bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of Alzheimer’s disease (AD) dementia and mild cognitive impairment (MCI) in the United States Medicare population
Authors: Zhang Haixin , Zhang Quanwu , Monfared Amir Abbas Tahami 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) is a chronic, neurodegenerative health condition. Mild cognitive impairment (MCI) is characterized by cognitive decline, without dementia. We aimed to estimate the prevalence of AD and MCI among Medicare beneficiaries.MethodPatients were identified from the US Center for Medicare and Medicaid Services (CMS) database using International Classification of Diseases (ICD) codes for AD (331.0, G30.9, G30.8, or G30.1,) and MCI (331.83 or G31.84). Both AD and MCI were identified using the search rule of 2 ICD codes ≥30 days apart ≤365 days from both Medicare fee‐for‐service (FFS: 2008‐2018) and Medicare Advantage (MA: 2015‐2018). US regions were derived using zip codes and categorized by National Center for Chronic Disease Prevention/Health Promotion regions. Yearly prevalence was defined as the number of cases of AD or MCI in each year divided by the Medicare population in the year. Confidence intervals were not reported due to small intervals.ResultThe prevalence of AD and MCI was 1.9% and 0.1% (2008), 2.5 and 0.2% (2009), 2.7 and 0.2% (2010), 2.7 and 0.3% (2011), 2.8 and 0.4% (2012), 2.8 and 0.5% (2013), 2.8 and 0.6% (2014), 2.8 and 0.7% (2015), 2.3 and 0.7% (2016), 2.4 and 0.9% (2017), and 2.3 and 1% (2018), respectively. About 1.2 million AD patients and 490,000 MCI patients were identified in 2018. The prevalence of AD vs MCI among demographic subgroups in 2018 was 1.81% vs 0.85% (men) and 2.75% vs 1.03% (women); 0.59% vs 0.35% (ages 65‐69 years), 1.16% vs 0.65% (70‐74 years), 2.45% vs 1.19% (75‐79 years), 4.56% vs 1.86% (80‐84 years), and 8.71% vs 2.67% (≥85 years); 2.46% vs 1.05% (Whites), 1.87% vs 0.54% (Blacks), and 2.18% vs 0.58% (Asians). The prevalence of AD vs MCI in 2018 was highest in the US Northeast, especially in New Hampshire (3.25% vs 1.64%), Maryland (3.23% vs 1.45%) and New Jersey (3.43% vs 1.40%).ConclusionAmong Medicare beneficiaries from 2008 to 2018, AD prevalence was generally stable, while MCI increased. Women, older age, White race, and Northeast region were associated with higher prevalence of AD and MCI in 2018.
Managing Your Own Wellness (MYOW): Intervention for improving wellness through dementia care partner’s self‐care
Authors: Ishado Emily , McKiddy Sarah , Rosser Aaron F , Sadak Tatiana 
Published: December 2023

AbstractBackgroundCaring for a person living with dementia (PLWD) can be a stressful and straining experience for family/friend care partners (CP), often leading to an increased risk for adverse psychosocial and health outcomes (e.g., depression, anxiety, mortality). Engaging in self‐care can reduce these risks and improve health. Yet, comprehensive tools that measure self‐care as a dynamic concept in the context of dementia caregiving do not exist. “Managing Your Own Wellness” [MYOW] checklist was created and validated to capture dementia CP self‐care behaviors and to inform the development of a brief, tailored person‐centered intervention. The study’s objective was to pilot test this intervention, with the ultimate goal of informing a new generation of CP interventions that address the complex and wide range of self‐care needs.MethodNineteen primary dementia CPs completed the study and participated in the baseline visit to establish a self‐care goal, three weekly check‐in coaching visits with the interventionist, and a final exit interview at week four. Measures at baseline, week four, and week 12 included MYOW, well‐being scale, single item tool for perceived strain and stress, and screening tools for depression and anxiety. Participants completed daily tracking forms to report their engagement and perception of progress in their selected self‐care activity. All interviews were transcribed and coded using thematic content analysis. Study measures were evaluated using correlation analyses.ResultsCP’s increased engagement in self‐care activities and improved sense of well‐being were captured by quantitative measures. Qualitative analysis revealed themes involving a change in relationship dynamics, evolution of the sense of self, shift in internal personal perspective (acceptance) and its effects on CP behaviors (increased patience, less frustration), and perception of PLWD interactions (more cooperative).ConclusionMYOW intervention had high acceptability and demonstrated high potential for broad dissemination. CP engaged in developing and following through on personalized self‐care goals and in tracking their progress. The impact of self‐care is dynamic and multi‐faceted. Focusing on brief daily wellness‐related activities has mutual benefits for CP and PLWD. Future research should be focused on further simplifying intervention protocols and measures and evaluating the intervention with a larger diverse sample of CP.
Novel Pyrazinoindolones As Amyloid‐Beta Aggregation Inhibitors
Authors: Rao Praveen Nekkar , Hejazi Leila , Shakeri Arash 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) is a devastating neurodegenerative condition which primarily affects the elderly population. One of hallmarks of AD is the accumulation of protein aggregates known as amyloid‐beta (Aβ) that promotes neurotoxicity and cognitive decline. Recent discoveries in the field led to the accelerated market approval of anti‐Aβ antibodies aducanumab and lecanemab. These are exciting discoveries. However, considering the cost and patient compliance issues with these biological therapies, discovering novel anti‐Aβ therapies that are based on small molecules is highly desirable due to several advantages over biological therapies including the ease of oral administration, reduced cost involved in bulk manufacturing and better stability on storage.MethodA library of novel pyrazino[1,2‐a]indole‐1(2H)‐one derivatives were designed using the computational modeling software Discovery Studio Structure‐Based‐Design (Biovia Inc, San Diego USA). Then synthetic chemistry protocols were optimized to prepare small molecule library and were characterized by 1H and 13C NMR and Liquid Chromatography Mass Spectrometry studies. The anti‐Aβ activity of these novel molecules toward Aβ40 aggregation was evaluated by fluorescence spectroscopy using the thioflavin‐T based aggregation kinetic studies. In addition, the online web tool SwissADME was used to calculate the physicochemical properties of pyrazino[1,2‐a]indole‐1(2H)‐one derivatives to assess their drug‐likeness, blood‐brain barrier permeability and pharmacokinetics.ResultA novel library of pyrazino[1,2‐a]indole‐1(2H)‐one derivatives were prepared by optimizing a four step or two step synthesis protocol starting from either phenylhydrazine or indole‐2‐carboxylic acid to afford pyrazino[1,2‐a]indole‐1(2H)‐one derivatives 5a–f. In the Aβ40 (5 μM) aggregation kinetics assay, they exhibited 14‐59% inhibition when tested at a range of concentrations (1, 5, 10 and 25 μM), demonstrating their anti‐Aβ properties. Their physicochemical properties suggest their drug‐likeness.ConclusionStructure‐activity relationship studies demonstrate that the fused tricyclic pyrazino[1,2‐a]indole‐1(2H)‐one is a suitable template to i) develop novel chemical tools to study and understand the mechanisms of Aβ40 aggregation and ii) discover novel small molecules as potential therapies for AD.
Incidence of Alzheimer’s disease (AD) dementia and mild cognitive impairment (MCI) in the United States Medicare population
Authors: Zhang Haixin , Zhang Quanwu , Monfared Amir Abbas Tahami 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) is a chronic, neurodegenerative condition. Mild cognitive impairment (MCI) is characterized by cognitive decline, without dementia. We aimed to estimate the incidence of AD and MCI among Medicare beneficiaries.MethodPatients were identified from the US Center for Medicare and Medicaid Services (CMS) database using International Classification of Diseases (ICD) codes for AD (331.0, G30.9, G30.8, or G30.1,) and MCI (331.83 or G31.84). Both AD and MCI were identified using the search rule of 2 ICD codes ≥30 days apart ≤365 days from both Medicare fee‐for‐service (FFS: 2008‐2018) and Medicare Advantage (MA: 2015‐2018). US regions were derived using zip codes and categorized by National Center for Chronic Disease Prevention/Health Promotion regions. Yearly incidence was defined as the number of new cases of AD or MCI in each year divided by the population at risk in the year. Confidence intervals were not reported due to small intervals.ResultThe incidence of AD and MCI per 10,000 person‐years was 82.9 and 4.9, 80.3 and 7.4, 74.5 and 9.3, 69.8 and 10.9, 65.3 and 13.4, 62.8 and 15.8, 60.7 and 17.4, 65.5 and 20.7, 61.4 and 22.4, 56.0 and 22.9, and 52.2 and 23.2 spanning from 2008 through 2018, respectively. In 2018, the incidence of AD and MCI per 10,000 person‐years by demographic subgroups was: 43 and 21 for men and 59 and 25 for women; 16 and 10 among those aged 65‐69 years, 30 and 18 for ages 70‐74 years, 58 and 30 for ages 75‐79, 102 and 44 for ages 80‐84, 176 and 57 for age ≥85 years old; 56 and 26 for Whites, 38 and 13 for Blacks, and 43 and 15 for Asians. The incidence of AD and MCI per 10,000 person‐years in 2018 was highest in the US Northeast, especially in New Hampshire (77 and 39), Vermont (74 and 47), and New Jersey (73 and 33).ConclusionAmong Medicare beneficiaries from 2008 to 2018, AD incidence generally decreased while MCI increased. Women, older age, White race, and Northeast region were associated with higher incidence of AD and MCI in 2018.
Chronic kidney disease is associated with cognitive dysfunction and cardiovascular remodeling in aged male and female Sprague‐Dawley rats
Authors: Santos Carla Rocha Dos , Grigorova Yulia N , McDevitt Ross A , Long Jeffrey M , Haghkar Mahdi , Wei Wen , Zernetkina Valentina I , Juhasz Ondrej , Morrell Christopher H , Rapp Peter R. , Sodhi Komal , Lakatta Edward G , Fedorova Olga V 
Published: December 2023

AbstractBackgroundCardiovascular diseases (CVD), including increased central arterial stiffness (CAS), accompany chronic kidney disease (CKD) development. An increase in pulse wave velocity (PWV), an index for CAS, is implicated in age‐associated changes in the brain and potentiates the development of CI in CVD and CKD in humans and animal models. The aim of this study was to determine whether inducing CKD accelerates the development of CI and CAS in aged male and female rats.MethodTen months‐old male and female Sprague‐Dawley rats were fed with 0.25% adenine diet to accelerate CKD (n = 10‐12; CKD‐male, CKD‐female) or regular diet (n = 8‐10; CNT‐male, CNT‐female) for 8weeks. Body weight (BW), blood pressure (BP), heart rate (HR), aortic‐PWV (aPWV), behavioral tests, blood urea nitrogen (BUN), creatinine and hematocrit were assessed at the endpoint. The anxiety‐like behavior was tested in open field test (OFT) and elevated plus maze (EPM). Morris water maze (MWM) and cross maze (CM) were used to test spatial memory. The data were analyzed using two‐way ANOVA.ResultCKD development in both sexes was accompanied by kidneys enlargement, increase in BUN and creatinine, and reduction in hematocrit. In CKD‐male the kidney function was more compromised with higher levels of BUN and creatinine vs. CKD‐female (Table 1). CKD‐male had lower BW and SBP vs. CNT‐male (Table 1). CKD induced a reduction in HR, increase in aPWV and aortic weight in both sexes vs. respective CNT‐groups (Figure 1). Both CKD‐male and CKD‐female demonstrated a tendency of increase in path length to find the hidden platform in MWM, e.g., both sexes had numerically impaired spatial memory. CKD‐male spent less time in the center of OFT, a measure of anxiety, and loss of spatial memory, with a reduction of spontaneous alternation task assessed by CM. CKD‐female exhibited higher level of anxiety spending less time in open arm of EPM vs. CNT‐female (Figure 2).ConclusionCKD development in old male and female Sprague‐Dawley rats was accompanied by an increase in CAS, cardiovascular remodeling, and cognitive dysfunction. In CKD, CI affected different cognitive domains in the old males than in the age‐matched females.Supported by NIA/NIH/IRP
Causal inference on strategies to increase conversational engagement for socially isolated older adults
Authors: Yuan Fengpei , Zhou Wenjun , Dodge Hiroko H , Morris Tyler , Zhao Xiaopeng 
Published: December 2023

AbstractBackgroundSocial isolation, characterized by a small social network and lack of contact, negatively impact the quality of life. Older adults are at an increased risk for social isolation, which is found to be a risk factor of cognitive decline and dementia. Enhancing social connectedness or interactions has been shown to be an effective intervention for slowing age‐associated cognitive decline and possibly delaying the onset of dementia. Here we aim to develop conversational chatbots which can provide engaging conversations with older adults with mild cognitive impairment (OAwMCI) to mitigate social isolation. To resemble human human interactions, chatbots have to adapt certain human strategies, such as empathy, during conversation.MethodOur study utilized causal structural learning and causal inference approaches to examine the dialogue strategy for engaging OAwMCI. We analyzed transcriptions from a clinical trial, I‐CONECT (ClinicalTrials.gov #: NCT02871921), which involved semi‐structured conversations between facilitators and participants. By using emotion recognition in conversation and dialogue act modeling, we produced a time series data of state (participant’s emotions and length of utterance per conversation turn), intervention (facilitator’s conversational strategies), and outcome (participant’s following emotions and engagement). A R package, pcalg, was used to identify causal relationships between the state, intervention, and outcome variables.ResultGraphical models implying causal relationships between certain factors were generated. Our analysis revealed that facilitators adjusted their dialogue strategies according to the participants' emotions and utterance. For example, facilitators expressed appreciation when a participant showed . Additionally, we found that the dialogue acts from facilitators influenced participants' emotions and engagement in the conversation. For instance, non‐opinion statements and yes/no questions from facilitators may affect participants’ verbal engagement and level of anger during the conversation.ConclusionFindings from this study are in line with real‐world human‐human conversation, and our next step is to explore how to use these findings to improve conversational chatbots. Future work shall also consider other crucial features into the state variable that might influence the dynamics of participants' status during the conversation, such as cognitive capacity and dialogue coherence. Our findings have the potential to inform the development of conversational tools and strategies to reduce social isolation among OAwMCI.
e‐FINGERPRINT Pilot Study: Assessing the feasibility of digital data collection and multidomain lifestyle guidance towards the prevention of cognitive decline and dementia
Authors: Giannakopoulou Parthenia , Majeed Azeem , Solomon Alina , Middleton Lefkos T , Kivipelto Miia 
Published: December 2023

AbstractBackgroundThe ongoing eFINGER‐PRINT Pilot Study is a is a pioneering virtual feasibility study to evaluate different methodologies for recruitment and digital phenotyping in the context of readiness cohorts. In addition, the pilot aims to test virtual cognitive and other tools in their ability to detect changes in cognitive performance and lifestyle parameters over time, and associations between changes across other key health outcomes. The one‐year study was initiated in May 2022.MethodCognitively unimpaired individuals (up to 500) aged 60+ years residing in London, were recruited through the Cognitive Health in Ageing Register for Investigational and Observational Trials (CHARIOT). Inclusion criteria include no dementia diagnosis, access to the internet and a suitable device and English competency with no significant visual or auditory disability. The study collects subjective demographics, comorbidities, and health behaviours, sleep, frailty, functional abilities, and subjective memory symptoms, through repeated 4‐monthly questionnaire surveys administered online. Longitudinal cognitive data were obtained via a validated online cognitive assessment platform, and included customised assessments shown to be sensitive to AD related cognitive decline. Furthermore, participants are invited to join a preventative multi‐domain lifestyle guidance, based on repeated self‐reported evaluations of modifiable risk factors and a healthy lifestyle index, using a mobile, application. By joining the application, participants receive also bi‐monthly online educational literature on dementia prevention and healthy ageing, including guidance on nutrition and physical exercise and are asked to complete a variety of e‐based mental activities, targeting cognitive domains, such as memory, mental agility, visuospatial, and attention.ResultA minimum recruitment rate of 20% and a retention rate of 50% will provide a methodological template for the e‐FINGER PRINT study. Furthermore, participant feedback and experience will aid in optimising recruitment processes, user acceptability and sustainability of the selected digital tools. A low attrition rate will indicate a positive user experience.ConclusionThe pilot study will inform the design of the eFINGER PRINT main study, a five years’ large‐scale virtual FINGER‐based study that will be conducted in Greater London (2023‐2028). Given the promise of economic sustainability, utility of e‐based tools for disease prevention can offer dramatic up‐scalability and allow for the implementation of a prescriptive medicinal approach.
Excessive mortality risk associated with new opioid use in older people with dementia
Authors: Jensen‐Dahm Christina , Janbek Janet , Gasse Christiane , Laursen Thomas Munk , Waldemar Gunhild 
Published: December 2023

AbstractBackgroundOpioids have been associated with an increased excess mortality‐risk in the general population. Older people with dementia have been prescribed opioids more frequent and the use of strong opioids has increased considerably over the past decade among older people with dementia. Whether opioids are associated with an excess mortality risk in older people with dementia is unknown.MethodMatched cohort study using nationwide registries. All Danish residents aged 65 years and older diagnosed with dementia between 01.01.2008‐31.12.2018 were included. Exposure was defined as first opioid prescription after dementia diagnosis (1 year washout before diagnosis). Persons exposed to opioids were matched with up to two unexposed persons on age and sex. Cox proportional hazards models were used to compare rates of death within 180 days after the initiation of opioid treatment and adjusted for potential confounders (time since diagnosis, nursing home residency, comorbidity, admission within 30 days, number of medications).ResultForty‐two percent (31,619/75,471) of older people with dementia redeemed a prescription for an opioid after their diagnosis of dementia. We matched 31,619 exposed persons to 63,235 unexposed. Among the exposed, 10,642 (33.7%) died within 180 days after initiating their first opioid prescription compared with 3980 (6.4%) of the unexposed, yielding a 4‐fold increased excess mortality risk (adjusted Hazard ratio (95% CI): 4.13 (3.98‐4.30)). Strong opioids were associated with a 6‐fold increased mortality risk (6.34 (6.00‐6.69)), whereas the risk was lower for weak opioids (2.52 (2.38‐2.67). Among those who had redeemed transdermal fentanyl as their first prescription, 65.3% died within the first 180 days compared with 6.7% in the unexposed with a risk of 8.03 (7.02‐9.18). The risk was greatest within the first 14 days, where the mortality (for all opioids) was increased 11‐fold (10.95 (9.87‐12.15)), but there was still a 2‐fold increased mortality risk after 90 days (2.36 (2.21‐2.52)).ConclusionNew opioid use was frequent among elderly with dementia, and this was associated with a markedly increased excess mortality, which is worrisome. The data calls for more research to identify sub‐groups with highest excess mortality risk to make a risk–benefit assessment and guidelines to assure appropriate prescribing.
Differential expression of mitochondrial energy producing genes in AD brains compromise ATP Synthesis and neuronal viability and stimulate inflammatory pathways and ROS synthesis
Authors: Castora Frank J , Kerns Kimberly A , Pflanzer Haley K , Shelton Morgan G , Coleman Randolph A. 
Published: December 2023

AbstractBackgroundMitochondrial dysfunction is a critical component in the pathogenesis of Alzheimer’s disease (AD) where deficits in oxidative capacity and energy production have been observed.MethodA focused array of 84 genes involved in energy production in mitochondria was used to determine whether changes in these genes compromise mitochondrial function and other important biological processes or pathways.ResultWe find that a majority of these genes is down‐regulated in AD brains. These AD‐related gene expression changes are seen to affect a number of biological functions and pathologic conditions, including metabolism of nucleotides, synthesis of ATP, and nerve cell viability. The most affected complexes appear to be RCI and RCV. Particularly important are NDUFA10, ATP5PD, and ATP5F1B. Others to note are UQCRC1, a component of RC III, and COX6A1, a component of RC IV. Interestingly, GAPDH, a gene seen to be down regulated in our previous study of mitochondrial biogenesis, is also found to be downregulated in the current study. Lastly, BCS1L, a ubiquinol‐cytochrome c reductase complex (RC III) chaperone involved in assembly of RC III is one of the more substantially up‐regulated genes (+8.02‐fold) in AD brains.ConclusionThere are significant gene expression changes in a small number of nuclear encoded mitochondrial genes involved in energy production in AD brains. These impact nucleotide synthesis and pro‐ and anti‐inflammatory pathways and reflect the mitochondrial dysfunction associated with neuronal cell death and AD..