bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trajectory of cognitive performance among virologically suppressed aging people living with HIV
Authors: Hiransuthikul Akarin , Apornpong Tanakorn , Gatechompol Sivaporn , Lwin Hay Mar Su , Han Win Min , Kerr Stephen , Ubolyam Sasiwimol , Ruxrungtham Kiat , Avihingsanon Anchale ,   HIV‐NAT 006 and 207 study team
Published: December 2023

AbstractBackgroundDespite the success of combination antiretroviral therapy (cART), cognitive impairment remains a problem for people living with HIV (PLWH), including those who are virologically suppressed. The presentation and course of cognitive impairment have changed significantly since the introduction of cART. We aimed to determine the trajectory of cognitive performance in a cohort of virologically suppressed aging PLWH.MethodThai PLWH aged ≥50 years followed in the HIV‐NAT 006 cohort were enrolled during 2015‐2017 to assess cognitive performance using the Thai‐validated Montreal Cognitive Assessment (MoCA), a cutoff of ≥25 as normal. The follow‐up MoCA was consecutively performed since 2021. Participants who had plasma HIV RNA of ≤50 copies/mL and completed the follow‐up MoCA were included in the analysis. Changes in the MoCA scores were calculated between the two visits.ResultAmong 181 eligible participants (69 [38.1%] female; mean [SD] age, 57.0 [5.7] years; 46 [25.4%] had education ≤6 years; mean duration of HIV infection, 18.0 [4.2] years), 104 (57.5%) had cognitive impairment at enrollment. There were statistically significantly higher proportion of female sex (45.2% vs 28.6%, p = 0.023) and participants who had education >6 years (85.6% vs 59.4%, p<0.001) among cognitively impaired (CI) than cognitively unimpaired (CU) participants. After mean 5.6 (0.4) years of follow‐up period, the mean difference of the MoCA score was ‐0.72 (95%CI ‐1.29 to ‐0.15, p = 0.01, d = 0.19) and there were statistically significant differences in the MoCA score changes between groups categorized by baseline cognitive performance (mean difference 3.25, 95%CI 2.09 to 4.41, p<0.001, after adjusting for sex assigned at birth, age, education levels, smoking status, depression, hypertension, and diabetes mellitus).The CU group showed a statistically significant decrease in the MoCA score (mean difference ‐2.58, 95%CI ‐3.26 to ‐1.90, p<0.001, d = 0.86), and 43/77 (55.8%) of CU participants developed cognitive impairment at follow‐up, while the CI group had comparable MoCA scores between the two visits (mean difference 0.65, p = 0.09) (figure).ConclusionCU virologically suppressed PLWH demonstrated a statistically significant reduction in cognitive performance compared to their CI counterparts over time. Further studies on the underlying pathological mechanisms and implementation of cognitive care services among virologically suppressed PLWH are warranted.
Deciphering the Roles of the Key Oligomerization Domains in Amyloid‐β to Design Amyloid Aggregation Inhibitors
Authors: Im Dongjoon , Kim Hugh Inkon 
Published: December 2023

AbstractBackgroundProtein folding issues are significant difficulties since they are linked to various diseases, including dementia. Fibrillar amyloid aggregates composed of misfolded proteins are pathological features of several neurodegenerative diseases. Numerous attempts have been made to treat neurodegenerative diseases by focusing on amyloid aggregates of pathologically disordered proteins. The first Alzheimer’s disease (AD) curative drug was introduced as a consequence of attempts to combat the most frequent kind of dementia. Even though antibody strategies reduce clinical deterioration in mild cognitive disease, alternate techniques must be developed over a single approach (i.e., antibody treatment). Recent studies have attempted to rationally design candidate drugs to improve existing therapeutic approaches or suppress the fibrillar amyloid aggregation process altogether. Prompted by previous findings, we rationally designed amyloid‐β (1‐42) point mutants to inhibit amyloid aggregation.MethodWe investigated the structural ensembles of the monomers using small‐angle X‐ray scattering. In addition, we performed hydrogen‐deuterium exchange mass spectrometry (MS) and ion mobility MS to elucidate the molecular principles governing Aβ42‐inhibitor interactions. We also used microsecond‐scale molecular dynamics simulations to investigate the structures and interactions, and combined them with electron transfer dissociation MS analysis to tackle challenges in identifying the multiple binding sites of intrinsically disordered protein complexes.ResultSpecifically designed mutations disrupt not only amyloid aggregation but reduce its cytotoxicity. Furthermore, we proposed minimal mutation sites to control amyloid‐β (1‐42) self‐assembly behavior. We are now determining the key domains of amyloid‐β (1‐42) that facilitate its self‐assembly to design aggregation inhibitors as potential therapeutic agents. We identified three critical hydrophobic domains (17LVF19, 32IGL34, and 41IA42) on amyloid‐β (1‐42) and investigated their role in the protein’s self‐assembly process. Our results suggest that interchain interactions in the central hydrophobic region (17LVF19) of amyloid‐β (1‐42) are essential for fibrillar aggregation and that their interaction with other domains is related to the accessibility of the central hydrophobic region for initiating the pathological cascade. Our findings shed light on the mechanisms underlying amyloid‐β (1‐42) self‐assembly and reveal key structural domains that aid in this process.ConclusionOur findings can be used to improve the rational design of amyloid‐β (1‐42) aggregation inhibitors in the future.
Ubiquitin‐Proteasome System in Different Staging of Dominantly Inherited Alzheimer’s Disease
Authors: Liu Haiyan , Li Yan , Hassenstab Jason J. , Gordon Brian A. , Benzinger Tammie L.S. , Timsina Jigyasha , Wang Lihua , Sung Yun Ju , Bui Quoc , Karch Celeste M. , Renton Alan E. , Cruchaga Carlos , Daniels Alisha , Morris John C , Xiong Chengjie , Perrin Richard J. , Bateman Randall J. , Llibre‐Guerra Jorge J , McDade Eric 
Published: December 2023

AbstractBackgroundBoth sporadic and dominantly inherited Alzheimer’s disease (DIAD) present with similar pathobiology and symptoms. A loss of proteostasis in AD has been identified with recent studies highlighting the role of ubiquitin‐dependent mechanisms in brain homeostasis and neurodegenerative diseases. The Ubiquitin Proteasome System (UPS) is responsible for the degradation of misfolded or aggregated proteins via an ATP‐dependent proteolytic mechanism. This process involves a cascade of ubiquitin transfer steps from E1 to E2 to E3 ligase. However, the role of the UPS in AD progression and symptom onset remains unknown.MethodIn this cross‐sectional study we aimed to examine changes in cerebral spinal fluid (CSF) levels of UPS proteins in individuals with DIAD enrolled in the Dominantly Inherited Alzheimer Network. Sample size included 176 asymptomatic mutation carriers (MC) (Clinical Dementia Rating® [CDR®] = 0), 103 symptomatic mutation carriers [CDR®>0] and 172 non‐carriers (NC). CSF levels of UPS proteins were measured using the SOMAscan high‐throughput proteomics assay. AD biomarkers (Aβ42, Aβ40, Tau, phospho‐Tau181, phospho‐Tau205, phospho‐Tu217, and Aβ‐ PET), imaging measures of neurodegeneration (MRI, FDG PET) and clinical data (estimated years from symptom onset (EYO), CDR® score, age, sex, ApoE status) were assessed.ResultThe ubiquitin‐fold modifier‐conjugating enzyme1, ubiquitin‐conjugating enzyme E2 K, E2 N, E3 ubiquitin‐protein ligase SMURF1, and small ubiquitin‐related protein modifier 2 and 3 levels were increased in MCs up to 10‐5 years before EYO, Figure 1, with highest levels found in symptomatic MCs. E3 ubiquitin‐protein ligase SMURF1 levels began increasing up to 10‐15 years before symptoms onset. Proteasome subunit beta type‐3 (PSMB3), 4 (PSMB4) and 9 (PSMB9) showed a similar pattern as ubiquitin ligase which significantly increased in symptomatic mutation carrier group. All the above ubiquitin enzymes positively correlated with Aβ‐ PET, CSF phospho‐Tau181, phospho‐Tau205, phospho‐Tau217 and negatively correlated with FDG PET, Figure 2.ConclusionOur study revealed E1, E2, E3 ligase, ubiquitin‐related modifiers (SUMOs), and proteasome components were involved in DIAD pathophysiology and correlated with AD biomarkers with some increasing over 10 years before symptom onset. Further investigation of the role of UPS will be needed to explore the molecular mechanism in the progression of DIAD.
Accelerated Ovarian Failure (AOF) is an Effective Transitional Menopausal Model for the Study of Alzheimer’s Disease
Authors: Mohammad Ahmad , Finch Michael , Pyle W Glen , Rouhana Sarah , Barry Ciara , MacPherson Rebecca EK 
Published: December 2023

AbstractBackgroundBiological females account for 70% of Alzheimer’s disease (AD) cases. It’s hypothesized that the estrogen depletion females experience during menopause is a factor in the pathogenesis of AD1. The gold standard rodent model of ovariectomy doesn’t allow for the examination of the gradual loss of estrogen that occurs in humans through perimenopause to menopause2. Administration of 4‐vinylcyclohexene diepoxide (VCD) has emerged as a rodent model of transitional menopause. The goal of this study was to determine how AD and neuronal markers were impacted by the gradual depletion of estrogen in a VCD model of transitional menopause.MethodMature CD1 female mice were injected with VCD (160 mg/kg/d IP for 15 days) to cause gradual ovarian failure over 120 days. A control group was also injected with a vehicle. Sample was collected at four timepoints, two representative of early and late perimenopause (60 and 120 days post injection) while the other two represented early and late menopause (137 and 176 days post injection). At each timepoint, novel object recognition testing (NORT) was performed to assess changes in behavior and memory2. At euthanasia, the prefrontal cortex and hippocampus were collected for protein analysis.ResultThe NORT demonstrated that the VCD groups at all timepoints had lowered activate memory recall. The prefrontal cortex western blotting results demonstrated that the VCD mice had lower NeuN content across all timepoints. NeuN is a marker of mature neurons which when lowered can have detrimental consequences on memory. SNAP25, a pre‐synaptic protein involved in neuronal synaptic communication, was also lower in the prefrontal cortex of VCD mice across all timepoints.ConclusionThe VCD model had impacts on active memory recall which was accompanied by reductions in neuronal and synaptic markers. This indicates that the loss of estrogen through transitional menopause results in early changes in neuronal markers and memory.1. Iqbal, J. & Zaidi, M. Understanding Estrogen Action during Menopause. Endocrinology 150, 3443‐3445 (2009).2. Mohammad, A., Finch, M. S., Sweezey‐Munroe, J. & MacPherson, R. E. K. Voluntary wheel running alters markers of amyloid‐beta precursor protein processing in an ovarian hormone depleted model. Front. Endocrinol. 13, 1069404 (2022).
Relationship between default mode network and posterior resting‐state electroencephalographic delta rhythms in cognitively unimpaired seniors and patients with dementia due to Alzheimer’s
Authors: Babiloni Claudio 
Published: December 2023

AbstractBackgroundAlzheimer’s disease dementia (ADD) is the most common neurodegenerative dementing disorder explaining about 60‐70% of 50 million patients worldwide (www.who.int). Some previous studies in ADD patients showed significant neurodegenerative processes as revealed by reduced gray matter volume in the cerebral cortex, including the default mode network (DMN), dorsal attention (DAN), and sensorimotor (SMN) cortical networks from structural magnetic resonance imaging (sMRI). Other studies in these patients reported the “slowing” of the resting‐state eyes‐closed electroencephalographic (rsEEG) rhythms reflecting vigilance dysfunctions. Here we tested the hypothesis of a significant relationship between these neurodegenerative and neurophysiological readouts, thus suggesting the sensitivity of rsEEG activity to intrinsic AD processes.MethodClinical, sMRI, and rsEEG rhythms in demographic‐ and age‐matched ADD (N = 45) and healthy cognitively unimpaired (Nold, N = 40) persons were available from an international archive (www.pdwaves.eu). Individual alpha frequency peak was used to determine the alpha frequency band on a personal basis. Fixed beta bands were considered. The eLORETA freeware estimated rsEEG sources in posterior (i.e., central, parietal, and occipital) cortical regions of interest. Freeware platforms served to estimate the normalized gray matter volume in the DMN, DAN, and SMN cortical networks from sMRI.ResultThe results (Fig. 1) showed: (1) lower DMN, DAN, and SMN volumes (maximum effects in the DMN), higher posterior rsEEG delta‐theta source activities, and lower rsEEG alpha source activities in the ADD than in the Nold group; (2) substantial inverse correlation between the DMN volume and the posterior rsEEG delta‐theta source activities in the ADD and Nold participants; and (3) a mediating effect of the posterior rsEEG delta‐theta source activities in the correlation between the DMN volume and the global cognitive status across all participants.ConclusionThese results suggest a prominent relationship between DMN atrophy and the posterior rsEEG delta‐theta rhythms across physiological and AD‐related aging. As such, they support the enrichment of the ATN model for an extension to “Physiology” (P) = A‐T‐P‐N, as the physiology of the oscillatory activity within large inter‐connected neuronal populations due to disruptive effects of AD‐related neuropathology can be additionally informative.
Correlation of cognitive function and kinematic movement during self‐feeding activity
Authors: Lee Joo‐Hyun 
Published: December 2023

AbstractBackgroundSelf‐feeding is the important activity that is most closely related to daily living using motor and cognitive abilities. Especially, movement of self‐feeding includes picking up the spoon and executing the sequence of movement correctly, so it can be related to cognitive aspects. The purpose of this study is to investigate correlation with the kinematic movement during self‐feeding and cognitive function using AI software programMethodThe subjects participated in 4 normal person. In this study, the ‘simulated feeding’ task in Jebsen Taylor Hand Function test was selected. ‘Simulated Feeding’ is a task of transferring 5 beans to cup with a spoon. During task performance, a laptop and a webcam were used to record a video image, and trajectory and time value were recorded from 2D web‐cam image. Cognitive assessment tool used Trail Making Test (TMT). The spearman correlation analysis was conducted to evaluate the correlation with factors of movement and cognition during self‐feeding.ResultIt is possible to determine how far or short the hand moved depending on the length of the trajectory. The average time value shows the subject spent more time to put the beans in the spoon than to put the beans in the cup. Also, movement of self feeding were positively related to cognitive aspects..ConclusionWe believe that quantitative assessment of movement is related to cognitive function during self‐feeding. Through this, the state of cognitive function can be indirectly confirmed. Future study will need to apply movement analysis to evaluate the cognitive decline of the elderly.
Conversational Artificial Intelligence for People Living with Dementia and their Care Partners: A Scoping Review
Authors: Gholizadeh Shadi , Freeman Amy K. , Botticelli Mark P. 
Published: December 2023

AbstractBackgroundThe inadequacy of the dementia care workforce in meeting the needs of a growing population of people living with dementia (PLwD) is a global public health challenge. There is a burgeoning interest in exploring the role of artificial intelligence‐enabled technologies, such as chatbots, neural network models, and other programs designed to intelligently simulate human conversations, in the dementia care landscape. The aim of this scoping review was to examine the themes and gaps associated with the use of these technologies in the dementia care space.MethodThree databases (PubMed, PsychINFO, and CINAHL) were searched for English‐language, peer‐reviewed articles using keywords relating to chatbots, virtual assistants, generative pre‐trained transformer technology (GPT‐3), and dementia. The search returned 26 articles after removal of duplicates with 13 selected for inclusion into the review.ResultTwo user groups were identified, PLwD and their family care partners. Chatbots, embodied conversational agents, and intelligent virtual agents were the identified technologies. The core uses of the technology centered around 1) diagnosis and monitoring of cognitive symptoms; 2) social connection and cognitive simulation; 3) memory aids and prompts for task completion, and 4) education, training, and social support for care partners. Five key themes emerged, including 1) the need for expanded studies that go beyond superficial and simple dialogues to more complex and realistic interactions; 2) the importance of a person‐centered approach that uses knowledge about the person to guide the technology; 3) small sample sizes and weak quality across studies; 4) the need for standardized criteria to evaluate the quality of human/technology interaction; and 5) the importance of co‐creation of technology with insights from PLwD and their care partners.ConclusionWith the growing capability to generate human‐like text for powering chatbots, conversational artificial intelligence has the potential to play an important role in the dementia care space, however the literature remains in its nascent stages. There is a need for well‐designed studies, utilizing multidisciplinary and participatory approaches, exploring the impacts of incorporating these technologies into the daily lives of PLwD and their care partners.
Intergenerational Social Mobility, Brain Structure, and Cognitive Trajectory: Findings from the Whitehall II Study
Authors: Liu Yingxu , Liu Yinghao , Cui Yuehua , Thyreau Benjamin , Zhang Ye , Taki Yasuyuki , Chen Honglei ,   Dementias Platform UK (DPUK) Data Portal
Published: December 2023

AbstractBackgroundPrevious studies on the effects of intergenerational social mobility on cognitive outcomes were not consistent, additionally, underlining brain anatomical variation is unclear. In the present study, we aim to examine the associations of social mobility with brain structure and cognitive trajectories in older adults.MethodsThe study included 771 participants, ages 69.8 ±5.2 years, of the Whitehall II ‐ MRI substudy (2012‐2016) with data on their father’s occupation, their own occupation in mid‐life, lifestyle (smoking, drinking, physical activity, social activity, sleep disturbances, auditory difficulty, depression, obesity, hypertension), neuroimaging (T1 structural MRI) and cognitive abilities (global cognition, crystallized cognitive ability, and fluid intelligence). Social mobility was classified into stable high social class, stable low social class, upward mobility and downward mobility group based on occupational shifts from father. We used the ANCOVA tests to assess the association of social mobility with gray matter volume (GMV) and cortical thickness (CT) in various brain regions, and the growth curve modeling (GCM) to evaluate its relations to cognition over 20 years, adjusting for social lifestyle covariates and associated GMV/CT regions identified above.ResultsSocial mobility was significantly related to 48 out of the 136 regions of GMV across the frontal lobe, limbic lobe, and temporal lobe; and to 4 out of the 68 regions of CT at the whole‐brain level. Stable high social class preserved the largest GMV and CT value; pair‐wise results suggest upward mobility preserved a larger GMV value than the downward mobility group (average diff. in cm3: 0.121, P<0.05); and similarly a larger CT value (average diff. in cm:0.029, P = 0.051). In GCMs, stable high social class (ref. downward mobility) had a higher entry score of fluid intelligence (b = 2.617, P<0.05), all other comparisons including the entry score and decline rate of cognitive abilities were non‐significant.ConclusionsOur results suggest a lack of direct association between social mobility and trajectories of global cognition and crystallized cognitive ability; instead, an indirect effect through preserving the value of brain GMV and CT may occur. Additionally, an adverse causal relationship between social mobility and fluid intelligence might happen.
Interventions to Improve Bathing Experience for People Living with Dementia: A Scoping Review of Randomized Controlled Trials
Authors: Gholizadeh Shadi ,   TheKey Research Group
Published: December 2023

AbstractBackgroundBathing has been identified as the most challenging activity of daily living and one that is a frequent source of conflict among persons living with dementia (PLwD) and their care partners. Research has shown a number of factors related to bathing challenges, including pain; discomfort due to a mismatch between preferences and approach; and anxiety or fear related to anosognosia,memory loss, or cognitive decline. There is a need for nonpharmacological, behavioral, evidence‐based approaches to help support an improved bathing experience for PLwD. Randomized controlled trials (RCTs) are the study design that enable researchers to most confidently determine the impact of an intervention on observed outcomes. The purpose of the present review was to determine the breadth of RCT evidence exploring interventions specifically developed to improve the bathing experience of PLwD and to report on any noted challenges with the feasibility of conducting RCTs in this area of inquiry.MethodTwo databases (PubMed and PsychINFO) were searched from inception through September 3, 2022 for English‐language articles using keywords relating to bathing/showering and dementia. The search returned 578 articles after removal of duplicates with only three meeting criteria for inclusion into the review.ResultThemes of successful interventions included a person‐centered approach that incorporated real‐time observations and flexibility in tailoring the intervention to the needs of the specific person, increasing self‐efficacy of the care partner, consistency in coaching and practicing of skills, and the incorporation of music. Although a number of challenges were identified with the feasibility of conducting an intervention overall with this aim and population (e.g., scheduling challenges), challenges specific to the RCT design were not identified.ConclusionThere is a dearth of high‐quality, RCT evidence exploring interventions to support in the bathing support of PwD. Because the Cochrane Handbook discourages inclusion of evidence from non‐randomized trials in reviews when it is feasible to conduct trials, it is recommended that future research in this area consider an RCT design. There is promising evidence that family and professional care partners alike can benefit from education and training specifically designed to improve the bathing experience.