bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mild pharmacological inhibition of mitochondrial complex I restores synaptic density in hippocampus of APP/PS1 mice assessed by 3D EM reconstruction
Authors: Keller Noah , Christensen Trace , Trushina Eugenia 
Published: January 2025

AbstractBackgroundAlzheimer’s disease (AD) is an age‐dependent neurodegenerative disorder with limited treatment options. As it progresses, synapse degeneration is the most important feature contributing to cognitive dysfunction. Mitochondria supply synapses with ATP for neurotransmitter release and vesicle recycling and buffer calcium concentrations. In AD, mitochondrial function is disrupted leading to energetic stress and synapse degeneration. We have identified a novel therapeutic strategy that blocks neurodegeneration and protects cognitive function in multiple mouse models of AD (amyloid and tau pathologies) via mild pharmacological inhibition of mitochondria complex I, which results in the activation of adaptive stress response and subsequent improvement of mitochondrial function.MethodAnalysis of mitochondrial morphology and synaptic density was done in the hippocampal CA1 tissue from APP/PS1 and non‐transgenic (NTG) mice treated with vehicle or mild complex I inhibitor CP2 for 14 months starting after the development of cognitive dysfunction and neurodegeneration. A serial block‐face scanning electron microscopy (SBF‐SEM) and three‐dimensional (3D) EM reconstructions were employed to determine the synaptic density and mitochondrial morphology and distribution associated with different dendritic spine types.ResultWe demonstrate that APP/PS1 mice have significantly reduced synaptic density in the hippocampus compared to the NTG littermates. CP2 treatment restores synaptic density to the levels observed in NTG mice evident by the increase in the number of synaptic densities visible in the electron micrographs. Mitochondrial morphology and association with synapses are currently being investigated.ConclusionOur data are consistent with previously conducted electrophysiology recording in acute brain slices from APP/PS1 and NTG mice treated with vehicle or CP2, demonstrating restoration of long‐term potentiation (LTP) after chronic CP2 treatment. Additionally, it suggests that 3D EM‐based assessment of synaptic density could serve as a surrogate marker for LTP and cognitive function useful for drug discovery.
Measuring preferences for meaningful activity in assisted living residents with dementia
Authors: Levy Sorah 
Published: January 2025

AbstractResidents with dementia living in assisted living settings report that participating in activities contributes to their psychosocial well‐being and evidence suggests it has the potential to address outcomes such as improved mood, reduced agitation, and increased feelings of social connection. However, assisted living residents with dementia are infrequently asked about their preferences and interests for activities and those preferences might change over time along with their cognitive or physical abilities. Further it can be challenging for staff to focus on engaging residents in meaningful activity when they have competing demands to perform other care responsibilities. There is a need for practical tools to help assisted living staff evaluate preferences and identify opportunities for meaningful activity for residents with dementia that are tailored to those preferences. The purpose of this study was to develop a measurement tool to evaluate preferences and establish goals for meaningful activity, the Assessment of Resident Preferences for Meaningful Activity Tool. This tool was developed specifically for assisted living residents with dementia and collects brief information about the resident’s background (e.g. where they grew up, what they did for work, hobbies etc.) and includes a list of short answer prompts about what is meaningful to the resident (e.g. “I feel good about myself when…”, “I feel accomplished when…”, “I feel a sense of joy when…”). The information collected in this tool is used to develop an individualized plan for engaging the resident in meaningful activity. The tool was completed with assisted living residents with moderate to severe dementia enrolled in the randomized controlled trial, Meaningful Activities for Managing Behavioral Symptoms of Distress (MAC‐4‐BSD). A description of the tool will be presented along with key strategies to facilitate the implementation of this tool in practice for engaging residents with dementia in meaningful activity.
Examining the associations between pain, function, and behavioral symptoms with engagement in meaningful activity among residents with dementia in assisted living
Authors: Holmes Sarah D 
Published: January 2025

AbstractBackgroundEngagement in meaningful activity is beneficial for residents with dementia and is associated with improved quality of life. Meaningful activity refers to activities that provide meaning and value to the person and are tailored to individualized interests and preferences. The purpose of this study was to examine factors associated with engagement in meaningful activity among residents with dementia in assisted living. Specifically, it was hypothesized that function, pain, and behavioral symptoms would be associated with engagement in meaningful activity after controlling for residents’ age, gender, comorbidities, and cognition.MethodThis study included baseline data collected from the randomized controlled trial, Meaningful Activities for Managing Behavioral Symptoms of Distress (MAC‐4‐BSD). Assisted living residents were eligible if they were ≥55 years old, live in a participating setting, and screen positive for dementia based on the Saint Louis University Mental Status exam (SLUMS) and AD8 Dementia Screening Interview. Residents were excluded if they were enrolled in hospice, admitted for short term respite, or had a significant neurological condition not related to ADRD. Residents’ engagement in meaningful activity was evaluated based on the Engagement in Meaningful Activities Survey (EMAS). Stepwise linear regression was used to examine resident factors associated with engagement in meaningful activity.ResultA total of 71 residents from 5 assisted living settings were included in the sample. Most participants were female (n = 52, 73%), White (n = 62, 87%), and mean age was 85 years old (SD = 8.2). Controlling for age, gender, comorbidities, and cognition, pain was significantly associated with engagement in meaningful activity (b = ‐2.1, p = .03). There were no associations between function and behavioral symptoms with engagement in meaningful activity (p>.05) and the model explained 6.1% of the variance in engagement in meaningful activity.ConclusionFindings from this study offer insights into residents’ engagement in meaningful activity in assisted living. Ongoing research is needed to consider the impact of the physical and social environment and other possible factors that may also be associated with meaningful activity.
The role of moderate‐vigorous physical activity and sedentary behavior on cognitive function: Cross‐sectional analysis in U.S. POINTER
Authors: Halloway Shannon , Leng Xiaoyan , Desai Pankaja , Stone Katie L , Baker Laura D 
Published: January 2025

AbstractBackgroundHealthy lifestyle behaviors can help prevent or delay cognitive impairment in older adults, including increasing moderate‐vigorous physical activity (MVPA). However, across studies examining effects of MVPA on cognitive function, findings are mixed. This may be partially explained by higher levels of sedentary behavior (SB) that may offset some benefit of MVPA. We aim to examine associations of MVPA and SB with cognitive function (global cognition, and the memory, executive function, and processing speed domains) and explore the degree to which SB offsets benefits of MVPA on cognitive function in older adults.MethodCross‐sectional analyses were conducted using baseline data from 1680 participants from the U.S. POINTER trial, a lifestyle trial to prevent cognitive decline in at‐risk older adults without cognitive impairment at baseline. Cognitive function (global cognition and three domains) was comprised of composites of memory, executive function, and processing speed derived from pre‐specified scores of the test battery. MVPA and SB were assessed using validated self‐report questionnaires. Multiple linear regression was conducted to examine separate and combined effects of MVPA and SB on cognitive function. Additional models were conducted to examine the MVPA*SB interaction. Covariates included age, sex, racial and ethnic background, and education.ResultOn average, participants were 68.4 years of age, 66.3% were of White racial background, 29.6% reported education less than college, and reported engaging in 4.3 hours/week of MVPA and 70.0 hours/week of SB. In the unadjusted models examining the separate effects of MVPA and SB with cognitive function, higher MVPA was related to better processing speed (b = .03, p = .005), while lower SB was related to better global cognition (b = ‐.002, p = .003), episodic memory (b = ‐.002, p = .026, executive function (b = ‐.002, p<.001), and processing speed (b = ‐.002, p<.001). These findings did not remain significant once adjusted for sociodemographics. The combined effects of MVPA and SB or the MVPA*SB interaction were not statistically significant.ConclusionAlthough MVPA and SB were found to be each separately related to better cognitive function in older adults, associations did not remain once considering the influence of sociodemographics. In our upcoming analyses, we will examine associations using objective measures of MVPA and SB.
Fostering Equity in Dementia Care: The Vital Role of Culturally Sensitive Technology
Authors: Khan Arshia A , Imtiaz Rana Z 
Published: January 2025

AbstractThis perspective abstract highlights the critical demand for culturally sensitive technology in dementia caregiving due to the heightened risk and unique challenges faced by individuals from diverse backgrounds. The escalating prevalence of dementia necessitates a caregiving paradigm shift, especially in the context of diverse cultural backgrounds. Research consistently underscores the existence of cultural disparities in dementia risk, diagnosis, and care outcomes, emphasizing the urgent need for culturally sensitive technology in dementia care.Individuals from diverse cultural backgrounds often face unique challenges in accessing and receiving adequate dementia care. These challenges may stem from variations in communication styles, beliefs, and societal attitudes toward dementia. Culturally sensitive technology has the potential to bridge these gaps by tailoring interventions to align with specific cultural contexts. It can enhance communication, understanding, and overall caregiving effectiveness, providing personalized support that respects the cultural nuances of those affected by dementia.Moreover, incorporating cultural sensitivity into technology design not only addresses disparities but also contributes to more inclusive healthcare practices. Culturally tailored technologies can empower caregivers with tools that recognize and respect diverse perspectives, fostering a more collaborative and patient‐centered approach. In essence, the need for culturally sensitive technology in dementia care is paramount to ensuring equitable access, improving outcomes, and promoting a holistic understanding of the multifaceted challenges faced by individuals from diverse cultural backgrounds affected by dementia. This imperative aligns with the broader goal of enhancing the quality of life for all individuals affected by dementia while fostering a more inclusive and compassionate healthcare environment.
BreatheBot Buddy: Fostering Cognitive Well‐being with a Cuddly Companion for Regulated Breathing
Authors: Khan Arshia A , Sawchuk Matthew , Saheel Sabir , Quigley Jack , Heck Detlef 
Published: January 2025

AbstractBackgroundRegulated breathing is increasingly recognized as a vital component in enhancing cognition. Scientific studies suggest that intentional and controlled breathing techniques, such as deep and rhythmic breathing, can promote relaxation, reduce stress, and improve oxygen flow to the brain [1, 2]. Consequently, this may contribute to heightened cognitive function, better concentration, and increased mental clarity, accentuating the importance of incorporating mindful breathing practices as a potential avenue for cognitive improvement [3].The increasing recognition of the cognitive benefits of regulated breathing is leading to the development of innovative technologies, such as robots, for better breathing practices. These technologies can be used to potentially enhance the cognitive well‐being and mindfulness of people in their daily routines.MethodsIn order to accomplish a breathing robot, the entire design consists of two linear actuators controlled by an L298N Motor Driver Interface and a Raspberry Pi 3B. The Raspberry Pi coordinates both linear actuators to extend, hold, and contract in opposite directions for 4 seconds at each stage. Additionally, the mechanical design utilizes two “push caps” that push at the sides of a contained space, such as a stuffed animal, simulating breathing (see Fig. 1). This design simulates a breathing pattern in any stuffed animal (see Fig. 2).ResultsThe developed robot underwent rigorous testing in both a lab and poster presentation setting. Various case studies were examined during the poster presentation, revealing the effectiveness of a tool designed to aid in regulated breathing. The present robot demonstrated increased participant engagement in mindful breathing practices, which suggests a promising avenue for leveraging robot‐assisted therapies to enhance cognitive well‐being in people.ConclusionThe present project aimed to build a robot that fosters cognitive well‐being through regulated breathing. The case study findings of this project highlight the effectiveness of a cuddly bear‐shaped robot as a valuable tool for promoting regulated breathing, offering positive implications for integrating such robotic assistance in enhancing cognitive well‐being.
Translating high throughput screens in C elegans and microglia to humans with Medicare data to repurpose drugs to treat Alzheimer’s disease
Authors: Litke Rachel R , Arora Arushi , Wang Yihan , Aldridge Melissa D , Ko Fred C , Sandin Sven , Sano Mary , Reichenberg Abraham , Mobbs Charles V 
Published: January 2025

AbstractBackgroundDespite increasing knowledge of the etiology of neurodegenerative diseases, translation of these benefits into therapeutic advances for Alzheimer’s Disease and related diseases (ADRD) has been slow. Drug repurposing is a promising strategy for identifying new uses for approved drugs beyond their initial indications. We developed a high‐throughput drug screening platform aimed at identifying drugs capable of reducing proteotoxicity in vivo (Aß toxicity in Caenorhabditis elegans) AND inhibiting microglial inflammation (TNF‐alpha IL‐6), both implicated in driving AD(figure attached with sample of results in C. elegans). These screens led us to prioritize 50 potentially protective FDA‐approved drugs. We propose to test our screening results in humans using administrative claims data collected from the Centers for Medicare and Medicaid ServicesMethodThis is an observational retrospective pharmaco‐epidemiological longitudinal cohort study. The cohort is a random sample of 1,000,000 beneficiaries, aged 65‐75 years, followed for 10 consecutive years, requested from CMS. Files include MedPar, Outpatient, Carrier, Hospice to maximize inclusion of AD beneficiaries according to Bynum algorithm, and Part D event for drug prescription details. We will use Cox regression, to compute Hazard Ratios and associated 95% confidence intervals, of the association between drug exposure status and the risk of ADRD. We will examine potential confounding by indication, drug target, and competing risks.Result1/We propose to assess if drugs which reduce Ab toxicity in a C. elegans model of AD AND reduce microglial inflammation reduce the risk of developing ADRD in humans, using Medicare claims. 2/We propose to assess if drugs which reduce inflammation, reduce the risk of developing ADRD in humans, using the Medicare claims.ConclusionThe end goal of the study is to identify drugs to be repurposed to treat ADRD and to accumulate strong epidemiological evidence in addition to the existing evidence from the model organism C. elegans and cell culture studies.
Arterial calcification in the heart‐brain axis and cognitive performance over time: a population‐based cohort study
Authors: Streiber Anna M , van den Beukel Tim C , vom Hofe Ilse , Neitzel Julia , Vernooij Meike W. , Bos Daniel , Vinke Elisabeth J. 
Published: January 2025

AbstractBackgroundIncreasing evidence shows a link between arterial calcification in the heart‐brain axis and cognitive performance. However, how calcification relates to acceleration of cognitive changes, and which specific cognitive domains are mostly affected, remains unclear. We assessed the impact of calcification in major arteries between the heart and brain on cognitive decline and focused on different cognitive domains.MethodWe included 1863 participants from the population‐based Rotterdam Study (mean baseline age 67.9 ± 5.7 years, 53% female) who underwent a non‐contrast CT‐scan between 2003 and 2006 to quantify calcification in the coronary artery, aortic arch, extracranial internal carotid artery, intracranial internal carotid artery, and vertebrobasilar artery. Between 2002 and 2016, these participants also underwent two to three cognitive assessments (average follow‐up time: 9 years). The impact of arterial calcification at baseline on cognitive test performance over time was investigated using linear mixed models with a random intercept. The arterial calcification burden at baseline was transformed into age‐specific percentiles and cognition variables were log‐transformed in case of non‐normality. An interaction term was integrated between age‐specific calcification percentiles and follow‐up time, to allow for different slopes for different calcification percentiles. Non‐linearity of age and follow‐up time were taken into account by using natural cubic splines. All models were adjusted for follow‐up time, age, sex, education, APOE‐e4 carriership, and cardiovascular risk factors.ResultThe age‐specific percentile curves of arterial calcification for each artery are presented in Figure 1. We found that a higher calcification burden was associated with worse baseline cognitive performance across various domains, specifically psycho‐motor functioning. Figure 2 highlights the cognitive trajectories in different arteries, showing that cognition declines faster in participants with higher calcification volumes across all cognitive domains. Importantly, the effect of calcification on cognitive performance differs across the arteries. Both intercept differences and accelerated cognitive decline seem most pronounced for calcification in the vertebrobasilar arteries.ConclusionA larger amount of arterial calcification in the heart‐brain axis, is robustly associated with accelerated cognitive decline over time, specifically in the psychomotor domain. Our findings suggest that arterial calcification in arteries closer to the brain exerts most influence on cognitive decline.
Association of coffee and tea intake with the risk of dementia: A prospective study
Authors: Yan Minqing , Shen Jie , Huang Yuhui , Wu Minyu , Zong Geng , Zheng Yan , Yuan Changzheng 
Published: January 2025

AbstractBackgroundThe role of coffee and tea intake in dementia prevention remains inconclusive across studies.MethodWe included 6,001 Health and Retirement Study (HRS) participants (67.5±10.0 years old, 59.0% female) without dementia at baseline and followed them until 2020. Coffee and tea intake (including caffeinated and decaffeinated coffee and tea) was assessed using a 163‐item semi‐quantitative food frequency questionnaire (FFQ) in 2013. Dementia diagnosis was ascertained using the Langa‐Weir Classification strategy. Cox proportional hazard models were used to evaluate the associations of coffee and tea intake with dementia.ResultDuring a median follow‐up of 7 years, 231 participants developed dementia excluding dementia cases within the first 2 years of follow‐up. Compared with participants who did not drink coffee, those drinking ≥2 cups/day were associated with lower risk of dementia (Hazards ratio [HR] = 0.62, 95% confidence interval [CI], 0.41, 0.94; P‐trend = 0.049). Associations were similar for caffeinated coffee (HR = 0.66, 95% CI = 0.46, 0.96) and decaffeinated coffee (HR = 0.49, 95% CI, 0.25, 0.99). Moderate intake of tea (>0 to < 2 cups/day compared with never) was also linked to a lower dementia risk (HR = 0.64, 95% CI, 0.47, 0.87 for >0 to <1 cup/day; HR = 0.55, 95% CI, 0.31, 0.98 for ≥1 to <2 cups/day). In addition, for caffeinated tea, drinking >0 to <1 cup per day was associated with a 43% lower risk of dementia (HR = 0.57, 95% CI, 0.43, 0.77), whereas no significant association were observed between decaffeinated tea and dementia.ConclusionHigher consumption of coffee and moderate tea intake were associated with lower risk of dementia.
Protective role of overweight in Alzheimer’s disease: New findings from Mendelian randomization study
Authors: Duan Hongzhe , Holmes Rachel , Wu Deqing , Feitosa Mary , Yashin Anatoliy I , Arbeev Konstantin , Ukraintseva Svetlana 
Published: January 2025

AbstractBackgroundWeight loss has been associated with Alzheimer’s Disease (AD), suggesting the possibility that overweight may be protective against AD. Mendelian Randomization (MR) is a common method of revealing causal relationships in observational studies. Our recent MR analysis using the Health and Retirement Study (HRS) data found that overweight has a causal protective effect on late‐onset‐AD. Here we expand this strategy to two other cohorts, the Long Life Family Study (LLFS) and Framingham Heart Study (FHS), to examine causal role of overweight in AD in these data.MethodFor this MR study, we created two binary variables: ‘exposure’ (group‐1 “overweight” BMI 25‐30 vs. group‐0 “normal weight” BMI 18.5‐25, at ages 65‐75) and ‘outcome’ (group‐1 “no AD” vs. group‐0 “AD onset after age 75”), using FHS original cohort (N = 610) and LLFS (N = 1979) data on individuals who survived age 75. To identify instrumental variables (IVs), we implemented a recently developed new strategy. We selected SNPs in eight obesity‐related genes (ADIPOQ, FTO, LEP, LEPR, INSIG2, MC4R, PCSK1, PPARG) and paired them with each other, then summed their minor alleles to create new ‘composite’ SNPs as candidate IVs. This strategy improved the MR effectiveness due to the exponentially increased number of to‐be‐tested IVs. R‐package MendelianRandomization was used. Analyses were stratified by sex. The relatedness of samples was addressed by using mixed model to calculate statistics. Causal effect was evaluated using weighted median and Inverse‐Variance Weighted (IVW). MR‐Egger regression was employed to address potential pleiotropy.ResultBeing overweight at ages 65‐75 had significant causal protective effect on AD onset after age 75 in LLFS White females (N_IV = 61, weighted median causal estimate = 1.15, p‐value = 1.44E‐4; IVW causal estimate = 0.57, p‐value = 1.33E‐2) and FHS White males (N_IV = 12, weighted median causal estimate = 1.22, p‐value = 2.71E‐2; IVW causal estimate = 0.90, p‐value = 1.33E‐2). MR‐Egger regression intercepts in both cases were not distinct from the origin.ConclusionOur MR study found causal protective effect of overweight on late‐onset‐AD in White participants of FHS and LLFS, in line with previous findings in HRS data. To confirm these findings in other race/ethnic groups, MR study of datasets with larger numbers of individuals of diverse backgrounds is warranted.