bluuebunny/crossref_metadata_2025_split huggingface dataset:
Digitial memory test for detecting and assessing cognitive impairment in parkinson's disease
Authors: Pei Zhong 
Published: January 2025

AbstractBackgroundThe objectives of the study is to assess the clinical utility of the MemTrax Memory Test for detection of cognitive impairment in patients with PD.MethodThe MemTrax and Montreal Cognitive Assessment (MoCA) were administered to 61 healthy controls (HC), 102 PD patients with normal cognition (PD‐N), 74 PD patients with mild cognitive impairment (PD‐MCI) and 52 PD patients with dementia (PD‐D). The MemTrax performance, MTx‐%C, MTx‐RT and MTx‐Cp, and the MoCA scores were comparatively analyzed. The MemTrax performances were assessed according to the areas under the receiver operating characteristic curve.ResultThe MoCA scores were similar between HC and PD‐N, however, MTx‐%C and MTx‐Cp were lower in PD‐N than HC(p<0.05). MTx‐%C, MTx‐Cp and the MoCA scores were significantly lower in PD‐MCI versus PD‐N and in PD‐D versus PD‐MCI (p ≤ 0.001), while MTx‐RT was statistically longer in PD‐D versus PD‐MCI (p ≤ 0.001). For the PD groups, the MemTrax performance strongly correlated with the MoCA scores. To detect PD‐MCI, the optimal MTx‐%C and MTx‐Cp cutoff were 75% and 50.0, respectively. To detect PD‐D, the optimal MTx‐%C, MTx‐RT and MTx‐Cp cutoff were 69%, 1.341s and 40.6, respectively.ConclusionThe MemTrax provides rapid, valid and reliable metrics for assessing cognition in patients with PD that could have practical clinical utility for identifying PD‐MCI at early stage and monitoring cognitive function decline during the progression of disease.
Relationship between Health Decision‐Making Roles and Subjective Memory Ability among Older Adults in Rural Community
Authors: Park Myonghwa , Kim Jinju , Kim Heejung , Seo Eunkyung , An Wonmi 
Published: January 2025

AbstractBackgroundOlder adults in rural areas often face the challenge of managing their health decisions due to limited access to medical services. Cognitive function, particularly the awareness and assessment of one’s memory abilities, plays a significant role in the decision‐making process. This study investigates the relationship between subjective memory ability and health‐related decision‐making among older adults in rural areas.MethodsThis research was conducted as a secondary analysis using data from a broader health advancement project in a rural South Korean locality. It examined the roles in health decision‐making, categorizing them into three: active (making decisions independently), shared (making decisions with family members), and passive (having decisions made by family members). Subjective memory ability was assessed on a scale from 0 to 10, reflecting perceived memory ability.ResultsThe study involved participants with an average age of 75 years. It found that 47.0% assumed active roles, 48.3% shared roles, and 4.6% passive roles in health decision‐making. Women predominantly assumed active roles (51.7%), while men were more likely to be in shared (50.1%) and passive roles (6.1%). Active roles peaked among those aged 70‐79 (48.1%), shared roles were most common under 70 (50.2%), and passive roles increased after 80 (10.0%). Regarding education, active roles were most frequent among college‐educated individuals, shared roles among middle/high school graduates, and passive roles among those with the least education. The average subjective memory ability scores varied with decision‐making roles: 5.85 for active roles, 5.77 for shared roles, and 4.57 for passive roles. Lower subjective memory ability scores were associated with a higher likelihood of assuming passive roles (p = .001).ConclusionThe study demonstrates that those with lower subjective memory ability scores tend to adopt passive roles, underscoring the influence of perceived autonomy on decision‐making. Therefore, developing support strategies that empower older adults, particularly those with cognitive challenges, to actively participate in their healthcare decisions is essential. Involving families in this process is also important, considering the preferences and cognitive capabilities of older adults.
Effect Of Horseradish (Moringa Oleifera) Seeds on Biochemical and Molecular Parameters in Paraquat‐Induced Parkinson Disease‐Like Symptoms in Fruit Flies
Authors: Aro Olayemi Philemon , Adefegha Adeniyi Stephen , Ogunsuyi Opeyemi Babatunde , Oboh Ganiyu 
Published: January 2025

AbstractBackgroundIn recent decades, epidemiological and experimental studies have looked into the role of pesticides, particularly the herbicide paraquat, in the development of Parkinson’s disease. Horseradish tree (Moringa oleifera) is an ethnobotanical plant with lots of therapeutic potential, but there is a dearth of information on the bioactive properties of the seed alkaloid extracts.MethodThis study examined the modulatory effects of various concentrations of an alkaloid extract from the seeds of Horseradish Tree (Moringa oleifera) on the survival rate of flies exposed to paraquat, as well as certain biochemical and molecular markers related to Parkinson’s disease in the heads of the flies.ResultThe findings showed that the survival rate of the treated flies was significantly (p<0.05) higher than that of paraquat‐induced flies. The catalase and total thiol content of the flies were found to be significantly lower in the paraquat‐induced flies, but this was ameliorated in the treated groups. In addition, when compared to their elevated levels in paraquat‐induced flies, monoamine oxidase and acetylcholinesterase activities in the treated groups were found to be significantly (P<0.05) reduced. In addition, the enhanced reactive oxygen species (ROS) of the paraquat‐induced groups were significantly reduced after being treated with alkaloid extracts. The findings of gene expression demonstrate that catalase and tyrosine hydroxylase (TH) mRNA expression levels were downregulated in the induced group but elevated in the treated groups, with the seed showing a significant upregulation in catalase expression compared to tyrosine hydroxylase (TH) mRNA expression.ConclusionAccording to the findings of this study, alkaloid extracts from Moringa seeds ameliorated impaired biochemical indices and, at the same time, upregulated genetic expression in paraquat‐induced flies. The results of this research indicate that extracts from M. oleifera seeds have neuroprotective potential, especially as it relates to Parkinson’s disease.
APOEε4 drives microglial activation in the medial temporal cortex in individuals across the AD spectrum
Authors: Ferrari‐Souza João Pedro , Lussier Firoza Z , Leffa Douglas Teixeira , Therriault Joseph , Tissot Cécile , Bellaver Bruna , Ferreira Pamela C.L. , Povala Guilherme , Benedet Andrea L. , Servaes Stijn , Stevenson Jenna , Rahmouni Nesrine , Macedo Arthur C. , Soucy Jean‐Paul , Gauthier Serge , Souza Diogo O. , Zimmer Eduardo R. , Rosa‐Neto Pedro , Pascoal Tharick Ali 
Published: January 2025

AbstractBackgroundMicroglial activation is an early phenomenon in Alzheimer’s disease (AD) that may occur prior to and independently of amyloid‐β (Aβ) aggregation. Compelling experimental evidence suggests that the apolipoprotein E ε4 (APOEε4) allele may be a culprit of early microglial activation in AD. However, it is unclear whether the APOEε4 genotype is associated with microglial reactivity in the living human brain. In individuals across the aging and AD spectrum, we tested the hypothesis that APOEε4 associates with microglial activation.MethodWe studied 118 individuals (79 cognitively unimpaired [CU], 23 with mild cognitive impairment [MCI], and 16 with AD dementia) from the Translational Biomarkers in Aging and Dementia (TRIAD) cohort. Individuals had available [18F]AZD4694 Aβ PET, [18F]MK6240 tau PET, [11C]PBR28 microglial activation PET, and magnetic resonance imaging (MRI), as well as APOE genotyping. To increase the reliability of our results, we only included high‐affinity binders for the [11C]PBR28 radiotracer. In a subgroup of 42 individuals with longitudinal clinical and MRI data, we further assessed longitudinal hippocampal atrophy and clinical deterioration.ResultVoxel‐wise analysis revealed that APOEε4 carriership was associated with increased [11C]PBR28 uptake mainly in the medial temporal cortex (Figure 1A and B), and this effect of APOEε4 was independent of Aβ and tau accumulation. Region‐wise analyses demonstrated that APOEε4 carriers presented increased [11C]PBR28 SUVR relative to noncarriers only in Braak I‐II regions (Figure 1C), which further supports that APOEε4‐related microglial activation occurs specifically in medial temporal structures. Lastly, we found that [11C]PBR28 uptake in brain regions vulnerable to APOEε4 effects is associated with subsequent hippocampal atrophy and clinical decline over 2 years (Figure 2).ConclusionThese results support a model in which APOEε4 plays a role in early AD progression by contributing to microglial activation in medial temporal regions. Our findings provide a rationale for the development of novel AD therapies targeting the interplay between ApoE and neuroinflammation.
Generation and validation of anti‐TREM2 agonistic antibodies to enable the advancement of drug targets in the TREM2/DAP12 signaling pathway for the treatment of Alzheimer Disease
Authors: Moussaif Mustapha , Javens‐Wolfe June , Palkowitz Alan D. , Richardson Timothy I. 
Published: January 2025

AbstractBackgroundTREM2 signaling has been implicated in Alzheimer’s Disease (AD). TREM2 regulates microglial states and functions such as phagocytosis. The most prominent TREM signaling adapter is DAP12, encoded by TYROBP. Understanding functional changes of this complex, and downstream effectors such as SHIP1, PLCG2 and the Scr family kinases Lyn and Hck, is required to evaluate a broad range of therapeutic hypotheses and drug targets for prioritization and enablement. The lack of available, well validated, and openly distributed experimental tools can limit early drug discovery efforts. Therefore, the IUSM Purdue TREAT‐AD Center has generated and validated TREM2 activating antibodies to enable the advancement of drug targets in the TREM2/DAP12 signaling pathway.MethodTo establish and validate anti‐TREM2 agonist antibodies, heavy and light chain variable sequences were identified from multiple publications including patent applications. Antibodies were formatted as either human IgG1, Fc null mutant IgG1 or antibody transport vehicle (ATV) Fc null mutant IgG1. They were expressed in mammalian ExpiCHO cells and tested ex vivo for agonism based on their ability to activate AKT and Syk phosphorylation in THP1 cells and TREM2/DAP12 overexpressing cells respectively. The strongest agonistic candidate was scaled, purified, and further characterized biophysically and functionally.ResultSeveral agonistic antibodies were identified. AL2p31 antibody showed binding specificity to human versus murine TREM2. Biophysical characterization using biolayer interferometry showed that binding kinetic parameters (KD, Kon, and Koff) were not significantly affected in LALAPG null mutant Fc background. AL2p31 specifically induced Syk phosphorylation in comparison to an isotype control. Analysis of antibodies formatted as bispecific IgG1 targeting both TREM2 and the human transferrin receptor (hTfR), confirmed that RS9‐F6 can bind both human and murine TREM2 and revealed the ATV 35‐21‐16 variant sequence as a binder for the hTfR.ConclusionThe mission of the IUSM Purdue TREAT‐AD Center is to enable and advance the next generation of drug targets for the treatment of AD. The validation of anti‐TREM2 agonistic antibodies as research tools will enable comprehensive studies of the TREM2/DAP12 signaling and potential drug targets within the pathway including SHIP1, PLCG2 and the Scr family kinase Lyn and Hck.
Confabulation and Fluctuating Memory: A Case of Alzheimer’s Dementia in a Culturally Diverse Patient
Authors: Dahroug Nada , Siddig Nidhal , Mezzoni Mayra , Abdelrahman Nadir G 
Published: January 2025

AbstractBackgroundConfabulation, the fabrication of details with short lucid intervals, hinders the diagnosis of Alzheimer’s and other dementias. This case report explores the complexities of diagnosing and managing Alzheimer’s dementia in a culturally diverse patient exhibiting fluctuating memory and confabulation, emphasizing challenges heightened by cultural and linguistic factors.CaseAn 84‐year‐old African descent man resided with his family in the United States, independent in his basic daily activities but struggling with instrumental tasks due to memory impairment. While demonstrating clear recollection at times, closer examination revealed fabricated details and disorientation regarding his current environment. Confabulation in this trilingual patient (English, German, and Arabic) posed additional challenges, necessitating a closer look at his cultural background, language barriers, and family dynamics. The patient was born and raised in Africa. He relocated recently to join his family in the US. The family was involved in managing medication adherence and therapeutic interventions. A specialist evaluated the patient, and the Montreal Cognitive Assessment (MoCA) indicated a score of 12/30, signifying moderate cognitive impairment. The assessment considered language nuances, cultural influences, and familial support. Laboratory tests were grossly unremarkable. Donepezil and Vitamin B12 were prescribed to the patient. Family members were educated regarding the use of storytelling as a therapeutic approach.ResultFamily involvement played a pivotal role in holistic care coordination. Despite prescribed medications, the family has not initiated treatment due to the risks of side effects. Melatonin was used as needed for sleep disturbances. Predominantly non‐pharmacological treatment approaches were implemented, including reorientation and redirection. Storytelling as a therapeutic approach was effective.ConclusionThis case underscores the significance of culturally sensitive approaches in cognitive assessment and holistic care coordination, emphasizing the need for continued research on Alzheimer’s presentation in diverse populations. The abstract serves as an invitation to discuss effective strategies for diagnosing and managing Alzheimer’s dementia in culturally diverse patients, promoting inclusivity and optimal care.
Correlation between blood biomarkers and neuropsychiatric symptoms: Siriraj cohort, Thailand
Authors: Senanarong Vorapun , Rattanabannakit Chatchawan , Nanthasi Witsarut , Wongkom Natthamon , Dujada Pathitta , Phoyoo Paphawadee , Wachirutmangur Lertchai 
Published: January 2025

AbstractBackgroundWe explored the relationship of neuropsychiatric symptoms (assesses by NPI) and Alzheimer disease pathophysiology from blood AB42/40, GFAB, NFL, and pTau181. We also investigated if age and cognition were related to these neuropsychiatric symptoms.Method222 subjects included 96 dementia, 66 MCI, and 60 normal controls (NC). Spearman correlation was used to calculation the correlation coefficient. Mann‐Whitney U test is used to compare biomarkers of those with and without subitem symptoms of NPI.ResultMean ages were 71.26±9.82 years old in dementia group, 68.83±8.01 years old in MCI group, and 59.28±9.22 years old in NC group. Sum of 12 NPI subscale scores showed significant low correlation (r=0.20‐0.29) were correlated with blood AB42/AB40, Ptau 181, NFL, and GFAB. Sum of 12 NPI subscale scores showed significant moderate correlation with age and global cognition (assessed by Thai mental state examination, TMSE). Blood pTau181 displayed low correlation with hallucination, depression, anxiety, apathy, and irritability subscale scores. There was a significant low correlation between blood AB42/AB40 and delusion and irritability subscale scores. Blood NFL showed low correlation with euphoria, a, apathy, disinhibition, irritability, and aberrant motor activity. Inflammation process appeared to be significantly related with psychosis, apathy, disinhibition, and irritability. After controlled by age and TMSE; only apathy and AMA NPI subscale scores were correlated to NFL and GFAB accordingly.ConclusionWe discovered that psychosis and mood factors of NP symptoms were related to blood pTau. While most frontal factors of NP symptoms showed significant relationship with axonal destruction and microglia activation/inflammation.This study was supported by grants from Health Systems Research Institute (HSRI), Thailand.
Brain EV‐Bound Proteins in Blood as a Robust Biomarker for Accurate Classification of Tau Tangles in the Brain
Authors: Ho Nicholas RY 
Published: January 2025

AbstractBackgroundBrain derived Extracellular Vesicles (EVs) was isolated from blood and their containing pthogenic proteins were quantified to develop a biomarker signature for the classification of Tau aggregation in the brain.MethodBrain derived EVs and their cargo were measured directly in the plasma of patients with AD and determined to be Tau‐PET positive (visual read) (n=10) and other age matched healthy controls (n = 22) at one time‐point. AD pathogenic proteins bound to EVs were quantified by in‐house custom developed immunoassays.ResultA signature of a variety brain derived EV bound total tau, P‐T231‐tau, and P‐S396‐tau was able to accurately classify Tau‐PET positive AD patients from healthy controls (AUC: 0.88 – 0.93)ConclusionBrain derived EV bound total tau, P‐T231‐tau, and P‐S396‐tau in blood show good potential as biomarkers to classify Tau aggregation in the brain
Self‐awareness impairment in Alzheimer’s Disease: Its Impact on Decision‐Making for Aging in Place
Authors: Compagne Charline , Trimaille Helene , Magnin Eloi , Tannou Thomas 
Published: January 2025

AbstractAlzheimer’s disease significantly impacts decision‐making abilities, potentially increasing risk‐taking behaviors and complicating the process of aging‐in‐place, particularly in cases of anosognosia (self‐awareness impairment). To understand how this affects patient and caregiver perspectives, we conducted a qualitative study to identify arguments used by older patients with Alzheimer’s disease and their family caregivers about aging‐in‐place. We included 18 dyads, each comprising an older adult living at home with mild dementia and their family caregiver. The older adults' arguments in favor of aging‐in‐place were primarily centered on maintaining a sense of safety and comfort through familiar surroundings and relationships, as well as preserving independence and lifestyle habits, which contribute to stability in their daily lives. Despite recognizing memory loss, many minimized or overlooked the associated risks in their thoughts about aging in place. Caregivers, while supportive of the desire for aging in place, emphasized the need for adaptability in daily functioning and proactive planning for foreseeable challenges. They advocated for external support strategies, including professional assistance, technology use, routine adaptations, and legal protective measures. Our study highlights the profound impact of anosognosia on the loss of adaptability, potentially undermining preventive strategies for aging in place. A deeper understanding of these factors is crucial for professionals in developing care and service plans tailored to individual needs. Such knowledge is vital in facilitating discussions and negotiations around care strategies, ensuring they address the needs and concerns of both patients and caregivers in the context of Alzheimer’s disease.
Enhancing the Wellbeing of Family Dementia Caregivers: The Impact of Gamification in the MapHabit Program
Authors: Gore Janelle , Montgomery Brittany 
Published: January 2025

AbstractBackgroundThe number of caregivers providing care for a family member or friend is on the rise. Dementia caregivers experience higher levels of stress and burden than caregivers of other chronic diseases due to the physical and emotional demands, and long duration of care provided. Thus, innovative tools are needed to aid in reducing caregiver stress and burden. MapHabit, is a novel mobile health assistive technology tool designed to support families affected by dementia by providing daily schedules and step‐by‐step visual routines and cues called maps, aiding the person living with dementia (PLWD) to complete various activities of daily living (ADLs). With repeated use of these maps, persons with memory impairment have reported an improvement in memory and caregivers have reported reduced stress and burden. Gamified features were integrated into MapHabit to evaluate whether cognitive engagement activities could improve an individual’s motivation to consistently engage with MapHabit. Building upon the demonstrated impact of MapHabit, this study explores the effects of implementing gamified features within the application to enhance the reduction of caregiver stress.MethodsA modified Zarit Burden Interview was used to assess caregiver burden. The Mini Mental State Examination was used to evaluate the cognitive function of the PLWD. Scores from the respective assessments were calculated based on the respective scale’s scoring guide for pre‐ and post assessments. Scores were then compared to determine the stress and an improvement in memory of the PLWD.ResultsThirteen participants engaged in the MapHabit with Gamification group for 6‐weeks. About 69% of caregivers reported a reduction in stress and burden post study and 69% of PLWD reported an improvement in memory. Preliminary findings suggest the introduction of gamification in the MapHabit program may aid in reducing caregiver stress and burden.ConclusionThis research has implications for the ongoing development of dementia support programs, emphasizing the potential of gamification as a supplementary tool to enhance the engagement of existing interventions supporting families affected by dementia.
Complement C1q is Associated with sTREM2, GFAP and Alzheimer’s Pathology: the ADNI & CABLE Study
Authors: Sheng Ze‐Hu , Wang Zhibo , Ma Lingzhi , Wang Zuo‐teng , Guo Fan , Tan Lan 
Published: January 2025

AbstractBackgroundComplement C1q, the initiator of the classical pathway of the complement system, is activated during Alzheimer’s disease (AD) development and progression and is especially associated with the β‐amyloid and tau pathology. However, whether C1q influences AD pathology by modulating glial cell communication is unclear.MethodAlzheimer’s Disease Neuroimaging Initiative (ADNI, N = 217) was used to explore the association between cerebrospinal fuid (CSF) C1q, soluble triggering receptor expressed on myeloid cells 2 (sTREM2), Glial fbrillary acidic protein (GFAP), and AD biomarkers. Chinese Alzheimer’s Biomarker and LifestylE (CABLE, N = 535) study was used to explore the association between plasma C1q, CSF sTREM2, GFAP, and AD biomarkers. Causal mediation analysis was conducted through 10,000 bootstrapped iterations to explore the mediating effect of sTREM2/GFAP on association between C1q and AD pathology.ResultWe found that CSF C1q was positively associated with CSF sTREM2, GFAP and AD core biomarkers (Aβ42; phosphorylated‐tau, p‐tau; and total tau, t‐tau) at baseline, and was also significantly related to CSF t‐tau and ADAS‐13 in longitudinal analysis. Moreover, mediation analysis revealed that CSF C1q modulated the level of CSF sTREM2 and contributed to tau pathology (as measured by CSF p‐tau/ t‐tau). In addition, Aβ pathology (as measured by CSF Aβ42) affected the development of tau pathology (as measured by CSF p‐tau) partly by modifying the levels of CSF C1q and CSF sTREM2. Furthermore, the plasma C1q was also significantly associated with CSF sTREM2.ConclusionOur fndings provide evidence to suggest that Complement C1q is linked to sTREM2 and mediates the correlation between Aβ pathology to tau pathology. It indicates that Complement C1q may be a major factor in the spreading from Aβ pathology to tau pathology in AD.