bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of hs‐CRP concentration on brain structure alterations and cognitive trajectory in Alzheimer’s disease
Authors: Zhang Ye 
Published: December 2023

AbstractBackgroundThis study investigated hs‐CRP concentration, brain structural alterations, and cognitive function in the context of AD (subjective cognitive decline [SCD], mild cognitive impairment [MCI], and AD).MethodWe retrospectively included 313 patients (mean age = 76.40 years; 59 with SCD, 101 with MCI, and 153 with AD) for a cross‐sectional analysis and 91 patients (mean age = 75.83 years; 12 with SCD, 43 with MCI, 36 with AD) in the longitudinal analysis. Multivariable linear regression analysis was conducted to investigate the relationship between hs‐CRP concentration, brain structural alterations, and cognitive function.ResultIn patients with SCD, hs‐CRP was inversely associated with gray matter volumes (GMVs) in the left supramarginal gyrus (pFDR = 0.044, 𝛽 = ‐0.22), and positively associated with GMVs in left lateral occipital gyrus (pFDR = 0.009, 𝛽 = 0.34) and left rostral middle frontal gyrus (pFDR = 0.038, 𝛽 = 0.29). In patients with AD, hs‐CRP was positively associated with GMVs in the left fusiform gyrus (pFDR = 0.017, 𝛽 = 0.22) and left inferior temporal gyrus (pFDR = 0.043, 𝛽 = 0.17). According to the longitudinal analysis, the interaction of diagnosis and hs‐CRP was associated with annual cognitive changes. Among these patients with AD, lower baseline hs‐CRP was correlated with greater future cognitive decline (r = ‐0.41, p = 0.0127).ConclusionOur study suggest that hs‐CRP may differentially affect the neuropathology of different stages of AD. For patients diagnosed with AD, elevated CRP level may be protective on brain structure alterations and future cognitive changes.
Latent Profile Analysis of Healthy Lifestyle Behaviors and its’ Association with Cognitive Decline in Older Adults
Authors: Halloway Shannon , Wagner Maude , Tangney Christy C , Lange‐Maia Brittney S , Bennett David A. A , Arvanitakis Zoe , Schoeny Michael E 
Published: December 2023

AbstractBackgroundLifestyle health behaviors, such as physical activity, cognitive activity, healthy diet, and social engagement, can improve cognition in older adults. We aim to identify profiles of late‐life lifestyle health behaviors related to subsequent maintenance of cognition and explore sociodemographics and health characteristics as effect modifiers.MethodAnalyses were conducted using data from 715 older adult participants from the Rush Memory and Aging Project who were dementia‐free at the first concurrent assessment of self‐reported lifestyle health behaviors (physical activity, cognitive activity, dietary habits, and social engagement) and with ³2 annual cognitive tests to assess changes in cognition. Neuropsychological test scores were grouped to form summary measures of global cognition, and five domains (episodic memory, semantic memory, working memory, perceptual speed, visuospatial memory). First, each participant was assigned to a specific group based on the initial levels of lifestyle behaviors using a latent profile analysis. Then, we assessed change in cognition among groups using linear mixed‐effects models adjusted for sex, education, and age at baseline. In additional models, we examined potential effect modifiers, including motor function, vascular risk factors (hypertension, diabetes, smoking), and vascular diseases (stroke, cardiac disease, congestive heart failure, claudication).ResultThree groups were identified: high engagement in behaviors (n = 183), moderate engagement (n = 441), and low engagement (n = 91). Participants in the high group were more likely to be women, younger, and with higher educational level, compared to the low group. Compared to the high group, the low group had a faster annual rate of decline in global cognition (mean difference [MD] = ‐0.06 [‐0.08;‐0.03], p<.0001) after full adjustment. In addition, compared to the high group, the low group showed a faster rate of decline in episodic memory, semantic memory, and perceptual speed, while the moderate group had a faster rate of decline for episodic memory only. There were no significant effects modifiers by any sociodemographic, motor function, or vascular health factor.ConclusionClassification in the moderate or high engagement group was related to better maintenance of cognition over time. Future research should examine multidomain intervention strategies that promote adoption of higher engagement in health behaviors targeting at least moderate levels.
Myeloid Differentiation Factor 2 Inhibition Protects Against Doxorubicin‐induced Microglial Activation and Senescence
Authors: Oo Thura Tun , Liang Guang , Chattipakorn Nipon , Chattipakorn Siriporn C 
Published: December 2023

AbstractBackgroundDoxorubicin, an anti‐tumor drug, generates neuroinflammation that leads to microglial senescence and chemo‐brain (1, 2). Toll‐like receptor 4 (TLR4) signaling pathway is mainly expressed in microglia and it plays a key role in developing doxorubicin‐induced neuroinflammation, microglial activation and chemo‐brain (3). Myeloid differentiation factor 2 (MD‐2) is known as an essential protein in activation of TLR4 signaling pathway (1). However, the effect of blocking TLR4 signaling via targeting MD‐2 on doxorubicin‐induced microglial activation and senescence has never been investigated.MethodThe human microglial clone 3 cell line (HMC3) was treated with three different doses of MD‐2 inhibitor (L6H21: 5μM, 10μM, 20μM) for 30 minutes, then with doxorubicin hydrochloride (DOX) (50nM) for 24 hours. After 24 hours treatment with L6H21 and DOX, the microglial cells were assessed for the TLR4 signaling, microglial activation, cell death and cellular senescence pathways.ResultDOX treatment activated TLR4 signaling pathway as well as microglia, as evidenced by significantly increased protein expressions of TLR4, MD‐2, tumor necrosis factor alpha and ionized calcium‐binding adapter molecule 1. In addition, DOX treatment induced microglial cell death and senescence, as shown by significantly increased protein expressions of Bcl‐2 associated X‐protein to B‐cell lymphoma 2 ratio and p16Ink4a. Treatment with L6H21 (5μM) attenuated not only TLR4 signaling along with microglial activation, but also apoptosis and cellular senescence in DOX‐treated microglia. L6H21 (10μM and 20μM) protected against TLR4 signaling along with microglial activation, apoptosis as well as cellular senescence in DOX‐treated microglia.ConclusionThese findings imply that MD‐2 inhibition could be the potential therapeutic strategy for attenuating DOX‐induced microglial activation and senescence.
References
1. Oo TT, Pratchayasakul W, Chattipakorn N, Chattipakorn SC. Emerging roles of toll‐like receptor 4 in chemotherapy‐induced neurotoxicity. NeuroToxicology. 2022;93:112‐27.2. Marques L, Johnson AA, Stolzing A. Doxorubicin generates senescent microglia that exhibit altered proteomes, higher levels of cytokine secretion, and a decreased ability to internalize amyloid β. Experimental Cell Research. 2020;395(2):112203.3. Ongnok B, Maneechote C, Chunchai T, Pantiya P, Arunsak B, Nawara W, et al. Modulation of mitochondrial dynamics rescues cognitive function in rats with ‘doxorubicin‐induced chemobrain’ via mitigation of mitochondrial dysfunction and neuroinflammation. Febs j. 2022;289(20):6435‐55.
Bridging the Brain‐Age Gap: Quantifying regional contributions using Shapley‐Owen values
Authors: Sinha Harsh , Raamana Pradeep Reddy 
Published: December 2023

AbstractBackgroundThe concept of brain age gap (BAG) is increasingly being used to express the deviation of brain from the normative trajectory. However, each brain region is subject to independent aging transformations due to differences in neurobiological processes. So, reducing high‐dimensional imaging features down to a single number for simultaneously evaluating brain health, capacity, and residual lifespan is an error‐prone task. Furthermore, brain age is observed to be correlated with chronological age. Therefore, there is need for a systematic empirical evaluation of BAG to understand contributions of different regions when considering BAG as a potential aging biomarker for age‐related neuroanatomical abnormalities. Although methods such as saliency maps have been proposed, there is need for a model‐agnostic technique that quantifies consistent feature contributions across various predictive models.MethodWe used morphological features estimated by Freesurfer from T1w (OASIS3 dataset) to train predictive models for BAG. The bias‐correction was performed using two strategies (i.e., scale‐down and scale up) on each of linear regression and XGBoost models as shown in Figure 1. We present feature importance for top‐10 features (based on median feature importance scores) across 100 bootstrap runs (Figures 2 and 3 respectively), along with correlations with chronological age. We use Shapley‐Owen feature attribution technique as a way of assigning importance to features.ResultAs shown in Figures 2 and 3, we found sub‐cortical, anterior cingulate, and ventricle volumes among the most relevant features. We also observe that SHAP determines an almost identical set of most relevant features for predicting corrected BAG irrespective of the predictive model (linear regression or XGboost) or the bias‐correction approach. Furthermore, we found the results to be consistent with prior literature e.g., subcortical brain volumes esp. gray matter. We also empirically observe that bias‐correction mitigates dependence on chronological age.ConclusionWe present a systematic empirical evaluation to identify the most relevant morphological features for predicting corrected BAG using SHAP. A consistent overlap of most relevant features irrespective of predictive model and the bias‐correction approach provides evidence for the robustness of using Shapley‐Owen values in explaining the contribution of morphological features for predicting corrected BAG.
Most caregivers who choose tube feeding for a relative with advanced dementia don’t want it for themselves
Authors: Cheng ‐ Heng Li , Cheong Chin Yee , Tay Poh Peng , Yap Philip Lin Kiat , Malhotra Chetna 
Published: December 2023

AbstractBackgroundAlthough long‐term enteral feeding in advanced dementia is not advocated, a significant proportion of people with severe dementia (PWSDs) receive nasogastric tube (NGT) feeding. Often, in the absence of advanced care planning by the PWSDs, their caregivers may need to make pivotal decisions on the issue. Hence, we assessed perceptions of caregivers of PWSDs regarding NGT feeding and the association between caregiver factors and NGT feedingMethodCommunity‐dwelling PWSDs with a FAST 6c score or higher, were recruited as part of the PISCES study, a prospective longitudinal cohort study. Their informal primary caregivers (family members in regular contact with the PWSDs and involved in main decision‐making process) were surveyed.Result215 caregivers of PWSDs enrolled in the study, of which 9.8% (n = 21) utilised NGT for their PWSD. Most (90.5%) caregivers of PWSDs receiving NGT reported that they understood the risks and benefits of NGT; most (85.8%) also agreed with the decision for NGT and reported that they believed it would allow the PWSD to live longer (85.7%). However, only 28.6% of caregivers wanted to be tube‐fed themselves if positions were reversed and 52.4% felt that tube feeding had reduced PWSDs’ quality of life. Comparing caregivers of PWSDs with and without NGT, there was no significant difference in their understanding of the natural course of dementia with only half of each group acknowledging that dementia can cause death (NGT 57.1% vs non‐NGT 56.1%, p = 0.969), nor difference in their knowledge of the PWSDs’ prognosis with majority indicating that they did not know how long the PWSD would live (NGT 85.7% vs non‐NGT 90.7%, p = 0.337). There was also no significant difference in their goals of care for the PWSDs with comfort reported as the primary goal for both groups (NGT 90.5% vs non‐NGT 92.3%, p = 0.773).ConclusionThere is a dissonance between caregivers’ self‐reported understanding and support of NGT use, and their preferences for NGT themselves, its perceived effect on PWSDs’ quality of life and goals of care. Further in‐depth qualitative exploration of the reasons underlying this discordance can provide more clarity on the issue.
Violence against elderly people with Dementia
Authors: Santos Lucas Neves , Alves Larissa Scoralich , Lourenço Lelio Moura 
Published: December 2023

AbstractBackgroundWith the fast aging of the world population, dementia has been one of the most prevalent diseases in older people, and quality dementia care is needed for a slow progression of the disease. Good practices are important on this topic, since the illness is extremely complicated to handle, being stressful and frustrating. Hence, it is important to know some actions and behaviors should be avoided, specially forms of violence against older people with dementia.MethodWe conducted a search of published research that presented the descriptors “violence” and “dementia” in their title. We also reviewed the summaries and sought for the theme “violence suffered by elderly people with dementia”. We searched four databases from inception to search date (December 2022), extracted data and conducted a narrative synthesis of evidence. Several studies were found, and we included based on the relevance for this review.ResultMost of the studies found in the scientific literature are focused on the violence made by people with dementia, and not the violence suffered by them, which is the focus of this review. In the studies used for this review, the characteristics of victims are listed as quiet, self‐effacing, with limited interpersonal coping skills, and excessive denial. In most studies, those who commit violence are men, caregivers, spousal and other family members. The most common types of violence are domestic, psychological, physical, verbal and negligence. The victims tend to remain in the abusive household because of many factors such as economic dependence, fear of major violence and children.ConclusionThere is a need for more studies focused on the violence suffered by elderly people with dementia in addition to a better detailing of factors such as gender, risk factors and how to prevent the violence. Family, caregivers and health professionals need to be attentive to some of the possible warning signs of abuse such as fractures and bruises that are not easily explained, chronic pain, post‐traumatic stress disorder, nightmares and other relevant situations that may alert to elderly abuse.
Short‐term high‐fat diet feeding induces cognitive decline, aggressiveness and anxiety‐like behavior in adult zebrafish (Danio rerio)
Authors: Picolo Victor Luna , Bem Andreza Fabro 
Published: December 2023

AbstractBackgroundObesity is a high‐ prevalence (13% of adult population in 2016), global health concern defined by a high body mass index (BMI). Several comorbidities are associated, including some affecting central nervous system (CNS), i.e. neurodegenerative diseases, cognitive deficit and psychobehavioral disturbs.MethodZebrafish has raised as a versatile and cheap model widely used to study human diseases, including obesity and neurological diseases. Therefore, our objective is verify the impact of a high‐fat diet on the central nervous system (CNS) using well‐ stablished behavioral tests. Animals was feed according with three dietary groups. The standard diet group (SD) received only 7.5 mg/fish of dry food, while the high‐fat diet groups received 5 mg/fish dry food plus 7.5 (HFD‐7.5) or 15 mg/fish (HFD‐15) of chicken egg yolk. Dietary fat content (w/w) was approximately 6.5%, 16.9% and 21.1%, respectively. After two weeks of diets ingestion, behaviors were assessed.ResultBoth HFD groups had obesogenic effects, indicated by increase on BMI, abdominal length and body weight compared with SD group. We show a HFD ingestion induced aggressive and anxiety‐like behavior on zebrafish, as measured by mirror‐induced aggression and novel tank diving test, respectively. Also, the higher concentration of HFD (HFD‐15) elicited cognitive deficit on inhibitory avoidance test while sociability was unaffected, as determined by the social preference test.ConclusionOur results are in accordance with evidences in obese human and rodent models, suggesting similar effects of fat intake. Therefore, we highlight the unexplored potential of zebrafish to elucidate this study field.
Virtual Reality Companion for Dementia Patients in Long‐term Care: A Feasibility Study
Authors: Frank Andrew R , Sheehy Lisa 
Published: December 2023

AbstractBackgroundPersons with dementia (PWDs) develop progressive cognitive and physical decline which often results in placement in long‐term care (LTC). Within LTC, PWDs are at high risk for social isolation, as friends and family members may not visit often, a problem exacerbated by the COVID‐19 pandemic.MethodThis project is developing a novel application for immersive virtual reality (VR), in which an avatar (i.e. a visual representation of a person) acts as an autonomous artificial companion for PWDs in LTC. This avatar is programmed to listen to PWDs through microphones embedded in VR goggles, and provide verbal interaction with PWDs through embedded speakers. In this way, the avatar can provide a source of conversation and socialization, available at any time, for any duration. This engagement may improve quality of life, and reduce responsive and reactive dementia behaviours.ResultOur virtual companion was trialed in 10 PWD (3 men; 7 women). Most PWD found the companion to be engaging, and this invited positive reminiscence in 3 PWD. VR goggles were generally well‐tolerated, though 2 PWD closed their eyes and/or did not respond. The ability to interact verbally in a conversational manner was easier in patients with milder dementia. There was some poor performance of the speech recognition software, which impacted the flow of the conversation. Significant verbal feedback was recorded on how to improve the avatar, and how to enhance the conversation.ConclusionAn autonomous artificial companion presented in virtual reality (VR) is feasible, and may benefit persons with dementia who are at risk of social isolation. Future iterations will incorporate improved speech recognition and artificial intelligence (AI)‐guided conversation generator software.
Abnormal Phosphorylation at Ser293 promotes the Oligomerization of Tau Repeat R2: A Computational Study
Authors: Man Viet H 
Published: December 2023

AbstractBackgroundIn tauopathies such as Alzheimer’s disease (AD), aberrant phosphorylation causes the dissociation of tau protein from microtubules. The dissociated tau then aggregates into sequent forms from soluble oligomers to paired helical filaments (PHF), and insoluble neurofibrillary tangles (NFTs). NFTs is a hallmark of AD, while oligomers are found to be the most toxic form of the tau aggregates. Therefore, understanding tau oligomerization with regard of abnormal phosphorylation is important to therapeutic development of AD. In this study, we investigated the impact of phosphorylated Ser293, one of 40 aberrant phosphorylation sites of full‐length tau protein, on monomeric and dimeric structures of tau repeat R2 peptidesMethodWild‐type tau repeat R2 (wtR2) was taken from an experimental structure of R2‐microtubule complex (PDB code 6CVN). The phosphorylated Ser293 R2 peptide (pS293R2) was obtained by phosphorylating the wtR2 at Ser293 residue. Extensive replica exchange molecular dynamics simulations using all‐atom force field and explicit solvent were carried out for five systems including two monomers (wtR2 and pS293R2) and three dimers (wtR2+wtR2, wtR2+pS293R2, and pS293R2+ pS293R2). The structures of R2 monomers and dimers sampled by the simulations were characterized and compared.ResultFor monomeric conformations, the phosphorylation enhances intramolecular interaction, compactness and β content. For dimeric cases, the phosphorylation increases intermolecular interaction, β‐sheet formation, and turn‐coil structural transition. Interestingly, the phosphorylated residue strongly interacts with cations, resulting in a pS293‐cation‐pS293 bridge in pS293R2+ pS293R2 system.ConclusionOur results suggest that abnormal phosphorylation at Ser293 accelerates the oligomerization of R2 peptides, and consequently it may promote tau aggregation. Furthermore, we also found a pS293‐cation‐pS293 bridge formed, thus uncovered the essential role of cation ions in the oligomerization of the phosphorylated R2 repeat. Our findings suggest that phosphorylation at Ser293 should be taken into consideration when screening the inhibitors of tau oligomerization.
Plasma phosphorylated tau 181 and modifiable risk factors for dementia in a large scale cohort of Australian older adults
Authors: Roccati Eddy , Collins Jessica M , Bindoff Aidan D , Alty Jane E , Bartlett Larissa , King Anna E , Vickers James C 
Published: December 2023

AbstractBackgroundUp to 40% of dementia cases could be prevented by addressing modifiable risk factors. Alzheimer’s disease (AD), the most common form of dementia, is preceded by up to decades of silent pathological change providing an ideal window for early detection and intervention. In this study, our objective was to examine the associations between modifiable risk factors and plasma phosphorylated p‐tau 181, a hallmark biomarker of early AD.MethodParticipants were recruited from the Island Study Linking Ageing and Neurodegenerative Disease (ISLAND), a prospective public health initiative in Tasmania, Australia’s southernmost island state. ISLAND participants were invited to complete a set of surveys online: a questionnaire on dementia risk factor adherence, demographic surveys and cognitive tests via the Cambridge Neuropsychological Test Automated Battery (CANTAB); Paired Associates Learning (PAL) and Spatial Working Memory (SWM). At four clinics across the state, participants also provided blood samples for measurement of plasma phosphorylated p‐tau 181 and genotyping for APOE.ResultA total of 738 participants (mean age 65.41 years, mean education 17.36 years, 71.8% female, 26.4% ε4+) took part in the study. We found gender‐specific effects on cognition, whereby identifying as male was associated with significantly lower learning ability (PAL) whilst identifying as female was associated with significantly lower executive function (SWM). In multivariate linear models, increasing alcohol consumption (measured in standard drinks per week) was significantly associated with lower plasma p‐tau 181. In adjusted models, no other modifiable risk factors examined were associated with p‐tau 181. Increasing age, identifying as male and possessing at least one APOE ε4 allele were all associated with higher plasma concentrations of p‐tau 181ConclusionHigher alcohol consumption, higher age, identifying as male and having an APOE ε4 allele were all associated with lower plasma phosphorylated tau 181. This contributes to evidence that both modifiable and non‐modifiable dementia risk factors are related to the biological precedents of AD. These associations were related to gender and genetics, therefore a panel of modifiable and non‐modifiable variables should be included in screening or diagnostic testing for pre‐clinical AD. More research is needed regarding specific alcohol types and biomarkers of AD.