bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigating the relationships between cognitive impairment score, cerebrospinal fluid measures and dementia diagnosis
Authors: Ilchovska Zlatomira Georgieva , Jung JeYoung , Mukaetova‐Ladinska Elizabeta , Hosseini Akram A. 
Published: January 2025

AbstractBackgroundCerebrospinal fluid (CSF) dementia markers are sensitive to cognitive decline, particularly memory (Hosseini et al, 2023).MethodsWe performed preliminary analyses on a neurodegenerative and non‐neurodegenerative patient dataset, collected as part of the CogNID study (IRAS reference: 250525, clinical trial reference: NCT03861884). We explore two questions, the first of which regards whether cognitive profile measured by the Addenbrooke’s cognitive examination (ACE‐R III) can predict diagnosis category, clustered into three groups: 1) Alzheimer’s Disease (AD; N=50), 2) non‐AD dementia conditions (e.g., frontotemporal dementia, Vascular Cognitive Impairment, Parkinson’s disease; N=46), and 3) a mixed, non‐dementia group serving as “control” (e.g., subjective cognitive impairment, post‐Covid‐19 brain fog; N=64). The second question asked whether, for a smaller subset of our participants with CSF dementia measures, there is any correlation between CSF dementia biomarkers and cognitive impairment. We explored these using regression analysis and Pearson’s correlation tests.ResultsFor our total sample with recorded ACE‐R III scores (N=160, Mage=59.3, SDage=6.4), participants’ memory (t=‐2.31, p=.02) and language (t=2.16, p =.03) scores predicted their diagnosis category. Post‐hoc split‐data regression analyses revealed only a significantly lower memory score for the AD group compared to control group (t=‐2.482, p=.015). None of the other comparisons showed a significant difference after multiple‐comparisons corrections. For our second question, we selected a subsample of our data with recorded CSF measures (N=56). We assessed the CSF measures of total 181‐Tau, phospho‐Tau and Amyloidß1‐42 in these participants in relation to their memory, attention and visuospatial, obtained from the ACE‐R III scores. We found a significant negative correlation between 181‐phospho‐Tau (but not total Tau) and memory scores (r=‐.37, p=.005), indicating that higher 181‐phospho‐Tau measures were significantly associated with impaired memory performance.ConclusionsThe preliminary analysis is limited by the high diversity of our neurodegenerative non‐AD group. A more detailed exploration of memory is crucial during diagnostic assessments of suspected AD.Disclosure and funding: AAH is funded by the UK Medical Research Council (MR/T005580/1).Reference: https://alz‐journals.onlinelibrary.wiley.com/doi/full/10.1002/alz.054530
Physical frailty and brain health: a prospective cohort study
Authors: Gao Pei‐Yang , Tan Lan , Yu Jin‐Tai 
Published: January 2025

AbstractBackgroundPhysical frailty is characterized as functional degeneration across multiple systems, which has been proposed as a risk factor for various health outcomes. However, the correlation between physical frailty and brain health, including brain function, brain disorders, and brain structure, remains unclear.MethodHere, 316905 participants from the UK Biobank were included in this prospective longitudinal study. Physical frailty was assessed by five phenotypes, including exhaustion, low grip strength, low physical activity, weight loss, and slow walking speed. Linear regression model and cross‐lagged panel model were firstly applied to evaluate the cross‐sectional and longitudinal relationship of physical frailty with brain function, including mental health and cognitive function. Cox proportional hazard model and Mendelian randomization analyses were further conducted to examine the longitudinal association and causal relationship between physical frailty and eight brain disorders. Finally, the cross‐sectional correlation between physical frailty and brain cortical and subcortical regions were assessed using linear regression model.ResultOver a median of 14.47 years follow‐up, 5943 (1.88%) new‐onset dementia were assessed. After adjusted covariates, a significant cross‐sectional and longitudinal relationship of physical frailty and five phenotypes with mental unhealth (four depression scales, life satisfaction, general mental status, and traumatic events) and worse cognition (reaction time, numeric memory, and fluid intelligence). Cox model and MR analyses revealed significant associations of physical frailty and five phenotypes with risk of incident dementia, Parkinson’s disease, stroke, sleep disorders, anxiety, major depressive disorder, and schizophrenia. Moreover, neuroimaging analyses emphasized the correlation of physical frailty with the cortical frontal cortex and subcortical regions including the thalamus, lateral ventricle, and hippocampus.ConclusionThis study provides evidence from multiple perspectives suggesting that physical frailty intervenes brain health and presents a strategy that early modification of physical frailty states may benefit the prevention of brain health.
Therapeutic potential of beta‐carotene on intracisternal injection of glucose oxidase‐induced senile dementia in diabetic rats
Authors: Muthuraman Arunachalam , Lim Khian Giap 
Published: January 2025

AbstractBackgroundSenile dementia (SD) is a deteriorative organic brain disorder and it comprises Alzheimer’s disease (AD) as a major variant. SD is shown impairment of mental capacities whereas AD is degeneration of neurons. According to World Health Organization (WHO) report; more than 55 million peoples have dementia and it is raising 10 million new cases every year. Further, it is expected to rise to 78 million in 2030 and triple by 2050. The glucose oxidase (E.C. 1.1.3.4; GOD) is an oxidoreductase enzyme and it oxidizes the β‐d‐glucose to d‐glucono‐δ‐lactone and hydrogen peroxide (H2O2). In the neuronal system, GOD & H2O2 cause rapid fluctuations of glucose levels, insulin resistance, oxidative stress along with microglial activation and neurodegenerations. Besides, only a few medications were approved for the symptomatic relief of SD i.e., donepezil, galantamine, rivastigmine, and memantine. Moreover, the most efficient and potential agents are not discovered yet. Hence, the present study was designed to investigate the beta‐carotene (BC) actions against the GOD‐associated SD in diabetic rats.MethodMale Sprague Dawley rats were used for the induction of diabetes by intraperitoneal injection of nicotinamide (50 mg/kg and streptozotocin 50 mg/kg), and SD was induced by intracisternal administration of GOD (50 U/5 µl at 1 µL/minute). The BC (50 and 100 mg/kg; p.o.) and donepezil (1 mg/kg; p.o.) were administered for 15 consecutive days. The cognitive function was assessed by the Morris water maze test and biomarkers i.e., blood glucose & insulin; serum nitric oxide (NO); tissue acetylcholinesterase (AChE), galectin‐1 (G1), NADPH oxidase (NOX4) activity & glucose transporter 1 (GLUT1) levels were evaluated.ResultGOD potentially changes the neurovascular unit in the brain which leads to a rise the insulin resistance (IR), NO, G1, & GLUT1 levels; and decreases the NOX4 activity. The GOD causes the potential cognitive dysfunctions. However, the treatment of BC attenuated the GOD‐associated cognitive dysfunction and biomarker changes.ConclusionThe present results revealed that BC possesses the ameliorative potential against GOD‐induced neurotoxicity and SD due to its anti‐oxidative, anti‐cholinesterase, reduction of IR, prevention of microglial activation, and enhancement of the glucose update actions.
Aryloxypropanolamine mitigates Alzheimer‐like phenotype by directly removing amyloid aggregates
Authors: Yoon Soljee , Lee Hee Yang , Cho Illhwan , Lee Donghee , Shin Jisu , Kim Kyeonghwan , Kim Jimin , Kim Hye Yun , Kim Ikyon , Kim YoungSoo 
Published: January 2025

AbstractBackgroundThe accumulation of amyloidogenic proteins is recognized as a primary biomarker, initiator of pathology, and a potential therapeutic target for Alzheimer’s disease (AD). An unbiased screening of a small molecule library was conducted to identify new chemical compounds exhibiting amyloid‐dissociative properties.MethodThe ability of aryloxypropanolamine derivatives to dissociate amyloid‐β (Aβ) aggregates was evaluated through in vitro assays. Subsequent assessments involved immunostaining, immunoblotting, and Morris water maze to examine the anti‐Alzheimer properties of the molecules using 5XFAD and transgenic APP/PS1 mice. Characterization of the target‐ligand interaction was also carried out through peptide mapping assay and constrained docking simulations.ResultAmong 11 derivatives, YIAD002 demonstrated the most significant dissociative effect against β‐sheet‐rich Aβ aggregates. Oral administration of the compound led to a significant reduction in amyloid burden, improved cognitive performance in the Morris water maze, and mitigated key clinical symptoms of AD, including tauopathy, neuroinflammation, and synaptic protein loss. Mechanistic studies indicated that YIAD002 directly interacted with the KLVFFA and IGLMVG domains of Aβ.ConclusionCollectively, our results demonstrate the potential of chemical‐driven dissociation of amyloidogenic proteins as a promising disease‐modifying treatment for AD.
Effect of increasing cognitive activity participation on functional connectivities within default mode network– a randomized controlled trial
Authors: Lee Allen TC 
Published: January 2025

AbstractBackgroundWe previously reported that increasing participation in Chinese calligraphy handwriting, one of the “Four Arts” traditionally mastered by intellectuals in China and currently widely practiced by older adults in the Chinese community, led to better working memory among individuals with subjective cognitive decline (but without mild or major neurocognitive disorder). Given that the default mode network (DMN) is closely correlated with the clinical symptoms and progression of Alzheimer’s disease, we aimed to investigate the effect of increasing calligraphy practice on the DMN.MethodCommunity‐living older adults who had been practicing Chinese calligraphy handwriting regularly (at least one hour of calligraphy practice per week) and experiencing subjective cognitive decline (but without mild or major neurocognitive disorder) were randomly allocated into either the control group, where they continued their usual practice of calligraphy, or the intervention group, where they doubled their amount of practice for 6 months. Functional connectivities within DMN were assessed before and after the intervention. This randomized controlled trial was funded by the Research Grants Council in Hong Kong (grant number: 24114519), registered with the Chinese Clinical Trial Registry (ChiCTR1900024433), and approved by the Clinical Research Ethics Committee of the Chinese University of Hong Kong (CREC Ref. No.: 2019.054).ResultsBy the end of 6 months, nearly all the functional connectivities that we examined within the DMN weakened in the control group, whereas those in the intervention group either strengthened or showed a lesser degree of weakening. Statistical significance was reached in the between‐group differences of the functional connectivities between medial prefrontal cortex and right lateral temporal cortex, medial prefrontal cortex and right inferior parietal lobe, left hippocampal formation and right lateral temporal cortex, and left hippocampal formation and right inferior parietal lobe.ConclusionIncreasing cognitive activity participation may have a positive neuromodulatory effect on functional brain network in older adults who are not yet having mild or major neurocognitive disorders. Our findings highlight the importance of staying cognitively active in late life for better brain health.
Peruvian healthcare system readiness for dementia: First insights from an ongoing research study
Authors: Serruto Francisco Tateishi , Porras Maria Lazo , Hawkins Jemma , Cuba María Sofía , Butler Christopher , Bernabe Antonio , Moore Graham , Landeiro Filipa , Cardenas Maria Kathia , Canseco Francisco Diez , Flores Miriam Lucar , Quinoso Silvana Perez León 
Published: January 2025

AbstractBackgroundPeru does not have official prevalence data of dementia, however, particular studies indicate that in urban areas 6.85% of the population over 65 years of age has it. Countries such as Peru have significant drivers of the condition such as low socio‐economic (monetary poverty 27.5%) and educational levels (21.9% of the population has only primary education). In order to prepare the health system and society in general, it is necessary to start multisectoral studies to understand the complexity of the challenge ahead. The IMPACT project aims to contribute to this.MethodMixed methods approach. Semi‐structured interviews with different stakeholders as well as secondary data review to cover 11 themes from the health system (policy environment, financing, infrastructure, service delivery in prevention and management issues, etc.) in three levels (macro, meso and micro) nnd in four different areas of PeruResultThe presentation still does not show results, as it is still ongoing. However, we are sharing some of the insights and learnings we have gained so far. Some of these are the following: limited and heterogeneous response due to the highly fragmented system, lack of political support, first level of care not designed or prepared to deal with dementia cases, reduced amount of specialists, adequate training for health providers attending this group, no guidelines for medical practices and limited research about its characteristics and needs. Also, age stereotypes and lack of awareness about dementia as a medical condition persist in all levels of the health system and society, negatively affecting the effectiveness of its response to their needsConclusionThese are some preliminary Conclusions: more research is needed, to address stereotypes, increase training for health providers, use technology to facilitate access to services, create models of effective implementation to generate impact on urgent issues and inclusion of preventive and long‐term care approaches
ApoE4 antibody ameliorates cognitive impairments and synapse loss in ApoE4/Tau‐P301S mice
Authors: Song Ha‐Lim , Kim Min‐Seok , Cho Mi‐Hyang , Mun Yeon‐Seon , Kim Na‐Young , Shin Jung‐Su , Kim Jun‐Sub , Kim Dong‐Hou , Yoon Seung‐Yong 
Published: January 2025

AbstractBackgroundThe Apolipoprotein E4 isoform (ApoE4), encoded by the APOE gene, stands out as the most influential genetic factor in late‐onset Alzheimer’s disease (LOAD). The ApoE4 isoform contributes to metabolic and neuropathological abnormalities during brain aging, with a strong correlation observed in APOE4‐positive Alzheimer’s disease cases between phosphorylated tau burden and amyloid deposition. Despite compelling evidence of APOE‐mediated neuroinflammation influencing the progression of tau‐mediated neurodegeneration, the molecular mechanisms underlying these phenomena remain largely unknown.MethodUtilizing Tau‐P301S mice crossed to APOE4‐knockin mice expressing human APOE4 (TauP301S/APOE4), the investigation tested the impact of anti‐mouse ApoE4 antibody, ADEL‐Y04, on memory enhancement and tau pathology reduction.ResultWe developed ADEL‐Y04, an anti‐mouse ApoE4 antibody specifically recognizing human ApoE4. Administration of ADEL‐Y04 in TauP301S/APOE4 mice demonstrated improvements in memory impairment. Synapse loss and pathological tau accumulation was also inhibited by ADEL‐Y04 administration.ConclusionOur findings suggest the potential for improving APOE4‐mediated tau pathology and memory impairment through the modulation of ApoE4. This provides avenues for intervention, indicating the possibility of ameliorating tau pathology and memory deficits by targeting APOE4.
Traumatic brain injury and cognitive resilience in the Framingham Heart Study
Authors: Hwang Phillip H , Durape Shruti , Price Eden , Gurnani Ashita S. , Ang Ting Fang Alvin , Devine Sherral A. , Choi Seo‐Eun , Lee Michael L. , Scollard Phoebe , Gibbons Laura E. , Mukherjee Shubhabrata , Trittschuh Emily H. , Sherva Richard , Dumitrescu Logan C. , Hohman Timothy J. , Saykin Andrew J. , Crane Paul K. , Tripodis Yorghos , Alosco Michael L. , Katz Douglas I , Dams‐O'Connor Kristen , Au Rhoda , Farrer Lindsay A. , Mez Jesse 
Published: January 2025

AbstractBackgroundSome evidence supports an association between traumatic brain injury (TBI) and greater risk of dementia, but the role of cognitive resilience in this association is poorly understood.Method2,050 participants from the Framingham Heart Study Offspring cohort who were aged ≥60 year and had a plasma total tau (t‐tau) measure at Exam 8 (2005‐2008), and a neuropsychological (NP) exam visit within five years were included. Plasma t‐tau was measured using the Simoa assay (Quanterix). NP factor scores were previously derived for memory, language, and executive function using confirmatory factor analysis. Information on TBIs was collected by comprehensive review of medical records, health history updates, exams, and self‐report. TBI occurrence and severity were operationalized using modified ACRM & VA/DoD criteria, respectively. Cognitive resilience was operationalized using a residual approach by regressing each NP factor score on the plasma t‐tau measure, adjusting for age at Exam 8, sex, education, time from blood draw, and APOE ε4 genotype. The adjusted residuals were then regressed on history of TBI (yes versus no), and severity of TBI (moderate‐to‐severe versus mild versus none).ResultThe sample was, on average, 67 years of age at Exam 8, 54% female, and college educated. No differences were observed in plasma t‐tau levels between those with and without TBI. Having a history of TBI was significantly associated with a reduction in resilience in executive function (β: ‐0.110; 95% CI: ‐0.175, ‐0.044; p: 0.001) as compared to not having a history of TBI. No significant associations were observed between history of TBI and resilience in memory or language. Greater TBI severity was significantly associated with worse resilience in executive function in a dose‐response manner (Ptrend: <0.001), with the association being strongest in the moderate‐to‐severe TBI group (β: ‐0.209; 95% CI: ‐0.340, ‐0.078; p: 0.002) followed by the mild TBI group (β: ‐0.082; 95% CI: ‐0.155, ‐0.010; p: 0.026).ConclusionHaving a TBI was associated with worse resilience to neurodegeneration in executive function, and most strongly among individuals with moderate‐to‐severe TBI. These results suggest that having a TBI may increase vulnerability to late‐life executive dysfunction after accounting for a primary neurodegenerative disease process.
A Prospective Study of Long‐Term Red Meat Intake, Risk of Dementia, and Cognitive Function in US Adults
Authors: Li Yuhan , Li Yanping , Gu Xiao , Liu Yuxi , Dong Danyue , Kang Jae H. , Wang Molin , Eliassen Heather , Willett Walter C. , Stampfer Meir J. , Wang Dong D. 
Published: January 2025

AbstractBackgroundPrevious studies yielded inconsistent results regarding the association between red meat intake and cognitive health. We aimed to prospectively examine the associations between processed and unprocessed red meat intakes and various cognitive outcomes.MethodWe assessed diet intake every 2‐4 years using food‐frequency questionnaires and ascertained incident dementia cases through self‐report and death records in 87,424 participants free from Parkinson’s disease or baseline dementia, stroke, cancer from the Nurses' Health Study (NHS). In a subset of 17,458 NHS participants, cognitive function was assessed using the Telephone Interview for Cognitive Status (1995‐2008). We longitudinally collected information on subjective cognitive decline from 33,908 NHS participants and 10,058 participants in the Health Professionals Follow‐Up Study.ResultDuring a follow‐up of 38 years (1980‐2018) in the NHS, we documented 6,856 dementia cases. Participants with processed red meat intake ≥ 0.25 serving/day, as compared to < 0.10 serving/day, had 15% higher risk of dementia (HR = 1.15; 95% CI: 1.08‐1.23; P
linearity <0.001). We found significant associations between higher processed red meat intake and accelerated aging in global cognition [1.61 years per 1 serving/day increment (95% CI: 0.20, 3.03)] and verbal memory [1.69 years per 1 serving/day increment (95% CI: 0.13, 3.25), both P
linearity = 0.03]. Participants with processed red meat intake ≥ 0.25 serving/day had a 14% higher likelihood of subjective cognitive decline compared to those with intake < 0.10 serving/day (OR = 1.14; 95% CI: 1.04–1.24; P
linearity = 0.004), while unprocessed red meat intake of ≥ 1.00 serving/day compared to < 0.50 serving/day was associated with a 16% higher likelihood of subjective cognitive decline (OR = 1.16; 95% CI: 1.04–1.30; P
linearity = 0.02). In substitution analyses, replacing 1 serving/day of processed red meat with 1 serving/day of nuts and legumes was associated with a 23% lower risk of dementia (HR = 0.77, 95% CI: 0.69–0.86), 1.37 fewer years of cognitive aging (95% CI: ‐2.49—0.25), and a 20% lower odds of subjective cognitive decline (OR = 0.80, 95% CI: 0.69–0.92).ConclusionHigher intake of red meat, particularly processed red meat, is associated with a higher risk of developing dementia and worse cognition.
Models for Predicting Dementia Risk in Low‐ and Middle‐Income Countries
Authors: Alshahrani Maha , Stephan Blossom CM , Siervo Mario , Sabatini Serena , Tang Eugene Yee Hing , Brain Jacob , Naheed Aliya , Pakpahan Eduwin , Robinson Louise , Mohan Devi 
Published: January 2025

AbstractBackgroundMost people with dementia reside in low‐ and middle‐income countries (LMICs) where resources, research, services, and support are often very limited. Research into dementia risk prediction is scarce in LMIC settings, and those prediction models developed in high‐income countries generally do not transport well to LMICs. This suggesting a dire need for LMIC specific dementia risk models.MethodWe synthesised the evidence from our three previous systematic reviews (covering all literature from inception to 2023 from PubMed, Embase, and PsychInfo) on dementia risk prediction modelling. The aim was to identify models that have been specifically developed and tested specifically in LMICs. There were no language or time restrictions applied.ResultTo date, over 50 different dementia risk prediction models have been developed and tested with only 7 models reported from two LMICs including five studies from China and two studies from Mexico. The models incorporated variables typically linked to dementia including demographics (e.g., age, sex, education), health (e.g., diabetes, hypertension, heart disease) and lifestyle (e.g., smoking and alcohol) variables. The 7 models also have varying degrees of predictive accuracy (c‐statistic range 0.65 [95%CI: 0.64–0.67] to 0.92 [95%CI: 0.88‐0.95]) and none has undergone external validation. These models have been developed using traditional statistical approaches including Cox and Logistic Regression. Further, model development has not considered factors such as socioeconomic status, literacy, access to healthcare, diet, stress, pollution, and workplace hazards that may be crucial in predicting dementia risk in LMICs.ConclusionThere is an urgent need to create context‐specific dementia prediction models to inform the development of risk reduction and preventative interventions in LMICs where dementia case numbers are greatest. Dementia risk model development and testing need to be extended to LMICs across different regions (e.g., Asia, Middle East, Global South, Africa) and income levels (e.g., low, lower‐middle, and upper‐middle income).RecommendationsGreater investment is needed into understanding dementia, and its risk factors in LMICs to inform the development of risk mitigation programs. Research should focus on developing accurate, resource‐conscious models with affordable and obtainable variables for identifying those individuals likely to benefit the most from interventions targeting risk reduction.