bluuebunny/crossref_metadata_2025_split huggingface dataset:
The UC Davis ADRC Cohort Study aimed to use established marketing techniques to recruit African Americans to participate in research and increase the center’s social media presence
Authors: Johnson David K , Walker Aliyah N 
Published: June 2023

AbstractBackgroundThe UC Davis ADRC Cohort Study aimed to use established marketing techniques to recruit African Americans to participate in research and increase the center’s social media presence. African American’s have been historically excluded from research at the same time they are disproportionately impacted by Alzheimer’s Disease. Current recruitment best practices for engaging underrepresented groups in research includes community outreach events, flyers, and recruitment in academic or clinical settings. Contemporary social media marketing methods allow us to reach very specific demographics, which can be helpful to find and recruit groups typically underrepresented in researchMethodWe hired a marketing firm to run a market analysis to identify what our target audience looked like. We developed ad content with people’s motivations for participating in mind. The ads included Alzheimer’s disease awareness, testimonial interviews from research participants, information on the center, or education on dementia. The campaign was a combination of ads through Facebook, google ads, twitter, Instagram, and yahoo ads. We supplemented our advertising with Facebook posts on the ADRC page to create a buzz of conversation around the videos. The ads when clicked on let to the ADC website, YouTube channel, Facebook page, or Study pages where people could sign up to be contacted for recruitment.ResultBecause of the campaign, our ADRC Facebook followers increased by 8%. The data on the participant recruitment funnel was 102 clicks to visit the ADRC recruitment webpage from Facebook Ads; 27 people signed up via study page; 7 were ineligible (usually no study partner); 6 were information seekers (adult children or <65yrs); and 13 were enrolled. The 13 participants completed all study visits that year. This direct marketing campaign netted over half of the annual 20 replacement volunteers needed by the intensive ADRC cohort study that usually takes a full‐time staff person 6‐8 months to recruit. By comparison, direct marketing/recruitment was incredibly efficient.ConclusionResearch centers may benefit from integrating common marketing methods for recruitment of underrepresented groups. There were some difficulties implementing the marketing plan with the IRB and research Center model. More research can be done to evaluate effective strategies for recruiting diverse participants.
A multivariable mendelian randomisation study of serum lipids and dementia risk within the UK Biobank
Authors: Pham Kitty , Mulugeta Anwar , Lumsden Amanda , Hyppönen Elina 
Published: June 2023

AbstractBackgroundAn unfavourable lipid profile has been associated with the increased risk of dementia or Alzheimer’s disease in both observational and genetic studies1,2. However, it is challenging to investigate each serum lipid measure individually due to the high correlation between the lipid traits. We aimed to discover causal associations between genetically instrumented serum lipid measures (low‐density lipoprotein cholesterol (LDL‐C), high‐density lipoprotein cholesterol (HDL‐C), triglycerides, apolipoprotein‐A1 (apoA) and apolipoprotein‐B (apoB)) and the risk of dementia.MethodWe conducted multivariable and univariable Mendelian randomisation (MR) analyses on 329,896 UK Biobank participants (age 37‐73 years) to examine the associations between each serum lipid measure and the risk of dementia. The multivariable approach allows us to assess the association of each lipid measure with the outcome, in cases where the genetic variants used to estimate the exposures are mediated by one another.ResultIn the univariable MR analyses, we found that genetically determined higher LDL‐C and apoB were both associated with increased risk of dementia, while higher HDL‐C and apoA were associated with decreased risk of dementia. Meanwhile, using multivariable MR analyses, in a model containing LDL‐C, triglycerides and apoB, only apoB remained significantly associated with increased risk of dementia.ConclusionOur findings suggests that when considering the correlation between lipid measures, apoB plays an important role in the previously reported association between serum lipids and increased risk of dementia.References:1Iwagami, M, Qizilbash, N, Gregson, J, Douglas, I, Johnson, M, Pearce, N, Evans, S & Pocock, S 2021, 'Blood cholesterol and risk of dementia in more than 1·8 million people over two decades: a retrospective cohort study', The Lancet Healthy Longevity, vol. 2, no. 8, pp. e498‐e506.2Zhang, X, Tian, Q, Liu, D, Geng, T, Ge, S, Zheng, D, Wu, L, Song, M, Hou, H, Wang, W & Wang, Y 2020, ‘Causal association of circulating cholesterol levels with dementia: a mendelian randomization meta‐analysis’, Transl Psychiatry, vol. 10, no. 145, https://doi.org/10.1038/s41398‐020‐0822‐x.
Feasibility analysis of the design of a psychosocial intervention in dementia: Sensitivity analysis
Authors: Rabaneda‐Bueno Rubén , López‐Ortega Mariana , Guzman Azucena , Robledo Luis Miguel Gutierrez , Torres‐Castro Sara 
Published: June 2023

AbstractBackgroundA multicomponent staff training intervention was conducted to improve residential dementia care. The purpose of this work is to present the simulation of the effectiveness of the intervention design over time.MethodPilot study with mixed methods, two‐arm randomized controlled clinical outcomes in 7 care homes in Mexico City. Staff outcome measures were: Maslach Burnout Inventory (MBI); Approaches to Dementia Questionnaire (ADQ); Sense of Competence in Dementia Care Staff (SCIDS). Residents' outcome measures were: Quality of Life‐Alzheimer’s Disease scale (QoL‐AD) and Neuropsychiatric Inventory‐Nursing Home Version (NPI‐NH). Using the functions of the R package powerlmm, we performed computer simulations based on linear changes over a period of up to 24 weeks. The measurements were divided into three time points corresponding to the schedule of our study (baseline, post‐intervention and follow‐up). In the different trials, we specified different numbers of subjects and group sizes, including those in the present study, always considering an unbalanced cluster design. We also considered the dropout rate of participants, which in this study was almost 30% and focused on the post‐intervention period, with no additional dropouts at follow‐up. We conducted simulations to determine the performance of our longitudinal study design with fewer or no unanticipated dropouts.Result55 residents and 126 staff participants were recruited in seven care homes. We found that the highest power was achieved for MBI: Personal fulfillment and SCIDS: Sustaining personhood, which were the only variables with a significant effect for the Time × Treatment interaction in the model inference. Focusing on the first of these variables and assuming the specific values for each input parameter, we see that our study design with 7 care homes was potentially capable of detecting a significant effect size of the growth effects of the intervention. Thus, the estimated sample size for a power of 80% would be nearly 85 participants, which corresponds to the complete data (i.e., no dropouts), and about 138 participants for a power of 90%.ConclusionA higher level design that includes more care homes would be sufficient to achieve effective estimates above the 80% threshold while maintaining the lowest number of participants.
Examining the influence of marital status on cognitive risk in a nationally representative sample of adults in India
Authors: Zanwar Preeti Pushpalata , KJ Vinod Joseph 
Published: June 2023

AbstractBackgroundInfluence of marital status on cognitive risk remains understudied in India with 17.7% of the global population.MethodsTo examine the influence of marital status (categorized as married, never married, widowed and other which included partnered, separated or divorced) on cognitive risk and to what extent marital status is a protective factor for cognitive decline. For this observational study design, we merged nationally representative harmonized Longitudinal Aging Study of India (LASI) and the harmonized Diagnostic Assessment of Dementia (LASI‐DAD) for 4096 adults 45 years and older and their spouses regardless of age from 2017 to 2019. We accounted for multistage, stratified, area probability cluster design of the complex survey using appropriate weights. The primary outcome was cognitive impairment based on cognition score without number series based on word recall, cognition tests and Jorm IQ code < 3.9 or > 3.9 or higher. The cognitive impairment was constructed as a 0/1 dummy variable coded 0 if the respondent was at low‐risk (mid‐tertile) or very low‐risk (top‐tertile) and coded 1 if the respondent was high‐risk (bottom‐tertile). We assessed proportion at risk for cognitive impairment by marital status and used chi‐square test to test significance at p<0.05 level. We ran logistic regression model on weighted population to examine the odds ratio of cognitive risk by marital status.ResultsOur weighted population was 4,716 adults, 64.0% were married, 0.93% were never married, 33.3% were widowed, and 1.8% were other. Those married had the lowest proportion of cognitive risk (43.0%) while never married had the highest proportion of cognitive risk (71.0%), followed by widowed (59.6%) and other (55.0%). In logistic regression, in comparison to married adults, cognitive risk was three times more likely for never married adults, AOR 3.17 [95% CI, 1.55‐6.48], and nearly two times more likely for widowed, AOR 1.58 [95% CI, 1.33‐1.88].ConclusionMarital status likely functions as a social determinant of cognitive decline in the Indian context. These findings are relevant to U.S. and other countries as the harmonized LASI, is a sister study of the harmonized U.S. Health and Retirement Study and data can be leveraged using cross‐country comparisons.
Virtual reality can improve autobiographical memory in people with dementia: pilot test in healthy people
Authors: Torres‐Castro Sara , Álvarez‐Cisneros Teresa , López‐Ortega Mariana , Rabaneda‐Bueno Rubén , Segura Blanca A. , Robledo Luis Miguel Gutierrez 
Published: June 2023

AbstractBackgroundWe have developed a reminiscence program for people living with dementia to improve their autobiographical memory and reduce neuropsychiatric symptoms. In this paper, the objective is to present findings from a pilot’s virtual reality experience with elderly people without dementia.Method4 people over 60 years of age from a non‐governmental organization in Mexico City that carry out active and healthy aging activities were invited to participate, the inclusion criteria: people without dementia or other mental health problems and who accepted participate voluntarily. A focus group was held to find out their perceptions about the use of virtual reality as a therapeutic tool. Afterwards, the virtual reality glasses were placed on each of the participants, with a duration of 10 minutes. The content of the video was related to images of childhood in a context of the 40’s and 50’s. At the end, the participants met again and commented on their experience. The conduct of the focus groups and the feedback was in charge of a psychologist, and accompanied by a staff of 2 engineers and three co‐investigators, for the care of the participants.ResultNone of the 4 participants had used virtual reality, one of them had only heard her grandchildren talk about it. They thought that technology can help in everyday life, but they were unaware that virtual reality could serve as a therapeutic tool to support people living with dementia. After using the virtual reality glasses, one of the participants remembered a brother who had died at the age of 5 years and that it was something she had never talked about, she imagined that it was really her brother and some tears flowed. Another participant commented that she had remembered her family when she was a child. In general, they commented that the experience was pleasant and they would like to continue using virtual reality.ConclusionIn this first approach in older people without dementia, the acceptance of the use of technology in a therapeutic environment and accompanied by mental health professionals to provide support and feedback about the content is shown.
ADAMTS4 as an enzyme cleaving at APP669 site
Authors: Kaneko Naoki , Yokoyama Miyabishara , Korenaga Akihito , Sekiya Sadanori , Iwamoto Shinichi , Matsuzaki Masaya , Tanaka Koichi , Tomita Taisuke , Ikemura Kentaro , Opoku Gabriel , Hirohata Satoshi 
Published: June 2023

AbstractBackgroundWe have previously identified APP669‐711 (a.k.a. Aβ(‐3)‐40) in human plasma using immunoprecipitation combined with matrix‐assisted laser desorption ionization time‐of‐flight mass spectrometry (IP‐MALDI‐MS) (Kaneko et al., Proc Jpn Acad Ser B Phys Biol Sci. 2014). Our assay has revealed that the composite biomarker, which is a combination of APP669‐711/Aβ1‐42 ratio and Aβ1‐40/ Aβ1‐42 ratio in human plasma, correlates with amyloid PET status (Nakamura et al., Nature 2018). Our previous research using cultured cells has suggested that A Disintegrin and Metalloproteinase with a Thrombospondin type 1 motif, type 4 (ADAMTS4) is involved in APP669‐711 production. Here, we present further evidence on the involvement of ADAMTS4 in the APP669 site‐cleavage.MethodWe prepared a recombinant APP substrate, which is APP81 corresponding to APP619‐699 sequence with a V5/His tag at the C‐terminus and a FLAG tag at the N‐terminus (FLAG‐APP81‐V5/His) for in vitro cleavage assay. Recombinant human ADAMTS4 protein and the tagged APP81 were incubated either alone or together at 37°C. The incubated samples were desalted and then analyzed by MALDI‐TOF MS. In vivo evaluation of ADAMTS4, we analyzed plasma samples from Adamts4‐/‐ mice and WT mice using IP‐MALDI‐MS.ResultIn vitro cleavage assay, N‐ and C‐terminal fragments cleaved at APP669, Aβ4th, Aβ12th site were detected in the mixture of the recombinant APP81 and ADAMTS4 proteins but not in the sample of substrate or enzyme alone. Furthermore, a peptide derived from double digestion by APP669 and Aβ12th site‐cleavages (i.e., APP669‐Aβ11) was also identified by MS/MS analysis. The analysis of mouse plasma showed that murine APP669‐711 level was decreased in Adamts4‐/‐ mice compared to WT mice.ConclusionThese results indicated that ADAMTS4 is one of the enzymes that can cleave the APP669 site directly and contribute to the generation of APP669‐711 in vivo.
Association between centrally active angiotensin‐converting enzyme inhibitors with dementia risk
Authors: Newby Danielle , Winchester Laura M , Sproviero William , Fernandes Marco , Ghose Upamanyu , Launer Lenore J. , Nevado‐Holgado Alejo J 
Published: June 2023

AbstractBackgroundHypertension is a well‐established risk factor for dementia and antihypertensive treatments could be important for disease prevention. Observational and animal studies suggest Angiotensin‐Converting Enzyme Inhibitors (ACEIs) are associated with reduced dementia risk whereas genetic studies show these drugs increase risk. One plausible explanation of this heterogeneity is that not all ACEIs cross the blood–brain barrier (BBB) and their association with disease risk may depend on whether or not the specific molecule crosses the blood brain barrier. We investigated the association of centrally vs non‐centrally active ACEIs with incident dementia compared using medical records from the USA (OPTUM).MethodsThis is a retrospective new‐user comparative cohort study using patients ≥50 years old with hypertension who were new users of centrally active ACEIs (captopril, fosinopril, lisinopril, perindopril, ramipril, trandolapril; n = 327,663 or non‐centrally active ACEIs (n = 30,867) (benazepril, enalapril, moexipril, quinapril). Patients were followed for up to 10 years (2006‐2018) during which 11,422 dementia cases were diagnosed. Stratified Cox proportional hazards models were used to estimate the hazard ratio (HR) of incidence all‐cause dementia and sub types over the follow up period, controlling for age, demographics such as geographic location and other comorbidities such as stroke, myocardial infarction and diabetes.ResultsIn unadjusted and adjusted models, new users of centrally active ACEIs had a slightly greater risk for all cause dementia and vascular dementia but not for Alzheimer’s disease. HR for unadjusted models were 1.08 (95% CI 1.01‐1.15), 1.34 (95% CI 1.13‐1.60) and 1.00 (95% CI 0.90‐1.12) for all cause dementia, vascular dementia and Alzheimer’s disease respectively. Whereas HR for adjusted models for all cause dementia, vascular dementia and Alzheimer’s disease were 1.16 (95% CI 1.09‐1.24), 1.35 (95% CI 1.12‐1.62) and 1.10 (95% CI 0.98‐1.23) respectively.ConclusionsOur results potentially indicate centrally active ACEIs are associated with a slightly higher risk of all‐cause dementia compared to non‐centrally active ACEIs. This work supports causal genetics studies which indicate links between ACE inhibitors in the brain with increased dementia risk. Future work will investigate whether other antihypertensive drug classes differ in risk based on blood brain barrier penetrating ability.
Retinal TDP43 pathology in Alzheimer’s disease, Parkinson’s disease and frontotemporal dementia
Authors: Dijkstra Anke A. , Morrema Tjado , de Ruyter Frederique J. Hart , Verbraak Frank D. , de Boer Johannes , Pijnenburg Yolande A.L. , Rozemuller Annemieke J.M. , Bouwman Femke H. , den Haan Jurre , Hoozemans Jeroen J.M. 
Published: June 2023

AbstractBackgroundAs an extension of the brain, the retina displays similarities with the brain in terms of anatomy and functionality. The accessibility of the retina provides a ‘window’ to the brain and a great potential for noninvasive imaging of neurodegenerative changes in patients. TAR DNA binding protein 43 (TDP‐43) is one of the main pathological hallmarks found in frontotemporal lobar degeneration (FTLD). Previously, we identified phosphorylated TDP‐43 (pTDP‐43) aggregation in the retina of FTLD cases with underlying TDP43 (FTLD‐TDP) pathology, including donors with C9orf72 and progranulin (GRN) mutations. The aim of this study is to assess the presence of pTDP‐43 in the retina across various neurodegenerative diseases and controls. This will provide insight in whether the presence of TDP43 pathology in the retina is exclusive for cases with FTLD‐TDP and potentially serve as an in‐vivo biomarker.MethodPost‐mortem eyes were collected by the Netherlands Brain Bank from donors with Alzheimer’s disease (AD), Parkinson’s disease (PD), frontotemporal dementia (FTD) and controls (N = 80). Nasal superior‐temporal quadrants were cut in sections of 10 µm. Immunohistochemical stainings were performed for phosphorylated TDP‐43 (pTDP‐43).ResultFTLD‐TDP cases showed pTDP‐43 immunopositive inclusions in the plexiform layers. Additionally, some AD cases showed sparse pTDP‐43 positive inclusions. Data of the other pathological groups will be available within a couple of months.ConclusionpTDP‐43 is abundantly present in the retina of FTLD‐TDP patients, while only sporadically seen in AD patients. With the advances in ocular imaging techniques, these findings provide a patient friendly retinal biomarker to diagnose FTLD‐TDP. This would be the first FTD specific biomarker, since no other pathology specific biomarkers for the various underlying pathological changes that are known to cause FTD (e.g. tau, FUS, etc), are currently available.
Kernel flow and the eye‐ brain connectome: Towards a more robust technique to identify high‐risk individuals before cognitive decline
Authors: DeBuc Delia Cabrera , Ramos Alberto R , Galor Anat , Sapahia Rishav , Hasalami Ardita , Fernandez Javier De Jesus , Habash Ranya 
Published: June 2023

AbstractBackgroundOptical brain imaging allows an understanding of the structure and function of neurons. Researchers can help patients who suffer from nervous system diseases, such as Alzheimer’s disease and Lewy’s Body Dementia, by exploring brain structure and function. Despite the advent of new PET diagnostics to image amyloid deposits in living patients' brains, there remains a need for more readily available and affordable diagnostic testing.MethodA time‐domain functional near‐infrared spectroscopy (TD‐fNIRS) system (Kernel Flow, Kernel Inc.) is presented. The system has been designed as a small modular device that can provide real‐time monitoring of tissue oxygenation in the brain as subjects take tests, perform cognitive tasks, and/or receive stimulation.ResultWe show the performance of the wearable TD‐fNIRS device in multiple settings and aim to use this technology to develop a protocol for identifying and tracking brain changes in aging and dementia from the preclinical stage of the disease.ConclusionLaboratory tests with study subjects and preliminary data recorded demonstrate the potential of the system as a clinical tool to be employed in multiple settings to not only monitor brain activity but with the potential for additional human neuroscience applications, making neuroimaging more accessible across health and science platforms.
Effects of T217 Phosphorylation on Tau Localization and Microtubule Binding
Authors: Rajbanshi Binita , Mandell James W , Bloom George S 
Published: June 2023

AbstractBackgroundBiomarker‐based early detection of Alzheimer’s disease (AD) is necessary for developing therapies that counter AD symptom onset. Promising biomarkers include tau phosphorylated at T181, T217 or T231, levels of which can be measured in cerebrospinal fluid or plasma. Little is known about functional consequences of tau phosphorylation at these sites, though, especially for taupT217. We thus sought to identify where taupT217 is localized in the brains of human AD patients and AD model mice, and in cultured mouse neurons, and, in a more functional context, to determine if phosphorylation at T217 affects tau binding to microtubules.MethodBrain tissue from human AD patients and AD model mice, and cultured mouse neurons were analyzed by western blotting and immunofluorescence microscopy to compare the intracellular localization of taupT217, taupT181, taupT231 (AT180 epitope) and taupS396,pS404 (PHF1 epitope). EGFP‐tau (2N4R) was expressed in CV‐1 African green monkey kidney fibroblasts as wild type (WT), T217A non‐phosphorylatable, and T217E pseudo‐phosphorylated tau versions of the fluorescent fusion protein. Fluorescence recovery after photobleaching (FRAP) microscopy was used to assay turnover rates of the EGFP‐tau fusion proteins on microtubules, a surrogate measurement of affinity.ResultIn human AD brains and AD model mice, taupT217 was abundant in the somatodendritic compartment and co‐localized with neurofibrillary tangles. In cultured neurons, taupT217 was concentrated in somatodendritic puncta that were closely associated with dendritic spines. Both in vivo and in cultured neurons taupT217 co‐localized only partially with taupT181 and taupT231. Exposure of cultured neurons to extracellular oligomers of tau, but not amyloid‐β, increased intracellular taupT217. In CV‐1 cells, EGFP‐tauT217E recovered from photobleaching faster than EGFP‐tauT217A or EGFP‐tauT217.ConclusionIntracellular taupT217 is enriched at locations that normally lack much tau and is increased by extracellular tau oligomers. TaupT217 is enriched near dendritic spines, suggesting a possible role for T217 phosphorylation in altering synaptic activity. The faster fluorescence recovery of EGFP‐tauT217E compared to EGFP‐tauT217A or EGFP‐tauT217 implies that T217 phosphorylation reduces tau’s affinity for microtubules.