bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations of resting heart rate with incident dementia, cognition, and brain structure: a prospective cohort study of UK biobank
Authors: Yue‐Ting Deng 
Published: January 2025

AbstractBackgroundResting heart rate (RHR) has been linked with an increased risk of dementia. However, evidence characterizing the associations of RHR with different dementia subtypes and their underlying mechanisms remains scarce. This study aims to investigate the relationships of RHR with different dementia types, cognitive function, and brain structural abnormalities.MethodThree hundred thirty‐nine thousand nine hundred one participants with no prior diagnosis of dementia from the UK biobank were analyzed. Cox regression and restricted cubic spline models examined the associations between RHR with all‐cause dementia (ACD) and its major subtypes—Alzheimer’s disease (AD) and vascular dementia (VaD). Logistic regression models assessed the associations of RHR with cognitive function, and linear regression models estimated the associations with hippocampal subfield volume and white matter tract integrity indexed by magnetic resonance imaging data.ResultDuring an average of 3148 (± 941.08) days of follow‐up, 4177 individuals were diagnosed with dementia, including 2354 AD and 989 VaD cases. RHR ≥ 80bpm was associated with ACD (HR: 1.18, 95% CI: 1.08–1.28, P < 0.001) and VaD (HR: 1.29, 95% CI: 1.08–1.54, P = 0.005) but not AD in multi‐adjusted models. A 10‐bpm increment of RHR demonstrated non‐linear effects in VaD, consisting of J‐shape relationships. Several heterogeneities were indicated in stratified analysis, in which RHR measures only showed associations with dementia incidents in relatively younger populations (age ≤ 65) and females. Apart from dementia analysis, elevated RHR was associated with worsening performance in fluid intelligence and reaction time of cognitive tasks, decreased hippocampal subfields volume, and poor white matter tract integrity.ConclusionRHR is associated with increased risks of ACD and VaD but also presented with few heterogeneities across different sex and age groups. Elevated RHR also appears to have deleterious effects on cognitive function and is distinctively associated with volume reduction in hippocampal subfields and impaired white matter tract integrity.
PFTAIRE peptide degrading cyclin Y and ameliorating cognitive deficits in mouse models of Alzheimer’s Disease
Authors: Cho Illhwan , Cha Minhae , Kim Hye Yun , Kim YoungSoo 
Published: January 2025

AbstractBackgroundCyclin Y (CCNY) is a member of cyclin protein family inhibiting long‐term synaptic plasticity, which is related to the learning and memory function in neuronal system. Recently, CCNY has been reported to associate with the cognitive deficits in Alzheimer’s disease (AD).MethodIn this study, we discovered PFTAIRE peptide to diminish CCNY protein level and to ameliorate cognitive dysfunction in AD. This peptide is derived from the domain of cyclin‐dependent kinase 14, a kinase degrading CCNY protein, and this domain is essential for the binding to CCNY. Utilizing solid‐phase peptide synthesis, PFTAIRE peptide was produced.ResultWe observed that PFTAIRE peptide binds to CCNY protein in in vitro studies. We confirmed the plasma and liver microsomal stability of the peptide and the ability to penetrate blood brain barrier. We intravenously injected PFTAIRE peptide to AD mouse models and performed behavior tests. PFTAIRE peptide prevents memory impairments in AD mouse models. In the proteomic analysis of the cortical brain section of mouse models, we observed the alteration of 93 proteins by the PFTAIRE peptide compared to non‐treated groups. Utilizing gene ontology, PFTAIRE peptide up‐regulated proteins related to release/transport neurotransmitter in brain synapse and down‐regulated proteins related to oxidative stress.ConclusionOverall, the discovery of PFTAIRE peptide suggests new approach for the development of therapeutics targeting AD.
Chrysin loaded Nanostructured lipid carrier (NLC) drug delivery system: Harnessing neuroprotective effects in the management of Alzheimer’s Disease
Authors: Khandale Nikhil B , Birla Devendra S , Bashir Bushra , Singh Sachin Kumar , Vishwas Sukriti , Gulati Monica , Dua Kamal 
Published: January 2025

AbstractBackgroundAlzheimer’s Disease (AD) poses a substantial global health burden, necessitating innovative therapeutic strategies. This study investigates the neuroprotective potential of a chrysin‐loaded Nanostructured Lipid Carrier (NLC) drug delivery system in AD management. Employing the high‐pressure homogenization method, chrysin‐loaded NLCs were meticulously formulated to optimize drug delivery efficiency. The research explores the multifaceted neuroprotective effects of chrysin, a naturally occurring flavonoid, within the context of AD pathology. The intricate mechanisms of action underlying the chrysin‐loaded NLCs are elucidated, shedding light on their potential to modulate key pathways implicated in AD progression. This study advances our understanding of tailored drug delivery systems, specifically highlighting the therapeutic promise of chrysin‐loaded NLCs for the nuanced management of Alzheimer’s Disease.MethodTo overcome these challenges, a Nanostructured lipid carrier (NLC) for Chrysin was devised, employing quality by design (QbD) based Box‐Behnken design (BBD). NLC offers numerous advantages, encompassing increased drug loading, facile preparation, exceptional stability, as well as enhanced bioavailability and permeability across the blood‐brain barrier.ResultThe optimized Chrysin‐loaded NLC formulation exhibited Particle Size, PDI, zeta potential, and drug loading as 66.45nm, 0.19, ‐22mV, and 98% respectively. The formulation was found to be stable after six months in accelerated stability studies. The formulation underwent various pharmacodynamic studies. Pharmacodynamic studies assessed cognitive and motor functions in rats, revealing significant improvements in cognition with both low and high doses respectively. Additionally, the biochemical investigations revealed that the Chrysin‐loaded NLCs effectively decreased the levels AChE enzyme, amyloid β, oxidative stress, and neuroinflammation.ConclusionThis study explores Chrysin‐loaded NLCs as a solution for challenges in Alzheimer’s Disease (AD) treatment. The optimized formulation overcomes Chrysin’s solubility issues, demonstrating improved bioavailability and permeability. Chrysin‐loaded NLCs hold promise as a neuroprotective for AD.
Presence and Severity of Lewy Body Pathology is Modulated by Sex and ApoE4 Zygosity in a Neuropathologically‐Confirmed Alzheimer’s Disease Cohort
Authors: Valcic Mila , Khoury Marc A , Fornazzari Luis R , Churchill Nathan W , Schweizer Tom A. , Fischer Corinne E. , Munoz David G. 
Published: January 2025

AbstractBackgroundThe APOE ε4 allele (ApoE4) is a known genetic risk factor for developing Alzheimer’s disease (AD). Previous work by our group demonstrated that female ApoE4 homozygotes with Lewy body (LB) pathology were significantly more likely to experience psychosis compared to female ApoE4 non‐carriers, whereas there was no dose‐dependent difference found in males (Valcic et al., 2022). The objective of this study was to examine LB pathology presence and severity in males and females across ApoE4 status, with a particular interest in female ApoE4 homozygotes.MethodDemographics, APOE genotype, and LB pathology data was collected in individuals with neuropathologically‐confirmed AD (n=1,234) from the National Alzheimer’s Coordinating Center (NACC). Bayesian Multilevel Regression was used to predict the probability of LB pathology presence in males and females across ApoE4 status (0, 1, 2 ε4 alleles). An Ordinal Regression was used to examine the relationship between LB pathology severity (brainstem‐predominant (mild), limbic or amygdala‐predominant (moderate), neocortical‐predominant (severe)) and ApoE4 status, stratifying by sex.ResultWhile males had a higher probability of exhibiting LB pathology compared to females, after stratifying by ApoE4 status, female ApoE4 homozygotes showed the highest probability of LB pathology at a 91.1% Highest Density Interval (91.1%HDI[0.12: 0.95]) across both sexes. Within females, ApoE4 homozygotes showed a significantly higher probability of having moderate to severe LB pathology relative to other groups (p =.02). Within males, there was no significant relationship between ApoE4 status and LB pathology severity.ConclusionThis study revealed that sex and zygosity modulate the effect of ApoE4 on presence of LB pathology and LB severity in neuropathologically‐confirmed AD patients. Specifically, female ApoE4 homozygotes had the highest probability of having LB pathology, as well as greater LB pathology severity. Future work should explore the association between LB pathology severity and psychosis while stratifying for sex and ApoE4 status.Reference: Valcic, M., Khoury, M. A., Kim, J., Fornazzari, L., Churchill, N. W., Ismail, Z., De Luca, V., Tsuang, D., Schweizer, T.A., Munoz, D.G, & Fischer, C. E. (2022). Determining Whether Sex and Zygosity Modulates the Association between APOE4 and Psychosis in a Neuropathologically‐Confirmed Alzheimer’s Disease Cohort. Brain Sciences, 12(9), 1266.
Epidemiological and genomic analyses identify drug classes associated with Lewy body dementia
Authors: Scholz Sonja W 
Published: January 2025

AbstractBackgroundLewy body dementia (LBD) is the second most common neurodegenerative dementia after Alzheimer’s disease which remains poorly understood. Disease‐modifying therapies for LBD are critically needed. We performed a population‐based case‐control study of U.S. Medicare participants with LBD and matched controls to identify drugs that are significantly associated with disease risk.MethodA total of 148,170 U.S. Medicare and 1,253,043 controls were included in the study. We estimated the association of LBD risk with 1,017 prescription drugs. We then applied genetic correlation analyses to genomic data generated for LBD and cardiovascular traits to investigate causal effects.ResultsUsing broadly adjusted logistic regression models, we discovered significantly reduced LBD risk associated with drugs used to treat cardiovascular diseases (antihypertensives: odds ratio = 0.72, 95% confidence interval = 0.70–0.74, p‐value = 0; cholesterol‐lowering agents: odds ratio = 0.85, 95% confidence interval = 0.83–0.87, p‐value = 0; and antidiabetics medications: odd ratio = 0.83, 95% confidence interval = 0.62–0.72, p‐value = 0). Notably, antidiabetic medications were associated with a larger risk reduction among Black LBD patients than other racial groups. Genetic correlation analyses identified shared genetic risk between LBD and low‐density lipoprotein cholesterol levels, hypertension, and type 2 diabetes mellitus.ConclusionsOur data suggest that the genetic architecture of LBD and cardiovascular traits overlap and that assiduous management of cardiovascular risk factors may be beneficial in this this patient population.Reference: Scholz SW et al., Brain Commun. 2023 Dec 18;6(1):fcad346.
Associations between serum metabolic syndrome indicators levels and cerebrospinal fluid pathological protein
Authors: Ding Jiayi , Quan Meina , Jia Jianping 
Published: January 2025

AbstractBackgroundMetabolic syndrome (MetS) was associated with an increased incidence of mild cognitive impairment (MCI) and progression to dementia. However, little is known about why this occurs. This study was to examine the correlation between the MetS indicators and cerebrospinal fluid (CSF) pathological protein biomarkers to investigate this mechanism.Methods70 normal cognition (NC), 79 MCI, and 150 dementia participants were included, with the results of lumbar puncture and peripheral blood biochemistry. The CSF levels of amyloid (Aβ) 42, total tau (T‐Tau), phosphorylated tau (P‐Tau) and Aβ42/40 ratio were selected as the biomarkers of pathological protein. The body mass index (BMI) and the plasma high density lipoprotein cholesterol (HDL‐C), uric acid (UA), low density lipoprotein cholesterol (LDL‐C), triglyceride (TG) and homocysteine levels were selected as markers of MetS. Linear regression model was used to analyze the correlation, controlling for age, sex and apolipoprotein E genotype.ResultsIn all participants, BMI and TG were negatively correlated and LDL‐C was positively correlated with CSF Aβ42/40 ratio. (Figure 1) UA and TG were negatively correlated with CSF T‐tau levels.(Figure 2) BMI, UA and TG were negatively correlated and HDL‐C was positively correlated with CSF P‐Tau concentrations. (Figure 3) In the NC group, no correlation was observed. In the MCI group, LDL‐C was negatively correlated with Aβ42/40. Higher levels of UA and TG were correlated with lower CSF T‐Tau concentrations. BMI and TG levels were negatively correlated and HDL‐C was positively correlated with CSF P‐Tau levels. In the dementia group, BMI was positively associated and LDL‐C was negatively associated with CSF Aβ42/40 ratio. HDL was negatively correlated with and homocysteine was positively correlated with CSF Aβ42 levels. UA and TG were negatively correlated with CSF T‐Tau levels. TG and homocysteine levels were negatively correlated and HDL‐C was positively correlated with CSF P‐Tau levels.ConclusionThe pathological proteins concentrations in the CSF of the elderly were differentially associated with MetS indicators in different stages of dementia. These findings suggest that serum lipids modulate CSF pathological proteins, which could offer new approaches to slowing disease progress and reducing the incidence of dementia.
Impact of Site Size on Data Quality in Early Alzheimer’s Disease Clinical Trials
Authors: Kott Alan , Wang Xingmei , Reksoprodjo Petra , Iacob Andrei , Miller David S. 
Published: January 2025

AbstractBackgroundClinical trial sponsors rely on research sites to identify and enroll appropriate study participants and to correctly and reliably assess symptom severity and function over the course of the trial. Low‐recruiting sites represent a large financial and operational burden and may negatively impact trial success either by selecting inappropriate participants and/or high prevalence of data quality issues. We previously reported that >60% of sites in schizophrenia clinical trials recruited ≤5 participants. Here we analyze 3 large dementia trials to assess the proportion of low‐recruiting sites and compare their data quality with the remaining sites.MethodData were obtained from 3 large early dementia clinical trials totaling 834 sites. Sites were divided into two groups based on the number of randomized subjects: 1. sites with more than 5 randomized subjects (high‐recruiting sites) and 2. sites with 5 or less randomized subjects (low‐recruiting sites). Data quality issues were defined as administration and scoring errors on relevant scales. These errors were summed per site and then compared by site size using Poisson regression with the site size, study and their interaction as predictors and the number of possible hits as exposure.Result71 (8.5%) sites did not randomize a subject, 43 (5.2%) sites randomized one subject, and 377 (45.2%) sites randomized ≤5 subjects. Overall, administration and scoring errors were more frequent at low‐recruiting sites (seen at 41.9% visits) compared to 35.3% at the high‐recruiting sites. 2 studies show significantly higher IRRs, 1.59 (1.46, 1.74) and 1.2 (1.15, 1.25) respectively, while the third study has an IRR close to 1 but not statistically significant.ConclusionOur results indicate that low‐recruiting sites (arbitrarily defined as randomizing ≤5 participants) are frequent in large dementia trials. These sites pose considerable cost to sponsors, but more importantly, are more likely to provide questionable data quality. While a single site like this only represents a small risk, in aggregate, they can pose a serious challenge. Clinical trial sponsors should therefore consider strategies to minimize the impact of low‐recruiting sites on study outcomes.
Validation of the Italian consensus recommendations for the biomarker‐based etiological diagnosis of mild cognitive impairment: study design and preliminary data
Authors: Solorzano Claudio Singh , Festari Cristina , Orini Stefania , Castagna Eleonora , Ramusino Matteo Cotta , D'Antonio Fabrizia , Crosta Adolfo Di , Masòtino Alessia , MASSA FEDERICO , Mazzonetto Alice , Panigutti Massimiliano , Ravì Noemi , Pievani Michela , Bonanni Laura , Bruno Giuseppe , Cagnin Annachiara , Gatta Roberto , Frisoni Giovanni B. 
Published: January 2025

AbstractBackgroundIn 2020, five Italian scientific societies issued diagnostic recommendations to improve the rational and combined use of biomarkers in the clinical practice of Italian memory clinics (Boccardi et al., 2020). The present project will aim to compare the most frequent diagnostic workups in three academic memory clinics before (pre‐recommendations: January 2018 ‐ December 2019) and after (post‐recommendations: October 2022 ‐ October 2023) the release of the recommendations to assess their implementation in clinical routine. Preliminary results on pre‐recommendations data are presented here.MethodWe retrospectively reviewed the medical charts of consecutive patients referred to the academic memory clinics of Padova, Chieti, and Roma for a first visit in the pre‐recommendations period. The collected information included socio‐demographic data, number and dates of clinical visits and biomarker exams (i.e., FDG‐, amyloid‐, tau‐PET, cerebrospinal fluid [CSF], DAT SPECT/PET, and cardiac MIBG scintigraphy). A diagnostic hypothesis was extracted for each clinical visit until the final diagnosis.ResultSince October 2022, 500 patients’ medical charts were reviewed. Patients were divided into three groups: 148 (30%) patients came to clinical observation not for diagnostic purposes (e.g., second opinion, disability claim), 242 (48%) received a diagnosis based on neuropsychological assessment and morphological imaging only, and 110 (22%) were in a biomarker‐based diagnostic pathway. The latter group included 31 patients with Alzheimer’s disease (AD), 19 with frontotemporal lobar degeneration (FTLD), 28 with a Lewy body spectrum disease (LBD), and 32 with non‐neurodegenerative aetiology or vascular dementia. Biomarker‐based diagnoses of AD, FTLD and non‐neurodegenerative diseases were commonly based on FDG‐PET (AD: 77%, FTLD: 84%, non‐neurodegenerative: 66%) and CSF (52%, 37%, and 44%). In LBD (n = 28), the first‐choice biomarker was FDG‐PET (61%), followed by DAT SPECT/PET (39%).ConclusionThis preliminary analysis outlines the most frequent diagnostic pathways, providing the prevalence of the use of biomarkers in Italian academic memory clinics in the pre‐recommendations period. Once the post‐recommendations data collection is completed, we will evaluate whether the recommendations are feasible and usable in real‐world clinical workups by applying process‐mining techniques (Gatta et al., 2020) to estimate the prevalence and type of deviations from the ideal pathway based on recommendations.
Systematic review of digital self‐management interventions in dementia care: Exploring the impact of wearable technology, smart homes, and mobile applications on patient outcomes
Authors: Cornelius Gary 
Published: January 2025

AbstractBackgroundThe increasing significance of self‐management in dementia care arises from earlier diagnosis, improved understanding of patient‐modifiable factors, and advancements in treatments. The growing acceptance of patient care planning, especially self‐management, is further supported by health professionals and public health initiatives aimed at extending healthspan.MethodThis systematic review evaluates the efficacy of self‐management tools in enhancing the quality of life for adults with dementia and mitigating undesirable behaviours associated with the condition. A comprehensive search spanning ten years across nine databases was conducted, leading to the screening of over eight hundred articles. A highly relevant collection of studies, focusing on adults with dementia’s interaction with digital technologies, was selected. These studies were analysed using the Mixed Methods Appraisal Tool (MMAT) and a custom‐designed characterization table to address specific research questions.ResultThe review highlights that self‐management approaches such as aiding functional independence, wellbeing support, engagement, monitoring, and detecting abnormal behaviour are effective. The studies utilized various assessment methods including multimodal sensing, caregiver feedback, and machine‐based prompting. Effective use of smart home sensors, health watches, wearable technologies, cameras, Internet of Things (IoT) networks, robots, and other devices was also noted.ConclusionTechnologies for self‐management notably enhance patient well‐being, with effective strategies including monitoring for abnormalities, socially assistive robots, machine prompting, sensory interventions, and cognitive support. Future research could improve by aligning interventions with individualized activities that promote well‐being, employing standardized outcome measures, and controlling for external factors such as known patient disease‐modifying factors.
Family carers experiences of compassion for self, other and receiving compassion
Authors: Kupeli Nuriye , Cooper Claudia , Bruun Andrea , Dillon Laura , Reilly Pepsi , White Nicola , Sampson Elizabeth L 
Published: January 2025

AbstractBackgroundFamily carers of people living with dementia provide care over many months or years with little to no formal support. Carers’ experiences of compassion for themselves and others including receiving compassion can influence their caregiving experience and the quality of care they provide. However, little is known about healthcare professionals (HCPs) understanding of how compassion is experienced by family carers and how best HCPs can support family carers to cultivate and maintain compassion for themselves and others.MethodsThis study used qualitative interviews to explore family carers experience of compassion for themselves and others (including receiving compassion from others) while caring for someone living with dementia. Inductive thematic analysis was used to explore and report the barriers and facilitators to family carers experiences of compassion.ResultsInterviews with ten family carers (nine current and one former carer) comprising of five daughters, three wives, one husband and one son were undertaken. Barriers and facilitators were identified for compassion for self, others and receiving compassion. While facilitators to compassion included having the opportunity to maintain an identify outside of caring role, positive memories, and shared understanding, experiences that made it difficult for carers to maintain compassion included the perception that one needs to sacrifice own needs and feelings of guilt and shame.ConclusionsPreliminary findings indicate that whilst carers of people living with dementia acknowledge that compassion is important, they indicate that the caring role could be a barrier to experiencing and maintaining compassion. Future research needs to focus on developing supportive interventions designed to addressing factors that may hinders carers abilities to cultivate and maintain compassion.