bluuebunny/crossref_metadata_2025 huggingface dataset:
Observation of Exceptional Stability in a Nonlinear Optical Crystal Under Extreme Conditions
Authors: Wang Yuejian , Barone Victor T , Khare Sanjay V. , Yang Ankun , Zhang Dongzhou , Ryu Young Jay , Menon Sidharth , Zhou Wei‐lin , Kanthan Prathisha Sri , Kozel Matthew
Published: January 2025

As a unique nonlinear optical material, Ba3(ZnB5O10)PO4 (BZBP) boasts a range of distinctive properties, including low anisotropic thermal expansivity, high specific heat, minimal walk‐off effect, large acceptance angle, non‐hygroscopicity, and high conversion efficiency. These features position BZBP as a highly promising candidate for crucial components in ultraviolet (UV) laser systems. Notably, all previous studies have been conducted under ambient pressures. In this research, synchrotron X‐ray diffraction and Raman spectroscopy are employed to investigate BZBP's behavior under extreme conditions. The findings revealed that BZBP remains exceptionally stable up to 43 Gigapascals (GPa), significantly extending its application range from ambient to high‐pressure environments. This stability enhancement opens new avenues for utilizing BZBP in optical systems designed to function under extreme conditions. Additionally, the study determined BZBP's bulk modulus (110 GPa) and linear compressibility along each lattice axis. Theoretical computations are used to assign the Raman modes, characterize their corresponding lattice vibrations, validate the experimental results, and elucidate the mechanisms underlying the material's remarkable stability.
Crystal‐Phase Engineering of Iridium‐Embedded Tungsten for Hydrogen Oxidation Electrocatalysis
Authors: Zhao Lei , Ouyang Bo , Yang Yisong , Li Jingtao , Xu Kun
Published: January 2025

Understanding the phase structure‐dependent catalytic performance is of great significance for the investigation of advanced electrocatalysts. At present, research in phase engineering of metal materials for electrocatalysis predominantly concentrates on the iron group, platinum group, and coinage group metals with A1‐, A2‐, and A3‐ type structures. However, the investigation of metal phase engineering beyond the above metal group with other types of structures for electrocatalysis is still poorly explored. Herein, using tungsten as a substrate to support iridium, it is shown that iridium‐embedded tungsten with diverse crystal phase structure (referred to as Ir/α‐W for A2‐type structure and Ir/β‐W for A‐15 type structure) exhibits distinct catalytic activity for hydrogen oxidation reactions (HOR) in alkaline medium. Notably, the mass‐normalized exchange current density (j0, m) of noble metal iridium in Ir/α‐W (518.3 A g−1Ir) is ≈1.8 times and 16.4 times higher than that of Ir/β‐W and Ir/C, respectively. In‐depth mechanistic studies suggest that the enhanced HOR performance on Ir/α‐W is attributed to the enhanced connectivity of the H‐bond network as well as the synergistic optimization of the adsorption binding energies of H and OH intermediate species. This study can inspire more scientific interest on the exploration of metal phase engineering for electrocatalysis.
Intrinsic Anti‐Freezing, Tough, and Transparent Hydrogels for Smart Optical and Multi‐Modal Sensing Applications
Authors: Zhang Xinyue , Lin Ye , Shen Shengtao , Du Zehang , Lin Ziqing , Zhou Piaopiao , Huang Hanlin , Lyu Xiaolin , Zou Zhigang
Published: January 2025

Hydrogels have received great attention due to their molecular designability and wide application range. However, they are prone to freeze at low temperatures due to the existence of mass water molecules, which can damage their flexibility and transparency, greatly limiting their use in cold environments. Although adding cryoprotectants can reduce the freezing point of hydrogels, it may also deteriorate the mechanical properties and face the risk of cryoprotectant leakage. Herein, the microphase‐separated structures of hydrogels are regulated to confine water molecules in sub‐6 nm nanochannels and increase the proportion of bound water, endowing the hydrogels with intrinsic anti‐freezing properties, high mechanical strength, good stretchability, remarkable fracture energy, and puncture resistance. Even after being kept in liquid nitrogen for 1000 h, the hydrogel still maintains good transparency. The hydrogel can exhibit excellent low‐temperature shape memory and intelligent optical waveguide properties. Additionally, the hydrogel can be assembled into strain and pressure sensors for flexible sensing at both room and low temperatures. The intrinsically anti‐freezing microphase‐separated hydrogel offers broad prospects in low‐temperature electronic and optical applications.
Biopolymer‐Based Flame Retardants and Flame‐Retardant Materials
Authors: Xu Ying‐Jun , Zhang Kai‐Tao , Wang Ji‐Rong , Wang Yu‐Zhong
Published: January 2025

Polymeric materials featuring excellent flame retardancy are essential for applications requiring high levels of fire safety, while those based on biopolymers are highly favored due to their eco‐friendly nature, sustainable characteristics, and abundant availability. This review first outlines the pyrolysis behaviors of biopolymers, with particular emphasis on naturally occurring ones derived from non‐food sources such as cellulose, chitin/chitosan, alginate, and lignin. Then, the strategies for chemical modifications of biopolymers for flame‐retardant purposes through covalent, ionic, and coordination bonds are presented and compared. The emphasis is placed on advanced methods for introducing biopolymer‐based flame retardants into polymeric matrices and fabricating biopolymer‐based flame‐retardant materials. Finally, the challenges for sustaining the current momentum in the utilization of biopolymers for flame‐retardant purposes are further discussed.
Imine‐Linked 3D Covalent Organic Framework Membrane Featuring Highly Charged Sub‐1 nm Channels for Exceptional Lithium‐Ion Sieving
Authors: Wu Tong , Qian Yijun , Zhu Zebin , Yu Weihao , Zhang Lifang , Liu Jie , Shen Xiaowei , Zhou Xi , Qian Tao , Yan Chenglin
Published: January 2025

Coupling ion exclusion and interaction screening within sub‐nanoconfinement channels in novel porous material membranes hold great potential to realize highly efficient ion sieving, particularly for high‐performance lithium‐ion extraction. Diverse kinds of advanced membranes have been previously reported to realize this goal but with moderate performance and complex operations gained. Herein, these issues are circumvented by preparing the consecutive and intact imine‐linked three‐dimensional covalent organic framework (i.e., COF‐300) membranes via a simple solvothermal approach and employing the intrinsically interconnected sub‐1 nm one‐dimensional channels for exceptional lithium‐ion sieving. The synthesized membranes with highly charged angstrom scale channels of ≈0.78 nm achieve an excellent Li+ permeance (0.123 mol m−2 h−1) with an ultrahigh Li+/Mg2+ of 36 in the binary system. The experimental measurement and theoretical calculation reveal that a channel size right exactly between Li+ and Mg2+ enables restricted Mg2+ penetration. Meanwhile, the ion affinity interaction screening with imine groups further strengthens the fast Li+ permeability but severely suppresses the Mg2+ passage. In particular, the synthesized three‐dimensional covalent organic framwork membranes also have a remarkable separation performance during a long‐term operation test without sacrificing trade‐off, demonstrating chemistry stability and mechanical integrity under the high‐salinity aqueous environment.
Visible‐Light‐Induced Difluoroalkylation of C(sp3)−H Bonds with Trimethylsilyl Chloride as a Dual‐Function Reagent
Authors: Wang Xiaochen , Wu Senhui , Ding Pengxuan , Liu Yuxiu , Song Hongjian , Wang Qingmin
Published: January 2025

Herein, we report a mild, operationally simple method for synthesis of α,α‐difluoroketones through selective single defluorination of trifluoroketones and subsequent difluoroalkylation of C(sp3)−H bonds at room temperature within a single step. By successfully difluoroalkylating unfunctionalized ethers and benzyl radical precursors, we demonstrated the broad applicability of this method. The mechanistic study supports that the success of the reaction is probably attributed to the dual roles of trimethylsilyl chloride under the photocatalyzed conditions: 1) fluoride anion scavenger; and 2) chlorine radical source which promote hydrogen atom transfer (HAT) reaction.
Multifunctional Crown Ether Additive Regulates Desolvation Process to Achieve Highly Reversible Zinc‐Metal Batteries
Authors: Wu Aohua , Zhang Shaojie , Li Qiaohui , Xue Wenxian , Li Chuanyang , Xi Baojuan , Mao Wutao , Bao Keyan , Xiong Shenglin
Published: January 2025

Aqueous zinc‐ion batteries have garnered significant attention due to their abundant materials, low production costs, and safety. However, these batteries suffer from severe side reactions, which are closely associated with the presence of a substantial amount of solvent at the electrode surfaces. Herein, 1,4,7,10,13,16‐hexaoxacyclooctadecane (18‐crown‐6) is added to the electrolyte to illustrate both theoretically and experimentally its contribution to the rapid desolvation aspect. It is shown that the addition of 18‐crown‐6 to the electrolyte greatly facilitates the desolvation of the solvated structure and prevents the collection of solvent molecules on the surface of zinc anode, thus inhibiting the hydrogen precipitation reaction. It also enhances the transference number of zinc ions, which makes the interfacial electric field on the zinc anode stable and thus promotes the orderly diffusion and uniform nucleation of Zn2+, and inhibits the growth of dendrites. As a result, the electrolyte containing 18‐crown‐6 as additives shows a stable cycle life, Zn||Zn symmetric cell is cycled for nearly 1700 h at 1 mA cm−2, showing a significant improvement in Coulombic efficiency. The assembled Zn||NH4V4O10 cell exhibits excellent electrochemical performance, reaching a capacity of 100.9 mAh g−1 even after 4000 cycles at 10.0 A g−1.
The Influence of Various Feeding and Pond Fertilization Strategies on Nile Tilapia (Oreochromis niloticus L.) Production and the Selectivity for Natural Versus Supplementary Diet in Semi‐Intensive Aquaculture Systems
Authors: Musa Safina , Aura Christopher Mulanda , Tomasson Tumi , Sigurgeirsson Ólafur , Kubiriza Godfrey Kawooya , Thorarensen Helgi
Published: January 2025

High feed costs constrain tilapia production, making exploring low‐cost feeding strategies important. We assessed the growth of tilapia over a period of 6 months, fed 1%, 2%, or 4% of body mass day−1 with and without fertilization in 18 liner ponds stocked with fingerlings (5.1 ± 0.71 g). Growth was significantly better in fertilized ponds than in unfertilized ponds. The best growth (320.7 ± 8.5 g) was in fertilized ponds where fish were fed 2%, achieving a 45% larger weight gain than in the group fed 4% in unfertilized ponds. These results show that with fertilization, the feeding can be reduced by half while still having better growth than in unfertilized ponds. In fertilized ponds fed 4%, the minimum nocturnal oxygen levels may have limited growth of the fish and, as a result, their final weight (180.1 ± 6.6 g) was lower than in groups fed 2% in fertilized ponds and 4% in unfertilized ponds. Fish up to 60–90 g rely mainly on zooplankton as a source of food, while fish of sizes ≥100 g rely mainly on supplementary feed. Analysis of the gut content of fish of different sizes suggested that tilapia up to 60–90 g do not consume the feed presented which instead ends up as an expensive form of fertilizer. The best economic return was in ponds that were fertilized and fed 2%. It is concluded that feed‐use and production costs may be reduced even further by fertilizing the ponds and restricting or omitting feeding of fish < 100 g and only commence feeding when the fish have reached around 100 g. The results of the finding have a wider applicability in developing countries where pond culture of tilapia is common.
Flood‐driven survival and growth of dominant C4 grasses helps set their distributions along tallgrass prairie moisture gradients
Authors: Wernerehl Robert W. , Givnish Thomas J.
Published: January 2025

Premise

Five C4 grasses (Bouteloua curtipendula, Schizachyrium scoparium, Andropogon gerardii, Sorghastrum nutans, Spartina pectinata) dominate different portions of a moisture gradient from dry to wet tallgrass prairies in the Upper Midwest of the United States. We hypothesized that their distributions may partly reflect differences in flooding tolerance and context‐specific growth relative to each other.

Methods

We tested these ideas with greenhouse flooding and drought experiments, outdoor mesocosm experiments, and a natural experiment involving a month‐long flood in two wet‐mesic prairies.

Results

Bouteloua promptly succumbed to inundation, so flooding intolerance likely excludes it from wet and wet‐mesic prairies. Competition is likely to exclude short‐statured Bouteloua from productive mesic sites. Schizachyrium is excluded from wet prairies by low flooding tolerance, demonstrated by all experiments. Sorghastrum had low flooding tolerance in both greenhouse and natural experiments, suggesting that physiological intolerance excludes it from wet prairies. Spartina had by far the greatest growth under the wettest mesocosm conditions; this and comparisons of species growth in monocultures vs. mixtures suggests that competition helps it dominate wet prairies. Indeed, quadrat presence of Spartina increased by 57% two years after flooding of two prairies, while that of upland grasses declined by 44%. The high flooding tolerance, lack of significant differences from other species in drought tolerance, and tall stature of Andropogon suggest that broad physiological tolerance combined with competitive ability allows it to thrive across the prairie moisture gradient.

Conclusions

Flooding helps shape the distributions of dominant prairie grasses, and its effects may become more important as extreme rain events continue to increase.
C–Centered Radicals: Generation, Detection, Stability and Perspectives
Authors: Velloth Archana , Kumar Piyush , Butt Shabana , Venkataramani Sugumar
Published: January 2025

C–Centered radicals are one of the classical reactive intermediates that have shown enormous utility in organic synthesis. Besides homolytic bond cleavages, the advancements of electron transfer‐based photoredox and electroredox processes are popular choices for their generation and synthetic explorations. Considering the widespread attention and versatility of C‐centered radicals in several fields, a systematic understanding of structural, stability, and reactivity aspects is crucial for the further development and futuristic applications of radical chemistry. In this regard, several topics pertaining to the generation, detection, and studies relevant to radical chemistry in general and thermodynamic and kinetic stability of the C‐centered radicals specifically, with a major emphasis on physical organic chemistry aspects, are presented. Besides portraying the factors governing their stability and reactivity, this contribution also discusses their challenges and perspectives.
FeCl3‐Promoted Conjugate Reduction of Exocyclic α,β‐Unsaturated Ketones with Polymethylhydrosiloxane
Authors: Zhang Yulong , Wang Hang , Gu Bin , Hu Bowen , Tang Xiaoxue , Chen Yushuang
Published: January 2025

A new iron catalytic conjugate reduction of exocyclic α,β‐unsaturated carbonyl compounds with PMHS has been established for the first time. The reaction utilized PMHS as readily available, non‐toxic, and mild reductant that can be handled in open air. This protocol exhibits high compatibility with various substituents, and gives excellent yields, providing an environmentally benign and efficient access to construct synthetically useful α‐benzyl cyclic ketone scaffolds.
How Do Common Marmosets Maintain the Balance Between Response Execution and Action Inhibition?
Authors: Samandra Ranshikha , Rosa Marcello G. P. , Mansouri Farshad A.
Published: January 2025

Socio‐dynamic situations require a balance between response execution and action inhibition. Nonadaptive imbalance between response inhibition and execution exists in neurodevelopmental and neuropsychological disorders. To investigate the underlying neural mechanisms of cognitive control and the related deficits, comparative studies in human and nonhuman primates are crucial. Previous stop‐signal tasks in humans and macaque monkeys have examined response execution (response time (RT) and accuracy in Go trials) and action inhibition (stop‐signal reaction time (SSRT)). Even though marmosets are generally considered suitable translational animal models for research on social and cognitive deficits, their ability to inhibit behavior remains poorly characterized. We developed a marmoset stop‐signal task, in which RT could be measured at millisecond resolution. All four marmosets performed many repeated Go trials with high accuracy (≥ 70%). Additionally, all marmosets successfully performed Stop trials. Using a performance‐dependent tracking procedure, the accuracy in Stop trials was maintained around 50%, which enabled reliable SSRT estimates in marmosets for the first time. The mean SSRT values across sessions ranged between 677 and 1464 ms across the four marmosets. We also validated the suitability and practicality of this novel task for examining executive functions by testing the effects of a natural hormone, oxytocin, on response execution and action inhibition in marmosets. This marmoset model, for reliable (millisecond resolution) assessment of the balance between response execution and inhibition, will further facilitate studying the developmental alterations in inhibition ability and examining the effects of various contextual and environmental factors on marmosets' executive functions.
The impact of stigma on the provision and coordination of dementia care
Authors: Jacobs Roxanne
Published: January 2025

Background

Care and support for people with dementia and their families in South Africa are largely inadequate. Responses to dementia are driven by a widespread lack of understanding of dementia amongst the general public, communities, and within local health, policy‐ and social care systems. This presentation will focus on the findings of a situational analysis completed within the STRIDE project (i.e. strengthening responses to dementia in developing countries) that provided an evidence base to inform priority‐setting for strengthening responses to dementia in South Africa.

Method

Evidence was generated on current provisions for older persons and their families through: (1) an in‐depth desk review; (2) multi‐stakeholder interviews; and (3) a SWOT‐analysis (strengths, weaknesses, opportunities, and threats).

Result

Our findings highlight the gaps in current service provision from diagnosis through to follow up support and end‐of‐life care. The findings show how structural factors (including stigma and discrimination) create barriers to diagnosis, support and care.

Conclusion

There is an urgent need for inter‐sectoral policy development in South Africa to support adequate health, social care, and long‐term care solutions for people with dementia and their families. This situational analysis provides an evidence base to inform priority‐setting and strengthening responses to dementia in South Africa.
Ophthalmic pathology in patients with primaryneurodegenerative diseases
Authors: Makhnovich Ekaterina Vladimirovna , Bogolepova Anna Nicolaevna , Kovalenko Ekaterina Аndreevna , Alekseevna Osinovskaya Nina , Beregov Mikhail Mikhailovich
Published: January 2025

Background

The priority problem of modern healthcare is irreversible dementia due to the steady increase in morbidity. Among irreversible dementias, Alzheimer’s disease takes the first place. Most often, only with sufficiently pronounced cognitive disorders, the doctor can diagnose Alzheimer’s disease, although it is obvious that the neurodegenerative process begins even before the clinical manifestations of the disease. Due to the common origin of the eye and the brain, we can say that the eye is a “window to the brain”. Many scientists note the similarities between gerontophthalmological diseases and Alzheimer’s disease.

Method

The study examined 60 patients who were divided into 2 groups: the first group included patients with Alzheimer’s disease, the second group included patients with vascular dementia. Each group included 9 men and 21 women, with an average age of 65.5 years. All patients underwent a comprehensive neuropsychological examination, using the short Mental Status Assessment Scale (MMSE), the Montreal Cognitive Function Assessment Scale (MoCA), the battery of tests for assessing frontal dysfunction (FAB), the clock drawing test. Also, all patients underwent ophthalmological examination of the visometry, measurement of intraocular pressure, examination of the anterior segment of the eye and fundus, and spectral optical coherence tomography.

Result

In the course of the study, significant ophthalmic pathology was detected in the group with neurodegenerative changes ‐ age‐related macular degeneration was found in 16.7%, pseudoexfoliative syndrome‐20%, primary open‐angle glaucoma‐46.7%.

Conclusion

This means that the risk of developing gerontophthalmological diseases increases in patients with neurodegenerative disorders. Therefore, we can assume that the retina is a mirror of neurodegenerative changes in the brain, which will allow to diagnose the disease at early stages and with the help of drug therapy to delay further development of the disease, resulting in reduced disability for patients and socio‐economic costs of society. The results obtained are promising for the early diagnosis of primary neurodegenerative diseases and indicate the need for further research on this topic.
New insight for early detection of Alzheimer's disease
Authors: Dey Sharmistha
Published: January 2025

Background

Recent research on Alzheimer’s disease (AD) has highlighted that the oxidative damage is the earliest event of disease. These oxidative modifications are closely associated with inflammatory molecules. It is necessary to explore these two pathways with AD pathophysiology and targeted for therapeutic intervention. At present, the most validated AD biomarker is Aβ levels in the cerebrospinal fluid (CSF) and tau PET scan. None of the techniques can be used to monitor the disease with the response of treatment. The present study focussed on novel molecules in these two pathways for establishing blood‐based biomarker and therapeutic interventions.

Method

Blood samples were collected from 46 AD patients, 37 mild cognitive impairment (MCI) patients and 35 geriatric‐control (GC). The levels of inflammatory molecules (LOX‐5, LOX‐12, GSK‐3β, p53, NFkb) and antioxidant molecules (FOXO, Sestrin, Sirtuins) were measured by using surface plasmon resonance and verified using Western blot in serum from AD, MCI, and GC. Statistical analysis, including Receiver Operating Characteristic (ROC), was done for further affirmation with all demographic data and clinical assessment score. The Alzheimer’s disease model neurotoxic SH‐SY5Y cell line was treated with antioxidant plant extract for rescue effect on SH‐SY5Y to see the effect on expression level of above mentioned proteins.

Result

The significant alteration of some of these proteins were observed in the blood of AD patients compare to MCI and geriatric control. These proteins also showed positive correlation with the known hallmark Tau, pTau and ab‐amyloid in the study group. A significant (p<0.0001) downhill correlation was found between Tau as well as p‐Tau181 levels with HMSE and MoCA score. The treatment with antioxidant plant extract showed rescue effect of neurotoxicity by enhancing antioxidant enzymes thereby decreased reactive oxygen species (ROS).

Conclusion

These proteins can serve as potential blood markers for the diagnosis of AD and supplementary antioxidant molecules can regulate and suppress their level by rescuing the neurotoxicity. This work has translational value and clinical utility in the future.
Meta‐Analysis & Review of Blood Neurofilament Light Performance in Diagnosis of All‐Cause Dementia
Authors: Schmidt Remington E , Shah Yogesh , Center Broadlawns Medical
Published: January 2025

Background

NfL is a non‐specific biomarker that elevates in the presence of axonal damage. In the blood, it has recently been explored as a potential test in evaluating the presence or absence of dementia.

Method

A systematic review and meta‐analysis of 58 studies examining plasma or serum NfL levels as measured on a single molecule array (SIMOA) platform was used to determine the discriminatory capacity of using NfL to distinguish between healthy controls and patients with dementia.

Result

NfL provides reasonable discriminatory capacity between healthy controls and patients with all‐cause dementia (serum AUC=0.85, plasma AUC=0.75). For a reasonable range of cutoffs, NfL is more specific than it is sensitive. The meta‐analysis demonstrated a roughly 2‐fold increase in NfL levels in dementia patients from cognitively healthy controls (1.84‐fold change plasma, 2.77‐fold change serum).

Conclusion

In the setting of memory care, NfL is likely to be most useful in detecting early dementia in patients presenting with subjective or mild cognitive impairment. As baseline NfL levels significantly change across a person’s lifetime, all NfL levels should be compared to population normals during their interpretation.
MicroRNA biomarkers in cerebrospinal fluid and plasma are associated with reduced cognitive decline in Alzheimer's Disease
Authors: Jiao Yang , Ding Yanfei , Niu Mengyue , Luo Ningdi , Zhong Min , Liu Jun , Zhao Aonan , Li Yuanyuan
Published: January 2025

Background

Despite the promising prospects of using microRNAs in Alzheimer's disease (AD) research, several challenges remain unresolved.

Method

Our study analyzed the changes in microRNA expression levels in cerebrospinal fluid (CSF) and plasma samples and their association with concurrent cognitive decline and hippocampal volume changes in patients with AD using the Alzheimer's Disease Neuroimaging Initiative database.

Result

We observed a significant decrease in plasma hsa‐mir‐125b‐5p levels (P=0.018), significant increase in plasma hsa‐mir‐26a‐5p levels (P=0.017), and significant decrease in mir‐185b‐5p levels in CSF (P=0.017). However, these microRNAs showed no significant differences between the control and AD groups across various ATN subtypes. Lower plasma hsa‐mir‐125b‐5p and hsa‐mir‐26a‐5p concentrations and CSF mir‐185b‐5p concentrations were associated with a faster increase in Alzheimer’s Disease Assessment Scale Cognition 13‐item scale scores (P= 0.011, P=0.009, P=0.018, respectively) and a decline in hippocampal volume (P=0.25, P=0.052, P=0.044, respectively), suggesting a potentially detrimental influence on cognitive and memory impairment in AD progression. CSF mir‐185b‐5p concentrations were positive for amyloid deposition (P= 0.0451, r=0.1754) and negative for fibrillar amyloid levels (P= 0.0392, r=‐0.1647), indicating their potential relevance in AD pathology and the development of AD.

Conclusion

These results highlight the role of CSF and plasma microRNA biomarkers in predicting cognitive and clinical decline in patients with AD.
CSF α‐synuclein reflects neurodegeneration in Alzhiemer's disease
Authors: Igarashi Kazuya , Kasuga Kensaku , Tsukie Tamao , Kikuchi Masataka , Miyashita Akinori , Iwatsubo Takeshi , Ikeuchi Takeshi
Published: January 2025

Background

The aim of this study is to investigate the clinical significance of cerebrospinal fluid (CSF) α‐synuclein (αSyn), a presynaptic protein, in Alzheimer's disease (AD) continuum.

Method

We analyzed 177 CSF samples obtained from participants of Japanese Alzheimer’s Disease Neuroimaging Initiative (J‐ADNI). To investigate the clinical utility of CSF αSyn, subjects were divided into cognitively unimpaired (CU) group (n = 46), mild cognitive impairment (MCI) group (n = 76), and AD dementia (ADD) group (n = 43). We measured CSF αSyn, amyloid β (Aβ)42, phosphorylated tau (pTau), total tau (tTau), Neurofilament Light chain (NfL), hemoglobin (Hb). Because high CSF Hb levels affect αSyn levels due to red blood cell contamination, 12 patients with CSF Hb levels of 1000 ng/mL or higher were excluded. We analyzed the correlation between CSF αSyn and age, gender differences, cognitive function, brain volume (entorhinal cortex, hippocampus, ventricle, cortex, white matter, gray matter, white matter hyperintensities), and each biomarker.

Result

CSF αSyn were significantly higher in the MCI and ADD groups than in the CU group, and significantly negatively correlated with the MMSE score. The hazard ratio for conversion to dementia was significantly higher in the CSF αSyn high and middle tertile groups compared to the low tertile group. CSF αSyn was also associated with baseline and 24‐month score change of MMSE, ADAS, CDR‐SB, and FAQ. CSF αSyn were significantly positively correlated with CSF pTau181, tTau, and NfL and hippocampal volume, but not with CSF Aβ42.

Conclusion

Our results suggests CSF αSyn is a biomarker reflecting neurodegeneration in the Alzheimer's continuum.
Diagnosis of Alzheimer's disease using highly specific amyloid and tau positron emission tomography
Authors: Matsuda Hiroshi , Hanyu Haruo , Kaneko Chikako , Yamao Tensho
Published: January 2025

Background

The Alzheimer's disease (AD) research framework has advocated defining AD as a function of the presence or absence of amyloidopathy (A), tauopathy (T), and neurodegeneration/neuronal injury (N) biomarkers, as well as the clinical syndrome. Recent advances have made it possible to perform A/T/N classification in vivo using neuroimaging techniques such as amyloid positron emission tomography (PET), tau PET, and MRI or fluorodeoxyglucose PET. Under this new framework, AD is diagnosed when both A and T are positive, regardless of whether N is positive or negative. In this study, we investigated this classification by PET using 18F‐NAV4694, which has a high dynamic range with low nonspecific accumulation of amyloid, and 18F‐MK6240, which specifically accumulates 3R/4R tau seen in AD, in patients with cognitive impairment and suspected AD.

Method

Twenty‐three patients with cognitive impairment and suspected AD (12 females, 11 males, 72.1 ± 6.6 years old, Mini‐Mental State Examination; MMSE score 25.3 ± 2.1) underwent both 18F‐NAV4694 (300MBq) and 18F‐MK6240 (185MBq) PET scans using semiconductor PET/CT (United Imaging Healthcare, uMI780). Structural MRI was analyzed using VSRAD (Voxel‐based Specific Regional analysis for Alzheimer's disease ) software for voxel‐based morphometry. In addition, amyloid and tau protein deposition were quantified using the Centiloid scale and standardized uptake value ratio (SUVR) with the whole cerebellum and cerebellar cortex as reference regions, respectively.

Result

Eleven patients were classified as A+T+N+ and one as A+T+N‐ and diagnosed with AD. The other classifications were A‐T‐N‐ in 5 patients, A‐T‐N+ in 2, and A+T‐N‐, A+T‐N+, A‐T+N‐, and A‐T+N+ in 1 each. The Centiloid scale of amyloid deposition did not significantly correlate with the MMSE score (r=‐0.368, p=0.083), but the composite SUVR of tau deposition did (r=‐0.463, p=0.025).

Conclusion

A/T/N classification by PET and MRI correctly diagnosed AD in 12 of 23 cases (52%). Tau PET with 18F‐MK6240 was found to be as important in the diagnosis of AD as amyloid PET, with 2 of 14 cases (14%) being 3R/4R tau negative despite being amyloid positive. These results suggest that highly specific amyloid and tau PET can be used to accurately diagnose AD, and that tau deposition correlates well with cognitive function.
Glymphatic System Efficiency, Choroid Plexus Volume, and Lateral Ventricle Volume Variations in Normal Individuals and Throughout the Progression of Alzheimer's Disease
Authors: Nakaya Moto , Kamagata Koji , Takabayashi Kaito , Uchida Wataru , Hagiwara Akifumi , Christina Andica , Wada Akihiko , Taoka Toshiaki , Naganawa Shinji , Abe Osamu , Aoki Shigeki
Published: January 2025

Background

Alzheimer’s disease (AD) progression is often characterized by the accumulation of amyloid and tau proteins, which can be linked to impaired brain clearance mechanisms, including the glymphatic system. Our research evaluates noninvasive MRI‐based indicators of brain clearance functionality, such as choroid plexus volume (CPV), lateral ventricular volume (LVV), and the perivascular space diffusivity index (ALPS index), throughout various stages of AD.

Method

We analyzed MRI data measuring CPV, LVV, and ALPS index from participants categorized as amyloid‐beta (Aβ)‐ negative healthy controls (HC), Aβ‐positive HC, Aβ‐negative subjective cognitive decline (SCD), Aβ‐positive SCD, mild cognitive impairment (MCI), and AD, using the Alzheimer's Disease Neuroimaging Initiative database. A General Linear Model was used for cross‐group comparisons of MRI metrics. Additionally, partial Spearman's Rank Correlation tests were conducted to investigate associations between MRI measures, neuropsychological assessments, and CSF biomarker levels within each group.

Result

The participant pool comprised 21 Aβ‐negative cognitively healthy individuals, 10 Aβ‐positive HCs, 21 patients with Aβ‐negative SCD, 9 with Aβ‐positive SCD, 19 MCI patients, and 26 AD patients. We observed increased CPV and LVV and decreased ALPS index in advanced stages of the disease. Notably, the ALPS index was significantly reduced in Aβ‐positive HCs compared to Aβ‐negative ones. In SCD subjects and across the AD spectrum, correlations were found between these MRI indicators of brain clearance and both tau protein levels and cognitive performance metrics.

Conclusion

Our findings suggest that MRI‐detected alterations in brain clearance metrics are associated with Aβ deposition and can be identified early in SCD that is linked to AD pathology.
Associations of C‐reactive protein and homocysteine with neuropsychological outcomes in older adults at risk of dementia
Authors: Yu Rachael , Michaelian Johannes C , Kong Shawn Dexiao , Ireland Catriona , Bassett Kimberley , Naismith Sharon L
Published: January 2025

Background

Inflammation is becoming increasingly recognised as a core feature of dementia and neurodegenerative processes. High‐sensitivity C‐reactive protein (hs‐CRP) and homocysteine are blood‐based markers of non‐specific inflammation used in clinical settings. This study aimed to 1) investigate the associations of hs‐CRP and homocysteine on neuropsychological performance (i.e. verbal memory, executive function, processing speed) in older adults attending a memory clinic; and 2) examine whether these associations differed for individuals at varying risk stages of dementia, i.e. with subjective cognitive decline (SCD) vs. mild cognitive impairment (MCI).

Method

We recruited older adults aged ≥ 50 years with new‐onset cognitive concerns without dementia. A fasting blood sample was used to obtain concentrations of serum hs‐CRP (mg/L) and plasma homocysteine (µmol/L). Hs‐CRP levels were grouped into low <1.0mg/L, moderate 1.0‐3.0mg/L, and high risk >3.0‐10.0 mg/L. A standardised neuropsychological assessment was conducted by a clinical neuropsychologist, and composite scores for each neuropsychological outcome were calculated as an average of z‐scores of all tests within the same domain. Classifications of MCI were determined by clinician consensus as having objective impairments in neuropsychological tests (≥1.5SDs below normative scores). Multiple regression analyses were conducted, adjusting for relevant demographic and clinical factors.

Result

The final sample consisted of 423 participants (Mean age = 67.37 years [SD = 8.15], 63.1% female, mean MMSE = 28.95 [SD = 1.35]), who were classified as either having SCD (n = 158) or MCI (n = 265). Hs‐CRP and homocysteine concentrations did not differ between SCD and MCI groups. In participants with SCD, high‐risk CRP concentrations were significantly associated with poorer executive function (β = ‐.226, 95% CI = [‐0.692, ‐0.059], p = .020) and processing speed (β = ‐.212, 95% CI = [‐0.584, ‐0.025], p = .033). There were no significant associations between CRP and neuropsychological outcomes in those with MCI, or in the total sample. Homocysteine was not associated with cognitive outcomes.

Conclusion

CRP may be involved in early disruptions to cerebral frontal‐subcortical pathways. Targeting inflammation in the earliest stages of cognitive decline, where subjective complains are paramount, may be a viable strategy for prevention.
The relationship between physiological biomarkers, physical function, and fall‐risk among people living with dementia
Authors: Hamill Sophia N , Dong Yanbin , Zhu Haidong , Huang Ying , Soares Andre , Waller Jennifer L , Young Lufei , Robinson‐Johnson Dawnchelle , Sams Richard , Hamrick Mark , Jehu Deborah A
Published: January 2025

Background

People living with dementia (PWD) have upregulated inflammatory pathways, exaggerated metabolic aging, and cellular aging. They also have declines in physical function and heightened fall‐risk. Understanding the physiologic factors that influence physical decline and fall‐risk in PWD is vital to assess and prevent adverse health outcomes, such as future falls. The purpose of this study was to explore the association between physiological biomarkers, physical decline, and fall‐risk in PWD.

Method

In this cross‐sectional study, we used the baseline data of n=42 PWD in residential care facilities from our pilot randomized controlled trial [NCT05488951]. We assessed fall‐risk with the Morse Fall Scale and pulled fall history in the last 6 months from incident reports in medical charts. Participants completed two 4‐meter usual pace walking trials. We assessed two trials of maximum quadriceps strength on each leg with a portable dynamometer. We drew fasted blood and measured inflammatory biomarkers (Interleukin(IL)‐1b, IL‐6, IL‐8, IL‐10, IL‐12p70, IL‐17A, IL‐18, IL23, IL‐33, chemokine ligand 2, tumor necrosis factor‐a, human interferon (INF)‐a2, INFg), metabolic aging (kynurenine), and cellular aging (telomere length). Separate multiple linear regressions were performed for each biomarker, with gait speed, leg strength, fall history, and the Morse Fall Scale as variables of interest. We controlled for age, sex, and the Montreal Cognitive Assessment in each model.

Result

Fall history (β=5.61, p=0.03) and older age (β=0.49, p=0.005) were associated with greater INF‐a2 (R2=0.49, p=0.07). Fall history (β=4.93, p=0.07) showed a trend for a relationship with greater IL‐10 (R2=0.50, p=0.04). Older age (β=0.28, p=0.009) and lower MOCA scores (β=‐0.40, p=0.04) were related to greater IL‐12p70 (R2=0.64, p=0.003). Older age (β=9.26, p=0.01), fall history (β=74.42, p=0.04), and poorer leg strength (β=‐7.40, p=0.06) were related to greater kynurenine (R2=0.49, p=0.02).

Conclusion

Our exploratory findings suggest that there may be a relationship between certain physiological biomarkers (INF‐a2, IL‐10, kynurenine), physical function, and fall history. These inflammatory and metabolic aging biomarkers may play an important role for physical function and fall‐risk in PWD. This preliminary research may have implications for screening and monitoring of physical decline and fall‐risk among PWD.
A brain MRI estimate of whole‐body aging in midlife predicts late life risk for Alzheimer’s disease
Authors: Whitman Ethan T. , Elliott Maxwell L. , Knodt Annchen R. , Moffitt Terrie E. , Caspi Avshalom , Hariri Ahmad R.
Published: January 2025

Background

Aging is the strongest risk factor for Alzheimer’s disease (AD). Accordingly, identifying biomarkers of accelerated aging is a major focus of AD prevention research. Current MRI‐based “aging clocks” (i.e., brain age) derive from cross‐sectional associations with chronological age. However, chronological age differs fundamentally from biological aging. We introduce a novel brain MRI proxy for biological aging in midlife developed in the Dunedin Study, a population‐representative longitudinal birth cohort, and demonstrate its ability to differentiate and predict AD in the Alzheimer’s Disease Neuroimaging Initiative (ADNI).

Method

The pace of whole‐body aging was determined by tracking physiological decline of 6 organ systems over 20 years in Dunedin Study members. An elastic‐net regression model was trained to estimate this pace of aging using a single T1‐weighted scan collected at age 45 from 860 Study members. We call this measure the Dunedin Pace of Aging Calculated from NeuroImaging or “DunedinPACNI.” We exported DunedinPACNI to ADNI and tested its association with current and future AD. Lastly, we compared DunedinPACNI to “brain age” using brainageR.

Result

DunedinPACNI estimated whole‐body aging with a cross‐validated accuracy of r=0.43 in Dunedin Study members. Derived in 6,199 T1‐weighted ADNI scans, DunedinPACNI was on average 0.40 standard deviations higher in MCI patients and 1.13 standard deviations higher in AD patients compared to healthy participants (MCI 95% CI:[0.36‐0.45]; AD 95% CI:[1.08‐1.19]). DunedinPACNI outperformed brainageR in differentiating MCI and AD patients from controls (MCI: b=.25; 95% CI:[.14‐.35]; AD: b=.68; 95% CI:[.56‐.80]). In 1,326 ADNI participants followed up to 16 years, baseline DunedinPACNI was associated with a higher probability of AD conversion (HR=1.58, 95% CI:[1.36‐1.84]) as was brainageR (HR=1.61; 95% CI:[1.42‐1.84]). DunedinPACNI and brainageR together predicted conversion more accurately than either measure alone (combined HR=2.10, 95% CI:[1.76‐2.51).

Conclusion

DunedinPACNI, a novel MRI proxy for longitudinal whole‐body aging during midlife, offers advantage over “brain age” in detecting neurodegenerative disease and predicting AD conversion in late life. DunedinPACNI can be applied to existing neuroimaging datasets to estimate whole‐body aging to better gauge early AD risk.
LOVOT: LOVE + ROBOT
Authors: Low Zheng Yi
Published: January 2025

Background

Social robots have been used in other countries for improvement of quality of life for persons with dementia.

Method

LOVOT was introduced as an adjunct to regular therapy sessions (either Physiotherapy or Occupational Therapy) and as an interactive companion during the patient’s inpatient stay. The project was carried out over a span of 6 weeks (weekdays) for a maximum of 10‐15 mins on an ad‐hoc basis.

Result

A total of 19 participants were recruited over this 6 weeks. These included 11 patients (age between 49 to 81 year old, 6 with formal diagnosis of dementia and 5 without one). The other 8 participants were staff members (age 29 to 57 year old, ranging from the medical doctors to nurses to allied health staff). We administered one common questionnaire on both groups of participants, this questionnaire is “Sociability of robot”. There is 3 components to this questionnaire and they are as follows:

1. Perceived sociability. This component received 78% positive feedback from the participants

2. Social influence, which received 74% positive feedback

3. Social presence, which had 70% positive feedback. However it is worth noting that 54% of the participants felt that LOVOT was not a real pet during the interaction.

We also administered a second questionnaire: Older People’s Quality of Life (QoL) for the group of patient participants. There is a total of 13 statements. Most statements received positive agreement and 2 statements that had higher disagreement (36%) were:

• “I look forward to things.”

• “I try to stay involved with things”

It was noticed that 3 out of 11 patient participants gave more than 50% neutral or disagreement to the above statements.

Conclusion

During the trial, some patients and their caregivers started to ask about LOVOT and wanted to interact with LOVOT as well. Staff in SCH looked forward to spending time with LOVOT after a long day of work and are already anticipating for the next LOVOT visit. Most respondents had positive experience with LOVOT with patients reporting it as an interactive partner and staff respondents reporting positive well‐being and a good form of stress relief from the hectic work day.
AHEADx: Revolutionizing Early Alzheimer’s Disease Diagnosis Through Blood with Integrated Acoustofluidics and Photonic PCR Technologies
Authors: Belcea Eric V , Johnson Kim G , Liu Andy , Luo Sheng , Sanders Laurie H , Lee Luke P , Huang Tony J
Published: January 2025

Background

This study introduces the Automated High‐purity Exosome isolation‐based AD diagnostics system (AHEADx). By analyzing and understanding the molecular cargo (proteins and miRNAs) carried by circulating exosomes, researchers found brain‐derived exosome (BDE) levels of P‐S396‐tau, P‐T181‐tau, and Aβ1‐42 are elevated up to 10 years prior to clinical symptoms. Currently, there is no available technology capable of simultaneously isolating and screening exosomal biomarkers for efficient and personalized precision medicine giving early AD diagnosis.

Method

This NIH funded study will develop and validate AHEADx via integrated acoustofluidics (i.e., the fusion of acoustics and microfluidics) and photonic PCR on‐chip technologies that are capable of fully automated, rapid, precise exosome isolation and accurate analysis for AD diagnostics. AHEADx consists of two units: a rapid (<1 min) acoustofluidic separation unit for exosome isolation from biofluids with high yield and purity (both >90%), and a rapid (<6 min) photonic PCR unit achieving detection limits of ∼1 copy/µL for nucleic acids and ∼5 copies/µL for proteins.

Compared with state‐of‐the‐art exosome isolation and analysis technologies, AHEADx system has the following advantages:

• Automated and fast operation in a point‐of‐care, handheld system

• High‐purity (>90%), high‐quality exosome isolation for accurate biomarker detection

• High‐sensitivity (∼1 copy/µL for nucleic acids and ∼5 copies/µL for proteins) detection of a comprehensive (∼20) panel of AD biomarkers

Result

To validate the potential for clinical use, we will test plasma samples from 100 AD patients and 100 healthy individuals all with known amyloid, phospho tau and total tau biomarker status measured in their CSF. The Duke University Neurology Biobank and the Duke University and University of North Carolina Alzheimer’s Disease Research Center (Duke/UNC ADRC) will provide samples.

Conclusion

We predict the AHEADx platform will be capable of the simultaneous isolation and analysis of exosome‐derived biomarkers for early AD neuropathological diagnosis. The AHEADx platform’s ability to accurately detect AD biomarkers in the preclinical stages as a point of care handheld instrument could revolutionize diagnosis of AD pathology in the office setting, enhance understanding of AD progression, and significantly impact research into effective treatments.