bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of the Alzheimer Society of Canada’s First Link program: Results of a caregiver client survey
Authors: Whate Alexandra , Sivananthan Saskia , Apostolides Haridos , Elliott Jacobi , Stolee Paul , Armstrong Joshua J. 
Published: December 2023

AbstractBackgroundIn Canada, the Alzheimer Society’s First Link program connects people living with dementia and their caregivers to the information, supports and services they need as early as possible and throughout the progression of their condition. As part of an ongoing national evaluation, the Alzheimer Society of Canada has conducted a survey to provide evidence of the impact of the program across Canada.MethodElectronic surveys were distributed to caregiver clients of the First Link program by six Provincial Alzheimer Societies (AB, MB, NB, NS, PEI, and SK) and one regional Alzheimer Society (Toronto, ON). The survey included questions about client demographics, healthcare service usage, caregiver confidence and caregiver experience, the latter of which was asked using a retrospective pre‐test post‐test design whereby clients were asked to report their current response or status, and also retrospectively recall their perceived response prior to their interaction with The Alzheimer Society. This approach will allow us to determine whether clients report having experienced change over time.ResultA total of 732 surveys were completed by caregivers across Canada. Results varied by province. Caregivers reported that since their connection to the Alzheimer Society they were ‘much’ or ‘a little’ more confident in their ability to: care for the person with dementia (59%), avoid crises (44.5%), and access services (55.2%). They also reported improvements in their knowledge (74.6%) and preparedness (56.8%). Less than 10% of clients reported lower levels of confidence in any of the areas. Of those accessing healthcare services, the Alzheimer Society was credited with connecting people to a variety of services, including counselling (48.2%), adult day programs (43.5%), and home care (22.2%). Of those accessing Long‐Term Care (LTC), similar proportions of participants reported that they accessed LTC later (13.7%) or sooner (11%) than they would have without involvement of the Alzheimer Society. Overall, 69.7% of participants felt that their journey with dementia was improved by their connection with the Alzheimer Society.ConclusionThe results of this survey help to demonstrate the significant role that the Alzheimer Society plays in the lives of caregivers and people living with dementia across the country.
Prospective Randomized Placebo‐Controlled Trial of Long‐Term Durability of Effect of One Year of Grape Consumption on Preventing Decline of Cerebral Function
Authors: Liu Stephen S. , Lu Josephine L. , Alcantara April R. , Varughese Deepu V. , Silverman Daniel H. 
Published: December 2023

AbstractBackgroundLong‐term impact of one year of grape consumption on regional brain metabolism and associated neuropsychologic status was examined across multiple years of follow‐up.MethodTwenty subjects (74.6±5.4 years) were randomized to consume an active grape formulation (36g reconstituted freeze‐dried grape powder) or placebo (matched for sweetness and appearance but free of polyphenols) twice daily for one year. Changes in brain metabolism were assessed by PET with radiotracer [F‐18]fluorodeoxyglucose and cognitive performance was measured through neuropsychological testing, at baseline, 1 year after initiating consumption of grape or placebo formulation, and again 2 to 3 years after completing the randomized regimen in half of the subjects on each arm, with all subjects remaining blinded to which regimen they had been assigned until after final assessments. Activity in 47 standardized volumes of interest (sVOI’s) were measured, voxel‐based analyses using statistical parametric mapping were conducted, and associations were examined between interval changes in metabolism and neuropsychologic status.ResultDuring the year while consuming formulations, subjects randomized to placebo underwent metabolic decline in 27 sVOI’s, including particularly inferior posterior temporal (p = 0.006) and inferior frontal (p = 0.004) areas, correlating with neuropsychologic decline, while significant (p<0.05) decline was seen in none of the 47 sVOI’s in the active formulation group. Voxel‐based analyses corroborated differential metabolic decline in placebo and active formulation groups, and direct difference‐of‐differences analyses further documented significantly more decline in the placebo group. Moreover, a significant difference in regional metabolism persisted at the end of follow‐up, after having discontinued randomized formulations for 28.1±5.7 months (40.0±5.4 after baseline), with mean medial temporal sVOI’s demonstrating significant decline in the group that had been randomized to placebo (‐4.6%, p = 0.009), but not in the group that had been in the active arm (‐1.5%, N.S.). Difference of magnitudes of long‐term metabolic decline between arms was significant in direct difference‐of‐differences analysis, and correlated with neuropsychologic decline (p<0.001) in both inferior posterior temporal and inferior frontal regions.ConclusionSubjects randomized to consume reconstituted grapes twice daily enjoyed long‐term protection from loss of cerebral function, as assessed more than two years beyond the last consumed dose.
Information Seeking and Technology Use Among Dementia Caregivers: Findings from a Statewide Survey of Diverse Caregivers in the U.S. South
Authors: Ruggiano Nicole , Winton Tish , Daquin Jane , Herzog Monica Anderson , Jiang Zhe , Gray Jeff 
Published: December 2023

AbstractBackgroundFamily caregivers are often tasked with decision making about their loved one’s health care treatment and daily care and have reported that such decision making can be challenging, overwhelming, and stressful (Gaugler et al., 2022; Miller et al., 2016; Ruggiano et al., 2019). For this reason, caregivers often report being highly active in seeking out information to improve their health literacy regarding dementia and caregiving, frequently turning to various information technologies (IT) to gather information (Bangerter et al., 2019; Soong et al., 2020). However, more research is needed on how IT can support health literacy and information seeking for vulnerable caregiver populations, such as caregivers who are rural‐dwelling, low‐income, and those from underserved racial/ethnic groups (Soong et al., 2020).MethodThis project involved a statewide survey of caregivers living in Alabama, a U.S. state that has large populations of rural, African American, and underserved residents. To recruit participants, community‐based organizations distributed flyers and two public radio campaigns made announcements about the project between June 2022 and December 2022. The survey included questions about: the sources participants used to learn more about dementia and caregiving; ease of gathering information from these sources; their level of trust in these sources; their experience with different types of IT; their current information needs; and participant demographics. Univariate and bivariate analyses were performed.ResultSeventy‐eight caregivers completed the survey: 50% identified as African American, 37.2% lived in rural communities, and 30.8% had household incomes of less than $30K per year. The survey revealed several findings regarding information seeking and technology use. Participants reported using an average of 4.8 sources to gather information. Level of trust in some information sources and interest in using certain types of IT for information seeking varied based on some demographics, including race, age, and income.ConclusionThe findings suggest that public education about dementia should not be a one‐size‐fits all approach and that strategizing public health education campaigns by source and technology platform may better facilitate health literacy of sub‐populations of caregivers, especially those who may be underserved or have challenges in navigating health and long‐term care systems.
Curriculum‐based CME Programming Results in Comprehensive Improvements in Knowledge, Competence, and Confidence in Diagnosing Early Forms of Alzheimer’s Disease Among a Global Audience of PCPs and Neurologists
Authors: Finnegan Thomas , Stan Adriana , McFarland Frances , Chatterjee‐Shin Piyali , Guedj Philippe , Cohen Sharon , Petersen Ronald C. 
Published: December 2023

AbstractBackgroundEarly diagnosis of Alzheimer’s disease (AD) is crucial for ensuring patients have timely access to essential care. Given the symptoms of early AD are often subtle, it is important that both primary care physicians (PCPs) and neurologists are able to diagnose their patients. Several sources of evidence have indicated that most PCPs and neurologists lack knowledge, competence, and confidence regarding recognition of early forms of AD. To address the clinical practice gaps, a series of CME‐certified programs covering the symptoms, assessment, and diagnosis of early forms of AD were developed.MethodThe data presented here are based on outcomes from four online CME‐certified multimedia programs housed on a single destination page. Each CME‐certified program utilized expert physicians to educate learners on recognizing early forms of AD. Each CME program asked a series of pre‐post questions designed to assess immediate changes in knowledge, competence, or confidence. The questions were grouped into clinically relevant themes. The educational effect for all of the programs was determined by using a paired‐samples t‐test to identify significant differences between pre‐ and post‐assessment responses for each question. Data across all four programs were collected from February 2022 through December 2022. All four programs were promoted to an audience of US‐ and ex‐US physicians.ResultParticipation across the four programs ranged from 543 to 2,510 PCPs and 256 to 1,025 neurologists. PCPs and neurologists demonstrated significant (P<0.05) pre‐vs post education improvements on the following themes: biomarkers in AD, clinical trial outcomes, cognitive assessment scales, diagnosis of AD, diagnosis of mild cognitive impairment (MCI), and symptoms differentiating AD from MCI. Participation in the education also significantly (P<0.001) improved confidence in the identification of early forms of AD among PCPs and neurologists. No substantial differences in knowledge, competence, or confidence were seen for either clinician group based on geographic location of the learner.ConclusionThe results indicated that clinicians who participated in CME‐certified curriculum‐based education in multiple formats were better prepared to recognize early forms of AD. Future education should continue to discuss the use of clinical strategies to recognize early forms of AD.
Perimenopause: A critical window to intervene to reduce the risk of cognitive impairment in females
Authors: Cirone Victoria , Hsu Chun Liang , Barha Cindy K , Liu‐Ambrose Teresa 
Published: December 2023

AbstractBackgroundTwo‐thirds of all persons with late‐onset Alzheimer’s disease (AD) are female. The transition to menopause, or perimenopause, negatively impacts the female brain and is proposed to contribute to a female’s greater lifetime risk for dementia. Declining 17‐β estradiol levels during perimenopause is associated with markers of AD pathology, such as reduced cerebral glucose metabolism. Preliminary evidence suggests APOE4‐positive perimenopausal females have greater amyloid In cognitively normal individuals, the T1‐weighted and T2‐weighted (T1w/T2w) ratio from magnetic resonance imaging can be used as a non‐invasive proxy measure of amyloid‐β deposition. Specifically, higher T1w/T2w ratios are associated with higher amyloid‐β accumulation in cognitively normal individuals. Thus, to better understand the impact of perimenopause on the female brain and cognitive health, we compared the T1w/T2w ratio, hippocampal volume, and cognitive performance in perimenopausal females vs. aged‐matched males.MethodsData was acquired from the Human Connectome Project. We included 44 perimenopausal females, defined by the Stages of Reproductive Aging Workshop + 10 Staging System, and 44 age‐matched males. Executive function was measured by the Flanker Task in the NIH Toolbox Cognition Battery and data were available for all 88 individuals. Hippocampal volume data were available for 23/44 perimenopausal females and 27/44 age‐matched males. T1w/T2w neuroimaging data were available for 19/44 perimenopausal females and 27/44 age‐matched males. Between‐group differences in these measures of interest were determined by analysis of covariance (ANCOVA). For the Flanker Task ANCOVA model, the Montreal Cognitive Assessment score and free estrogen levels were included as covariates. For hippocampal volume model, intracranial volume was included as a covariate. For the T1w/T2w ratio model, the Pittsburgh Sleep Quality Inventory score was included as a covariate.ResultsPerimenopausal females performed significantly worse vs. their male counterparts on the Flanker Test (mean difference: ‐28.194; p = .000). Compared with age‐matched males, perimenopausal females had a significantly smaller hippocampal volume (mean difference: ‐544.829; p = .033) and higher T1w/T2w (mean difference: 0.290; p = .042).ConclusionOur results support the hypothesis that the menopause transition is a critical window to intervene to reduce the risk of cognitive impairment in females.
An Integrative Multi‐Omics Approach Reveals Molecular Signatures Associated with Age and High‐Fat Diet in Mouse Models of Alzheimer’s Disease
Authors: Pandey Ravi S , Kotredes Kevin P , Garceau Dylan , Haber Annat , MahmoudianDehkordi Siamak , Shantaraman Anantharaman , Duong Duc M. , Seyfried Nicholas T , Kaddurah‐Daouk Rima F. , Sasner Michael , Howell Gareth R , Oblak Adrian L , Lamb Bruce T , Carter Gregory W 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) is a complex, multifactorial pathology with high heterogeneity in biological alterations. Our understanding of cellular and molecular mechanisms from disease risk variants to various phenotypes is still limited. Therefore, it is required to integrate the information from multiple data modalities for thorough exploration of endophenotype networks, biological interactions related to disease and thus accelerate our understanding of heterogeneity in Alzheimer’s disease.MethodIn this study, we performed multi‐level omics in a cohort of mouse models expressing humanized Abeta and two genetic risk factors (APOE4 and Trem2*R47H) at multiple ages for both sexes. Data from multiple omics platforms (transcriptomics, proteomics, and metabolomics) were analyzed at single‐omic level as well as integrated in an unbiased fashion, considering interaction between modalities using multi‐omics factor analysis (MOFA). We also systematically aligned multimodal mouse data to relevant human studies cohort.ResultMulti‐omics integration identified major components of heterogeneity explaining the variance within the cohort and differentially associated with age, sex, and high fat diet. Enrichment analysis of genes and protein associated with these components were significantly enriched for multiple AD‐related processes. Specifically, components associated with age and diet related heterogeneity exhibited overrepresentation of immune response and metabolic processes as well as increased levels of long‐chain acylcarnitine’s and reduced levels of spermidine in aged and high‐fat diet fed AD mouse models, similar to human AD. In addition, we observed weak correspondence between change in protein and RNA expression in mouse models compared to controls, similar to recent results from the ROSMAP cohort, which reported weak correlation between protein and RNA expression. We also identified a negative correlation for the change in RNA expression between male and female mice.ConclusionWe identified axes of variation within a cohort of LOAD mouse models using integrative multi‐omics approach. Our analysis revealed multiple interaction between distinct multi‐omics molecular signatures associated with Alzheimer’s disease. We determined that mRNA profiling alone provides an incomplete picture of molecular mechanism of AD. In this study, we highlighted that assembling multi‐omics measurements reveal interrelated pathway alterations in AD and the ability to identify biomarkers combinations that may inform clinical practice.
Examining the relationships between cognitive function and physical and mental health: interim findings from HKMMSOP
Authors: Chan Wai‐Chi , Lam Linda Chiu Wa C.W. , Lee Allen TC , Fung Ada WT , Ma Suk Ling , Cheng Calvin Pak Wing , Wong Samuel YS , Lai Frank HY 
Published: December 2023

AbstractBackgroundPopulation ageing is associated with an increase in the number of persons with dementia, which constitutes a significant public health issue. The Hong Kong Mental Morbidity Survey for Older People (HKMMSOP) was carried out to evaluate the local prevalence of dementia and the factors that modulated the disease development.MethodParticipants aged 60 or over, stratified with age groups, were recruited through random sampling of residential addresses in Hong Kong. They underwent an assessment of their cognitive function (Montreal Cognitive Assessment, MoCA; Clinical Dementia Rating, CDR), physical health (Cumulative Illness Rating Scale, CIRS) and mental health (Clinical Interview Schedule‐Revised, CIS‐R; Short Warwick‐Edinburgh Mental Wellbeing Scale, SWEMWBS). Associative factors of neurocognitive disorders were determined by multinomial regression, with neurocognitive disorders as dependent variables.ResultIn this interim analysis, 4369 participants of HKMMSOP were included. Their mean age was 69.6, and there was a slight female preponderance (56.3%). On average, they received 8.8 years of education, and their mean MoCA score was 23.8 (SD 4.9). Using CDR, 71.8% were evaluated as having normal cognition, 23.1% with a mild neurocognitive disorder (ND), and 5.2% with a major ND. Older or less educated participants had a higher risk of developing mild and major ND (p<0.001). But the relationships between cognition and physical and mental health differed in the mild and major ND groups. Among those with mild ND, a higher CIRS total score (p<0.001), a higher CIS‐R total score (p<0.001) and a lower SWEMWBS score (p = 0.002) were significantly associated with CDR. However, only CIRS total score (p = 0.004) and SWEMWBS score (p<0.001) remained significant in the major ND group.ConclusionPoorer physical and mental health and lower mental well‐being and life satisfaction were associated with an increased risk of mild ND. But as the disease progressed, lower mental well‐being and life satisfaction and poorer physical health remained significant factors. On the contrary, a higher level of mental symptoms, as exemplified by CIS‐R, was not significantly associated with major ND. It sheds some light on the factors that may modulate the course of the disease and appropriate preventive measures.
Development of a patient‐reported outcome measure for Alzheimer’s disease: the Alzheimer’s Disease‐Health Index (AD‐HI), a fully validated tool to bolster clinical trial and research infrastructure
Authors: Rosero Spencer , Varma Anika , Seabury Jamison , Weinstein Jennifer , Engebrecht Charlotte , Dilek Nuran , Arky Abigail , Santos Elizabeth , Heatwole Chad 
Published: December 2023

AbstractBackgroundAs therapeutic advancements are made in Alzheimer’s Disease (AD) and Mild Cognitive Impairment (MCI), it is important to have a fully validated, sensitive, and reliable disease‐specific patient‐reported outcome measure (PRO) to accurately measure changes in AD and MCI symptomatic disease burden. The U.S. Food and Drug Administration has encouraged the use of PROs to measure therapeutic benefit of potential new treatments. This research describes the development, testing, and validation of a novel, multifactorial PRO: The Alzheimer’s Disease‐Health Index (AD‐HI).MethodsWe conducted interviews and a large cross‐sectional study involving individuals with AD and MCI and their caregivers to determine what symptoms and issues are most important to patients (Figure 1). Questions were selected for the AD‐HI based on their importance to patients with MCI and AD, potential to respond to therapeutic intervention, and generalizability to the broader MCI and AD patient population as determined through qualitative interviews and a cross‐sectional study. We beta tested the initial version of the AD‐HI with individuals with MCI and AD to determine its clarity, ease of use, and relevance to those with MCI and AD. We performed test‐retest reliability, known groups validity, internal consistency, and area under the curve analyses of the AD‐HI to assess the statistical characteristics, performance, and clinical meaningfulness of the outcome measure.ResultsThe content of the AD‐HI was validated using a cross‐sectional study of 104 patients. The final version of the AD‐HI contains 9 subscales that measure disease burden in the following areas: 1) Memory, 2) Cognitive health, 3) Fatigue, 4) Sleep, 5) Social health, 6) Communication, 7) Emotional health, 8) Physical health, and 9) Pain. The AD‐HI was identified as easy to use, relevant to the patient population, responsive, and clear during beta testing. The ADCR‐HI was shown to be reliable during test‐retest reliability testing with 22 individuals and able to distinguish between patient cohorts with different disease severities.ConclusionThe AD‐HI is a is a valid, sensitive, and reliable marker of disease burden in AD This disease‐specific outcome measure is available for use by researchers, clinicians, patient organizations, and companies to measure changes in disease burden during therapeutic trials.