bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alzheimer’s disease is associated with increased modularity and assortativity: Evidence from structural and metabolic connectivity
Authors: Khokhar Sunil Kumar , Kumar Manoj , Kumar S Sandeep , Manae Tejaswini , Thanissery Nithin , Ramakrishnan Subasree , Arshad Faheem , Nagaraj Chandana , Mangalore Sandhya , Alladi Survana , Gandhi Tapan K , Bharath Rose Dawn 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) is a progressive disorder associated with cognitive dysfunction that alters brain connectivity and assessing these altered connectivity patterns has become a topic of increasing interest. In this study, we examine the structural and metabolic connectivity using cortical thickness and [18F] Flouro deoxyglucose (FDG)‐positron emission tomography (PET) to identify the network modification in patient with AD when compared to mild cognitive impairment (MCI). To examine our hypothesis; we quantified a relatively newer graph theory measures including assortativity and modularity. We aimed to unravel the multimodal network alterations using simultaneous MRI‐PET acquisitions.MethodsPatients who underwent simultaneous FDG‐PET and MRI study on a 3T MRI were recruited for this exploratory study. After appropriate pre‐processing of structural‐MRI and PET‐metabolic data, graph measures were obtained using the BRAPH toolbox, and subsequently; global and nodal network measures were used to derive group‐level differences (corrected p<0.05). Regions that revealed significant differences were correlated with the cognitive scores (ACE‐III).Results83 demographically matched patients [MCI (n = 27), and AD (n = 56)] were analysed. There were no significant differences between the groups in the mean age (MCI 63.52 ±9.19 years and AD 63.73 ±9.60 years), gender (M: F) MCI 20:7 and AD 26:30, or the mean duration of disease (MCI 2.23±1.92 and AD 2.95 years) other than ACE scores (MCI‐87.30±5.53 and AD 46.02 ±20.61, p value <0.001) and the CDR (MCI‐very mild and AD‐Moderate and Severe). Patients with AD revealed significantly increased assortativity at the global level in both structural and metabolic connectivity analysis. In addition, metabolic connectivity revealed increased modularity and decreased participation coefficient in patients with AD. Cortical thickness and SUV abnormalities in several regions in bilateral parietotemporal lobes were proportional with the cognitive scores (ACE‐III).ConclusionProbable erroneous and homophilic network segregation paralleling the aging associated loss of whole brain integration was found proportional to the memory scores. Further studies in larger cohorts are required to ascertain the clinical relevance of these findings as an imaging biomarker.
Nowhere to run, nowhere to hide ‐ targeting the immune system in AD with multimodal plasma therapeutics
Authors: Lehallier Benoit , Feng Chunmiao , Nanasi Tibor , Gonzalo Ricardo , Minguet Carla , Ortiz Ana Maria , Bravo Isabel , Lohr Scott , Boada Mercè , Lopez Oscar L. , Páez Antonio , Cerezo Cesar , Costa Montserrat , Braithwaite Steven P 
Published: December 2023

AbstractBackgroundAge‐related diseases, especially Alzheimer’s Disease (AD), have multifaceted nature because of the different factors and pathways contributing to these diseases. Multi‐modal plasma therapies have the potential to impact multiple pathways and modulate different mechanisms of diseases in a safe and versatile way. Here we discuss insights from deep plasma proteomics profiling in patients from the GRF6019 and AMBAR clinical trials in which multi‐modal plasma therapeutics were used and limited cognitive decline was observed.MethodThe GRF6019 phase 2 trials were based on the infusion of a complex plasma fraction while the AMBAR phase 2b/3 trial used plasma exchange and albumin replacement (PE‐Alb). Patients in these trials were mild‐to‐moderate AD and 1143 plasma samples were analyzed using the SomaScan platform. The trajectories of 7k proteins were analyzed using classic and new machine learning techniques.ResultGRF6019 infusion resulted in an acute and broad impact on the plasma proteome but the detectable long‐term effects on molecular level were minimal. Pathways analysis of protein trajectories pointed out to the immune system, ECM remodeling but also brain specific biological processes linked to neurons and axon guidance, suggesting that various biological pathways were significantly modulated (q<0.05). PE‐Alb treatment also induced an acute effect on several hundreds of proteins (461 proteins with log2FC←1 & q<0.05) but some proteomics changes lasted for weeks after the end of the intensive period (25 proteins with q<0.05). A significant part of these changes (19% of acute and 56% of lasting response proteins) were related to immune and inflammatory‐related pathways. In addition, several individual proteins from the immune pathway were associated with improvement of CDR‐SB or ADCS‐CGIC at the end of the AMBAR trial suggesting that multiple parts of the immune system might need to be targeted to slow‐down AD progression.ConclusionAD has multifaceted nature and plasma therapeutics have proven safety, efficacy, and versatility. The proteomics results from these trials shed the light on the underlying mode of action of multi‐modal plasma‐derived therapies and demonstrate that they can modulate multiple pathways relevant to AD, with a strong effect on the immune and inflammatory responses which may contribute to slowing down AD progression.
Early changes of fecal short‐chain fatty acid levels in patients with mild cognitive impairments
Authors: Chen Shengdi 
Published: December 2023

AbstractBackgroundMild cognitive impairment (MCI) is with great risk for the conversion to Alzheimer’s disease (AD). The aim of present study wanted to explore whether fecal Short‐chain fatty acids (SCFAs) could be used as the biomarker for the identification of MCI patients and to examine the relationship between fecal SCFAs and amyloid‐β deposition in the brain.MethodsA cohort of 32 MCI patients and 27 NC were recruited in our study. Fecal levels of SCFAs were measured using chromatography and mass spectrometry. Disease duration, ApoE genotype, body mass index, constipation, and diabetes were evaluated. To assess cognitive impairment, we used the Mini‐Mental Status Examination (MMSE). To assess brain atrophy, the degree of medial temporal atrophy (MTA score, Grade 0‐4) was measured by structural MRI. β‐amyloid positron emission tomography (PET) with 18F‐AV‐45 was performed in seven MCI patients to detect and quantify Aβ deposition in the brain.ResultsCompared with NC, MCI patients had significantly lower fecal levels of acetic acid, butyric acid, and caproic acid. Among fecal SCFAs, acetic acid performed the best in discriminating MCI from NC, achieved an AUC of 0.752 (p = 0.001, 95% CI: 0.628‐0.876), specificity of 66.7% and sensitivity of 75%. By combining fecal levels of acetic acid, butyric acid and caproic acid, the diagnostic specificity was significantly improved, reaching 88.9%. To better verify the diagnostic performance of SCFAs, we randomly assigned 80% of participants into training dataset and 20% into testing dataset. Only acetic acid showed significantly difference between these two groups in the training dataset. Based on the fecal levels of acetic acid, we achieved the ROC curve. Next, the ROC curve was evaluated in the independent test data and 66.7% (4 in 6) of MCI patients, and 80% (4 in 5) of NC could be identified correctly. Subgroup analysis showed that reduced fecal SCFAs in MCI group were negatively associated with Aβ deposition in cognition‐related brain regions.ConclusionOur findings suggest that gut metabolite SCFAs have the potential to serve as early diagnostic biomarkers for distinguishing patients with MCI from NC and could serve as potential targets for preventing AD.
Association of resting heart rate with cognitive decline and brain age in older adults: a large‐scale cohort study in the UK Biobank
Authors: Wang Jiao , Yang Wenzhe , Dove Abigail , Qi Xiuying , Xu Weili 
Published: December 2023

AbstractBackgroundThe relationship of resting heart rate (RHR), a common indicator of cardiovascular health, with cognitive decline is unclear. We aimed to investigate the association of RHR with cognitive trajectory and brain age assessed by brain Magnetic Resonance Imaging (MRI) in the UK Biobank.MethodWithin the UK Biobank 18,210 chronic brain disorders‐free participants aged 60+ were followed for up to 16 years. RHR was assessed by blood pressure monitor and categorized into <60, 60‐69 (reference), 70‐79, and ≥80 beats per minute (bpm). Cognitive function including global cognition, numeric memory, prospective memory, pairs matching, fluid intelligence, and reaction time was collected at baseline and each follow‐up wave. A subsample of 10,458 participants underwent brain MRI (T1‐weighted MRI, T2‐FLAIR, T2∗, diffusion‐MRI, task fMRI, and resting‐state fMRI) to detect brain age and brain predicted age difference (PAD) using Lasso regression. Data were analyzed using mixed‐effects model and linear regression model.ResultCompared to reference group, RHR≥80 bpm was associated with faster decline in global cognition (β: ‐0.03, 95% confidence interval [CI]: ‐0.05, ‐0.01) and reaction time (β: ‐0.03, 95% CI: ‐0.07, ‐0.01). In the MRI data analysis, RHR≥80 bpm was associated with older brain age (β [95% CI]: 0.50 [0.25, 0.76]) and bigger brain PAD (β [95% CI]: 0.50 [0.26, 0.74]).ConclusionHigher RHR is associated with faster cognitive decline and older brain age. Monitoring and controlling elevated RHR could be a promising interventional target in preserving cognitive function.
Development of a framework capturing the interactions of people with dementia and their facilitators in virtual CST sessions: A proposal
Authors: Wong Winsy Wing Sze , Choy Jacky Chak Pui 
Published: December 2023

AbstractBackgroundTelehealth has been gaining much attention, especially since the COVID‐19 pandemic. A virtual version of Cognitive Stimulation Therapy (CST), based on the conventional face‐to‐face CST (Spector et al., 2003), has been developed, with feasibility reported in Perkins et al. (2022). The present study proposes an analytic framework for capturing the verbal and nonverbal interactions of people with dementia (PwD) and their facilitators during virtual CST sessions delivered via tablet computers and video conferencing tool.MethodExisting models/frameworks for capturing verbal and nonverbal interactions of PwD and their communication partners were identified and evaluated. Quantifiable parameters/features which are observable/applicable to virtual CST sessions were incorporated into the new framework.ResultA newly proposed framework, primarily based on the conversation analysis (Perkins et al., 1998) of PwD and coding system of co‐verbal gestures of people with aphasia (Kong et al., 2015), has been developed. Issues specific to virtual delivery of CST have been considered and accommodated in the framework.ConclusionThe proposed framework will help researchers investigate and quantify the verbal and nonverbal interactions during virtual CST. Its potential in enhancing treatment outcomes, in terms of training of facilitators, and investigations of the relation between the behaviors of PwD during sessions and treatment gains in different aspects, will be discussed.
References:Kong, A. P. H., Law, S. P., Kwan, C. C. Y. et al. (2015). A coding system with independent annotations of gesture forms and functions during verbal communication: Development of a database of Speech and GEsture (DoSaGE). Journal of Nonverbal Behaviors, 39, 93‐111.Perkins, L., Fisher, E., Felstead, C., Rooney, C., Wong, G. H., Dai, R., … & Spector, A. (2022). Delivering cognitive stimulation therapy (CST) virtually: Developing and field‐testing a new framework. Clinical Interventions in Aging, 17, 97.Perkins, L., Whitworth, A., & Lesser, R. (1998). Conversing in dementia: A conversation analytic approach. Journal of Neurolinguistics, 11, 33‐53.Spector, A., Thorgrimsen, L., Woods, B., Royan, L., Davies, S., Butterworth, M., & Orrell, M. (2003). Efficacy of an evidence‐based cognitive stimulation therapy program for people with dementia. British Journal of Psychiatry, 183, 248‐254.
Relationships of Psychiatric Comorbidities with the Risk of Hospitalization for Motor Vehicle Crash Injury in Young‐Onset Dementia: A Nationwide Population‐Based Study in Taiwan
Authors: Liu Chih‐Ching 
Published: December 2023

AbstractBackgroundAlthough the association between young‐onset dementia and hospitalization for motor vehicle crash injury (MVCI) has been shown, little is known about the relationship between the risk of MVCI and psychiatric comorbidities in young‐onset dementia. This study investigates the which psychiatric comorbidities in young‐onset dementia increases the risk of MVCI.MethodIn this retrospective population‐based cohort study, we identified 39,344 dementia aged 40‐64 years from the Taiwan National Health Insurance Research Database (NHIRD) entries between 2006 and 2012. MVCI‐related hospitalization was determined using linked data from the Police‐reported Traffic Accident Registry and the NHIRD between 2006 and 2015. We performed the Cox regression model to estimate the association of the risk of hospitalization for MVCI with young‐onset dementia comorbid with specific psychiatric disorders, including anxiety disorders, depressive disorders, bipolar disorders, alcohol‐related disorders, other substance‐related disorders, and insomnia.ResultOf the 39,344 participants included in the study, all participants encountered 1,013 hospitalizations for MVCI in the 222,239.8 person‐years observed, representing incidence densities of hospitalization for MVCI of 45.58 (95% CI 42.77‐48.39) per 10,000 person‐years. The incidence densities of hospitalization for MVCI increased when young‐onset dementia comorbid with anxiety disorders (56.17 per 10,000 person‐years), depressive disorders (58.61 per 10,000 person‐years), bipolar disorders (83.55 per 10,000 person‐years), alcohol‐related disorders (85.64 per 10,000 person‐years), other substance‐related disorders (84.79 per 10,000 person‐years), and insomnia (59.80 per 10,000 person‐years). However, the risk of hospitalization for MVCI was only significantly increased when young‐onset dementia comorbid with bipolar disorders (HR, 1.60; 95% CI: 1.21‐2.13), alcohol‐related disorders (HR, 1.55; 95% CI: 1.27‐1.90) and insomnia (HR, 1.26; 95% CI: 1.07‐1.47).ConclusionYounger adults with dementia comorbid with specific psychiatric disorders rise the risk of hospitalization for MVCI, which suggests the reinforcement transport safety in those population is needed.
What attributes have been included in discrete choice experiments related to health technologies used in the early detection, diagnosis and treatment of neurodegenerative conditions? A systematic literature review
Authors: Kamran Ifrah , Ardle Ríona Mc , Ternent Laura , Slight Sarah 
Published: December 2023

AbstractIntroductionAlzheimer’s disease (AD) and Parkinson’s disease (PD) are the most common neurodegenerative conditions. Information on the preferences of patients, health care professionals and the public on the early detection, diagnosis and treatment of these conditions is limited. Understanding preferences is essential to improve health‐related outcomes. Discrete choice experiments (DCEs) are a widely used method to elicit preferences. A previous systematic review identified the attributes that were included in DCEs related to health technologies, although none of the included studies related to neurodegenerative conditions.AimsTo identify attributes and their respective levels used in the design of discrete choice experiments that examined preferences for early detection, diagnosis and treatment for AD and PD.MethodFour large databases (Cinahl, Embase, Medline, Scopus, Web of science) were searched between January 2015 and October 2022. Search terms included grouped into sets relating to discrete choice and dementia. The search was limited to peer reviewed studies in English and related to the use of health technology (defined as the application of organised knowledge and skills in the form of devices, medicines, vaccines, procedures, and systems) in the early detection, diagnosis or treatment AD or PD. Studies included people diagnosed with AD or PD, members of the public or clinicians. This review was registered with PROSPERO (registration number: CRD42023365169), adhered to PRISMA guidelines and used a DCE quality assessment tool devised by Mandeville et al. (2014).ResultsA total of 196 studies were identified, eight of which were included. Two studies focused on AD and six studies on PD. The average number of attributes included in the DCEs was 4.5 (SD 0.57), the average number of levels per attribute was 3.4 (SD 0.80). The most common attributes used in DCEs were as follows: risk of side effects, cost, device type, oral medicines required, duration of ON time and increase in daily ON time (the period when medication for Parkinson’s is effective is ON time). There was no overlap in attributes within studies reporting on AD.ConclusionPreference researchers can incorporate the attributes identified into surveys in order to support the development of clinical decision‐making frameworks.
The Effect of Hippo Pathway Inhibitor Xmu‐mp‐1 on Cognitive Impairment in a Rat Model of Alzheimer’s Disease: Protection against Oxidative Stress, Tau Hyperphosphorylation, and Neurodegeneration
Authors: Sahu Manas Ranjan , Mondal Amal Chandra 
Published: December 2023

AbstractBackgroundAlzheimer’s Disease (AD), the most common form of dementia, is a growing global health concern with unmet clinical therapeutics. AD can be attributed to amyloid beta aggregation and tau hyperphosphorylation‐induced oxidative stress and neurodegeneration in the brain. Previous studies have implicated a hyper‐activated Hippo signaling pathway with neuronal loss in neurodegenerative disorders, including AD. However, it is still unknown if suppressing the Hippo pathway can rescue neuronal death in AD.MethodIn this study, we investigated the cognitive impairment ameliorative effect of the novel Hippo signaling inhibitor, Xmu‐mp‐1, in a rat model of AD. Adult male Wistar rats were stereotaxically injected with a well‐known AD inducer Streptozotocin (STZ), to mimic AD‐like features. A pharmacological antagonist of Hippo signaling component MST1 called Xmu‐mp‐1 was administered intraperitoneally at a dose of 0.5mg/kg body weight for 14 days. Then the effect of Xmu‐mp‐1 on cognitive impairment was assessed using the Morris water maze test and novel object recognition test. Further, we did biochemical and histopathological studies to explore the effect of Xmu‐mp‐1 on several AD‐associated pathophysiological changes, including oxidative stress, tau hyperphosphorylation, and neurodegeneration.ResultXmu‐mp‐1 significantly improved the cognitive impairment of the AD rats in the Morris water maze test and the novel object recognition test (n = 7). Biochemical analysis of the brain hippocampal and cortical tissues revealed that Xmu‐mp‐1 also ameliorated the AD‐associated oxidative stress burden as the levels of anti‐oxidants (SOD, Catalase, GSH) significantly increased and the levels of oxidative stress biomarkers (protein carbonyl and lipid peroxidation) significantly reduced after Xmu‐mp‐1 treatment in the AD rats (n = 6). Moreover, the level of tau phosphorylation, a prime characteristic of AD, was also reduced following Xmu‐mp‐1 treatment (n = 3). Finally, neuronal death was also found to be rescued after Xmu‐mp‐1 treatment in AD rats (n = 3).ConclusionXmu‐mp‐1 exhibits a neuroprotective role against AD as it improves the cognitive impairment induced by STZ. Further mechanistic investigations into the neuroprotective role of Xmu‐mp‐1 revealed that Xmu‐mp‐1 provides protection from oxidative stress, tau hyperphosphorylation, and aberrant neurodegeneration under an AD background. Future studies can explore the therapeutic potential of Hippo signaling inhibition against AD in more detail.
Estimating the potential for prevention of dementia in Germany
Authors: Blotenberg Iris , Hoffmann Wolfgang , Thyrian Jochen René 
Published: December 2023

AbstractBackgroundAs the German population ages, the number of people with dementia is predicted to rise considerably in the upcoming decades. In the absence of a disease‐modifying treatment, prevention is key to curb the growing numbers of dementia cases. In order to tailor prevention approaches to the German context, knowledge about the potential for prevention in Germany and the most prevalent modifiable risk factors is vital.MethodWe calculated population attributable fractions (PAF) for eleven potentially modifiable risk factors for dementia. Relative risks were taken from a recent review, prevalence estimates and weights were calculated using data from the German Ageing Survey. Weights were used to adjust for associations between risk factors, they were calculated using a principal component analysis based on tetrachoric correlations between risk factors. Potential impact fractions (PIF) were calculated to estimate the effect of a reduction in risk factor prevalence on the future number of dementia cases.ResultMore than a third of dementia cases in Germany are associated with eleven potentially modifiable risk factors. The largest number of cases are associated with hearing impairment and hypertension, among others. A significant reduction in risk factor prevalence could theoretically reduce the number of dementia cases in 2050 by more than 150.000.ConclusionThe number of dementia cases in Germany is rising, but there is considerable potential for prevention. Further advancement of prevention approaches for healthy ageing and their implementation into routine care should be fostered.