bluuebunny/crossref_metadata_2025 huggingface dataset:
Ag‐Cu Nanoarchitecture for Enhanced LSPR Absorption: the Role of Surface Roughness and near‐field Interactions
Authors: Kumar Sanjay , Curda Pavel , Maskova Hana , Doudová Lenka , Pleskunov Pavel , Kuzminova Anna , Hejduk Libor , Sterba Jan , Kylián Ondřej , Rego Ryan O. M. , Stranak Vitezslav
Published: January 2025

The plasmonic properties and biosensing performance of a nanocomposite with incorporated Cu and Ag nanoparticles (NPs) are studied experimentally. The concept's viability is verified by detecting specific anti‐decorin‐binding protein A (DbpA) from Borrelia afzelii antibodies, typically produced by a living organism in response to Lyme disease infection, carried out in real‐life negative and positive blood sera. It is shown that the addition of Cu NPs on top of silver NPs regularly boosts the plasmonic absorption caused by optical and electrical changes in the vicinity of the surface compared to silver NPs only. The Finite‐difference time‐domain (FDTD) simulations of near‐field interaction in different environments propose suitable Cu–Ag coupling modes responsible for the modulation of the localized Surface Plasmon Resonance (LSPR) bands. Furthermore, the increased surface roughness, resulting from the architecture of combined nanoparticles of different metals, significantly enlarges the effective surface area for sensing applications, which consequentially leads to better species immobilization. The observed distinguishable differences between the negative and positive sera of LSPR response, and the high sensitivity and selectivity together with high stability of the nanocomposite (suppressed aging) opens a door for concepts of rapid, low‐cost, sensitive LPSR‐based biodetection platforms.
Microneedles with Interdigitated Electrodes for In Situ Impedimetric VEGF Sensing
Authors: Das Ritu , Istif Emin , Cebecioglu Rumeysa , Ali Mohsin , Atik Yasin , Dağ Çağdaş , Celikbas Eda , Demirci Gozde , Acar FundaYagcı , Hasanreisoğlu Murat , Beker Levent
Published: January 2025

Continuous monitoring of protein biomarkers in interstitial fluid (ISF) is essential for improving patient care and outcomes. This study presents a novel electrochemical impedance spectroscopy (EIS) sensor utilizing microneedles (MNs) patterned with interdigitated electrodes for the detection of vascular endothelial growth factor (VEGF). The MNs, are fabricated from flexible polylactide (PLA) using a simple molding technique, followed by metal deposition with an interdigitated pattern to serve as a platform for the EIS sensor. After functionalization with anti‐VEGF antibodies, impedance measurements are conducted to detect VEGF levels, demonstrating a significant change in impedance in response to varying concentrations of the target biomarker. The MNs can easily penetrate rat skin by hand, puncturing without mechanical breakage. This innovative approach enhances the sensitivity and specificity of biomarker detection and paves the way for continuous monitoring applications in diagnostics and preventative medicine.
Metabolic‐Immune Suppression Mediated by the SIRT1‐CX3CL1 Axis Induces Functional Enhancement of Regulatory T Cells in Colorectal Carcinoma
Authors: Zi Ruiyang , Zhao Xiang , Liu Limei , Wang Yijie , Zhang Rui , Bian Zhiheng , Jiang Haoran , Liu Taorui , Sun Yixin , Peng Han , Wang Xuesong , Lu Fanghao , Zhang Chao , Zhang Fan , Qin Qing , Liang Houjie , Li Jianjun , Wei Zhihao , Dong Yan
Published: January 2025

Metabolic reprogramming of tumor cells dynamically reshapes the distribution of nutrients and signals in the tumor microenvironment (TME), affecting intercellular interactions and resulting in metabolic immune suppression. Increased glucose uptake and metabolism are characteristic of many tumors. Meanwhile, the progression of colorectal carcinoma (CRC) relies on lipid metabolism. Therefore, investigating the role of glucolipid metabolic reprogramming on tumor immunity contributes to identifying new targets for immune suppression intervention in CRC. Our previous work demonstrated that SIRT1 is the hub gene involved in glucolipid metabolic conversion in CRC. Here, it is found that upregulated SIRT1 in CRC cells increases Treg functionality by promoting the secretion of CX3CL1. The CX3CL1‐CX3CR1 signaling activated transcription factors SATB1 and BTG2, promoting the differentiation of TCF7+ Treg cells into functionally enhanced TNFRSF9+ Treg cells. Multiplex immunofluorescence (mIHC) analysis of a CRC tissue microarray confirmed the promoting effect of CX3CL1 on Treg infiltration. Additionally, the therapeutic efficacy of CX3CR1 inhibitor monotherapy and combination therapy is validated with the PD‐1 antibody in the humanized subcutaneous CRC mouse model. This study elucidates a potential mechanism that metabolic reprogramming of cancer cells collaborates with subsequent immunosuppression to promote CRC progression.
A Dual‐Targeting Biomimetic Nanoplatform Integrates SDT/CDT/Gas Therapy to Boost Synergistic Ferroptosis for Orthotopic Hepatocellular Carcinoma Therapy
Authors: Meng Wen , Chen Ting , Li Xueping , Li Yi , Zhang Lu , Xu Yigang , Song Tianqiang , Qi Ji , Xiong Qingqing , Li Wen
Published: January 2025

The development of efficient therapeutic strategies to promote ferroptotic cell death offers significant potential for hepatocellular carcinoma (HCC) treatment. Herein, this study presents an HCC‐targeted nanoplatform that integrates bimetallic FeMoO4 nanoparticles with CO‐releasing molecules, and further camouflaged with SP94 peptide‐modified macrophage membrane for enhanced ferroptosis‐driven multi‐modal therapy of HCC. Leveraging the multi‐enzyme activities of the multivalent metallic elements, the nanoplatform not only decomposes H2O2 to generate oxygen and alleviate tumor hypoxia but also depletes glutathione to inactivate glutathione peroxides 4, which amplify sonodynamic therapy and ferroptotic tumor death under ultrasound (US) irradiation. Meanwhile, the nanoplatform catalyzes the Fenton reaction to produce hydroxyl radicals for chemodynamic therapy. Elevated intracellular reactive oxygen species trigger the cascade release of CO, leading to lethal lipid peroxidation and further enhancing ferroptosis‐mediated tumor therapy. This nanoplatform demonstrates robust anti‐tumor efficacy under US irradiation with favorable biosafety in both subcutaneous and orthotopic HCC models, representing a promising therapeutic approach for HCC. Additionally, the findings offer new insights into tumor microenvironment modulation to optimize US‐triggered multi‐modal cancer therapy.
Breaking the Trade‐Off Between Electrical Conductivity and Mechanical Strength in Bulk Graphite Using Metal–Organic Framework‐Derived Precursors
Authors: Zhang Yuqing , Wang Junzhuo , Zhang Yinghan , Zheng Qi , Wang Lianjun , Jiang Wan
Published: January 2025

High‐performance bulk graphite (HPBG) that simultaneously integrates superior electrical conductivity and excellent strength is in high demand, yet it remains critical and challenging. Herein a novel approach is introduced utilizing MOF‐derived nanoporous metal/carbon composites as precursors to circumvent this traditional trade‐off. The resulting bulk graphite, composed of densely packed multilayered graphene sheets functionalized with diverse cobalt forms (nanoparticles, single atoms, and clusters), exhibits unprecedented electrical conductivity in all directions (in‐plane: 7311 S cm⁻¹, out‐of‐plane: 5541 S cm⁻¹) and excellent mechanical strength (flexural: 101.17±5.73 MPa, compressive: 151.56±2.53 MPa). Co nanoparticles act as autocatalysts and binders, promoting strong interlayer adhesion among highly graphitized graphene layers via spark plasma sintering. The strong nano‐interfaces between graphite and Co‐create critical bridges between graphene nanosheets, facilitating highly efficient electron migration and enhanced strength and stiffness of the assembled bulk nanocomposites. Leveraging these exceptional properties, practical demonstrations highlight the immense potential of the robust material for applications demanding superior electromagnetic interference shielding and efficient heating. An innovative approach, which effectively decouples electrical conductivity from mechanical properties, paves the way for the creation of HPBGs tailored for diverse application sectors.
Effectiveness of advanced dressings in preventing surgical site infections compared to that of standard dressings in gastrointestinal surgery: A systematic review and meta‐analysis for guideline revision by the Japanese Society for Surgical Infection
Authors: Kouzu Keita , Tsujimoto Hironori , Shinji Seiichi , Shinkawa Hiroji , Tamura Koji , Sato Yukio , Munakata Koji , Fukuda Yasunari , Koike Daisuke , Miyake Hiromu , Hosoda Yohei , Uchino Motoi , Ohge Hiroki , Shimizu Junzo , Haji Seiji , Mohri Yasuhiko , Yamashita Chizuru , Kitagawa Yuichi , Kobayashi Motomu , Hanai Yuki , Nobuhara Hiroshi , Yoshida Masahiro , Mizuguchi Toru , Mayumi Toshihiko , Kitagawa Yuko
Published: January 2025

Introduction

This is a systematic review and meta‐analysis of the efficacy of wound coverage using advanced dressings specifically for the prevention of surgical site infections (SSI) in gastrointestinal surgery, as part of the update of the SSI prevention guidelines of the Japan Society for Surgical Infection (JSSI).

Methods

After searching CENTRAL, PubMed, and ICHUSHI‐Web in July 2024, we included randomized controlled trials (RCTs) comparing advanced dressings and standard dressings for surgical wounds in gastrointestinal surgery (PROSPERO No. CRD42024569084). Three authors independently screened the RCTs. We assessed the risk of bias and certainty of the body of evidence for the extracted data. The primary outcome was superficial SSI, and the secondary outcomes were length of postoperative hospital stay, costs, and allergy. This study was partially supported by the JSSI.

Results

A total of seven RCTs and 927 patients were included. The use of advanced dressings significantly lowered the risk of SSI compared to that associated with standard dressings (risk ratio: 0.54, 95% confidence intervals: 0.34–0.88). The certainty of the evidence was rated as moderate. According to the subgroup analysis, advanced dressings reduced the risk of SSI in colorectal surgery. Advanced dressings did not reduce the length of postoperative hospital stay or costs compared to that of standard dressings. Allergies were reported in only one patient using silver‐impregnated dressings.

Conclusion

The use of advanced dressings for primary wounds in gastrointestinal surgery was associated with a significantly lower risk of SSI than that associated with standard dressings.
Revolutionizing Bone Regeneration: Vascularized Bone Tissue Engineering with Advanced 3D Printing Technology
Authors: Fan Jiaxuan , Ding Zichuan , Cai Yongrui , Lai Yahao , Huang Chao , Jiang Boyi , Zhou Zongke , Luo Zeyu
Published: January 2025

The repair and functional reconstruction of bone defects resulting from trauma, surgical resection, degenerative diseases, and congenital malformations are major clinical challenges. Bone tissue engineering has significant advantages in the treatment of severe bone defects. Vascularized bone repair scaffolds are gradually attracting attention and development because of their excellent biomimetic properties and efficient repair efficiency. Three‐dimensional (3D) printing technology, which can be used to fabricate structures at different scales using a wide range of materials, has been used in the production of vascularized bone repair scaffolds. This review discusses the research progress in 3D printing for vascularized bone repair scaffolds. Angiogenesis‐osteogenesis coupling in the bone regeneration process is first introduced, followed by a summary of the 3D printing technologies, printing inks, and bioactive factors used to fabricate vascularized bone repair scaffolds. Notably, this review focuses on structural design strategies for vascularized bone repair scaffolds. Finally, the application of vascularized bone repair scaffolds in medicine, as well as challenges and outlooks for future development, are described.
Deep extractive denitrogenation with Cu‐based ionic liquids and mechanistic insights
Authors: Wu Peiwen , Wang Bangzhu , Li Hongping , Ma Shaojie , Chen Linlin , Liu Jixing , Chao Yanhong , Zhu Wenshuai , Xu Chunming
Published: January 2025

A major challenge in the extractive denitrogenation (EDN) of fuel oils lies in achieving high nitrogen removal efficiency with minimal extractant usage. To address this, a series of Cu‐based ionic liquids (ILs) ([Bmim]Cl/CuCl2‐X) with different cation‐to‐anion ratios were synthesized and characterized. The cation‐to‐anion ratio was found to be crucial in determining the predominant anions present in the ILs. Among the synthesized Cu‐based ILs, [Bmim]Cl/CuCl2‐1 exhibited outstanding EDN performance, achieving 100% nitrogen removal with minimal ionic liquid consumption. The anion [CuCl3]− was identified as playing a key role in the EDN process, where the unoccupied orbitals of Cu and the chloridion in [CuCl3]− facilitate effective coordination with nitrogen atoms in organic nitrogen compounds. This coordination forms Lewis acid–base interactions, which are essential for deep EDN. The study not only introduces an efficient Cu‐based ionic liquid but also provides insights into optimizing ionic liquid design for better extraction performance.
Risk of Raynaud's Phenomenon Among Workers in the Occupational Disease Surveillance System
Authors: Yeo Ryann E. , Eros Fanni R. , Demers Paul A. , Sritharan Jeavana
Published: January 2025

Introduction

Raynaud's phenomenon (RP) is linked to occupational exposures such as vibration, cold temperature, and chemicals. However, large cohort studies examining RP by occupation and sex are scarce. To address this gap, this study aimed to assess risk of RP by both occupation and sex in a large cohort of workers in Ontario, Canada.

Methods

Workers with accepted lost‐time compensation claims were linked to physician billing records to identify diagnoses of RP between 2002 and 2020. A 3‐year washout (disease‐free) period was applied, and follow‐up was limited to 5 years. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for diagnoses of RP, adjusted for age at start of follow‐up, birth year, and stratified by sex.

Results

A total of 7,131 RP cases were identified among 810,739 workers. Among men, higher risks were observed for truck drivers (HR = 1.23, 95% CI = 1.08–1.41), driver‐salesmen (HR = 2.54, 95% CI = 1.21–5.34), those in mining and quarrying‐related cutting, handling, and loading (HR = 2.57, 95% CI = 1.29–5.15), and construction trades laboring and elemental work (HR = 1.70, 95% CI = 1.24–2.34). Among women, higher risks were observed for those working in waitressing and related (HR = 1.70, 95% CI = 1.22–2.38), food and beverage preparation (HR = 1.34, 95% CI = 1.02–1.76), and electrical equipment fabricating and assembling (HR 1.96, 95% CI = 1.08–3.55).

Conclusion

Study findings show elevated risks of RP among various occupations, with notable differences between men and women. These differences may be attributable to variations in potential exposures and susceptibility to RP. Findings underscore the need for large cohort studies to examine RP across various occupational groups and both sexes.
Osteoporosis Caused by Monoallelic Variant of WNT1 Gene in Four Pediatric Patients
Authors: Wang Qiao , Liu Min , Cao Bing‐Yan , Su Chang , Meng Xi , Ding Yuan , Ren Xiao‐Ya , Gong Chun‐Xiu
Published: January 2025

Pediatric patients of autosomal dominant early onset osteoporosis conferred by heterozygous mutation in the WNT1 (OMIM: 615221) were rarely reported, and therapy in pediatrics is relatively inexperienced. The clinical and genotypic characteristics and treatment process of four children with osteoporosis caused by WNT1 monoallelic variation were analyzed. The patients admitted from June 2023 to January 2024. All patients presented multiple vertebral compression fracture, two of them experienced recurrent peripheral fragility fractures. The age of the first fractures occur between 2 years and 12 years. Lumber BMD by dual‐energy X‐ray absorptiometry were decreased (height adjusted z score of −8.06 to −3.50). Four monoallelic variants in WNT1 (c.505G>T, c.616G>A, c.677C>T and c. 506G>A with transcript ID. NM_005430.4) were identified in the probands, and relatives carrying mutations presented with a bone phenotype, consistent with autosomal dominant inheritance. Novel variant c.616G>A was analyzed by 3D protein structural modeling. Subsequent to the treatment of zelodronic acid on all four patients, lumbar BMD improvement by 0.061–0.251 g/cm2. Our data showed that the age of onset of osteoporosis by monoallelic variants in WNT1 is significantly earlier than the age of onset in the general population. Severe osteoporosis is also exhibited in pediatric patients, not just in aging patients with WNT1 variant. Zoledronic acid treatment is effective in short‐term observation for pediatric patients with improvement of bone pain and BMD, and no more facture during treatment.
Discovery and Characterization Small Molecule Modulators of Striatal‐Enriched Protein Tyrosine Phosphatase (STEP) for Alzheimer’s Disease Therapeutics
Authors: Wu Jiaqian , Han Ye Na , Cosford Nicholas , Tautz Lutz
Published: January 2025

Background

A pathological hallmark of Alzheimer’s disease (AD) is the accumulation of amyloid‐beta peptide (Aß). Potential treatments targeting Aß production such as γ‐secretase inhibitors have had limited success. A promising alternative approach involves addressing early synaptic dysfunction by modulating molecules like striatal‐enriched protein tyrosine phosphatase (STEP), whose levels and activity are upregulated by Aß. The current model of STEP function is that it opposes the development of synaptic strengthening, and that high levels of STEP contribute to the cognitive deficits in AD. Importantly, genetic reduction or chemical inhibition of STEP reverses the cognitive and cellular deficits in an AD mouse model, validating STEP as a drug target in AD.

Method

Using 19F nuclear magnetic resonance (NMR) spectroscopy, a library of 1,000 fluorine‐containing fragments was screened to identify novel STEP binders. Initial hits were validated using a combination of biophysical binding assays including 19F NMR, 1D WaterLOGSY NMR, microscale thermophoresis (MST), and isothermal titration calorimetry (ITC). Based on a potent and selective fragment, STEP‐targeted protein degraders were designed, synthesized, and characterized in cellular experiments.

Result

Several potent and selective fragments were identified and validated. Based on the most potent binder, five proteolysis targeting chimera (PROTAC) molecules were initially synthesized and characterized. These compounds demonstrated degradation of STEP in SH‐SY5Y neuroblastoma cells. One STEP PROTAC was able to penetrate the blood‐brain barrier and showed potent degradation efficacy in vivo.

Conclusion

Our fragment‐based discovery platform to identify novel STEP binders for the development of specific degrader molecules has yielded first‐in‐class STEP PROTACs. By targeting STEP and thus synaptic dysfunction, our research could provide valuable insights into the early stages of AD pathogenesis and contribute to the development of effective therapeutic strategies for this devastating disease.
Optimizing metabolic stability of phosphodiesterase 5 inhibitors: Discovery of a potent N‐(pyridin‐3‐ylmethyl)quinoline derivative targeting synaptic plasticity
Authors: ZUCCARELLO ELISA , Zhang Hong , Acquarone Erica , Deng Shi‐Xian , Landry Donald W. , Arancio Ottavio , Fiorito Jole
Published: January 2025

Background

There are no cures for Alzheimer’s disease (AD), a progressive neurodegenerative disorder characterized by elevation of beta‐amyloid and tau proteins besides neuronal death and causing cognitive impairment. Phosphodiesterase 5 (PDE5) is a cyclic guanosine monophosphate‐degrading enzyme involved in numerous biological pathways including those relevant to memory formation. PDE5 inhibition offers the potential to attenuate AD progression by acting at the downstream level of beta‐amyloid and tau elevation. None of the existing PDE5 inhibitors has been developed to be used in CNS diseases or possesses the selectivity required for chronic administration to an elderly population with comorbid conditions such as AD patients. We now propose to find PDE5 inhibitors (PDE5Is) that are tailored to the use in AD patients

Method

Our strategy used a combination of drug discovery, biochemical and electrophysiological techniques. We identified the quinoline scaffold of our lead compound 7a, 4‐((3‐chloro‐4‐methoxybenzyl)amino)‐8‐cyclopropyl‐3‐(hydroxymethyl)quinoline‐6‐carbonitrile, as a starting scaffold for a structure activity relationship study aimed at identifying the suitable isosteric substitutions, with the purpose of obtaining new PDE5Is that are more stable than compound 7a, while maintaining potency and selectivity towards other PDE isoforms. The most potent PDE5Is, showing an IC50 in the nano‐molar range, were advanced toward an in vitro metabolic stability assay, and compounds with the highest potency and microsomal stability were tested for phase I and II metabolic identification. Out of these small molecules, the most potent and stable quinoline derivate, compound 4b, was tested in electrophysiological experiments assessing long‐term potentiation (LTP), a type of synaptic plasticity thought to underlie memory formation.

Result

The characterization of compound 7a properties revealed high PDE5 potency (IC50 = 0.27 nM) and great selectivity, but low in vitro human microsomal metabolic stability (half‐life = 20.5min). The second‐generation PDE5Is, compound 4b (8‐cyclopropyl‐3‐(hydroxymethyl)‐4‐(((6‐methoxypyridin‐3‐yl)methyl)amino)quinoline‐6‐carbonitrile), (IC50 = 20 nM) had improved in vitro microsomal stability (t1/2 = 44.6 min), and an outstanding phase I and II metabolic profile. Both compounds ameliorated the deficit in LTP, a cellular surrogate of memory, after exposure of hippocampal slices to tau oligomers.

Conclusion

These data suggest that compounds 7a and 4b are important leads in the pharmacologic restoration of cell‐to‐cell communication and memory in AD.
Synergistic influence of education and marriage on the risk for cognition loss among the older people in China
Authors: Sun Ning
Published: January 2025

Background

The study was aim to prove that both rationality and emotion are indispensable for older people to maintain their ability to live independently during the twilight of their lives.

Method

The resilience of older people to dementia were investigated by considering the interactions between educational levels and marriage status. Four sociodemographic variables (age, sex, educational level, and marital status) were collected from 1177 older Chinese participants, whose mini‐mental state examination scores (MMSE scores) were measured.

Result

A lower educational level coupled with being widowed caused a greater risk for severe cognitive impairment (relative risk [RR] 1.48; 95% confidence interval [CI] 1.20‐1.82; p < 0.001) for high‐aged older participants (age range: ≥80) than for their low‐aged counterparts (age range: ≥60 and <80). In contrast, a higher educational level coupled with being married leveled this age‐related risk for cognitive loss (RR 0.91; 95% CI 0.65‐1.27; p = 0.62).

Conclusion

Further findings suggest that the synergistic influence of education and marriage was observed only among high‐aged older people. Being both well‐educated and married is associated with a delayed cognitive function for older people. However, longevity is a prerequisite for realizing this benefit.
Latent atrophy factors in Primary Progressive Aphasia due to Alzheimer´s disease and linguistic features, across different cultural settings
Authors: Calandri Ismael Luis , Groot Colin , Wesseling Alex J. , Garcia Florentina Morello , Allegri Ricardo , Barkhof Frederik , Jonkman Laura E. , Pijnenburg Yolande A.L. , Ossenkoppele Rik
Published: January 2025

Background

Primary Progressive Aphasia (PPA) is a clinical entity that encompasses various neurodegenerative etiologies. Based on differential linguistic profiles, PPAhas been classified into three phenotypes (i.e., semantic [svPPA], non‐fluent [nfvPPA] and logopenic [lvPPA]), each characterized by unique atrophy patterns. Linguistic classification encounters a cultural barrier, as, e.g., certain features (like surface dyslexia) are difficult to objectify across languages, limiting the classification's generalizability. Our aim is to create an atrophy pattern detection model to predict PPA subtypes, independent of the cultural context that modifies linguistic features.

Methods

We extract latent gray matter atrophy factors (LF) in a cohort of 134 Dutch‐speaking individuals with a clinical diagnosis of PPA. We use a data‐driven Bayesian modeling framework using latent Dirichlet allocation, and uncovered four LF’s from standardized gray matter density images (adjusted for age, sex, and MRI scanner). For each subject, the probability of belonging to each of the four LF’s was calculated. The probability assignment to each LF was compared against the linguistic phenotype assigned by a neurologist and AD biomarker status. The model was also applied to post‐mortem MRI data from 4 subjects to examine their neuropathological correlates.

Results

the 4 LF’s are shown in Figure 1. LF1 (“svPPA‐like”) showed left‐predominant temporo‐polar atrophy; LF2 (“nfvPPA‐like”) left‐predominant fronto‐opercular and insular atrophy; LF3 (“lvPPA‐like") left‐predominant posterior‐parietal involvement; LF4 (“other”) parieto‐occipital. Higher LF1 probability was significantly associated with a clinical svPPA diagnosis (non‐standarized b=11, 95%CI[7.2‐15.0], p<0.001), higher LF2probability with a nfvPPA diagnosis (7.2[4.0‐11.0], p<0.001), and higher LF3 probability with lvPPA (9.0[5.9‐13], p<0.001). Higher LF3 probability was associated with a higher frequency of positive AD biomarkers (7[4.6‐11], p<0.001; Figure 2). Model generalizability will be tested by classifying 35 Spanish‐speaking subjects with PPA from Argentina based on their atrophy pattern (data presented at the conference).

Conclusion

Our model demonstrates a strong ability to predict phenotypic classification and AD pathology through MRI. It can contribute to standardizing diagnostic performance across different cultural settings.
Communicating with patients about the new disease‐modifying treatment(s) for Alzheimer’s disease: the perspective of memory clinic professionals
Authors: Visser Leonie N.C. , Fluitman Tjeerd , van Gils Aniek M. , van der Veere Pieter J. , van Harten Argonde C. , Vijverberg Everard G.B. , van der Flier Wiesje M.
Published: January 2025

Background

The first disease‐modifying treatments (DMTs) for Alzheimer’s disease (AD) have been approved in the USA, marking profound changes in AD‐diagnosis and treatment. This will bring new challenges in terms of clinician‐patient communication. We aimed to collect the perspectives of memory clinic professionals regarding the most important topics to address and what (tools) would support professionals and their patients and care partners to engage in a meaningful conversation on whether (or not) to initiate treatment.

Methods

Semi‐structured interviews were conducted with 16 professionals (10 neurologists, 4 geriatricians, 2 other; 7 female) with >5 years of experience in various Dutch memory clinics. We described the context of (at the time hypothetical) EMA approval, and asked questions such as ‘How would you communicate with patients about DMTs?’(Table 1). The transcribed audio‐recordings were analyzed by means of thematic analysis using MaxQDA software.

Results

A first overarching theme concerned the ambivalence that professionals expressed towards DMTs. On the one hand, they considered approval of the first DMTs as a hopeful development. On the other hand, they expressed caution considering expected effects, risks of (serious) side effects, and burdensome procedures. Professionals therefore emphasized the need for shared decision‐making (SDM) with patients and care partners. Second, to enable SDM, they stressed that professionals and patients must comprehend essential information, including the mechanisms of AD and DMTs, benefits, and potential negative aspects, and that patients/care partners express their needs, expectations, and personal circumstances. Third, professionals anticipated challenges, including the required consultation time and insufficient knowledge/experience with DMTs and/or SDM. They would therefore value education and communication tools, also for patients and care partners, to help them prepare for consultations and increase understanding (Table 2).

Conclusion

A broad representation of memory clinic professionals emphasized that initiating DMT for AD is a preference‐sensitive decision. SDM is not a new concept in memory clinics, yet professionals considered SDM imperative and more complex in the DMT‐context, because of the uncertainties regarding effects, risk of side effects, and burden of DMT‐administration/monitoring. To support professionals and patients in having a meaningful conversation about DMT‐initiation, educational materials and communication tools are needed.
Association of Acquired Immunodeficiency Syndrome with Alzheimer`s Disease‐Related Dementia in HIV‐Infected Individuals
Authors: Lee Young‐gun , Lee Eunyoung , Bang Jihwan
Published: January 2025

Background

Cognitive decline often follows human immunodeficiency virus (HIV) infection, yet the specific risk factors for developing Alzheimer’s disease and related dementia (ADRD) in HIV patients remain elusive.

Method

To investigate the association between acquired immune deficiency syndrome (AIDS) status at the time of HIV diagnosis and the risk of ADRD, we conducted a retrospective cohort study using data from a nationwide claim database spanning 2008 to 2021. During the study period, 13,289 patients were newly diagnosed with HIV infection and were prescribed antiretroviral therapy (ART). Among them, a total of 3,929 individuals over 40 years old, with a follow‐up exceeding 3 years and without dementia diagnosed within two months post‐HIV diagnosis, were included. Cox proportional hazards regression models for ADRD requiring medication such as anti‐cholinesterase inhibitor or memantine were performed using baseline presence of AIDS as a predictor, after adjusting for age, sex, insurance type, and comorbidities.

Result

Among the 3,929 participants (median age: 45 [IQR 15] years; 90.9% male), with a median follow‐up of 7.6 (IQR 5.0) years, 114 patients were diagnosed with ADRD. HIV individuals with AIDS at baseline had a higher risk of ADRD (hazard ratio [HR], 2.21; 95% confidence interval [CI], 1.51 – 3.31) compared to those without AIDS. The risk was more prominent in individuals under 50 years old (HR, 5.39; 95% CI, 2.22 – 13.05) than in those 50 years or older (HR, 1.68; 95% CI, 1.07 – 2.63; P for interaction = 0.03).

Conclusion

This study underscores the need to stratify the management of cognitive impairment in newly diagnosed HIV patients based on their baseline AIDS status and age.
The effectiveness of psychological therapies for anxiety or depression, for people living with atypical dementia
Authors: Baou Celine El , Saunders Rob , Buckman Joshua , Richards Marcus , Cooper Claudia , Bell Georgia , Fearn Caroline , Pilling Stephen , Crutch Sebastian J , Zimmermann Nikki , Brotherhood Emilie V , John Amber , Stott Joshua
Published: January 2025

Background

Prior research has highlighted that people living with dementia experiencing depression or anxiety can benefit from psychological therapies delivered in primary care. Yet, studies have mainly focused on common dementia types, leaving a gap in evidence for more atypical dementias, and especially those that are not memory‐led. This evaluation is crucial, given the unique challenges posed by these subtypes, such as syndrome‐specific symptoms of changes in personality or visual processing. This study assesses the effectiveness of psychological therapies provided in primary care settings for individuals with atypical dementia subtypes.

Method

Linked national data from over 2 million individuals in the UK who received a course of therapy in NHS Talking Therapies for Anxiety and Depression services were used to identify 523 individuals with atypical dementias who attended therapy between 2012 and 2019. We compared their depression and anxiety outcomes to a cohort of individuals with no diagnosis of dementia.

Result

People with atypical dementia had similar outcomes compared to people with typical dementia [Reliable improvement from depression and anxiety symptoms: AdjOR 1.08 (0.86; 1.36) p = 0.4850], but their therapy outcomes were poorer when compared to the matched cohort without dementia [Reliable improvement: AdjOR 0.70 (0.53; 0.91) p = 0.0150].

Conclusion

People with atypical dementia who experience depression or anxiety may benefit from psychological therapies provided in primary care. Their outcomes are poorer than those of people who do not have dementia. These results suggest a need to increase access to psychological therapies for people with atypical dementia and offer interventions that are better tailored to their specific experiences.
Deriving meaningful within‐patient change thresholds for the ADCS‐ADL in trials of early and mild‐to‐moderate Alzheimer’s disease ‐ a caregiver‐rated, anchor‐based analysis of the Tauriel and Lauriet trials
Authors: Ritchie Marina , Datta Seema , Lansdall Claire J , Monteiro Cecilia , Toth Balazs , Teng Edmond
Published: January 2025

Background

Clinical outcome assessments (COAs) that measure functional capacities are key tools to evaluate efficacy in Alzheimer’s disease (AD) clinical trials. The Alzheimer’s Disease Cooperative Study Activities of Daily Living (ADCS‐ADL) scale is frequently used to assess changes in both basic and instrumental activities of daily living, but there is no clear consensus on what magnitude of change on this scale may be considered clinically meaningful. To address this question, we conducted anchor‐based analyses (as recommended by the FDA) to explore meaningful within‐patient/participant change thresholds on the ADCS‐ADL.

Methods

Our anchor‐based analyses (and supportive distribution‐based analyses) used data from two phase 2 semorinemab trials, Tauriel (NCT03289143; early AD) and Lauriet (NCT03828747; mild‐to‐moderate AD). The Caregiver Global Impression of Change‐Alzheimer’s Disease (CaGI‐Alz), a caregiver‐reported measure on subjective change in participant function, served as the anchoring scale. To determine if anchor‐based analyses were appropriate, we first examined correlations between the ADCS‐ADL change scores and CaGI‐Alz ratings at Weeks 25 and 49 for both trials, along with Week 61 for Lauriet, and Week 73 for Tauriel. To determine meaningful change thresholds, we analyzed the mean changes on the ADCS‐ADL for participants rated as performing “somewhat worse” on CaGI‐Alz. Those rated as demonstrating“no‐change” were used for comparison.

Results

Correlations between the ADCS‐ADL and the CaGI‐Alz scales were consistently stronger at Week 49 and later time points (Table 1). For those rated as “somewhat worse,” mean decline on the ADCS‐ADL ranged from approximately 5 to 8 points across time points, and uniformly exceeded distribution‐based thresholds. Larger declines on the ADCS‐ADL were associated with “somewhat worse” ratings in patients in Lauriet (mild‐to‐moderate AD) compared to Tauriel (early AD) and at later time points in both trials (Table 2). Patients rated as “no change” by the caregiver experienced some decline on the ADCS‐ADL, although generally less than the declines seen in those rated “somewhat worse.”

Conclusion

The anchor‐ and distribution‐based approaches suggest that clinically meaningful change on the ADCS‐ADL may be greater than the 2 points that has previously been postulated (Dysken et al., 2014). Higher change thresholds may be required to reflect meaningful changes perceptible to caregivers.
Hippocampal Functional Organization Mediates the Impact of the Cortical Iron on the Cognition in Women with Suspected Coronary Microvascular Dysfunction
Authors: Silemek Arzu C Has , Wertheimer Jeffrey C , Wei Janet , Dumitrascu Oana M , Kremen Sarah , Xie Yibin , Li Debiao , Nelson Michael D , Tan Zaldy S , Merz Noel Bairey , Sati Pascal , Gao Wei
Published: January 2025

Background

Women with suspected coronary microvascular dysfunction (CMD) may be at higher risk of experiencing cognitive decline due to cerebral small vessel disease, a known contributor to Alzheimer’s disease and related dementias (ADRD). A potential underlying mechanism that could accelerate this cognitive decline is the accumulation of brain tissue iron, which has been previously linked to changes in brain function potentially caused by oxidative stress and cell death. Therefore, we aim to elucidate whether a similar mechanism could affect women with suspected CMD by investigating the potential role of iron deposition on the brain’s functional organization and its effect on cognition using advanced magnetic resonance imaging (MRI).

Material and Methods

Twenty‐seven women with suspected CMD [Age; median (range) = 54 (29‐76)], drawn from ongoing cohorts (3R01HL146158‐04S1,3U54AG065141‐04S1), underwent a 3T MRI protocol, including submillimeter T2* 3‐dimensional echo‐planar‐imaging for assessing iron deposition with high‐resolution quantitative susceptibility mapping (QSM) and resting‐state fMRI (rs‐fMRI). Iron content was quantified by total‐generalized‐variation based QSM analysis. Functional integrity was determined via graph theoretical approach (i.e., nodal degree). Cognitive assessment was also performed using the NIH Toolbox. Mediation analysis was conducted using Python Statsmodels.

Results

Most of the women with suspected CMD showed lower performance in processing speed, working memory, executive function, and attention (Figure 1A). We found a significant association between elevated iron levels in paracentral gyrus and lower functional connectivity in left hippocampus (p=0.005, adjusted‐r2=0.19) (Figure 1B). Elevated iron level in the paracentral gyrus showed an impact on cognitive performance in the domains of executive function and attention (p<0.0001, coefficient=531.09) as well as language functions and crystalized abilities (p=0.036, coefficient=362.45), mediated by functional connectivity in the left hippocampus (indirect effect on executive function / language: p = 0.034 / 0.038, coefficient = ‐254.54 /‐ 213.06) (Figure 1C).

Conclusions

Our results suggest that changes in hippocampal functional organization are associated with cortical iron deposition and mediate its impact on cognitive performances. These changes may increase the risk of cognitive decline/ADRD or in women with suspected CMD. Future research in a larger cohort with a longitudinal design is necessary to validate and expand upon these findings.
Association of lifestyle activities with cognitive function and Alzheimer’s disease CSF biomarkers: an examination of cognitively normal adults in the Stanford Aging and Memory Study (SAMS)
Authors: Lu Olivia , Mormino Elizabeth , He Zihuai , Carr Valerie A , Trelle Alexandra N. , Young Christina B. , Romero America , Vossler Hillary , Park Jennifer , Skylar‐Scott Irina Anna
Published: January 2025

Background

It is increasingly clear that delaying the onset of Alzheimer’s disease (AD) dementia by several years can meaningfully lower its prevalence. The goal of the present study is to examine the relationship between lifestyle activities and cognition function as well as cerebrospinal fluid (CSF) biomarkers of AD to determine whether these activities can serve as protective factors for AD resistance and resilience.

Methods

173 cognitively normal older individuals (mean ± SD, 69 ± 6.4 years) were recruited to the Stanford Aging and Memory Study (SAMS) and completed the Community Healthy Activities Model Program for Seniors (CHAMPS) questionnaire regarding current social, cognitive, and physical activity (Table 1). They also underwent APOE genetic testing and a detailed neuropsychological evaluation. The following cognitive domains were evaluated after conversion to z‐scores: global cognition (cognitive composite), executive function, working memory, attention, episodic memory, visuospatial function, and language (see Table 2 for definitions). 127 participants completed lumbar punctures, and levels of Aβ‐40, Aβ‐42, p‐tau181, and total tau were measured in the CSF. Cross‐sectional regression models included age, sex, years of education, and APOE status as co‐variates. Benjamini‐Hochberg corrections for multiple hypotheses were completed.

Results

There was a significant association between social activity (frequency/week) and global cognition (β = 0.20, p = 0.03), executive function (β = 0.15, p<0.05), and working memory (β = 0.26, p = 0.01) but not episodic memory, visuospatial function, or language function. There was also a significant association with attention prior to correction for multiple hypotheses (β = 0.17, p = 0.04) but not afterward (Table 2). Additionally, there was a significant association between cognitive activity (hours/week) and global cognition (β = 0.19, p = 0.03) as well as executive function (β = 0.25, p = 0.007) but not with other cognitive domains tested (Table 3). There was no association between light or moderate caloric expenditure and cognitive measures. There was also no significant relationship between CSF biomarkers and levels of social, cognitive, and physical activity.

Conclusions

In a well‐characterized cohort of cognitively normal older adults, higher levels of social and cognitive activity were associated with higher cognitive scores on tasks of executive function but not episodic memory. The mechanism mediating this relationship appears to be independent of both Aβ and tau burden.
Associations of early‐life factors and risk of incident dementia: a cohort study of 247,841 participants
Authors: Ou Ya‐nan , Tan Lan , Yu Jin‐Tai
Published: January 2025

Background

Life‐course models are increasingly recognized in dementia prevention but have too often focused on mid to later life, thereby missing major opportunities for prevention much earlier. This study aimed to reveal the associations between early‐life factors and incident dementia risk, and the underlying brain imaging alterations.

Method

Eight early‐life factors (maternal smoking around birth, birth weight, part of a multiple birth, breastfed as a baby, adopted as a child, comparative height at age 10, comparative body size at age 10, and child maltreatment) in the UK BioBank (UKB) were investigated. Multi‐adjusted Cox proportional hazard model and restricted cubic spline model were performed to investigate the longitudinal associations. Linear regression analysis was performed to reflect the statistical dependencies with brain imaging measurements.

Result

A total of 247,841 UKB participants with a mean age of 59.9 (SD 5.5) years old and a female percentage of 57.2% were included. Over a mean of 8.7 (SD 2.7) years of follow‐up, 3,661 all‐cause dementia (ACD) were recorded. Maternal smoking around birth and shorter height at age 10 was associated with an 13%‐20% increased risk of dementia. Approximate linear relationship between birth weight and dementia risk was revealed. Maintaining the specific birth weight window (3.73‐5.00 kg) was related with lowest vascular dementia (VaD) risk. Physical neglect was related with all of the three dementia outcomes (HR:2.56 for ACD, HR:2.91 for Alzheimer’s disease [AD], HR:6.87 for VaD). Extensive associations exist between early life factors and dementia‐related brain structures, especially middle temporal lobe and hippocampus.

Conclusion

Early risk factors are closely associated with late‐life dementia risk. Policies investing in early child development may contribute to improve lifelong brain health to prevent late‐life dementia.
Occupational complexity and cognitive resilience in the Framingham Heart Study
Authors: Hwang Phillip H , Feng Irena , Durape Shruti , Gurnani Ashita S. , Ang Ting Fang Alvin , Devine Sherral A. , Choi Seo‐Eun , Lee Michael L. , Scollard Phoebe , Gibbons Laura E. , Mukherjee Shubhabrata , Trittschuh Emily H. , Sherva Richard , Dumitrescu Logan C. , Hohman Timothy J. , Saykin Andrew J. , Crane Paul K. , Au Rhoda , Farrer Lindsay A. , Mez Jesse
Published: January 2025

Background

Greater occupational complexity may be protective against dementia in later life, but it is unclear if it contributes to cognitive resilience and whether different aspects of occupational complexity are associated with resilience. We examined relationships between occupational complexity related to data, people, and things, and cognitive resilience to neurodegeneration.

Method

1,699 participants from the Framingham Heart Study Offspring cohort who were aged ≥60 years, had a plasma total tau (t‐tau) measure (a marker of neurodegeneration), and a neuropsychological (NP) exam visit within five years of the plasma t‐tau measurement were included. Plasma t‐tau was measured using the Simoa assay (Quanterix) on samples collected at Exam 8 (2005‐2008). NP factor scores were previously derived for memory, language, and executive function using confirmatory factor analysis. Occupational data were collected at the NP exam, from which occupational complexity was disaggregated into data complexity, people complexity, and things complexity according to the 1970 US Census Dictionary of Occupational Titles. Cognitive resilience was operationalized using a residual approach by regressing each NP factor score on the plasma t‐tau measure, adjusting for age, sex, education, time from blood draw, and APOE ε4 status. The adjusted residuals were then regressed on each type of occupational complexity, dichotomized into higher complexity versus lower complexity.

Result

The sample was, on average, 70 years of age, 53% female, and had 15 years of education. Higher data (β = 0.20, 95% confidence interval (CI) = 0.15‐0.25, p<0.001), people (β = 0.11, 95% CI = 0.07‐0.15, p<0.001), and things (β = 0.05, 95% CI = 0.01‐0.09, p = 0.015) occupational complexity were most strongly associated with resilience in executive function. Higher data (β = 0.10, 95% CI = 0.05‐0.15, p<0.001) and people (β = 0.07, 95% CI = 0.03‐0.11, p = 0.001) occupational complexity were associated with resilience in memory. Higher data (β = 0.07, 95% CI = 0.01‐0.12, p = 0.014) occupational complexity was associated with resilience in language.

Conclusion

Specific types of occupational complexity contribute to resilience to neurodegeneration in specific cognitive domains differently. Occupational complexity may offer the most resilience in executive function and occupations with high data complexity may offer the most cognitive resilience.