bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in cerebrospinal fluid synaptic proteins precede and coincide with Alzheimer’s pathology and govern cognitive function
Authors: Oh Hamilton Se‐Hwee , Wyss‐Coray Tony 
Published: January 2025

AbstractBackgroundThe buildup of brain amyloid‐beta and tau protein aggregates do not sufficiently explain the heterogeneity in cognitive impairment in Alzheimer’s disease (AD).MethodTo elucidate drivers of cognitive impairment, we measure the levels of 7,000 proteins, in addition to amyloid‐beta‐42 (Ab42) and phospho‐tau‐181 (PTau181), from the cerebrospinal fluid of 2,000 individuals from healthy to severe dementia.ResultWe identify synapse proteins as the strongest correlates of cognitive impairment. We use machine learning methods to derive a cognitive impairment signature, provided as the ratio between YWHAG and NPTX2, which increases with impairment severity (r=0.57) and explains resilience versus susceptibility to AD pathology. We find YWHAG:NPTX2 also increases with age in healthy individuals before PTau181:AB42 and increases 25 years before symptom onset (as early as PTau181:AB42) in autosomal dominant AD.ConclusionOur work reveals that synapse alterations precede and coincide with AD pathology accumulation and are the arbiters of cognitive decline. Additionally, we propose the CSF YWHAG:NPTX2 ratio as a biomarker for monitoring synapse health and predicting future cognitive decline in living people.
Effect of dietary habits on Alzheimer’s disease progression
Authors: Choi Seong Hye , Jeong Jee Hyang , Minn Yangki 
Published: January 2025

AbstractBackgroundResearch on the relationship between diet and dementia among Koreans are lacking. This study investigated the association between dietary habits and dementia progression over 3 years in patients with Alzheimer’s disease dementia (ADD).MethodThis study included 705 patients with mild‐to‐moderate ADD. Dietary habits were assessed using the Mini Dietary Assessment Index, comprising 10 questions. Outcome measures included the Clinical Dementia Rating scale‐Sum of Boxes (CDR‐SB), Seoul‐Instrumental Activities of Daily Living, Caregiver‐Administered Neuropsychiatric Inventory (CGA‐NPI), and neuropsychological test battery (NTB) z‐scores, which were evaluated annually over 3 years.ResultIn Q10 (eat all food evenly without being picky), the 3‐year mean differences in CDR‐SB (increases in scores represent worsening) compared to the “rarely” group were –1.86 (95% confidence interval [CI] = –3.64 ∼ –0.09, P = 0.039) for the “usually” group and –2.23 (95% CI = –4.40 ∼ –0.06, P = 0.044) for the “always” group. In Q7 (add salt or soy sauce to food, when eating), the 3‐year mean differences in CDR‐SB compared to the “always” group were –2.47 (95% CI = –4.70 ∼ –0.24, P = 0.030) for the “usually” group and –3.16 (95% CI = –5.36 ∼ –0.96, P = 0.005) for the “rarely” group. The “rarely” and “usually” groups in Q7 showed significantly less decline in NTB z‐score and CGA‐NPI compared to the “always” group.ConclusionEating a balanced diet and reducing salt intake were associated with a slower decline in dementia severity, cognition, and behavioral alterations in patients with ADD.
Dental caries, dental hygiene and selfcare, and use of dental health services, and risk of cognitive decline – an 11‐year follow‐up cohort study
Authors: Asher Sam , Suominen Anna Liisa , Stephen Ruth , Ngandu Tiia , Koskinen Seppo , Solomon Alina 
Published: January 2025

AbstractBackgroundCurrent evidence links poor oral health, especially tooth loss, with impaired cognition. However, role of underlying causes of tooth loss e.g., dental caries is not known. Moreover, concerning cognition, impact of dental hygiene and selfcare, and use of dental health services is yet to be studied. This study assesses various dental‐health related variables against 11‐year cognitive decline.MethodStudy included ≥30 years old individuals (N = 2958) who participated in the Finnish Health 2000 and its follow‐up Health 2011 Surveys. Dental caries for all teeth (except third molars) and dental hygiene or presence of plaque at 3 teeth/sites were clinically assessed at baseline (2000). Dental selfcare was assessed through daily brushing frequency, and number of visits to dental healthcare professionals in past 12 months indicated use of dental health services. Cognitive assessment at baseline (2000) and follow‐up (2011) was done via cognitive test battery including verbal fluency, immediate and delayed word recall. To assess overall cognition, a composite cognitive score was calculated both at baseline and follow‐up as a sum of individual cognitive tests. For each cognitive test, including composite cognitive score, 11‐year cognitive decline was calculated as difference between scores in 2011 and 2000. Exposure‐Outcome associations were analyzed via binary logistic regression and adjusted for multiple relevant covariates.ResultAfter adjustments poor oral hygiene demonstrated by having plaque at ≥2 teeth was associated with decline in verbal fluency and delayed recall. Inadequate dental selfcare demonstrated by brushing <1 times daily and extensive use of dental health services demonstrated by ≥2 visits to different dental healthcare professionals in the past 12 months were both associated with decline in total immediate recall. However, no association for dental caries was observed.ConclusionPreliminary results indicated higher risk of cognitive decline in individuals with poor oral hygiene, inadequate oral hygiene practices and recent history of multiple visits to dental healthcare facilities. In light of these findings, future studies into the factors influencing these modifiable patterns are recommended.
Neuroprotective Effect of Filgrastim against Rotenone induced Parkinson’s disease in Rats
Authors: Chaudhary Hema , Agrawal Mohit 
Published: January 2025

AbstractBackgroundParkinson’s disease is an hypokinetic disorder characterized by selective loss of dopaminergic in substantia nigra pars compacta (SNPc) region of mid‐brain. Dopaminergic degeneration of neurons is considered to be due to oxidative stress, neuroinflammation, neurons mitochondrial dysfunction and glutamate excitotoxicity etc. Filgrastim has been reported to produce anti‐oxidant, anti‐inflammatory and neuromodulatory actions in previous studies.MethodIn the current study we have investigated the role of filgrastim against rotenone induced motor deficit and biochemical abnormalities in Wistar rats. Rats were treated with 1.5mg/kg rotenone subcutaneously for 35 days. filgrastim (50,100 and 200 mg/kg i.p.) was administered after 30 minutes of rotenone administration from day 7th to 35th day. Rotenone caused significant reduction in motor functions and body weight and produced elevation in striatal oxidative burden. The biochemical analysis revealed that there is reduction in the level of anti‐oxidants (GSH, Catalase, and SOD) in the animals following rotenone administration.ResultWhereas filgrastim treated rats were stable and regained their body weight. In addition filgrastim significantly attenuated rotenone induced motor deficit and striatal oxidative stress.ConclusionOutcomes of the current study suggest neuroprotective potential of filgrastim and its ability to correct movement disability and thus could prove to be useful candidate molecule in the management of motor disorders.
Implementing a Dementia‐Friendly Communities programme across local authorities in the East of England
Authors: Windle Greg 
Published: January 2025

AbstractThere are many types of Dementia‐Friendly Communities (DFCs), and communities define and implement them in different ways. Toolkits from the World Health Organisation and Dementia Friendly America have defined specific goals for DFCs, and in 2013, Alzheimer’s Society created a national recognition programme for UK DFCs to respond to the diversity of interpretations. Key elements of the programme included People (awareness and training), Process (support and signposting) and Place (physical support and community). The complex implementation of DFCs in diverse regions has not been extensively studied, and the Alzheimer’s Society DFC accreditation programme for England ended in 2023.In order to keep continuity, regional governments in England are developing their own frameworks for implementing DFCs. County‐level local governments have convened a number of district councils to agree to continue with a DFC scheme in 2024 as a key part of the delivery of the county‐level dementia strategy for 2023 through 2028. This dementia strategy covers a broad range of community concerns, but it does not consider detailed implementation questions. A task force made up of local government officials, clinical commissioning group representatives, admiral nursing representatives, care home leaders and voluntary organisation heads is developing and implementing the new DFC programme. The continued DFC programme takes a federal structure, with a county‐wide set of criteria for defining levels of dementia‐friendly services in the community. Each local government within the county then has flexibility to tailor the criteria to their own population, business and service landscape.As DFCs in the East of England adjust to this new administrative framework, we are using an evaluation and implementation framework to measure individual and community impact and describe implementation consideration for this method of DFC administration. The main focus of implementation science has been in clinical practice, but there is a growing focus on the importance of evidence‐based public policies and their implementation. In detailing the implementation of this innovative community care programme, we consider implementation domains of Contextual Factors, Implementation Strategies, Service and Patient Outcomes, Implementation Outcomes, Economic Evaluation, Stakeholder Involvement and Engagement and Patient and Public Involvement and Engagement.
Long‐term impact of COVID‐19 infection on cognitive dysfunction among Chinese older adults: a national cross‐sectional online study
Authors: Huang Qing , Wu Jingnan , Li Liming , Yao Shi , Wang Yan , Li Yatian , Cui Lili 
Published: January 2025

AbstractBackgroundThe effects of the SARS‐CoV‐2 virus (COVID‐19) on the central nervous system predispose to cognitive dysfunction in older adults. However, limited information is available on how long this impact will last. This study aims to assess the cognitive decline in Chinese older adults after COVID‐19 using a cross‐sectional study.MethodA nationwide cross‐sectional study was conducted among 1698 individuals over 50 years old who completed an online questionnaire survey on their cognitive impairment. Based on the Subjective Cognitive Decline Questionnaire (SCD‐Q), we designed a self‐administration SCD‐18 questionnaire that assess perceived subjective decline in attention, comprehension, memory, emotion, motivation and sleep. The scores of each evaluation index in the SCD‐18 questionnaire ranges from 0 to 6, with higher scores indicating a greater possibility of cognitive dysfunction. We compared differences in relevant cognitive function between different participants and performed a multiple linear regression analysis to identify factors that might be associated with cognitive function.ResultOlder adults who were infected with COVID‐19 had significantly higher SCD‐18 scores than uninfected participants (P = 0.005). Among the infected participants, the SCD‐18 scores of females were significantly higher than that of males (P = 0.007), especially in memory (P<0.001), and rural participants had higher SCD‐18 scores than urban participants (P<0.001). Specifically, the SCD‐18 scores of the infected participants for 1‐6 months were significantly higher than that of the uninfected participants (P = 0.003), especially in comprehension (P = 0.011), memory (P<0.001), motivation (P = 0.016), and sleep (P = 0.008). Participants infected for more than 6 months did not have significantly different SCD‐18 scores from uninfected participants (P = 0.118), suggesting that cognitive function gradually recovered. Regression analysis indicated that female and rural area were associated with cognitive impairment.ConclusionThe cognitive function of older adults due to the COVID‐19 pandemic has changed over time. Female and rural area were the risk factors for cognitive decline. Therefore, further long‐term interventions for vulnerable older adults with a history of COVID‐19 should be considered to maintain cognitive health.
Loneliness among people living with dementia: results from the English Longitudinal Study of Ageing
Authors: Tapia‐Muñoz Thamara , Miranda‐Castillo Claudia 
Published: January 2025

AbstractBackgroundLiterature often focuses on loneliness as a risk factor for dementia. However, loneliness among those living with dementia (PLWD) is yet to be further explored.MethodSecondary analysis of the English Longitudinal Study of Ageing. Across ELSA waves 1 to 9, we identified 181 participants who reported being diagnosed with dementia and randomly selected 775 (10%) non‐dementia participants (NDP) from wave 2 (2004‐2005). For PLWD, the baseline was the year they reported the diagnosis. For NDP, the baseline was information from waves 1 and 2. We obtained a two‐year lagged loneliness for a subsample (n = 70 PLWD and n = 569 NDP). We computed multiple linear regression models using bootstrap errors with 1000 iterations to describe the average levels of loneliness among people living with dementia in England.ResultBoth groups did not differ in their socioeconomic characteristics except for age. PLWD were, on average, 76 years old (Sd = 9.74), and NDP was 66 years old (sd = 9.53). The average level of loneliness was 4.71 (sd = 1.74) for PLWD and 4.07 (sd = 1.47) for NDP. At baseline, the loneliness prevalence was 15.76% among PLWD and 7.55% for NDP. Among PLWD, the average 2‐year lagged loneliness was 4.72 (sd = 1.79), and 21% reported problematic loneliness, and among NDP, it was 4.18 (sd = 1.52) and 10%, respectively. Adjusted baseline levels of loneliness were statistically significantly higher among PLWD (Coef. = 0.694; 95% CI: 0.393‐0.994). For the 2‐year lagged loneliness, dementia and non‐dementia participants did not significantly differ in their levels of loneliness.ConclusionPublic policies should consider tackling loneliness among people living with dementia.
Alzheimer’s Disease Prediction and Implications for Insurance
Authors: Wittrock Julia , Schmitz‐Luhn Björn 
Published: January 2025

AbstractBackgroundThe possibilities to determine the individual risk of persons to develop future Alzheimer’s Disease and dementia have greatly increased in recent years. Promising and little invasive methods, e.g. blood or urine tests, may soon be available as predictive or early‐detection measures even for the general population. However, the knowledge incurred may be of interest not only for the affected persons themselves, but also for third parties. Particularly, the results of predictive tests may prompt disclosure or notification obligations to insurers, in turn affecting availability or affordable premiums for life or health insurance plans. This can be a substantial obstacle and burden for individuals considering to undergo predictive diagnosis. As predictive methods become more readily available, the problem gains pressing practical importance.MethodWe analyze existing legislation and jurisprudence in a variety of jurisdictions to investigate what regulations are in place for dealing with individual risk probabilities, and to what extent these are applicable or transferable to the particular problematic aspects regarding the prediction of Alzheimer’s Disease and/or dementia.ResultExisting insurance law, where in place, strikes only a rudimentary balance, and for a limited scope, mostly genetic diagnostics only. At the same time, access to disease prediction by non‐genetic means is quickly growing, and legal protections, rights and duties are largely unregulated in spite of a similar conflict of interests. The associated uncertainties for the involved parties keep increasing, and there is a pressing need for rules bringing the conflicting interests into a fair balance.ConclusionWe present efforts and their shortcomings to reduce the tension between the interest of insurers in offering affordable and calculable premiums on the basis of individual risk factors, and the particular need of affected persons to protect the results of predictive examinations due to their high sensitivity. We show how this tension could be sensibly resolved by taking into account ethical and societal values, considering the complex interests at stake.
Health Literacy, Blood Pressure Variability, and Domain‐specific Cognitive Changes
Authors: Ihara Keiko , Opsasnick Lauren , Bonham Morgan , Batio Stephanie , Yoshino‐Benavente Julia , Curtis Laura M , Bailey Stacy C , Wolf Michael S , Kim Minjee 
Published: January 2025

AbstractBackgroundBoth limited health literacy (HL) and elevated blood pressure variability (BPV) in later life have been associated with the risk of dementia and cognitive impairment. However, little is known about the relationship between HL, BPV, and domain‐specific cognitive decline. We aimed to examine this relationship among primary care older adults.MethodEnglish‐speaking adults aged 55‐74 were recruited from an academic general internal medicine practice and federally qualified health centers in Chicago between 8/2008 and 6/2010. HL was measured by the Newest Vital Sign. BPV was assessed by variation independent of mean systolic blood pressure calculated from all blood pressure measures obtained during routine ambulatory visits that occurred in calendar years 2008 – 2012. Five cognitive domains (processing speed, inductive reasoning, and working, long‐term, and prospective memories) were assessed through 15 tests at baseline, which were repeated three additional times at a 2.5‐year interval. Changes in Z‐scores were calculated from baseline (T1) to the last available assessment (T4 or T3) for each of the five cognitive domains. We examined associations between BPV and domain‐specific cognitive changes with univariate and multivariable regression, adjusting for a priori covariates including baseline age, sex, race, hypertension, number of chronic conditions excluding hypertension, cognitive function, HL, and interval between cognitive assessments.ResultA total of 299 participants (age 63.3 ± 5.3; 73% female; 26% non‐Hispanic Black, 67% non‐Hispanic White; 1.8 ± 1.3 chronic conditions; 51.8% with hypertension at baseline) were included in analyses (Table 1). Median interval between cognitive assessments was 8.4 years (IQR 8.2‐8.7). Baseline hypertension (β, 1.00; 95% confidence interval (CI), 0.28‐1.71; p = 0.006) and limited HL (β, 1.42; CI, 0.65‐2.20; p<0.001) were significant predictors of 5‐year BPV (Table 2). Greater 5‐year BPV was significantly associated with decline in long‐term memory (β, ‐0.035; CI, (‐0.064)‐(‐0.007); p = 0.016), but not with changes in other cognitive domains, after adjusting for a priori covariates (Table 3).ConclusionLimited health literacy in later life is associated with greater variability of systolic blood pressure over five years, which was, in turn, associated with greater decline in long‐term memory over a median follow‐up of eight years.
Towards a sole β‐amyloid‐centered definition of Alzheimer’s disease? Risks and alternatives
Authors: Villain Nicolas , Hanseeuw Bernard J , Planche Vincent 
Published: January 2025

AbstractAimsThe Alzheimer Association (AA) has proposed new diagnostic criteria for Alzheimer’s disease (AD) based on biomarkers coinciding with β‐amyloidosis onset. However, there are concerns regarding the implications of these criteria.MethodsWe reviewed several perspectives, including disease definition, public health, philosophy, therapeutic, and diagnostic.Results1. Disease definition – the AA definition displays limited and heterogeneous predictive capabilities of lifetime clinical progression in asymptomatic individuals, and a different disease label may be used, as seen in other examples in medicine (eg MGUS and multiple myeloma).2.	Public health – the majority of the A+ population is asymptomatic, and the AA definition may reduce the association between the “label” AD and dementia or subsequent progression to dementia, which could impact public health decisions.3.	Philosophy – the clinical and biological definitions of AD are based on different medical‐philosophical theories of disease (Nordenfelt vs. Boorse), and if the AA criteria are widely adopted, there may be misconstrued perceptions among stakeholders.4.	Therapeutic – an amyloid definition of AD disconnects the biological endpoint from the clinically relevant outcome, which has led to the approval of aducanumab without demonstrating clinical impact. This raises concerns about future decisions regarding asymptomatic individuals.5.	Diagnostic – the AA framework lacks clear guidelines on linking clinical situations with AD biological changes, which may result in misdiagnosis and overdiagnosis in patients with abnormal biomarkers.ConclusionsDefining AD based solely on β‐amyloidosis is risky and reduces association with clinically relevant outcomes. Diagnosing AD should instead involve symptoms or a high probability of developing them. The IWG framework takes a cautious approach, focusing on symptom onset. Future IWG developments could expand the “preclinical AD” label by integrating specific biomarkers that can predict severe cognitive decline in asymptomatic patients.
RWD insights into the global cost of Alzheimer’s and dementia
Authors: Jönsson Linus 
Published: January 2025

AbstractIt is well recognised that Alzheimer’s disease and related dementia disorders (ADRD) are associated with very high societal costs. The total global costs of dementia have been estimated to over 1.3 trillion US$ annually (Wimo, Seeher et al. 2023). Real‐world data (RWD) sources such as national patient registers, claims databases, disease and quality of care registers, offer an opportunity to assess resource utilisation and cost, as they reflect routine clinical practice in representative patient populations. However, as the majority of the costs of dementia fall outside of the health care system, most RWD sources offer only a partial view of the costs of dementia. Globally, only about 16% of costs are health‐care related, while 34% are related to social care and 50% are attributed to informal care (Wimo, Seeher et al. 2023). Most RWD sources specific for ADRD do not collect data on resource utilization or costs, though some offer opportunities for record linkage with databases containing such data. Therefore, most knowledge about costs of dementia has been derived from smaller observational studies with the specific purpose of assessing costs of care (Jonsson, Tate et al. 2023).New methods for diagnosing and treating ADRD are being introduced, including amyloid‐targeting antibody therapies and blood biomarkers. RWD will play a key role in ensuring the appropriate and cost‐effective use of these technologies. To assess the cost implications of introducing these technologies in routine care, disease registries and other RWD sources need to be expanded to include key measures of resource utilization, including informal care and community care services.