bluuebunny/crossref_metadata_2025_split huggingface dataset:
EEG Alpha Rhythm Abnormalities During the Transition from Wakefulness to Light Sleep in Patients with Mild Cognitive Impairment Due to Neurodegenerative Diseases
Authors: Carpi Matteo , Salamone Enrico Michele , Jakhar Dharmendra , Lizio Roberta , Noce Giuseppe , Lopez Susanna , Güntekin Bahar , Yener Görsev , Taylor John‐Paul , Arnaldi Dario , Percio Claudio Del , Babiloni Claudio 
Published: January 2025

AbstractBackgroundVigilance and sleep disturbances in Alzheimer’s and related diseases, even at the stage of mild cognitive impairment (MCI), have been extensively documented, showing abnormal daytime naps and alterations in the sleep‐wake cycle. However, the EEG correlates of the transition from wakefulness to light sleep have not yet been compared between MCI patients due to Alzheimer’s vs. other neurodegenerative diseases. Therefore, it is unclear whether there are specific features of these correlates in Alzheimer’s disease (AD) patients. This issue was investigated in the present study for the first time.MethodData were analyzed from an international database (https://www.pdwaves.eu/) comprising neuropsychological tests, long resting‐state EEG recordings, cerebrospinal fluid biomarkers, and MRI. For this study, 18 ADMCI patients, 9 NOADMCI patients, and 11 age‐ and sex‐matched healthy (Nold) participants showing transitions from wakefulness to light sleep during the EEG recording were selected based on the evaluation of two researchers blinded to the diagnoses. EEG periods were classified into four classes according to Hori et al.’s criteria: eyes open, eyes closed, EEG flattening, and EEG ripples (the last two representing drowsiness/light sleep stages). Individual alpha frequency peak (IAF) was obtained and used to determine EEG delta, theta, and alpha (1, 2, and 3) bands. Regional EEG cortical sources (Frontal, Parietal, and Occipital) were estimated using eLORETA freeware and the ratio of the source current density for the eyes closed and ripples conditions (EC/R) was considered as the EEG correlate of sleep‐wake transitions.ResultParticipants’ characteristics are reported in Table 1. The ANOVA showed a 2‐way interaction between Group and Band (p<.001), unveiling reduced EC/R source activity in the alpha 2 (p‐values<.001) and alpha 3 (p‐values<.001) bands in the ADMCI and NOADMCI groups (Figure 1). No differences in EEG source activity were found between the ADMCI and NOADMCI groups (p>.05).ConclusionThe preliminary results of the present study showed widespread abnormalities in the cortical neurophysiological mechanisms oscillating at alpha frequencies in patients with Alzheimer’s and related diseases at the stage of MCI, but no differences between Alzheimer’s and non‐Alzheimer’s diseases. Future studies should cross‐validate these findings with larger clinical populations and test their relationship with night sleep disorders.
Associations between plasma biomarkers and brain amyloid and tau pathologies in a population‐based cohort without evidence of cognitive impairment
Authors: Dresse Menayit Tamrat , Ferreira Pamela C.L. , Bellaver Bruna , Zeng Xuemei , Sehrawat Anuradha , Chen Yijun , Povala Guilherme , Lafferty Tara K , Villemagne Victor L , Kamboh M. Ilyas , Cohen Ann D , Klunk William E , Pascoal Tharick A. , Ganguli Mary , Shaaban C. Elizabeth , Snitz Beth E. , Karikari Thomas K 
Published: January 2025

AbstractBackgroundPlasma biomarkers have been widely evaluated as surrogate markers for brain Alzheimer’s disease (AD) pathology. However, studies in diverse populations with lower socioeconomic status (SES) are limited. We evaluated associations between different plasma biomarkers and brain amyloid beta (Aβ) and tau positron emission tomography (PET) in a longitudinal cohort of cognitively normal participants from a medically‐ and economically‐underserved Rust Belt region of Western Pennsylvania, USA.MethodWe measured plasma Aβ42/40, p‐tau181, p‐tau231, p‐tau217, NfL, and GFAP at baseline (n=111) and in a subset (n=65) at two‐year follow‐up in the MYHAT‐NI cohort. Aβ PET and tau PET were assessed using [11C] PiB and [18F] AV‐1451, respectively, and level of functioning with Clinical Dementia Rating (CDR). We included only cognitively normal participants (CDR = 0).ResultThe baseline median age was 76.7 years; 60 (54.1%) were females, and 18 (16.2%) were APOE ε4 carriers. The follow‐up cohort had a median age of 77.7 years, with 12 (18.5%) APOE ε4 carriers and 33 females (50.8%). All plasma biomarkers showed stronger associations with Aβ PET standard uptake value ratio (SUVR) in the Aβ‐positive vs. negative participants. However, only the associations for plasma p‐tau217 (rho=0.74, P<0.001), p‐tau231 (rho=0.48, P=0.02) and Aβ42/40 (rho= ‐0.43, P=0.04) in the Aβ PET‐positive group were significant. Voxel‐wise association models of Aβ PET accounting for age, sex, and CDR showed the strongest associations in the following decreasing order for plasma p‐tau217>Aβ42/40>GFAP>p‐tau181. No significant correlation with tau PET SUVR was observed for the plasma biomarkers.ConclusionPlasma p‐tau217 showed the strongest association with neuroimaging measures of brain Aβ in this cognitively normal group of older adults with lower SES. These results suggest that plasma p‐tau217 might be important to screen for evidence of brain amyloidosis in cognitively normal individuals. Future work will investigate the effects of specific comorbidities and demographic factors on the outcomes and if these change over the course of the two‐year follow‐up period.
Plasma Biomarkers, Hippocampal Volume and Cognitive Effects of Oral ALZ‐801: The Phase 2 Biomarker Study and its Long‐Term Extension in APOE4 Carriers with Early Alzheimer’s Disease
Authors: Abushakra Susan , Hey John A. , Blennow Kaj , Hort Jakub , Prins Niels D. , Kesslak Patrick , Pak Winnie , Shen Larry , Zhu Xinyi , Li Caiyan , Albayrak Adem , Bracoud Luc , Suhy Joyce , Power Aidan , Tolar Martin 
Published: January 2025

AbstractBackgroundALZ‐801 (valiltramiprosate) is an oral inhibitor of amyloid oligomer formation in development as a disease‐modifying AD treatment, including a fully enrolled APOLLOE4 Phase 3 trial in 325 APOE4/4 homozygotes. A Phase 2 study is evaluating ALZ‐801 effects on plasma biomarkers, brain volumes and cognitive outcomes in APOE4 carriers. Plasma p‐tau181 reduction over 104 weeks is primary endpoint. A study extension includes active treatment over additional 104 weeks for a total of 208 weeks (4 years). Long term analyses include plasma p‐tau181, Aβ42/40, p‐tau217, GFAP and other emerging biomarkers. Hippocampal volume and cognition are additional outcomes.MethodThis active study enrolled 84 APOE4 carriers (MMSE ≥22; positive CSF+ biomarkers) who receive ALZ‐801 265 mg BID. CSF/plasma biomarkers were conducted at Dr. Blennow’s laboratory (Simoa, EuroImmun assays). MRIs analyzed by Clario at baseline, 52, 104, and in the long‐term extension (LTE); cognitive and biomarker tests are every 26 weeks. Biomarkers are analyzed on observed cases, hippocampal volume (HV) and cognitive tests are analyzed by MMRM with two‐sided p‐values; with Spearman’s correlations of biomarker‐clinical outcomes.ResultBaseline mean age was 69 years, MMSE 26, 51% females, and 70% MCI; and 83 subjects had any post‐treatment efficacy assessment. Total of 75 and 70 subjects completed 52 and 104 weeks. At 104 weeks, plasma p‐tau181 reduction was 31% (p=0.045), Aβ42 reduction was 4% (p=0.042). Hippocampal volume (HV) versus untreated matched subjects from ADNI showed ∼20% less atrophy (p<0.002). Immediate and delayed memory scores (Rey test) remained at baseline levels versus 21% decline in matched ADNI subjects (p<0.0001). Memory stabilization correlated with reduced HV atrophy (r= 0.44, p=0.0002). In the 66 ongoing LTE subjects, cognitive and HV ADNI comparisons and biomarker‐cognitive correlations at 130 weeks will be reported. Most common TEAE was mild nausea, with no ARIA‐E.ConclusionBiomarker positive APOE4 carriers showed significant plasma p‐tau181 and Aβ42 effects, with promising HV effects that correlated with cognitive benefit. Sustained long term benefits on these outcomes over 2.5 years could support disease modification with a continued favorable safety profile of ALZ‐801. Correlations of plasma biomarkers to long‐term clinical and imaging outcomes provides valuable insights into ALZ‐801 effects in AD.
Plasma GFAP use for population enrichment of clinical trials in preclinical Alzheimer’s disease
Authors: Bellaver Bruna , Povala Guilherme , Ferreira Pamela C.L. , Bauer‐Negrini Guilherme , Lussier Firoza Z , Leffa Douglas Teixeira , Ferrari‐Souza João Pedro , Rodrigues Matheus Scarpatto , Soares Carolina , Oliveira Markley Silva , Rahmouni Nesrine , Tissot Cécile , Therriault Joseph , Servaes Stijn , Stevenson Jenna , Benedet Andrea L. , Ashton Nicholas J. , Langhough Rebecca E. , Betthauser Tobey J. , Christian Bradley T. , Wilson Rachael E , Zetterberg Henrik , Blennow Kaj , Tudorascu Dana , Zimmer Eduardo R. , Karikari Thomas K , Rosa‐Neto Pedro , Johnson Sterling C. , Pascoal Tharick Ali 
Published: January 2025

AbstractBackgroundWe showed that plasma GFAP (a proxy of astrocyte reactivity) abnormality is key to unleashing Aβ effects on tau phosphorylation in preclinical AD. This suggests that selecting cognitively unimpaired(CU) individuals with both high Aβ and plasma GFAP could offer an early time window in the disease, but with an increased risk of developing tau pathology. Here, we tested the utility of plasma GFAP for population enrichment in clinical trials focusing on CU individuals.MethodWe assessed 195 CU individuals from TRIAD (n=84) and WRAP (n=111) cohorts with plasma GFAP and Aβ‐PET at baseline and Tau‐PET ([18F]MK6240) at baseline and follow‐up. The annual rate of progression in Tau‐PET was measured as follow‐up minus baseline uptakes divided by time between scans. Aβ positivity was determined as Centiloid>20. Astrocyte reactivity positivity(Ast+) was defined based on plasma GFAP of younger Aβ‐. Effect size was calculated as the mean change in Tau‐PET divided by the SD. Estimated sample size was calculated testing a hypothesized 25%drug effect on tau accumulation reduction in the medial temporal lobe (MTL) and temporal neocortex (Neo‐T) as secondary outcomes with 80% power at a 0.05 level.ResultsA significant annual rate of MTL tau‐PET accumulation was observed in both Aβ+/Ast‐ and Aβ+/Ast+ groups (Figure 1A), while Neo‐T Tau‐accumulated only in the Aβ+/Ast+ group (Figure 1B). The Aβ+/Ast+ group has a larger effect size on Neo‐T tau accumulation (0.97) compared to Aβ+/Ast‐ (0.33) and all individuals Aβ+ (0.61; Figure 2C). Plasma GFAP as an enrichment strategy reduced the sample size of clinical trials using changes in the Neo‐T as outcome in 60% (Figure 2D), with 59% reduction in clinical trial costs (Figure 3B). Plasma GFAP as an enrichment strategy for changes in MTL tau accumulation did not provide significant advantages over using Aβ only (Figure 2‐3). Larger effect sizes in Tau‐PET accumulation were observed in WRAP than TRIAD cohort.ConclusionThe use of Aβ+/Ast+ for population enrichment would reduce up to 59% clinical trial costs aiming to detect changes in Tau‐PET compared to using Aβ only. To conclude, clinical trials focusing on preclinical AD would benefit from enrolling individuals with both Aβ pathology and astrocyte reactivity to select individuals enhancing trial cost‐effectiveness.
The impact of obstructive sleep apnea on cognitive decline in adults with Down Syndrome – preliminary findings
Authors: Assunção Cecilio Ana Paula , Carvalho Claudia Lopes , Gonçalves Aline Souza , Hasan Rosa , Sennes Luiz Ubirajara , Forlenza Orestes Vicente 
Published: January 2025

AbstractBackgroundSleep‐related breathing disorders are commonly reported in the Down Syndrome (DS) population, but data on its prevalence and severity are scarce, especially for the adult population. The increase in life expectancy and premature aging in patients with DS reinforces the need for an assessment of sleep quality. This study evaluated sleep‐disordered breathing in adults with DS using sleep measures by polysomnography. The aim of this study is to define the association between the severity of obstructive sleep apnea (OSA) in adults with DS and the clinical diagnoses of stable cognition versus prodromal dementia and dementia. Furthermore, it was possible to correlate sleep respiratory variables in these groups.MethodAll participants underwent a sleep study Type 1 Polysomnography, analyzed according to the American Academy of Sleep Medicine (AASM). The diagnostic criteria for OSA and its severity were based on the description of the Diagnostic and Statistical Manual of Mental Disorders (DSM‐5). A multidisciplinary consensus including psychiatrists and geriatricians classified the participants into three diagnostic groups: stable cognition, prodromal demetia, and dementia. A neuropsychological assessment was carried out, according to the Cambridge Examination for Mental Disorders of Older People with Down’s Syndrome and Others with Intellectual Disabilities (CAMDEX‐DS). The Kruskal‐Wallis test was applied to evaluate our results.Result3 participants had dementia (mean AHI 17,80 events/h), 7 were classified as prodromal dementia (mean AHI 42,60 events/h) and 28 were in the stable cognition group (mean AHI 36,42 events/h). It was not possible to determine statistically significant evidence between the AHI and the diagnoses. The correlation between respiratory sleep variables demonstrated a strong association between AHI, AHI in NREM sleep and ODI values. Furthermore, the higher the AHI or ODI values, the lower the minimum oxyhemoglobin saturation. However, it was not possible to observe a correlation with the mean oxyhemoglobin saturation.ConclusionStudies show that OSA is the main sleep disorder in the DS population, demonstrating the importance of early diagnosis. In our analysis, it was not possible to define a correlation between OSA and clinical diagnoses, possibly because there are few non‐control cases. Being preliminary data, clinical and polysomnographic follow‐up will support our preliminary hypotheses.
Voxel‐wise Florzolotau (APN‐1607) Tau PET Covariance Patterns in Alzheimer’s Disease and Progressive Supranuclear Palsy
Authors: Blazhenets Ganna , Brumberg Joachim , Endo Hironobu , Hsu Jung‐Lung , Frings Lars , Schroeter Nils , Hellwig Sabine , Chang Chiung‐Chih , Higuchi Makoto , Meyer Philipp Tobias 
Published: January 2025

AbstractBackgroundFlorzolotau (APN‐1607) tau‐PET has shown distinct patterns of binding in patients with AD and 4‐repeat tauopathies. We aimed to establish disease‐specific tau covariance patterns in AD and PSP/CBS and validate them as user‐independent quantitative biomarkers for reference‐region‐free evaluation of tau‐PET in an independent clinical cohort.MethodWe analyzed Florzolotau PET data from four different cohorts. The derivation dataset included 30 Aβ‐ healthy controls (HC) and 30 patients each with Aβ+ AD and PSP with Richardson’s syndrome (PSP‐RS). The validation dataset included 44, 51, 6, 15, and 17 patients with AD, PSP/CBS, MSA, LBD, and FTD, respectively. First, we applied scaled sub‐profile modelling principal components analysis to the derivation dataset to define the AD‐ and PSP‐RS‐related covariance patterns. Second, the topographic profile rating algorithm was applied to each scan to calculate AD‐ and PSP‐RS‐related pattern scores.ResultThe AD‐ and PSP‐RS‐related patterns are described in Figures 1 and 2. In the derivation dataset, the AD‐ and PSP‐RS‐scores showed strong increases compared to HC (both p<0.001, AUC‐ROC=0.994 and 0.898, respectively). AD‐scores showed a significant negative association with age (r=‐0.66, p<0.001) and MMSE (r=‐0.64, p<0.001) in AD, while PSP‐RS‐scores correlated with the PSP rating scale (r=0.43, p=0.018) in PSP‐RS. In the validation dataset (Figure 3), AD‐scores were highest in AD (p<0.001 vs. all other, AUC‐ROC[AD vs. all other]=0.946) and were negatively associated with age and MMSE in AD (r=‐0.62, p<0.001 and r=‐0.49, p=0.002, respectively). PSP‐RS‐scores were highest in the PSP/CBS (p<0.001 vs. all other [at least p<0.05 vs. each group], AUC‐ROC[PSP/CBS vs. all other]=0.734), though also relatively increased in FTD and MSA. UPDRS‐III scores (off‐state) were available in 23 PSP/CBS patients and significantly associated with PSP‐RS‐scores (r=0.60, p=0.002).ConclusionModelling with principal components analysis allows for reference‐region‐free quantification of tau imaging data by constructing disease‐specific covariance patterns. When applied to Florzolotau, AD‐ and PSP‐RS‐related patterns showed high discrimination power in both the derivation and the clinically heterogeneous validation cohorts. PSP‐RS‐related pattern expression in FTD and MSA may be related to PSP pathology and known striatal off‐target binding, respectively. Strong association with respective disease severity scores further advocates for use of AD‐ and PSP‐RS‐related patterns as potential quantitative biomarkers of tau pathology.
Analysis of medical reports of guardianship proceedings of people with dementia a sample from Belo Horizonte, Minas Gerais, Brazil
Authors: Real Mariana S L C , Barbosa Izabela G , Carvalho Carla V , Romano‐Silva Marco Aurelio , Bicalho Maria Aparecida Camargos , de Moraes Edgar Nunes , Viana Bernardo M 
Published: January 2025

AbstractBackgroundDementia syndromes are chronic health conditions that lead to significant cognitive decline and functional impairment, including acts of civil life. Concerning the latter, a guardianship petition maybe needed when patients or family are at risk.MethodsRetrospective cross‐sectional study of documentary research on 72 electronical guardianship proceedings involving adults with dementia. The study sample comprises reports from six out of twelve Family Courts within the Court of Justice of Minas Gerais, with twelve reports collected from each selected court. The results were analyzed using descriptive statistics, involving mean, standard deviation, median, minimum and maximum. For statistical analyzes the software SPSS Version 20.0 for Microsoft Windows was used. When comparing continuous variables, the non‐parametric Mann‐Whitney test and the Kruskal‐Wallis test were used. The study was approved by the ethics committee by Federal University of Minas Gerais.ResultsThe sample had median age of 82.5 years with high level of education by Brazilian standards with a median of 8 years, and mainly composed by elderly women (68,1%) and widows (41,7%). Notably, 76.4% of guardianship proceedings were petitioned by sons, with predominance of daughters appointed as guardians. Geriatrics and Family Physicians (54.1%) stood out as the specialties that issued the majority of the initial medical reports. Alzheimer’s Disease Dementia (ADD) (61.1%) was the most prevalent diagnosis with a predominance of women (67.3%) and older people with a mean of 84.9 years (SD 8,6). In second place, vascular dementia (VD) (15.3%) followed by unspecified etiology of dementia (12.5%). In the non‐Alzheimer dementia group, the median age was 79.5 years (p = 0.016). In relation to education, there was no statistically significant difference between the group of patients with Alzheimer’s disease and non‐Alzheimer’s disease (p = 0.547).ConclusionsThe present work identified that the majority of medical reports were related to ADD and VD and were made by geriatricians and family physicians. This points to the importance of these specialties regarding the protection and promotion of rights of people with these dementias.
What does engagement mean to you? Exploring the experiences of the League older adult advisory group for social robot technology research
Authors: Martin Susanna E. , Zhang Cindy C. , Robillard Julie M. 
Published: January 2025

AbstractBackgroundCo‐creation methods are increasingly being used in the research and development of technologies that support older adults living with dementia and their care partners to live well. Use of collaborative methods to engage with the dementia community helps to ensure that research processes and end solutions are sensitively designed, reflective of needs and values, and responsive to priorities. Engagement also has proximal benefits for older adults: Being involved in purposeful activity has been shown to positively impact health and wellbeing outcomes. However, despite these benefits, the value of co‐creation methods in dementia research remains under‐investigated from the perspectives of older adults themselves. Here we seek to address this gap in the context of social robot research exploring the impact and value that older adults derive from engaging in dementia technology research.MethodWe carry out semi‐structed interviews with older adults who are members of a lived experience advisory group, known as the League. League members provide ongoing consultation on research activities carried out at the Neuroscience, Engagement and Smart Tech Lab.League members also complete surveys, including a subset of questions from the Patient Engagement In Research (PEIR) Framework, to capture quantitative responses on key components of engagement. We adopt a social‐technical perspective to generate a holistic appreciation for the impacts of engagement.ResultIndividual perspectives captured in this mixed methods study reveal that older adults have unique experiences with technology, and technology research, that modulate their level of engagement and the meanings that they derive from participation. Results demonstrate the impact that engagement has on biopsychosocial factors, roles, and identity, and underscore the ethical imperative of human‐centered research methods.ConclusionInsights will support the evidence base for person‐centred, co‐creation methodologies in dementia research, and showcase the potential for meaningful engagement to support the health and wellbeing of older adult collaborators.