bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bioinformatics pipeline to guide post‐GWAS studies in Alzheimer’s: a new catalogue of disease candidate short structural variants
Authors: Lutz Michael W , Chiba‐Falek Ornit 
Published: December 2023

AbstractBackgroundShort structural variants (SSVs) including indels are common in the human genome and impact disease risk. The role of SSVs in late onset Alzheimer’s disease (LOAD) has been understudied. Previously we developed a bioinformatics pipeline that characterizes and prioritizes candidate regulatory SNPs in enhancers located in LOAD‐GWAS regions. Here we developed a bioinformatics pipeline of SSVs within LOAD‐GWAS regions to prioritize regulatory SSVs based on the strength of their predicted effect on transcription factor (TFs) binding sites. The impact of the genes and TFs prioritized by the pipeline are assessed in two LOAD single cell rna‐seq datasets.MethodsThe pipeline utilized publicly available functional genomics data sources. Primarily, candidate cis‐regulatory elements (cCREs) from ENCODE and publicly available single‐cell RNA‐seq data from LOAD patient samples from human prefrontal cortex brain samples obtained from UCI MIND’s Alzheimer’s Disease Research Center (ADRC) and ROSMAP. For TF binding analysis we employed motifs from MotifDb. In addition, we used various bioinformatics software including motifbreakR.ResultsWe catalogued 1230 proximal CTCF‐bound candidate cis‐regulatory elements in LOAD‐GWAS regions, 912 showed epigenetic evidence in relevant brain tissue. We catalogued 426 indels in these cCREs. These indels disrupted 391 TFs, 362 of these had snRNA‐seq data from LOAD samples. Of note, TF motifs within the APOE‐TOMM40, SPI1 and MS4A2 regions were significantly disrupted by the candidate regulatory indels. Amongst these TFs are RUNX3, SPI1 and SMAD3. Interestingly, these significant findings with the APOE‐TOMM40, SPI1 and MS4A2 regions are consistent with our prior results for SNPs.ConclusionsThis study provides an analytical framework to catalogue noncoding indel variation in cis‐regulatory elements located in LOAD‐GWAS loci and characterize their likelihood to perturb TF binding. The approach integrates multiple data types to prioritize genes and variants for validation experiments using disease models and gene editing technologies.
Contribution of Life Course Cardiovascular Risk Factors to Racial Disparities in Dementia Incidence
Authors: Ferguson Erin L , Vittinghoff Eric , Hazzouri Adina Zeki Al , Allen Norrina , Fitzpatrick Annette L. , Yaffe Kristine 
Published: December 2023

AbstractBackgroundRacial disparities in dementia outcomes exist in the United States. Targeting modifiable risk factors, including cardiovascular risk factors (CVRFs), is a conceivable way to reduce health disparities. Life course CVRFs are often higher in non‐White adults and are associated with risk of dementia, but it is unknown whether they contribute to racial disparities in dementia and cognition.MethodUsing a pooled cohort of 4,159 White and 939 Black participants aged 65‐95 years, we conducted a mediation analysis to estimate the proportional effect of race on dementia that is explained by four CVRFs imputed over the life course (20‐49, 50‐69, and 70‐89 years of age): body mass index, fasting glucose, systolic blood pressure, and low‐density lipoprotein cholesterol.ResultCompared to White participants, Black participants had greater risk of dementia (adjusted OR = 1.37; 95% CI: 1.17‐1.60). BMI and fasting glucose over the life course were significant mediators of the effect of race on dementia risk, mediating 39.1% (95% CI: 10.5‐67.8%) and 8.2% (95% CI: 0.1‐16.2%) of the effect, adjusted for sex and age. All four CVRFs together were also significant mediators of the effect of race on scores on global cognition and processing speed, accounting for approximately 11% of the effect.ConclusionWe found that CVRFs across the life course partially explain disparities in dementia risk and cognition in late‐life. Improved prevention and treatment of CVRFs across the life course may be important to reduce health disparities for dementia.
Neurocognitive analysis of topographical memory disorder in Alzheimer’s disease from fictional autobiography
Authors: Taiebine Mohamed 
Published: December 2023

AbstractBackgroundTopographical disorientation is very common in Alzheimer’s disease as dementia worsens; however, it is often one of the earliest manifestations. This study examined whether fictional autobiography might be a source for analyzing linguistic features in terms of toponomy and neurocognitive aspects of topographical disorientation in Lalla Fatma, a patient with Alzheimer’s disease. Additionally, we investigated how the toponymy of old, current, and new names overlapped in the novel About my Mother (2016), which was written by the Moroccan author Tahar Ben Jelloun.MethodThe neurocognitive approach followed the taxonomy described by Aguirre and D’Esposito (1999) to determine the clinical subtype that best described topographical disorientation or spatial agnosia from Lalla Fatma’s discourse. Text mining and toponymic approaches were used to develop patterns of spatiotemporal themes across novel corpora coupled with computational analysis (T‐Lab plus 21).ResultIn Ben Jelloun’s narrative, the overlapping of Tangier and Fez creates a temporal framework to remap memories that have been trapped between the walls, ramparts, and fortresses of imperial Moroccan cities. Lalla Fatma’s house in Tangier seems to have been neglected, similar to her dilapidated and lost memories. The house involves seeking self and identity in a physical and material reality that is subject to spatiotemporal disorientation. It was also a trigger for expressing the present moment of melancholy and nostalgia aggravated by Lalla Fatma’s declining health and mental status. According to the taxonomy by Aguirre and D’Esposito (1999), two types of topographical disorientation have been found in the novel (landmark agnosia and anterograde disorientation)ConclusionThis study provides evidence suggesting that fictional autobiography should be investigated cross‐culturally in terms of linguistic and neurocognitive aspects in the context of Alzheimer’s disease.
Quality of life in patients with subjective cognitive impairment compared with those diagnosed with mild cognitive impairment or dementia referred to a rural and remote memory clinic
Authors: Sun Gloria , Kirk Andrew , Karunanayake Chandima P , O'Connell Megan E , Morgan Debra G 
Published: December 2023

AbstractBackgroundPerceived cognitive decline is a significant source of anxiety for many patients, especially as awareness of dementia grows. We sought to compare whether quality of life (QOL) in patients with subjective cognitive impairment (SCI) who performed normally on a neuropsychological battery significantly differed from those diagnosed with mild cognitive impairment (MCI), Alzheimer’s disease (AD), or non‐Alzheimer’s dementia (non‐AD) at initial assessment in a rural and remote memory clinic.Method610 patients referred to our Rural and Remote Memory Clinic (RRMC) between 2004‐2019 were included in this study. As part of their RRMC assessment, each patient and their caregiver independently rated the patient’s QOL using the Quality of Life of the Patient (QOLPT) scale. We compared self‐reported and caregiver‐reported patient QOL scores in those with SCI (n = 166) to those diagnosed with MCI (n = 98), AD (n = 228), and non‐AD (n = 118).ResultPatients with SCI self‐reported significantly lower QOL compared to patients with AD (mean 34.55 vs 35.96, p<0.05). Interestingly, the reverse was seen in caregivers: SCI caregivers rated patient QOL higher than AD caregivers (mean 34.61 vs 31.72, p<0.001). Patients with SCI also reported lower QOL than patients with MCI (mean 35.55 vs 36.97, p<0.05). SCI caregivers reported higher patient QOL than their non‐AD counterparts (mean 34.61 vs 31.17, p<0.001). Caregiver‐rated patient QOL was higher in those with MCI compared to AD (mean 34.52 vs 31.72, p<0.001). Patients with MCI self‐reported higher QOL scores compared to patients with non‐AD (mean 36.97 vs 34.81, p<0.05). Similarly, MCI caregivers reported higher patient QOL than non‐AD caregivers (mean 34.52 vs 31.72, p<0.001). No other comparisons were statistically significant.ConclusionAlthough they lacked clinically significant cognitive deficits, patients with SCI self‐reported significantly lower QOL than patients with MCI and AD, although patients with MCI self‐reported higher QOL than patients with non‐AD. Conversely, caregiver‐reported patient QOL was higher for patients with SCI than patients with AD and non‐AD. MCI caregivers also reported higher patient QOL compared to AD and non‐AD caregivers. This shows that SCI seriously impacts QOL. More work needs to be done on how we can better support patients with SCI to improve their QOL.
Cataracts are associated with smaller gray matter brain volume among participants in the UK Biobank
Authors: Ferguson Erin L , Buto Peter , Thoma Mary , Wang Jingxuan , Glymour M. Maria , Hoffmann Thomas J. , Choquet Hélène , Andrews Shea J , Yaffe Kristine , Casaletto Kaitlin B. , Brenowitz Willa D 
Published: December 2023

AbstractBackgroundVisual impairments, including reduced visual acuity and cataracts, are emerging as novel and modifiable risk factors for Alzheimer disease (AD) and related dementias (ADRD). However, it is unclear whether vision impairments or cataracts are associated with structural integrity of brain regions linked to ADRD or other brain regions. We investigate associations between visual acuity, cataracts, genetic risk for cataract, and brain volumes.MethodWe analyzed 33,923 UK Biobank participants aged 55‐82 without dementia at enrollment who underwent brain MRI. Subsets had usable genetic data (n = 29,963) and visual acuity exams (n = 7,837). Participants self‐reported history of cataracts. The following imaging volumes were generated from FreeSurfer segmentations: hippocampal volume, total brain volume, and total gray matter volume. We additionally included an AD signature region defined as the cortical thickness averaged across six relevant brain regions. We calculated a genetic risk score (GRS) for cataract using 43 previously‐reported genetic variants. Linear regressions estimated the associations between brain volumes and visual acuity or self‐reported cataract, separately with adjustment for demographic and clinical confounders, intracranial volume, and imaging center. Linear regressions for brain volume using cataract GRS adjusted for ancestry principal components, sex, age, intracranial volume, and imaging center.ResultThe sample was an average of 66.0 years (SD = 6.26) at imaging, with a cataract prevalence of 2.5% (n = 863). History of cataract was associated with significantly smaller total gray matter volume (β = ‐2483 mm3, 95% CI: ‐4225 to ‐741). Increased genetic risk for cataract was significantly associated with smaller total gray matter (β = ‐485 mm3, 95% CI: ‐732 to ‐138) and total brain volume (β = ‐707 mm3, 95% CI: ‐1192 to ‐221). Neither cataract nor cataract GRS was associated with hippocampal volume or the AD signature region. Poor visual acuity (worse than 20/40 vision) was not significantly associated with any brain volumes.ConclusionHistory of and genetic risk for cataract is associated with smaller total gray matter volume, but not hippocampal volume. Our results suggest that cataract may increase risk of neurodegeneration independent of typical AD, but more investigation is needed.
Association between Trust of Researchers and Interest in Participation in Alzheimer’s Disease Biomarker Research
Authors: Wang Sophia , Epperson Francine , Eliacin Johanne , Polsinelli Angelina J , Raelly‐Muze Laureen , Asper Joseph , Van Heiden Sarah , Saykin Andrew J. 
Published: December 2023

AbstractBackgroundThe study examined whether trust in researchers affects interest in AD (Alzheimer’s disease) biomarker research participation, specifically AD blood biomarkers and MRI and PET neuroimaging, and whether this was independent of other factors commonly associated with hesitancy to participate in research, including race and knowledge of AD.Methods258 community‐dwelling Black and 141 non‐Hispanic White adults (age ≥ 55) who had never participated in AD research completed a survey about their perceptions of AD biomarker research. The survey asked participants to select one of three responses, “Yes,” “Unsure,” and “No” to 6 trust statements, with yes being the highest level of trust. Questions specifically assessed whether survey participants trusted researchers to keep information confidential, be honest, component, not cause harm, treat them equally, and share results with them and their community. Those who answered yes to all 6 questions were categorized as having very high trust, and those who answered no or unsure to any of the 6 questions were categorized as having lower trust. Ordinal logistic regression models were used for the analysis of outcome variables with three possible responses (i.e. interest in participation in an AD biomarker study and individual procedures, motivators for research participation). We adjusted for age, education, sex, race, and knowledge about AD.ResultParticipants with very high trust in researchers were less hesitant about doing AD biomarker research (OR 0.32 (95% CI (0.20‐0.52), P < 0.001). Participants with concerns about confidentiality, study risks, and being treated equally had greater hesitancy about doing AD biomarker research (P’s < 0.05). Concerns about researchers’ competency were associated specifically with lower interest in doing neuroimaging procedures (P’s < 0.05). Very high trust in researchers was associated with greater interest in return of results, particularly brain scans (OR 1.92 (95% CI 1.06‐3.48), P = 0.032).ConclusionEven after other factors known to affect AD research participation, trust remains a highly significant factor affecting the interest in AD research participation in blood biomarker neuroimaging procedures. Recruitment strategies for AD biomarker research may need to address participants’ trust concerns, specifically confidentiality, study risks, and equity.
The cultural adaptation process of the Savvy Caregiver program with the Native Hawaiian community
Authors: Jackson Alexandra , Dillard Adrienne , Kekauoha Puni , Balaz Poki'i , Dutro Natlie , Lee Kia'i , O'Sullivan Kelly , Okamoto Scott , Lewis Jordan P. , Hepburn Kenneth , Weaver Raven 
Published: December 2023

AbstractBackgroundFamily caregivers are at increased risk for experiencing multiple negative health outcomes, yet unpaid caregivers provide the majority of care for people living with Alzheimer’s disease and related dementias (ADRD).1‐3 Among Native Hawaiians (NHs), family or ʻohana caregiving is an important and common responsibility.4,5 As NHs face substantial health disparities, including a high burden of chronic disease across the lifespan, family caregivers are an important population to prioritize to promote health.6‐8 While effective evidence‐based interventions have been developed to promote caregiver mastery and wellbeing,9‐11 there are no programs specifically tailored to NH culture, language, and values.MethodWe aimed to culturally adapt the Savvy Caregiver program with the NH community, while maintaining fidelity to the original program. We invited community members with expertise in NH culture, caregiving, and ʻōlelo Hawaiʻi (Hawaiian language) to participate in monthly meetings and work alongside the research team in adapting the Savvy Caregiver program. The goals, scope of work, and expectations for the research team and CAB were established from the outset. The Community Action Board (CAB) intentionally chose to be an “action” board as they serve as cultural experts that suggest, review, and approve all changes to the curriculum and will support the dissemination of the program.ResultThe CAB suggested modifications ranging from surface (e.g., images, terms) to deep structural adaptation (e.g., “talk story,” storytelling, cultural values, norms, and Hawaiian ways of knowing). The research team reviewed and incorporated the CAB members’ expertise. All deep structural changes were reviewed to maintain program fidelity resulting in an adapted intervention that will be pilot tested in the community.ConclusionWhile this is an ongoing and iterative process, we anticipate our approach and inclusion of a CAB has led to the effective adaptation of the Savvy Caregiver program. We also anticipate these partnerships will support the institutionalization and scaling up of the program to reach the NH community. Next steps will assess whether fidelity and the core components of the original intervention were maintained after cultural adaptation.
Agmatine prevents the memory impairment and the dysfunction of hippocampal GSK‐3β and ERK signaling induced by Aluminum nanoparticle in mice
Authors: Izadi Sadegh , Rezaei Amin , Esmaili Zahra , SoukhakLari Roksana , Moosavi Maryam 
Published: December 2023

AbstractBackgroundThe growing usage of Aluminum nanoparticles (Al‐NP) and its exposure may influence body function. Considering the proposed relationship between Al and the pathogenesis of Alzheimer’s disease (AD) and the concern about the effect of this nanoparticle on brain health and cognitive function, the use of neuroprotective agents might be helpful. According to the reported neuroprotective effects of agmatine, in the present study the possible protective effect of agmatine was assessed in mice model of Al‐NP induced memory impairment. was investigated in the present study. In addition, due to the roles of hippocampal Glycogen synthase kinase 3 beta (GSK‐3β) and ERK signaling in memory and its disorders, these pathways were also investigated.MethodAl‐NP (10 mg/kg/p.o.) with/without agmatine (5 or 10 mg/kg/i.p.) was administered to adult male NMRI mice for 5 days. Novel object recognition (NOR) test session was used to assess cognitive function. Following the behavioral assessments, the hippocampi were used to determine the phosphorylated and total levels of GSK‐3β and ERK as well as GAPDH using western blot analysis.ResultThe results showed that Al‐NP impaired NOR memory in mice while agmatine 10 mg/kg prevented the memory deficit induced by Al‐NP. Furthermore, Al‐NP activated GSK‐3β as well as ERK signals within the hippocampus while agmatine prevented the effects of Al‐NP on GSK‐3β and ERK signals within the hippocampus.ConclusionBesides supporting the neuroprotective effects of agmatine, these findings suggest the possibility of the connection of hippocampal GSK‐3β and ERK signaling in the neuroprotective effect of this polyamine against Al‐NP.
Interoperability of the MIITRA atlas with complementary atlases: development of a comprehensive array of gray matter labels
Authors: Niaz Mohammad Rakeen , Ridwan Abdur Raquib , Wu Yingjuan , Zhang Shengwei , Bennett David A. A , Arfanakis Konstantinos 
Published: December 2023

AbstractBackgroundIn order to enhance the functionality of the MIITRA atlas and its interoperability with complementary atlases, a comprehensive set of gyral‐based, cytoarchitecture‐based, and functional connectivity‐based gray matter labels were constructed in MIITRA space.MethodT1w images from the 400 older‐adults included in the construction of MIITRA atlas were nonlinearly registered using ANTs SyN to the MNI152 6thgen,MNI Colin, and the ICBM2009c templates, and volumetric labels from Harvard‐Oxford,Julich,AAL3,Buckner,CoBrALab,Hammersmith and Princeton Visual atlases were warped to the space of each participant. The ANTs‐derived transformations used to build the MIITRA T1w template were used to map the corresponding gray matter labels from raw space to exact physical locations in the final MIITRA space following a multi‐atlas correction scheme to correct for residual misregistration. T1w images from a separate group of 100 older‐adults for evaluation were nonlinearly normalized to the MIITRA template and the inverse transformation was applied to the gray matter labels to transform them to each individual’s space. The T1w image of each individual was nonlinearly registered to every other individual and the labels from the 99 other older‐adults were transformed to each individual. Pair‐wise Jaccard index for each label was calculated in every individual’s native space. The same procedure was followed for the labels obtained directly from the respective source templates.ResultThe overlap was higher for the AAL3 labels obtained from MIITRA with an average pair‐wise Jaccard index of 0.59 and standard deviation of 0.08, compared to 0.55±0.1 for the AAL3(Fig1A) labels obtained from the MNI Colin template. The pair‐wise Jaccard index for the Julich(Fig1C) and CoBrALab labels(Fig2A) was 0.54±0.13 and 0.75±0.17 from MIITRA and, 0.53±0.14 and 0.74±0.17 from ICBM2009c. For the Harvard‐Oxford(Fig2B), Buckner(Fig2C), Hammersmith(Fig1B) and Princeton Visual(Fig2D), the pairwise Jaccard was 0.68±0.14, 0.61±0.07, 0.71±0.10 and 0.35±0.06 respectively from MIITRA and 0.66±0.11, 0.61±0.08, 0.67±0.11 and 0.32±0.08 respectively from MNI152 template. Heat maps representing the Jaccard‐index for each template are shown in Fig3.ConclusionGray matter labels from MIITRA showed higher pair‐wise overlap suggesting that labels from MIITRA space allows more consistent segmentation of the gray matter of the older‐adult brain compared to the labels obtained from templates constructed using younger or middle‐aged data.
Community NGO intervention for Alzheimer’s patients rehabilitation
Authors: Pal S , Roy T , Guha B 
Published: December 2023

AbstractBackground
Alzheimer’s patients Rehabilitation services aren’t well‐developed concept in resource‐Poor nations due to poor economics & lack of expertise. With limited resources we wanted to explore these rehabilitation services in rural villages.
Rural/tribal areas of India lung Alzheimer’s patients [Ca] patients lack rehabilitation support available only in city hospitals. Our 12‐year CBO is training youth volunteers & traditional faith halers in marginalized communities to provide rehabilitation.MethodAround 1340 cases of Alzheimer’s will be in rural/tribal of India by 2025, but hospitals lack dedicated Rehabilitation program. patients returning to villages after onco‐therapy in cities urgently need Rehabilitation support to suit their economic, social, cultural background. Since August 2018 Our NGO clinic started free advise on Rehabilitation. [n = 91]. With 6 trained nurses, two physicians, we screened patients. Average age 62 years, M:F ratio 75:25. Our support services devised as‐per need of Patients in consultation with family & stretched over 21 months included conselling, physiotherapy, occupational therapy, rehabilitation. Responses assessed with Quality of life scale by Flanagan Quality of Life Scale (QOLS) & psychological evaluation by Likert psychometric scale. This presentation demonstrates project in developmental stages & basic operational facts. Initially started as practically oriented guidance center & later developed in well‐organized set‐up offering free rehabilitation services in villages. It comprises NGO staff and traditional faith healers.ResultOur program highlights variability of psychological & Socio‐medical aspects in rehabilitation. Patents needed medical interventions in 18%, psychological approaches in 84% while remaining 16% needed combination of both.ConclusionThis is pilot project running on community donation. We plan to document, evaluate this in large sample size, but resource restriction didn’t permit. To overcome this, we plan networking of European NGO’s, advocacy experts at AAIC‐2023 Venue for better study design, technical support & collaborative efforts. I do not claim “I transformed whole community of patients but we had certainly taken initiative by this cost‐effective approach”.