundRising knowledge about fundamental molecular mechanisms of diseases, the possibility to digitally collect a wealth of lifestyle data, and increasing diagnostic capabilities in early risk prediction make it as easy as never before to calculate a personalized risk for future diseases. Knowing and influencing that risk becomes a matter of personal choice and responsibility. Consequences both on the individual and on the societal level result from this predictive turn in medicine. By means of the evolving accessibility and reliability of biomarker‐based diagnostics and risk prediction in Alzheimer’s disease (AD), we address the ethical perspective on this highly relevant topic.MethodIn the ethical part of the PreTAD project, we pursue a Mixed‐Methods approach and will (1) conduct a survey with 150 individuals within the healthy population (50 per participating country; baseline + 6‐month follow‐up). Participants will be surveyed with quantitative standardized tests, newly developed questions, and by utilizing hypothetical scenarios of AD biomarker risk disclosure. Employing hypothetical scenarios serves to reveal the needs and attitudes of healthy individuals regarding early prediction of AD. We will (2) conduct 40 narrative interviews (baseline + 6‐month follow‐up) with healthy individuals, healthy individuals at risk (AD family history or APOE4 carriers), individuals diagnosed with subjective cognitive decline (SCD) (> 4 weeks), and individuals with recent (≤ 4 weeks) SCD diagnosis.ResultPredictive knowledge can be associated with different perspectives on the self, discrimination and (self‐)stigmatization. We therefore address self‐perception, self‐determination as well as identity and authenticity with regard to the attitudes of people sharing different prior experiences with AD. We want to learn about the relationship between identity, authenticity and attitudes toward a personalized risk profile for future disease. Additionally, we aim at highlighting the individual’s needs in the course of an AD risk prediction in different groups of individuals, providing a detailed analysis of this phenomenon in a trinational and interdisciplinary (clinical, ethical, legal and linguistic) perspective.ConclusionIn this presentation, we will outline the methodology of a multilevel ethical analysis on fundamental questions of the paradigm shift towards predictive medicine ‐ exemplified by AD.