bluuebunny/crossref_metadata_2025_split huggingface dataset:
Home Cognitive Stimulation Activity in Thai Patients with Mild Cognitive Impairment and Mild Dementia
Authors: Rattanabannakit Chatchawan , Jinatongthai Wirarat , Thana‐Udom Kitikan , Senanarong Vorapun 
Published: December 2023

AbstractBackgroundThis study aims to investigate the characteristics of home cognitive stimulation activities for Thai patients with mild cognitive impairment (MCI) and mild dementia.MethodA cross‐sectional, questionnaire‐based study was conducted on Thai patients with the diagnosis of MCI and mild dementia. Patients’ characteristics, ability to use IT device or telecommunication technology, and home cognitive stimulation activities were collected. All activities were divided and calculated into sub‐scores of cognitive, religion‐related, and physical activities according to its frequency.ResultThere were 157 patients with a mean age of 76.2±7.9 years, 65.6% were female. 46.5% were diagnosed with MCI, and 53.5% with mild dementia. 47.1% had a graduate or higher degree. The mean MoCA score was 20.8±4.7. 51% of patients were able to use IT devices (smartphones, tablets, or computers). Patients with MCI were able to use IT devices more than patients with mild dementia (79.5% vs. 26.2%, p<0.001). As many as 29.3% of them were able to use a teleconference technology such as video call or Zoom application. Among the 25 home cognitive stimulation activities collected (excluding watching television), only 7 activities that participants ≥30% rated as frequent (≥3 days per week) were doing chores (63.1%), working out (51.0%), listening to music (50.3%), praying (43.3%), reading (38.2%), cooking (33.1%), and texting via mobile (31.8%). The activities they engaged the least were playing cards, board games, doing crossword puzzles, and drawing (rated as frequent 0.6%). Compared with patients with mild dementia, patients with MCI exhibited higher scores in all sub‐scores (all p<0.01). The cognitive activity sub‐score had an inverse correlation with the patient’s age and geriatric depression scale (r = ‐0.340 and ‐0.171, both p<0.05). Patients who were able to use smart devices or video call/conference applications were found to be more likely to have higher scores in every activity sub‐scores (all p<0.01).ConclusionIn this study, Thai patients had limited home activities, particularly those with dementia. However, about half of them were able to use IT devices, which may correlate with a higher cognitive activity score. Thai individuals with MCI or mild dementia may have room for improvement in the cognitive intervention delivered at home via teleconference.
Clinical value of CSF TMEM106B in familial and sporadic frontotemporal lobar degeneration
Authors: Rojas Julio C. , Cobigo Yann , Wise Amy B. , Li Jingyao , Loureiro Joseph , Worringer Katie , Heuer Hilary W. , Ljubenkov Peter A. , VandeVrede Lawren , Staffaroni Adam M. , Lago Argentina Lario , Ramos Eliana Marisa , Prudencio Mercedes , Marks Jordan M. , Cook Casey N. , Pernieel Jolien , Rademakers Rosa , Petrucelli Leonard , Boeve Brad F. , Rosen Howard J. , Boxer Adam L. ,   ALLFTD
Published: December 2023

AbstractBackgroundTMEM106B, a lysosomal trafficking protein, is an important genetic susceptibility risk factor for frontotemporal lobar degeneration (FTLD). In GRN mutation carriers, minor allele homozygosity in the TMEM106B rs1990622 SNP modulates the risk of FTLD. TMEM106B is often the main component of amyloid fibrils in FTLD with TDP43 aggregates. TMEM106B has been quantified in human brain specimens, but its role as a fluid biomarker is unknown. Here, we investigate the clinical value of CSF TMEM106B in FTLD.MethodsCSF TMEM106B was quantified with SOMAmer proteomics (v3.0, SomaLogic®) in an original cohort of C9orf72, GRN and MAPT symptomatic and asymptomatic mutation carriers and family non‐carrier controls, recruited through ALLFTD (n = 182), and a validation cohort of sporadic neuropathology‐confirmed FTLD‐tau and FTLD‐TDP43, clinically‐diagnosed progressive supranuclear palsy – Richardson syndrome (PSP‐RS) and age‐matched controls (n = 96). CSF TMEM106B was correlated with disease severity, measured by the Frontotemporal Lobar Degeneration module global scores (CDR+NACC/FTLD); brain volume, measured with Bayesian linear mixed‐effect modeling, using age, sex and total‐intracranial volume‐corrected permutations with threshold‐free cluster enhancement; and CSF neurofilament light chain (NfL) measured with Simoa. TMEM106B SOMAmer specificity was validated in cell culture overexpression systems and human brain specimens with high TMEM106B burden.ResultsIn both cohorts, there were no differences in CSF TMEM106B by sex, phenotype or neuropathological diagnosis, except for lower levels in PSP‐RS compared to controls (‐0.31 Log2‐fold change, p < 0.001). CSF TMEM106B did not correlate with age. Regardless of disease‐causing mutation, lower CSF TMEM106B was associated with worse disease severity (Figure 1 and 2). CSF TMEM106B was lower in homozygous TMEM106B rs1990622 protective allelein C9orf2 and MAPT, but not in GRN mutation carriers (Figures 3). CSF TMEM106B showed a trend for inverse correlation with NfL in the whole sample (r = ‐0.135, p = 0.052), and correlated positively with left frontal volume in symptomatic FTLD mutation gene carriers (p < 0.05).ConclusionCSF TMEM106B is quantifiable in CSF in vivo. CSF TMEM106B levels are affected by an interaction of disease severity and FTLD and TMEM106B genotypes. Further work is needed to determine its value as a clinical biomarker.
Longitudinal associations of depression and diabetes with Alzheimer’s disease and related dementias risk among American Indian and Alaska Native people
Authors: Goins R. Turner 
Published: December 2023

AbstractBackgroundAlzheimer’s disease and related dementias (ADRD) research worldwide indicate that it is more common in indigenous than in non‐indigenous populations. The increased risk for ADRD among indigenous people may be partially due to the population’s high rates of depression and diabetes. Thus, we examined the relationship of depression and diabetes, alone and together, with incident ADRD in a large sample of American Indian and Alaska Native people (AI/ANs).MethodWe used data from the Indian Health Service (IHS) Improving Health Care Delivery Data Project with a sample of 65,801 AI/ANs aged ≥ 45 years. The IHS Data Project includes data for a purposeful sample of AI/ANs who lived in 15 IHS service units, which are IHS geographic classifications located throughout the United States. We used Cox proportional hazard models to estimate associations between ADRD risk and baseline depression and diabetes.ResultWe found that 2.3% of our sample received an ADRD diagnosis during FY2010‐13. Compared to persons with neither depression nor diabetes, unadjusted models indicated that those who had both depression and diabetes had twice the risk of developing ADRD (Hazard Ratio (HR) = 2.02, 95% CI = 1.72‐2.37). The unadjusted risk among those with depression only was 77% higher (HR = 1.77, 95% CI = 1.50‐2.08). Adjusted analyses showed that the HR for those with depression and diabetes was 1.82 (95% CI = 1.53‐2.16) and those with depression only had a hazard ratio of 1.70 (95% CI = 1.44‐2.00) for ADRD. The association between depression and diabetes and depression only with ADRD risk was stronger for persons aged 45 to 64 years compared to persons aged ≥ 65 years. In the adjusted models, we did not find a relationship between only having diabetes and ADRD risk.ConclusionOur findings suggest that depression by itself and depression with diabetes increases the risk of ADRD in AI/ANs aged ≥ 45 years. In the future, ensuring clinical and behavioral services for AI/ANs include regular mental health screening and depression treatment might help decrease ADRD risk. Such efforts may also focus on middle‐aged persons.
Multi‐channel segmentation allows simultaneous estimation of classic tissue compartments, WMH and enlarged perivascular spaces
Authors: Gunter Jeffrey L. , Przybelski Scott A. , Sparrman Kohl Johnson , Cogswell Petrice M , Radford Jonathan Graff , Knopman David S. , Petersen Ronald C. , Vemuri Prashanthi , Jack Clifford R. , Persons Benjamin 
Published: December 2023

AbstractBackgroundLarge neuroimaging studies like ADNI‐4 now include T1‐weighted, T2‐weighted and FLAIR images at isotropic1mm resolution for investigation of both neurodegenerative and cerebrovascular disease. These three input types allow segmentation of GM, WM, DeepGM, WMH, and CSF compartments. Additionally, this supports automated assessment of enlarged perivascular spaces (PVS). Our objective was to propose a unified framework for segmentation of intracranial classes and PVS while reducing human effort.MethodsFLAIR and T2‐weighted images are aligned to the T1‐weighted image.. Standard SPM12 unified segmentation using all three input images establishes deformations between subject and template space and bias field corrections. Extended tissue priors including deep GM are deformed into subject space. Adding mean intensities from high probability deep GM voxels as seeds and using the extended prior set, segmentation is re‐started, refining model parameters, deformations and bias‐field estimates. The procedure repeats, adding a WMH channel, resulting in a segmentation including GM, WM, CSF, deep GM, WMH and nuisance classes. Frangi filters are applied to the T1‐ and T2‐ weighted images. Filter response images are smoothed, averaged, masked and inserted in place of the CSF prior. Probability maps of vessel‐like shapes with CSF‐like contrast are estimated to identify PVS. Visual grading was also performed for comparison.ResultsThe method was applied to 300 participants. Visual quality control found two instances of poor WMH over‐segmentation. Perivascular space maps were all visually reasonable. Standard segmentation classes were visibly superior to single T1‐based segmentation. Figures 1,2 present examples. Pearson correlations of PVS fractional volume with multiple human raters’ PVS counts in CSO/CR was over 0.7 in a subset of 125 participants (Figure 3).ConclusionModern dementia protocols include high‐resolution T1‐weighted, T2‐weighted, and FLAIR images that can be used together as inputs to extend probabilistic segmentation adding deep grey and WMH classes with automated PVS assessment.
Defining research engagement with African American participants in Alzheimer’s disease research studies: A qualitative study
Authors: Romano Raymond R , Full Kelsie , Velez Marina , Williams Tasha , Cowley Pam , Cambronero Francis E , Jefferson Angela L. 
Published: December 2023

AbstractBackgroundDiverse recruitment of racial and ethnic groups affected by Alzheimer’s disease (AD) into research is an important public health priority. Black/African American older adults are more likely to develop AD compared to White older adults; however, representation of Black/African American individuals in AD research studies is estimated to be as low as 2.5 percent. Improved engagement with underrepresented communities is essential to increasing representation. Here, we define a theory of research engagement from a grounded theory approach in collaboration with Black/African American participants enrolled in two ongoing Alzheimer’s disease cohort studies at Vanderbilt University Medical Center.MethodVanderbilt Memory and Aging Project and Tennessee Alzheimer’s Project participants (n = 18, 68±10 years) who self‐identify as Black or African American were invited to participate in focus groups on research engagement. Focus groups were hosted in a community location. Pre‐discussion, participants completed the Measuring Trust in Medical Researchers scale. Each session lasting 90 minutes was moderated by a trained staff member, audio‐recorded, and subsequently transcribed. Data were analyzed following methodology described by Strauss and Corbin (1990, 1998) and modified by Charmaz (2006). Open coding to identify themes was independently conducted by 3 team members, and codes were refined using an iterative process.ResultThe overall mean score of trust in medical research was 43.9±7.4 (range = 36‐59) suggesting a moderate amount of trust. Participants expressed inclusion in the process and experiencing benefits from research as motivators for research engagement. Participants voiced a desire to better understand inclusion and exclusion criteria and an interest in hearing about the cohort and previously used methods of recruitment. Some members communicated the importance of a welcoming and passionate environment as a driver for engagement.ConclusionOur initial work defining research engagement identified key concepts important to our local community. Working together with the community to define research engagement helps immerse participants in the research process. These concepts are well established in the literature, and lessons learned from our focus groups will help define a theory of engagement with local context that can be used to evaluate our future activities.
Impaired Microtubule Dynamics Are a Driver of Tau Phosphorylation
Authors: Parato Julie , Qu Xiaoyi , Richters Emily , Sproul Andrew , Bartolini Francesca 
Published: December 2023

AbstractBackgroundThe microtubule cytoskeleton is both stable and dynamic, and both states are necessary for normal neuronal function. Stable microtubules support long‐term structures like dendrites and axons, while dynamic microtubules promote synapse maintenance and are mostly composed of tyrosinated a‐tubulin, a condition that affects microtubule associated protein binding and motor protein recruitment. We have recently shown that human iPSC neurons carrying the familial AD APP London V717I mutation have impaired microtubule dynamics and significant increases in tubulin post‐translational modification (PTMs) associated with microtubule longevity. These changes result from decreased levels of the enzyme tubulin tyrosine ligase (TTL), which refreshes detyrosinated tubulin to its original, tyrosinated state. In human AD brains, TTL levels also decrease, while long‐lived microtubule PTMs increase. Here, we report that by compromising normal microtubule dynamics or by reducing TTL expression alone we can drive tau phosphorylation in rodent hippocampal neurons and explore the mechanisms by which this regulation occurs.MethodHuman cortical neurons derived from iPSC lines in which the London familial APP mutation V717I was knocked into one allele of the IMR90 control using CRISPR/Cas9, were used as a cellular model of familial AD. Inhibition of microtubule dynamics was performed with taxol or through lentiviral knockdown of TTL. Microtubule dynamics were measured by confocal time‐lapse microscopy in neurons expressing EB3‐EGFP, a protein that tracks the growing plus ends of microtubules. Immunoblotting was performed to measure protein levels.ResultWe found that in addition to increased levels of p262 tau, APP London neurons possess higher levels of active AMPK, a kinase that can phosphorylate serine 262 on tau and an important regulator of tau pathology in vitro and in vivo. We also demonstrate that decreasing microtubule dynamics with taxol or TTL silencing alone is sufficient to promote tau phosphorylation and that inhibition of AMPK or knockdown of its regulatory subunit can prevent it.ConclusionThese findings demonstrate that reduced levels of TTL and loss of dynamic microtubules drive AMPK‐mediated tau phosphorylation and suggest that TTL‐dependent loss of dynamic microtubules may contribute to tau pathology in AD.
Understanding molecular and cellular mechanisms of APOE4‐mediated susceptibility to tau‐related cognitive impairments in the miBrain model
Authors: Forton‐Juarez Ana , Suhy Natalie , Goldman Camille , Mesentier‐Louro Louise A. , Rooklin Rikki , Blanchard Joel 
Published: December 2023

AbstractBackgroundAPOE4 is the strongest genetic risk factor for Alzheimer’s disease with Tau pathology, namely hyperphosphorylation (p‐Tau) and aggregation of Tau into neurofibrillary tangles (NFTs) being correlated with poor cognitive outcomes in AD. Instances of mild traumatic brain injury (TBI) have been associated with increased susceptibility to neurodegenerative diseases such as AD and related dementias. We hypothesize that human APOE4 carriers’ brains are more susceptible to increased tau pathology with instances of TBI further increasing the severity.MethodUsing the 3D multi‐cellular integrated human brain (miBrain) model, which recapitulates key brain tissues through the co‐culturing of all hiPSC‐derived major brain cell‐types, Tau pathology can be induced with treatment of Tau fibrils or by increasing endogenous phosphorylated Tau with methotrexate.ResultAPOE4/4 miBrain cultures exhibit increased Tau pathology compared to isogenic APOE3/3 miBrains. Combinatorial genetic mixing experiments revealed that the increase of Tau hyperphosphorylation is dependent on the presence of APOE4 microglia.ConclusionData suggests that microglia facilitate the accumulation of p‐tau in APOE4 genetic backgrounds in an in vitro 3D model.
Dementia and Nutrition: A Multidisciplinary Massive Open Online Course for Health Care Professionals, Students and Non‐Professionals
Authors: Schüssler Sandra , Pleyer Brigitte Ursula , Ulbrich Eva , Maurer Lisa , Holasek Sandra , Staubmann Wolfgang , Hatz Manuela , Resinger Eva , Tatzer Verena , Fabianits Helga , Selzer‐Haslauer Ulrike , Roller‐Wirnsberger Regina , Horn Natalie Sofia , de Beaulieu Maurice Chales , Paletta Lucas , Zuschnegg Julia 
Published: December 2023

AbstractBackgroundMore than 55 million people worldwide have dementia. This number will increase in the future, causing strains on healthcare systems. In‐depth knowledge about dementia and its negative effects, such as nutritional problems, is necessary to pursue targeted prevention strategies and to provide adequate treatment and care. Therefore, the aim of the project was to develop a Massive Open Online Course (MOOC) on dementia and nutrition for the healthcare sector. Such MOOCs can reach many users and have proven effective for self‐directed continuous professional development.MethodsThe MOOC was developed for students and professionals in health care as well as for non‐professionals, like relatives of people with dementia, in German‐speaking countries as a joint project from 2021‐2022. Different disciplines (dietetics, nutritional scientists, nursing scientists, occupational therapists, speech and language therapists, nutritional geragogists, medical doctors, technological disciplines, social scientists) and institutions, like universities, developed the content of the MOOC based on design principles, international literature and expert knowledge. The online course was made available free of charge on the iMooX platform of the Technical University of Graz, Austria (https://imoox.at/mooc/).ResultsThe MOOC consists of 6 lessons which can be completed in a period of 6 weeks. The lessons include the following topics: (1) background information on dementia, like prevalence of dementia and costs; (2) risk factors for dementia, prevention and nutrition concepts; (3) impact of dementia on eating behaviors; (4) practical aspects of nutrition in dementia, like appetite stimulation; (5) activities of daily living & eating support; and (6) new technologies (e.g. robots, virtual reality) for prevention and support of eating problems. The content is delivered to the participants by means of videos and learning materials via various end devices. Each lesson ends with a quiz. Participants who answer at least 75% of the self‐assessment questions correctly receive a certificate.ConclusionThe MOOC was successfully launched on January 17, 2023 (https://imoox.at/course/demern) and has already had more than 200 participants in the first round. In the future, an English‐language version is planned in order to further increase the number of people that can profit from the MOOC.
Cost of informal dementia care by US state, 2010‐2019
Authors: Lastuka Amy , Breshock Michael , Swart Vivianne , Dieleman Joseph L 
Published: December 2023

AbstractBackgroundThere are significant costs associated with dementia care throughout the world. These are expected to rise as populations age. Informal (unpaid) care represents a large fraction of these costs, although it is challenging to measure. In the United States, estimates of the cost of informal dementia care are dated and measured only at the national level. To fill this gap, we estimated the cost of informal care attributable to dementia through 2019 for each US state.MethodThe value of informal care is estimated as the replacement cost (cost of an equivalent number of hours of paid care) and opportunity cost (expected cost of forgone wages of the caregivers). We combine data from the Behavioral Risk Factor Surveillance System, the National Health and Aging Trends Study (NHATS), and the Health and Retirement Study to estimate caregiving hours at the state level from 2010‐2019. NHATS data are used to estimate the fraction of caregiving hours attributable to dementia.ResultIn 2019, the average annual per‐patient cost of informal care attributable to dementia was $42,271 ($37,338‐$47,898) using the replacement cost method and $19,769 ($15,711‐$25,029) using the opportunity cost method. These estimates imply a national cost of $207.2B ($183.1B‐$234.8B) or $96.9B ($77.0B‐$122.7B) per year, respectively. State‐level estimates show significant variation in informal caregiving hours per prevalent case of dementia. In 2019, the annual replacement cost of informal care provided per patient ranged from $15,885 ($13,941 ‐$17,979) in Nebraska to $71,438 ($63,155 ‐$80,316) in New Mexico. The opportunity cost had a larger spread in relative terms, ranging from $6,653 ($5,233‐$8,417) in Nebraska to $36,831 ($29,071‐$46,833) in Missouri. Co‐occurrence of diabetes mellitus prevalence is associated with more informal care hours for the average adult living with dementia, while average years of education of the caregiver is associated with fewer informal care hours.ConclusionThe hours spent on informal care per prevalent case of dementia vary dramatically by state. This work adds to our understanding of health and demographic factors that are associated with hours of informal care, which can help policymakers plan for future increases in dementia prevalence and assess policy to support caregivers.