bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimization of plasma extracellular vesicle enrichment for in‐depth lipidomic profiling in Alzheimer’s disease
Authors: Su Huaqi , Fowler Christopher J , Bush Ashley I , Masters Colin L , Barnham Kevin J , Reid Gavin E , Vella Laura J 
Published: December 2023

AbstractBackgroundLipid dyshomeostasis is associated with various disorders including Alzheimer’s disease (AD). The work from our laboratory (Su et al, JEV 2021), and others, suggests that extracellular vesicles (EVs) contain lipid biomarkers that could aid in the diagnosis of AD and diseases associated with impaired lipid metabolism.Knowing the lipid content of EVs is a key first step to discovering EV‐based lipid biomarkers in blood. Some studies have reported the lipid content of ‘’EVs’’ in blood. However, used EV isolation techniques that are known to co‐isolate free lipid and lipoproteins.Here we: 1) demonstrate the importance of size exclusion resin size to isolating highly enriched EVs for lipidomic analysis, 2) have developed a reference EV plasma lipidome for the research community and 3) determining if plasma EVs report on lipid dyshomeostasis in Alzheimer’s disease.MethodHuman plasma EVs were isolated using an assortment of commercially available kits or by density fractionation and size exclusion chromatography and characterised by western blot, transmission electron microscopy, and quantitative mass spectrometry based proteomic and lipidome analysis.ResultOf the high‐throughput EV isolation kits tested, the majority were unable to separate lipoproteins from EVs for the purposes of EV lipidomics. We then relied on comparing labor intensive methods (density gradient and size exclusion) to identify a combination of techniques that isolate the analytes of interest, EV proteins and lipids. Quantitative proteome and lipidome analysis strategies are being applied to highly enriched EVs with the goal of providing the reference lipidome of EVs in plasma and in Alzheimer’s disease.ConclusionTo enhance the confidence of EV lipid identification and reveal the lipidome of EVs in plasma, our study compared and identified techniques to enrich EVs and deplete non‐EV associated lipid and protein from human plasma. These findings serve as a reference resource and the foundation for research investigating plasma EV lipids as Alzheimer’s disease biomarkers.
Correlates of caregiver burden in African immigrants with personal experiences of dementia
Authors: Nkimbeng Manka 
Published: December 2023

AbstractBackgroundDementia care and caregiving needs of African immigrants are not fully understood. This paper describes the correlates of caregiver burden in a sample of first and second generation African immigrants with personal experiences of dementia. Data comes from the Immigrant Memory Collaborative; a community‐based participatory research project with African immigrants in a Midwestern state in the United States.MethodWe used linear regression modeling to determine whether discrimination and where the person with dementia resides were associated with caregiver burden.ResultOf the 155 care givers in the sample, 32% (49) were foreign‐born. The mean caregiver burden score in this sample was 6.7(0‐12, range). Compared to those born in the United States, caregivers who were born in Africa were older (31 vs 41) and majority female (20% vs 51%). Older age was associated with a decrease in caregiver burden score (b: ‐0.071 95% CI [‐0.11, ‐0.03]) and higher every day discrimination was associated with higher caregiver burden score (b: 0.22, 95% CI [0.14, 0.29]). The burden score for caregivers of a person living with dementia residing in Africa was lower but this was not statistically significant (b: ‐1.36 95% CI [‐2.72, 0.009]).ConclusionIn this sample, high discrimination experiences and younger age were associated with greater caregiver burden. Many African immigrants have never heard of dementia prior to migrating to the United States (U.S.) but currently provide care both to persons living with dementia in the U.S. and back home in their countries of origin. There is need for outreach and education towards improved dementia care and caregiving for African immigrants.
Associations of AHA’s Life’s Essential 8 health behaviors with cognitive function among U.S. Black and White midlife adults
Authors: Shen Yuqi , Master Lindsay , Beydoun May A , Zonderman Alan B , Buxton Orfeu M. , Gamaldo Alyssa A. , Evans Michele K 
Published: December 2023

AbstractBackgroundLife’s Simple 7 (LS7), originally proposed as the seven most important predictors of heart health, is associated with negative cognitive outcomes (Thacker et al., 2014). The recently updated Life’s Essential 8 (LE8) includes sleep. Limited research has investigated the association between LE8 and cognition, particularly within Black and White adults. We hypothesize that higher composite LE8 scores will be associated with better cognitive performance, particularly within Black adults.MethodCross‐sectional analyses were conducted including adults from the Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) study conducted in Baltimore, MD. Study participants (36‐76 years old; 41% male; 61% Black) completed all LE8 (Lloyd‐Jones et al., 2022) and global cognition measurements in wave 4 data collection (2013‐2017). Cognitive performance on a computerized cognitive battery (Joggle Research) yielded a total global cognition score and individual domains (e.g., working memory, attention). Linear regression analyses were stratified by race and poverty status (below 125% Federal poverty guidelines), education attainment (high school), and reading literacy (median split) respectively. Covariates included age, sex, sleep apnea, and depression. All reported models were fully adjusted.ResultAmong Black adults, higher LE8 scores (better CVH) were associated with better working memory only among individuals living above the poverty level (all b unstandardized; b = 0.008, p = .016), or only with high school education (b = 0.009, p = .027). Among White adults, higher LE8 score was associated with better working memory, particularly among individuals living above poverty level (b = 0.014, p = .002), having an education above high school (b = 0.019, p = .002), or high literacy (b = 0.021, p<.001) . Additionally, higher LE8 scores were associated with better attention, and higher global cognition score among individuals living above poverty (b = 0.015, p = .042; b = 0.039, p = .025) or with a high literacy on (b = 0.023, p = .014; b = 0.049, p = .027).ConclusionHigher score of LE8 was associated with better working memory among both U.S. Black and White adults. However, higher LE8 scores were associated with performance across a larger variety of cognitive domains within White adults from diverse socioeconomic indicators. These findings illustrate unique LE8 and cognition associations when disentangling socioeconomic heterogeneity within racial groups.
The role of sleep disturbances in the association between housing conditions and subjective cognitive impairment
Authors: Johnson Dayna A 
Published: December 2023

AbstractBackgroundAdverse housing conditions such as crowding, air pollution, or insufficient heat are associated with cognitive impairment. However, the mechanism linking adverse housing conditions and cognitive impairment is not fully understood. Adverse housing can affect sleep – an essential physiologic activity for cognitive function, yet this pathway is understudied. We tested associations between housing condition, sleep disturbances, and cognitive impairment.MethodsThis study utilized data from the Health and Retirement Study, a longitudinal panel study among adults (2020). Participants (n = 2,639) completed questionnaires on housing, sleep disturbances, and cognition. Housing was measured by self‐reported ratings of their homes physical condition (1‐excellent to 5‐poor). Sleep disturbances were self‐reported as trouble falling asleep, trouble waking up during the night, and trouble with waking up too early and not being able fall asleep again, and each item was scored from 0 (rarely/never) to 2 (most of the time). Cognitive impairment was defined as a participant rating of fair or poor regarding their memory at the present time. Logistic regression models were fit to test associations between housing and sleep and cognitive impairment after adjustment for age, sex, and race.ResultsThe sample had a mean age of 66.2+10.6 years, and 60% were female, 21.4% Black, 64.6% White, and 11.4% other racial group. The prevalence of cognitive impairment and sleep disturbance was 28.7% and 42.8%, respectively. Individuals living in adverse housing conditions had 32% and 48% higher odds of sleep disturbances [Adjusted Odds Ratio (aOR) = 1.32, 95% confidence interval (1.21, 1.43)] and cognitive impairment [aOR = 1.48 (1.36, 1.62)], respectively. Sleep disturbances were associated with higher odds of cognitive impairment, OR = 2.04 (1.71, 2.44). After adjustment for sleep disturbances, the association between housing condition and cognitive impairment was slightly attenuated, aOR = 1.40 (1.28, 1.54).ConclusionsLiving in adverse housing conditions were associated with greater sleep disturbances and subjective cognitive impairment. Results suggest that sleep may explain a small portion of the association between housing conditions and cognitive impairment, but a formal test of mediation is needed. Housing and sleep may be points of intervention for reducing cognitive impairment.
MIITRA atlas: high resolution FOD template of the older adult brain
Authors: Wu Yingjuan , Ridwan Abdur Raquib , Niaz Mohammad Rakeen , Bennett David A. A , Arfanakis Konstantinos 
Published: December 2023

AbstractBackgroundHigh quality fiber orientation distribution (FOD) template of the older adult brain facilitates white matter studies in older adults. This work compared several methods to construct an FOD template of the older adult brain in the space of the MIITRA atlas(Wu et al.,2022).MethodT1w and DWI data from 400 non‐demented older adults (50% male;64.9‐98.9 yrs;54% white,43% black)(Bennett et al.,2018;Barnes et al.,2012) participating in the construction of the MIITRA atlas were used.Method 1: FOD‐based single modality registration(cost function:mean squared difference)(MRtrix3).Method 2: The nonlinear transformations generated from MIITRA T1w and DTI template construction were applied to the FODs(Wu et al.,2021).Method 3: Multichannel registration based on T1w, T2w, FA and MD information with equal weights(cost function:cross‐correlation)(ANTs).Method 4: Multichannel registration based on T1w and FOD information with equal weights(cost function:cross‐correlation)(MRtrix3).Method 5: Multichannel registration based on T1w, FA and FOD information with weights of 4,3,3 respectively(cost function:cross‐correlation)(MRtrix3).Method 6: Same as Method 5 followed by FOD registration performed on the FOD data that were already transformed by Method 5(cost function:cross‐correlation)(MRtrix3).The FOD templates generated with different methods were compared by visual inspection, image sharpness of the total apparent fiber density (AFD) map, precision of spatial normalization of FOD data used in template construction, and spatial matching with the existing MIITRA T1w and DTI templates.ResultThe FOD templates generated with Methods 2, 3 and 6 exhibited higher image sharpness(Fig.1A). Fiber crossings were more clearly defined in the FOD templates generated with Methods 1,4,5,6(Fig.1B). Method 6 allowed higher ACC and lower MSD of spatially normalized FOD data, indicating higher precision in spatial normalization(Fig.2A,B). Method 2 provided the highest spatial matching with the existing MIITRA templates, followed closely by Methods 4,5,6(Fig.2C,D). Overall, the FOD template generated with Method 6 achieved high image quality, was constructed based on precisely matched FOD data, and exhibited high spatial matching to the existing MIITRA templates(Fig.3).ConclusionAn FOD template of the older adult brain was constructed for the MIITRA atlas. The new template exhibits high image quality, is constructed based on precisely matched FOD data, and exhibits high spatial matching to other existing MIITRA templates.
Understanding Physiotherapy Students’ Perceived Preparedness To Work With People Living With Dementia: A Qualitative Study
Authors: Quick Stephen M , Lawler Katherine , Shannon Michelle M , Soh Sze_Ee , McGinley Jennifer L , Peiris Casey L , Snowdon David A , Callisaya Michele L 
Published: December 2023

AbstractBackgroundDementia is a major cause of disability, and physiotherapists play a vital role in the care of people with this condition. Entry‐to‐professional practice physiotherapy students have been found to be ‘somewhat confident’ in working with this population, however comprehensive data about their practice experiences, their preparedness to care for people living with dementia and any educational gaps have not been previously reported. The aims of this study were to 1) determine physiotherapy students’ experiences in caring for people who have dementia, 2) determine how prepared students were to work with people who have dementia upon graduation and 3) determine if there any areas where students require further education regarding dementia, and how this would be provided.MethodsThis was a qualitative study using an interpretive description approach. Participants were 17 physiotherapy students from entry‐to‐professional practice education programs in three universities in Victoria, Australia, in their final year of study, having completed at least 15 weeks of clinical placements. Students participated in semi‐structured interviews. Thematic analysis was undertaken, with themes/subthemes derived and a qualitative thematic framework generated.ResultsThe overarching theme was that students’ experience of providing care for people with dementia was overwhelming. The three sub‐themes were: 1) students experience significant challenges when working with people with dementia, 2) students experience a range of emotions when working with people with dementia, and 3) the quality of dementia learning experiences during entry‐to‐professional practice training was perceived by students as mostly inadequate. Students described the importance of supervisors during clinical placements, and suggested incorporating ‘real‐life’ scenario classroom training to assist them to learn to manage the challenging symptoms of dementia.Discussion/ConclusionPhysiotherapy students believe that entry‐to‐practice dementia education is currently insufficient. These findings have important implications for the future planning and delivery of physiotherapy dementia education.
The association of Life’s Essential 8 and brain structure integrity in midlife
Authors: Dintica Christina S. , Jiang Xiaqing , Habes Mohamad , Erus Guray , Yaffe Kristine 
Published: December 2023

AbstractBackgroundIdeal cardiovascular health has previously been associated with a lower risk of dementia and less cognitive decline in midlife. We investigated if the American Heart Association’s (AHA) “life’s essential 8” (LE8) factors for ideal cardiovascular health are related to brain structure integrity in midlife.MethodsWe included 607 participants from the Coronary Artery Risk Development in Young Adults study with information on LE8 at mean age of 45 (SD = 3.4) and MRI examination ten years later. LE8 factors were dichotomized according to AHA guidelines as yes/no on high blood pressure (≥120 systolic or ≥80 diastolic blood pressure); high BMI (≥25); low physical activity (≤300 exercise units); currently smoking; high cholesterol (≥200); high fasting glucose (≥100); poor diet (<median score on the MedDiet); and poor sleep (≤6 or ≥9 hours per night, and combined into a score ranging from 0 to 8, with higher score indicating worse cardiovascular health. A brain age was derived using previously validated high dimensional neuroimaging pattern analysis, quantifying individual differences in age‐related atrophy. White matter hyperintesities (WMHs) and white matter (WM) microstructural integrity (mean diffusivity [MD] and fractional anisotropy [FA]) were assessed using MRI. Linear regression and structural equation modeling were used to examine the relationships between LE8, brain age, WMHs, FA, and MD, adjusted for age, sex, education, and race.ResultsThe range of LE8 was 0‐7 among the participants (median = 2, interquartile range = 2). Having 0‐3 LE8 risk factors was associated with a younger brain age, while having 4+ risk factors was associated with a higher brain age relative to chronological age (Figure 1). Moreover, a higher LE8 score was associated with greater MD (β: 0.16, 95% CI: 0.09 to 0.23), and lower FA (β: ‐0.15, 95% CI: ‐0.22 to ‐0.08), but not with WMHs. The indirect effect of the LE8 score on brain age through MD and FA was (β: 0.50, 95% CI: 0.28 to 0.75), hence the proportion mediated was 75% (Figure 2).ConclusionA higher cardiovascular risk as defined by the AHA is associated with a higher brain age in midlife, a majority of which can be explained by markers of early WM deterioration.
End of life in early onset familial Alzheimer’s disease: Bioethical issues and the cognition specialist’s role
Authors: Giordano Ximena , Fernandez Maria Cecilia 
Published: December 2023

AbstractAlzheimer’s disease (AD) is the most common cause of dementia in the world. Genetic factors are key contributors to all forms of AD, but in some families, it is possible to identify a specific genetic cause for early‐onset familial Alzheimer’s disease (EOFAD). When a genetic cause is identified, it is important that relatives are aware of the implications and alternatives in order to assess how they would like to proceed, based on their values, beliefs, and preferences. This may present ethical challenges for the neurologist due to questions about their decision‐making capacity.The purpose of this presentation is to report the case of a 66‐year‐old patient diagnosed with EOFAD 11 years ago, in its final stage of the disease, whose husband inquires about the possibility of adopting end‐of‐life measures, and to analyze from it the bioethical aspects and the cognition specialist’s role in this issues.Given the progressive nature of dementia, it is critical to identify the patient’s social support network early on. The late stage of dementia is associated with a significant decline in a person’s autonomy and will require full‐time assistance. The carers experience sadness and guilt as well, as the realisation that end‐of‐life is approaching and decisions regarding palliative care become imminent, so it is necessary to analyze how far to adopt life support measures, since these will prolong life. Regarding our patient, with the support of a bioethics committee, it was decided to take end‐of‐life measures by stopping enteral nutrition.Advising on end‐of‐life approach options and especially encouraging the patient to complete advance directives in early stages of the disease, with the fundamental support of a bioethics committee, is the future challenge of the specialist in cognition.References ‐Gauthier S, Webster C. 2022. World Alzheimer Report 2022: Life after diagnosis: Navigating treatment, care and support. London, England: Alzheimer’s Disease International.‐M. Congedoa, R. I. Causarano. Ethical issues in end of life treatments for patients with dementia. European Journal of Neurology. 2010; 17: 774‐779.
Deletion of microRNA‐21 exacerbates multiple phenotypes associated with Alzheimer’s disease through the RECK and ADAM10 pathway in a mouse model of Aβ amyloidosis
Authors: Kim Byungwook , Tate Mason , Wijeratne H.R. Sagara , Karahan Hande , Philtjens Stéphanie , Sharify Ahmad Daniel , Al‐Amin Mamun Md , Kim Jungsu 
Published: December 2023

AbstractBackgroundmicroRNAs have emerged as a new class of therapeutic targets that regulate the expression of target genes by binding their 3’‐untranslated regions. Growing evidence suggests that dysregulation of microRNAs may contribute to the onset and/or progression of various diseases. However, the functional and therapeutic implications of microRNA dysregulation in Alzheimer’s disease (AD) remain largely unclear. To gain insight into the roles of microRNAs in AD pathogenesis, we recently performed unbiased microRNA profiling with entorhinal cortices of AD and age‐matched non‐demented subjects. We found that miRNA‐21 (miR‐21) expression was markedly increased in AD patients. In addition, miR‐21 levels were increased in oligomeric amyloid‐beta (Aβ)‐treated neurons, suggesting that miR‐21 induction is directly associated with Aβ pathology. Therefore, we investigated the pathogenic/therapeutic potential of miR‐21 in AD.MethodTo investigate the role of miR‐21 in amyloid pathology in vivo, we crossed APP/PS1 mice with mir‐21−/− mice to generate APP/PS1;mir‐21+/+, APP/PS1;mir‐21+/− and, APP/PS1;mir‐21−/− mice. We evaluated the changes in the pathological features of AD, such as Aβ levels, amyloid plaques, and gliosis in these mice. Moreover, to investigate the effects of miR‐21 deletion on spatial learning and memory functions, we performed the Morris Water Maze (MWM) and Contextual fear conditioning (CFC) tests.ResultDeletion of miR‐21 increased the levels of insoluble and soluble Aβ40 and Aβ42 levels, as well as increased Aβ‐positive and X‐34‐positive plaque deposition in the cortex and hippocampus. CD45‐positive, IBA1‐positive microgliosis, and GFAP‐positive astrogliosis were also increased in the brain of APP/PS1;mir‐21+/− and APP/PS1;mir‐21−/− mice compared to APP/PS1;mir‐21+/+ mice. Mechanistic studies identified RECK as a potential target gene of miR‐21. miR‐21 deficiency upregulated the RECK protein level, leading to the inhibition of ADAM10 activity. This finding was also corroborated by the decrease in the soluble APPα level. Furthermore, we demonstrated that miR‐21 deficiency decreased spatial learning and contextual memory in MWM and CFC tests, respectively in APP/PS1 mice.ConclusionTaken together, our results demonstrated that miR‐21 may regulate multiple AD‐associated pathologies. Therefore, modulation of miR‐21 may represent a novel potential therapeutic strategy for AD.
Association of mild cognitive impairment, dementia and vitamin B12 levels in older adults
Authors: Aguilar‐Navarro Sara Gloria , Gutiérrez Lidia Antonia , Hernandez Maria Duadalupe Palacios , Mimenza Alberto Jose 
Published: December 2023

AbstractBackgroundVitamin B12 deficiency has been associated with the development of multiple pathologies. However, it is still controversial if the deficiency is associated with cognitive impairment. Objective: To determine the association between cognitive performance and the vitamin B12 levels.MethodCross‐sectional study including 241 adults aged 60 or older, treated as an outpatient at a tertiary care hospital, who had serum levels of vitamin B12. Participans underwent a cognitive assessment and assigned to one of three groups: normal cognition (NC), mild cognitive impairment (MCI), and dementia. Vitamin B12 levels were classified in three categories: sufficiency (>400 pg/ml), subclinical deficiency (201‐400 pg/ml), and absolute deficiency (≤200 pg/ml). Univariate and multivariate linear regression analyzes were used to assess the association between cognitive performance and vitamin B12 levelsResultMean age was 81.4 ± 8.0 years and 68% were women. The prevalence of absolute and subclinical B12 deficiency was 17.8% and 39.8%, respectively. Eigthy participants (33%) had MCI and 70 (29%) dementia. Those with MCI and dementia had lower vitamin B12 levels compaired with NC after adjusting for age, sex and education level (p = 0.019).ConclusionThis study suggests a statistically significant association between global cognitive performance and serum levels of vitamin B12 in older adults