bluuebunny/crossref_metadata_2025_split huggingface dataset:
Training and Accompaniment Model for Expanding ADRD Research in LMICs – The Atlantic Fellows for Equity in Brain Health Experience
Authors: Valcour Victor 
Published: December 2023

AbstractBackgroundOften, global health programs are designed to train individuals from low‐ and middle‐income countries (LMICs) with training provided in more resourced regions. Subsequently, the trainees return to their home community with limited additional resources. When research is funded, capacity‐building is rarely prioritized and partnership for core administrative and study management needs is absent. A program of ‘accompaniment’ where programs partner with trainees after their training period is less frequent and could alter the landscape of research capacity building for dementia.MethodsThe Atlantic Fellows for Equity in Brain Health program provides both a one‐year in‐residence learning experience and seeks to accompany fellows as they return to their home community. Resources and activities in the post‐training period include funding for small pilot projects, networking and community building, training in grants management, support for logistic and administrative activities related to grants, partnering with grant and manuscript writing and assistance with data collection and management.ResultsOver seven years, Atlantic Fellows have received 137 Pilots Awards ($25k each) for activities in 41 countries. Many of these awards serve as launching pads for future funding. For example, the Multi‐Partner Consortium for Dementia Research in Latin America (ReDLat) grew out of a Pilot awarded to an Atlantic Fellow from Latin America uniting 14 research centers across six Latin American countries aiming to identify the unique genetic and social determinants of health that drive Alzheimer’s disease and related dementias. Work is underway and includes prominent capacity building activities with more than $12M in committed from global partners. More than 1454 individuals have been enrolled. Eleven Atlantic Fellows are directly involved in the project. Other examples include work in Brazil that has now been transformed into US National Institutes of Health funding. New work is currently launched in East Africa leading to competitive research applications under review.ConclusionsAn intentional model of accompaniment can achieve substantial impact on dementia research in LMICs.
A global approach to the epidemiology of cognitive ageing and dementia: Cohort Studies of Memory in International Consortium (COSMIC)
Authors: Sachdev Perminder S. 
Published: December 2023

AbstractCOSMIC (COhort Studies of Memory in International Consortium) is an international consortium of longitudinal studies of cognitive aging and dementia, currently comprising 57 cohorts from 39 countries across 6 continents, comprising 186,000 participants (49% White, 8% Black, 21% Asian, 20% Hispanic, 2% Other). COSMIC embraces the power of collaboration through horizontal partnerships, with pooled and coordinated analyses after rigorous harmonization to examine ethno‐geographic differences in risk/protective factors and biomarkers, harness data from under‐represented populations, and permit cross‐validation in a field notorious for non‐replicable results. Analyses thus far have demonstrated that the cross‐national variation in prevalence of MCI is lower than generally reported, with commonality of most risk factors. The effect sizes of risk factors do, however, vary in populations, with APOE*4 and diabetes being associated with greater rates of decline in Asian than White populations. High school education is a significant threshold for protection against cognitive decline in later life, especially in Black and Asian populations. Physical activity shows a dose‐dependent relationship with incident dementia, suggesting that older adults should do three to six hours of physical activity per week for maximum cognitive benefits. The range and depth of such findings continues to grow, as is the community of researchers in both high and low‐middle income countries. With its global reach, open sharing of data and diverse network of researchers, COSMIC is creating a truly global epidemiology of dementia that is needed to deal with the world‐wide inequity in research, and meet the ambitious goals of the 2017 World Health Assembly to address the global epidemic of dementia and the hopes of people at risk of dementia everywhere.
Enhancing diversity in global ADRD Research: African Dementia Consortium (AfDC) and the Alzheimer Disease Sequencing Project (ADSP)
Authors: Akinyemi Rufus 
Published: December 2023

AbstractThe World Health Organization (WHO) Dementia Research Blueprint was recently launched with priorities including enhancing greater diversity and inclusivity in dementia research with adequate representation of different geographic, ethnic and regional populations. This aligns with one of the primary goals of the Alzheimer Disease Sequencing Project (ADSP) to develop and provide a rich and diverse dataset of clinical, genomic, and biomarker data that can be analyzed to accelerate our understanding of AD with implications for better prediction and discovering novel precision diagnostics and therapeutics. The increasing population of the elderly in Africa, huge genetic heterogeneity of indigenous African populations and recent findings of ancestry‐ specific protective variants in the region of the APOE ε4 gene in a modest African AD cohort provide a strong rationale to enhance indigenous African involvement in global AD genomic studies. The ADSP is collaborating with the African Dementia Consortium (AfDC) to increase the ADSP’s global resource by including underrepresented participants of African ancestry from both the United States and multiple countries in Africa. The study in Africa involves multiple sites in nine African countries operating under the AfDC. We are identifying and enrolling participants and obtaining DNA and plasma samples for whole genome sequencing and biomarker assays. In addition, socio‐demographic, clinical, and neurocognitive data will be obtained on all participants using protocol‐guided evaluation procedures that have been developed to accommodate different cultures and to support phenotype harmonization, and for joint studies of biological and social risks. This collaboration, and the integrated approach toward data harmonization and management is a prototype for global ascertainment of complex human diseases.
Age‐ and Sex‐ dependent changes in Translocator Protein 18 kDa (TSPO) expression, cellular sources, and association with amyloid‐β plaques in the 5XFAD murine model of Alzheimer’s Disease
Authors: Perez Daniel Andres Martinez , McGlothan Jennifer L. , Guilarte Tomás R 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) is a neurodegenerative disorder that affects cognition, memory, and social abilities with devastating effects on individuals and families. The hallmark AD pathology is the formation of amyloid‐β‐(Aβ)‐plaques and Tau neurofibrillary tangles leading to neurodegeneration. Neuroinflammation, and microglia activation, also play an important role in the initiation and progression of AD, a process that begins earlier than cognitive decline. TSPO is a well‐validated and widely used biomarker of neuroinflammation that is expressed in glial cells, and it is markedly increased in the brain of AD subjects and in AD animal models. Previous studies have not assessed a detailed trajectory of TSPO in the progression of AD. In the present study, we determined the age‐and sex‐dependent increase in brain TSPO levels, cellular sources, and association with Aβ‐plaques in parallel with behavior.MethodBehavioral performance was measured using the Barnes Maze (cognition) in male and female wild‐type (WT) and 5XFAD mice at 3 months (3M), and 7 months (7M). To evaluate pathological endpoints, we measured Aβ‐load (number, size, and % area covered), TSPO quantitative autoradiography using the TSPO‐specific radioligand [3H]‐DPA‐713, and quadruple‐label immunofluorescent confocal imaging to determine the cellular sources of the TSPO response and its association with Aβ‐plaques.ResultAt 3M, we observed no significant differences in behavioral performance between WT and 5XFAD in either sex. At 7M, 5XFAD males showed no cognitive dysfunction, however, there was a significant cognitive impairment in 5XFAD females. We found an increase of Aβ‐plaques in an age‐and sex‐dependent manner. TSPO autoradiography showed a significant increase in TSPO levels in 5XFAD mice in both sexes and ages with a higher increase in females. Furthermore, we show that TSPO expression is colocalized with plaque‐associated microglia and not astrocytes.ConclusionThese results indicate that brain TSPO is an early biomarker of neuroinflammation and TSPO levels increase at the same time that Aβ‐aggregation and much earlier than cognitive decline. Furthermore, the increase in TSPO levels was associated with microglia surrounding or embedded with Aβ‐plaques suggesting a role in plaque formation.
Developing Integer‐based Risk Scores for Predicting the Risk of Incident Cognitive Impairment in Cognitively Normal Older Adults
Authors: Petersen Kellen K. , Nallapu Bhargav Teja , Grober Ellen , Lipton Richard B. , Morris John C. , Hassenstab Jason J. , Gordon Brian A. , Davatzikos Christos , Ezzati Ali 
Published: December 2023

AbstractBackgroundWe aimed to developed integer‐based risk scores for predicting incident cognitive impairment up to 10 years in initially cognitively normal older adults.MethodsParticipants were 479 older adults (aged 60 to 90) from longitudinal studies of aging and Alzheimer’s disease from the Knight ADRC at Washington University in St. Louis. The primary outcome was incident cognitive impairment, defined as conversion from Clinical Dementia Rating (CDR®) 0 to >0. The sample was divided into training (60%) and test (40%) sets. Feature‐sets were formed from combinations of four categories of variables: demographics (D), genetics (G), cognitive measures (C), and biomarkers (B) (Details in Figure 1 legend). Utilizing a modified version of the AutoScore‐Survival algorithm, variables were ranked based on variable importance using reduction in predictive accuracy due to replacement with a random permutation value in combination with Random Survival Forests. Variables were iteratively included in constructing risk score models based on coefficients of Cox regression models.ResultsFive risk score models were developed using five feature‐sets. All models retained age, APOE4 status, free recall from the Free and Cued Selective Reminding Test, hippocampal atrophy, and Tau positivity when included as potential variables in the feature‐sets. The risk score derived from the DGCB model had a Harrell’s concordance index (C‐index) of 0.754 and integrated Area Under the ROC Curve (iAUC) of 0.792. The best performing model without biomarkers used the DGC feature‐set and had a C‐index of 0.694 and iAUC of 0.699 while the risk score using the DG feature‐set only had a C‐index of 0.632 and iAUC of 0.647. Participants who had risk scores in the top quartile of the DGCB model risk score had an increased rate of conversion to CDR > 0.ConclusionsWe developed five risk score models for predicting incident cognitive impairment. Risk scores consisted of different sets of measures which differed in ease‐of‐access and costs. Using such simple risk scores that do not include biomakers as clinical decision support tools is practical in the clinical setting. Including biomarkers in risk scores provides slight improvement to classification accuracy, emphasizing their importance in research settings.
Plasma biomarkers of Alzheimer´s disease in the continuum of dementia with Lewy bodies
Authors: Diaz‐Galvan Patricia , Przybelski Scott A. , Algeciras‐Schimnich Alicia , Lesnick Timothy G. , Schwarz Christopher G. , Senjem Matthew L. , Gunter Jeffrey L. , Jack Clifford R. , Min Paul H , Jain Manoj K. , Miyagawa Toji , Forsberg Leah K. , Fields Julie A. , Savica Rodolfo , Graff‐Radford Jonathan , Ramanan Vijay K , Jones David T. , Botha Hugo , St. Louis Erik K , Knopman David S. , Graff‐Radford Neill R , Ferman Tanis J , Petersen Ronald C. , Lowe Val J. , Boeve Brad F. , Kantarci Kejal 
Published: December 2023

AbstractBackgroundPatients with dementia with Lewy bodies (DLB) may have Alzheimer´s disease (AD) pathology. Plasma biomarkers of beta‐amyloid (Aβ), phosphorylated tau (pTau), and neurodegeneration are sensitive to AD neuropathologic changes in AD dementia. While these plasma biomarkers are well tested in the AD continuum, their performance for concomitant AD pathology in the DLB continuum is still unclear.MethodWe included patients with isolated REM sleep behavior disorder (iRBD; n = 15), with mild cognitive impairment with Lewy bodies (MCI‐LB; n = 37), and with DLB (n = 70) from the Mayo Clinic Alzheimer’s Disease Research Center. Cognitively unimpaired individuals (CU; n = 100) included from the Mayo Clinic Study of Aging were balanced on age and sex. A panel of plasma biomarkers of Aβ40, Aβ42, p‐tau181, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) measures was obtained. We calculated the ratio of plasma Aβ40/42. Lower Aβ40/42 indicates increased Aβ pathology. Plasma Aβ40, Aβ42, GFAP, and NfL were measured using the Simoa® Neurology 4‐Plex E Advantage kit and pTau‐181 was measured with the Simoa® pTau‐181 Advantage V2 kit. Both were run on a Quanterix HD‐X analyzer. AD imaging biomarkers were assessed on PET using Pittsburgh compound B (PiB) for Aβ and 18F‐Flortaucipir for tau.ResultHigher levels of plasma GFAP were observed in the MCI‐LB (p = 0.014) and DLB (p<0.001) groups compared to CU (Figure). DLB patients also showed higher levels of plasma pTau181 (p<0.001) and NfL (p<0.001). Higher amyloid and tau PET standardized uptake value ratio (SUVr) in the DLB continuum were associated with higher levels of plasma p‐tau181, NfL, and GFAP (p<0.001). After accounting for age, plasma Aβ40/42 did not correlate with amyloid or tau PET SUVr.ConclusionIn the DLB continuum, abnormal levels of GFAP in plasma can be detected as early as the prodromal stages of the disease. Plasma pTau181 reached abnormal levels in the DLB stage. Higher plasma GFAP, NfL, and p‐tau181 are associated with higher amyloid and tau PET SUVr in the DLB continuum. Plasma biomarkers have the potential to contribute to screening and early diagnosis in the DLB continuum, which has implications in designing new treatments.
Syzigium aromaticum may protect against paraquat mediated toxicity via p53 and Sestrin2 modulation
Authors: Rai Nitish , Dey Sharmistha 
Published: December 2023

AbstractBackgroundNumerous environmental risk factors, particularly neurotoxins, have been linked to the development of sporadic Parkinson’s disease (PD), even though its exact cause is still unknown. The common spice Syzigium aromaticum has the greatest ORAC (Oxygen Radical Absorbance Capacity) value according to the National Institute on Aging. One of the three components of healthy ageing, vata, is calmed by Syzigium aromaticum while also stimulates nerves. The study investigated the rescue effect of Syzigium aromaticum ethanolic extract against paraquat (PQ) mediated PD type toxicity and elucidated the underlying molecular mechanism using the cell line.MethodThe cold extraction method was used to prepare the Syzigium aromaticum ethanolic extract by powdering, soaking in ethanol and stirring for 72 h. Then the supernatant was gradually aliquoted and filtered with Whatman filter paper no 1. Paraquat, at different doses, was used to generate PD type toxicity in SH‐SY5Y cells for 24, 48, and 72 hours, and MTT test was used to measure the cytotoxicity. The rescue effect was demonstrated by simultaneously treating cells with 100 mM PQ and various doses of Syzigium aromaticum and then performing MTT assay. The protein expression studies was done using western blot technique to elucidate the underlying mechanism.ResultThe toxicity experiment showed that PQ‐treated cells exhibited significant cell death, with the maximal toxicity occurring after 72 hours. However, the cells treated with Syzigium aromaticum were protected from the PQ‐induced cell death. Syzigium aromaticum exhibited rescue effect in proportion to its dose. The western blot analysis of PQ treated SH‐SY5Y cells demonstrated a dose‐dependent increase in the levels of p53, Setrin2, and phosphorylated AMPK (P‐AMPK). The levels of AMPK, mTOR and p70S6K remain unchanged, however, the phosphorylated p70S6K (P‐p70S6K) levels were declined. When cells were simultaneously treated with PQ and increasing dose of Syzigium aromaticum, the levels of p53, Sesn2, and P‐AMPK lowered similar to control. Further, there was an increase in the level of phosphorylated p70S6K (P‐p70S6K) in proportion to the dose of Syzigium aromaticum.ConclusionThe current study showed that the Syzigium aromaticum ethanolic extract prevented PQ‐induced cell death in SH‐SY5Y by targeting p53 and sestrin2.
Prevalence of Dementia in a Diverse Cohort of Adults with Hip Fracture
Authors: Lee David R , Lo Joan C , Chandra Malini , Lee Catherine , Gilsanz Paola 
Published: December 2023

AbstractBackgroundThere is a 2.5‐fold increased risk of hip fracture for persons living with dementia compared to persons without dementia. Independently, the risk of hip fracture and Alzheimer’s Disease and Related Dementias (ADRD) increase with age and vary by sex and race and ethnicity. However, few studies have examined racial and ethnic variations in dementia prevalence among older US adults who experienced a hip fracture.MethodThis retrospective observational cohort study included adult health plan members aged ≥50y in a large Northern California healthcare system during 2000‐2019 who had a hip fracture event during follow‐up to 2021. ADRD diagnosis (ICD‐9/10) was obtained from clinical encounters within 5 years prior to and including the hip fracture hospitalization. Modified log‐Poisson regression models were performed with ADRD as the outcome and race and ethnicity as the primary predictor, adjusting for age and sex. Sensitivity analyses expanded the definition of prevalence of ADRD to include ADRD diagnoses up to 3 months after hip fracture.ResultAmong 46,622 adults with hip fracture (mean age 80.6 ± 9.9y, 69.7% female, 78.8% non‐Hispanic White (NHW) race), ADRD prevalence was 21.0% based on diagnoses prior to and during hip fracture hospitalization, increasing to 24.2% when including diagnoses within 3 months post‐hip fracture. ADRD prevalence was significantly higher in Black (29.2%), Hispanic (22.5%), and Asian (22.0%) adults compared to NHW (20.3%) adults. Expanding the definition found similar observations except no significant differences for Hispanic and Asian adults (see Figure). Adjusting for age and sex, Black (RR = 1.47, 95%CI 1.35‐1.59), Hispanic (RR = 1.15, 95%CI 1.07‐1.24) and Asian adults (RR = 1.12, 95% CI 1.04‐1.21) had greater risk of prevalent ADRD compared to NHW adults. Sensitivity analysis results were similar.ConclusionAt least 1 in 5 adults with hip fracture had diagnosed ADRD, with higher prevalence among racial and ethnic minority populations. Age‐ and sex‐adjusted risk was highest in Black adults and modestly higher in Hispanic and Asian adults. Hip fractures and ADRD are serious public health concerns leading to increased morbidity and mortality, and understanding differences among high risk groups will aid in the development of socially appropriate patient and caregiver interventions.
APOE E4 as a moderator for gait speed and executive function
Authors: Soo See Ann , Sandhu Gurveen Kaur , Zailan Fatin Zahra , Leow Yi Jin , Lee Faith Phemie Hui En , Ghildiyal Smriti , Koh Chen Ling , Kandiah Nagaendran 
Published: December 2023

AbstractBackgroundGait speed has been found to be associated with cognitive function (Liu, 2022) with slower walking speed related to poorer cognition (Hoogendijik, 2020). Slower gait speed was found to be associated with poorer global cognitive function, verbal memory and executive function (Watson, 2010). Additionally, APOE E4 carriers with slow gait speed have been found to perform worse on the MMSE than APOE E4 carriers without slow gait and APOE E4 non‐carriers with slow gait (Sakurai, 2017).We aim to evaluate the moderating effects of APOE E4 status on gait speed and cognition in a pre‐dementia community population in Singapore.MethodWe recruited 534 participants from the community who completed a detailed neuropsychological assessment and APOE genotyping. To test for the moderating effects of APOE E4 with gait speed and cognition, we performed a multiple generalized linear model controlling for covariates of age, sex and education.ResultThe cohort included 186 subjects with subjective cognitive decline and 348 mild cognitive impairment subjects from Dementia Research Centre (Singapore). Mean age of the cohort was 62.55, SD = 9.55, mean education years was 13.97, SD = 3.45 and majority were women (57.1%). The presence of slow gait speed among our cohort was 4.7% and there were 12.6% APOE E4 carriers. There were no significant differences in walking gait between APOE E4 carriers and non‐carriers (p = 0.235). APOE E4 moderated the effect of slow gait speed on executive function. APOE E4 non‐carrier interacted with slow gait speed, resulting in worse performance on the trail making task B (β = 71.97, p = 0.003), digit span backwards (β = ‐2.23, p = 0.037), and colour trails 2 (β = 64.01, p<0.001).ConclusionAPOE E4 status moderates the effect of slow gait speed on executive function. APOE E4 non‐carriers with slow gait speed are at risk for poorer executive function.
Prevalence of dementia screen positive among older adults in rural Kenya: results from a dementia screening program
Authors: Muyela Levi A. , Musyimi Christine W. , Farina Nicolas , Mutunga Elizabeth Kasimu , Masila Joe , Ndetei David 
Published: December 2023

AbstractBackgroundSub‐Saharan African countries have the fastest growing rates of older people, yet little is known about the number of cases of dementia. In Kenya, the little we know about dementia is derived from studies involving the few individuals who receive a diagnosis, but typically in the more advanced stages of the condition when carers have reached a crisis point. Effective and routine data screening is important for the early detection of dementia, but also provides insights into the number of people living with cognitive and functional impairment associated with dementia. We aimed to describe the number of people screening positive for dementia within rural Kenya, and identify factors associated with screening positive.MethodCommunity Health Workers conducted an opportunistic household survey among community‐dwelling residents aged 60 and above in rural Kenya. The brief Community Screening Instrument for Dementia (CSID), which allows for potential cases of dementia to be identified without the need for specialist tools or intensive training was used to identify number of people living with dementia and socio‐demographic information collected. This is an interim analysis of the data.Result672 older adults (M = 71.0 years old; SD = 8.96) were screened for dementia. Participants were predominantly Kamba (n = 664, 98.8%) and from Makueni county (n = 617, 91.8%). 209 people screened positive for dementia (31.1% (95%CIs 27.6 to 34.8). Males (OR = 0.67, 95%CIs 0.52 to 0.87) and people who were literate (OR = 0.51, 95%CIs 0.41 to 0.64) were less likely to screen positive for dementia. Screening positive for dementia was also associated with old age, with the oldest age group (90 years+) being 3.7 times more likely to screen positive for dementia than the youngest group (60‐64 years) (OR = 3.67, 95%CIs 2.54 to 5.37).ConclusionThese findings form the first‐ever dementia screening programme in rural Kenya and highlight the numbers of people living with cognitive and functional impairment, potentially indicating dementia. Although such cases need to be clinically confirmed, these data can support the planning, policy development and inclusion of dementia care within policy discussions.