bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring effect of known Alzheimer disease genetic loci in the Peruvian population
Authors: Cornejo‐Olivas Mario , Rajabli Farid , Kushch Nicholas A. , Mena Pedro Ramon , Illanes‐Manrique Maryenela , Adams Larry D. , Whitehead Patrice L. , Hamilton‐Nelson Kara L. , Milla‐Neyra Karina , Marca Victoria , Sarapura‐Castro Elison , Manrique‐Enciso Carla , Mejía Koni K. , Isasi Rosario , Castro‐Suarez Sheila , Araujo‐Aliaga Ismael , Custodio Nilton , Montesinos Rosa , Griswold Anthony J. , Dalgard Clifton L. , Beecham Gary W. , Cuccaro Michael L. , Vance Jeffery M. , Pericak‐Vance Margaret A. 
Published: December 2022

AbstractBackgroundNative American populations are substantially underrepresented in Alzheimer disease (AD) genetic studies. The Peruvian (PE) population with up to ∼80 of Amerindian ancestry (AI) provides a unique opportunity to assess the role of AI ancestry in AD. We performed whole‐genome sequencing in PE case‐control study to assess the effect of the known AD loci in PE population.MethodsWhole‐genome sequencing was performed in 96 AD cases and 145 unrelated cognitive healthy controls from PE population. We calculated the global ancestry (principal components) using the EIGENSTRAT approach. We tested 21 AD lead variants from the recent large non‐Hispanic White (NHW) GWAS of AD (Kunkle et al. 2019). We performed association analyses using logistic regression model with accounting for age, gender, and population substructure (first three principal components). We used Bonferroni approach for multiple test correction.ResultsLogistic regression analysis confirmed association of APOE with AD (rs429358, OR=3.6, CI:1.9‐7.0; pv &lt; 8.4e‐05) in PE population. CLU loci (rs9331896, pv=9.3e‐04) passed the significance threshold after Bonferroni multiple test correction. Two AD loci demonstrated nominal associations (pv<0.05), which were EPHA1 (rs10808026, pv = 0.028), and FERMT1 (rs17125924, pv=0.022) loci.ConclusionOur results showed that known AD APOE and CLU loci are significantly associated with AD in PE population. Some of the genes demonstrated suggestive associations, but further analysis with a larger sample size is on‐going to determine if these reflect true associations.
Feasibility of community‐based remote, biometric data collection in persons with Alzheimer’s disease and behavioral symptoms
Authors: Rhodus Elizabeth K. , Kryscio Richard J , Barber Justin M , Burhan Amer M. , Jicha Gregory A 
Published: December 2022

AbstractBackgroundAging at home with Alzheimer’s disease (AD) is progressively difficult due to cognitive dysfunction interfering with persons’ functional activity and behavioral regulation. Community‐based collection of biometric data via wearable devices provide an innovative approach as a measure of behavioral symptomology. This study analyzes feasibility of remote, biometric data collection during a non‐pharmacological, home‐based randomized controlled trial of older adults with AD.MethodsIndividuals, aged 65 or older, with diagnosis of AD as primary dementia type and behavioral symptoms who resided in the community were included in this prospective study. ActiGraphs were mailed to care partners who implemented device use and management. Feasibility was assessed via accepting and wearing of the device by the person with AD through care partner facilitation at baseline and post‐intervention (continuous wear for 6 days at both time points). Baseline actigraphy data (mean motor activity; MMA) were assessed to determine utility of acceptance/wearing the device as means to collect biometric data. Secondary analyses assessed Pearson correlation of demographic information including cognition measured by the Montreal Cognitive Assessment and the Neuropsychiatric Inventory‐Questionnaire (NPI‐Q).ResultsTwenty‐one participants with AD engaged in the study. Eighteen participants completed baseline data collection (three caregivers refused the device on behalf of person with AD). Fourteen participants or 66.7% (95% CI: 46.6% to 86.8%) also completed post‐intervention data collection (one dropout in mid‐study and three care partners refused the device at second time point). Baseline MMA data were measured: 24‐hour MMA = 608,913; daytime MMA = 253,534; evening MMA = 308,113; nighttime MMA = 47,079. Age (x̄ = 77.8±1.7; r = ‐.56, p‐value = 0.038) was negatively correlated and cognitive impairment (x̄ = 11.13±2.3; r = .789, p‐value = 0.002) was positively correlated with 24‐hour MMA. NPI‐Q total and emotional items (agitation, anxiety, liability) were not correlated in this sample.ConclusionCommunity‐based biometric data collection for older adults with AD and behavioral symptoms is feasible. Behavioral disturbance and care burden likely lowered acceptability of the device. Future power calculations anticipating 66% compliance maybe sufficient for primary outcome analyses in community‐based data collection. Additional studies are needed to validate wearable devices as a primary outcome measure for behavioral symptoms in community‐based participants as this study was not sufficiently powered for such analyses.
Admixed ancestral composition with Amerindian predominance at the Peruvian Alzheimer Disease Initiative (PeADI)
Authors: Cubas‐Montecino Diana , Rajabli Farid , Illanes‐Manrique Maryenela , Kushch Nicholas A. , Mena Pedro Ramon , Whitehead Patrice L. , Hamilton‐Nelson Kara L. , Milla‐Neyra Karina , Marca Victoria , Sarapura‐Castro Elison , Manrique‐Enciso Carla , Mejía Koni K. , Isasi Rosario , Castro‐Suarez Sheila , Araujo‐Aliaga Ismael , Custodio Nilton , Montesinos Rosa , Griswold Anthony J. , Dalgard Clifton L. , Beecham Gary W. , Cuccaro Michael L. , Vance Jeffery M. , Cornejo‐Olivas Mario , Pericak‐Vance Margaret A. 
Published: December 2022

AbstractBackgroundCurrent genetic studies for AD and other dementias are making efforts to incorporate underrepresented populations including admixed Latinos. Peruvian population is characterized by admixed ancestry with a significant Amerindian component, which varies according to specific regions across Peru. The Peruvian Alzheimer Disease initiative (PeADI) was developed to ascertain a cohort for AD and other related dementias for genetic studies in Peru. We aim to determine the patterns of continental ancestry by regions across Peru.MethodsOver the last 3 years, The PeADI study has recruited 212 unrelated cognitive participants through collaborative health centers and community outreach ascertainment strategies. Cases were assessed by neurologists following NINDS‐ADRDA criteria. Controls were screened using MMSE, Clock drawing test and Pfeffer functional activities questionnaire. Genome‐wide genotyping was performed by Illumina screening array. PC‐AiR and model‐based. The cohort was divided into five regions (Northern, Southern, Lima, Central Highlands, and Amazonian) based on place of birth of the participant or the ancient known ancestor.ResultsThe global Admixture analysis showed that Peruvians have a substantial Amerindian component (63.6%), followed by European (35.9%), African (2.5%) and East Asian (2.1%) components. When analyzed by regions, we found that the Central region concentrates the highest Amerindian ancestry (72.7%), followed by the Northern region (58.2%), Lima and Callao (57%), the Amazonian region (55.6%), and the Southern region (55.1%). The highest European ancestry is located in the Amazonian region (42.1%), while the Central region has the lowest (26.6%). African and East Asian ancestry has little influence in Peru, being the Northern with the higher African component (4.1%), and Lima and Callao the region with the higher East Asian component (3.5%). There is no significant for Amerindian component across five regions (p=0.054); however, Central highlands region has higher Amerindian component compared to Lima (p=0.005), the Northern (p=0.005) and Southern(p=0.017) regions.ConclusionOur results confirmed the ancestry admixture of the Peruvian population with predominance of the Amerindian component. The Central region concentrates the highest Amerindian ancestry compared with other regions across Peru.
A Multi‐domain Lifestyle Intervention does not Improve Health and Cognitive Outcomes Among APOE e4 Carriers after 4‐months
Authors: Gills Joshua L. , Jones Megan , Campitelli Anthony , Paulson Sally , Madero Erica N. , Myers Jennifer Rae , Bryk Kelsey Nicole , Glenn Jordan M. , Gray Michelle 
Published: December 2022

AbstractBackgroundAlzheimer’s Disease (AD) currently affects 24 million individuals worldwide, this rate is expected to triple by 2050. The greatest genetic risk for AD is apolipoprotein E (ApoE; e4 allele carriers), e4 carriers typically exhibit abnormal regulation of lipoprotein metabolism. It is important to understand whether multi‐domain lifestyle interventions can mitigate cognitive decline and improve overall health in ApoEe4 carriers. Thus far, the data are mixed due to sample sizes and methodological limitations. Therefore, the purpose of this present investigation is to determine if a digital multi‐domain intervention (MDI) can improve health and cognitive outcomes in cognitively at‐risk e4 carriers over 4 months.MethodAdults 45‐75 years old participated in this present investigation, each participant was randomly assigned to a health coaching intervention group (HC; n=61 non‐carriers; n=24 e4 carriers) or health education control group (HE; n=62 non‐carriers; n=20 e4 carriers). Participants completed weight, height, venous blood draw, a digital memory and associative learning test during baseline and 4‐month follow‐up visits. A 2 (time) x 2 (group) x 2 (APOE) factorial‐ANOVA was utilized to examine differences in the dependent variables (body mass index (BMI), cholesterol, triglycerides, memory, learning). Age, sex, and education were accounted for.ResultTriglycerides significantly increased among HC e4carriers compared to HC non‐carriers (p=.009). BMI significantly increased among carriers regardless of intervention group compared to non‐carriers (p< .001). Cholesterol values showed a decreasing trend among HC non‐carriers, HE carriers, and non‐carriers compared to no change among HC carriers (p=.118). At both time points, e4 carriers in HE and HC exhibited significantly lower scores on memory tasks compared to non‐carriers (p=.020). HC non‐carriers saw a significant increase in associative learning scores, HC e4carriers and HE group (e4 carriers and non‐carriers) showed decreases in an associative learning task (p=.016).ConclusionHC e4 carriers are unresponsive to a MDI lifestyle intervention compared to non‐carriers after 4‐months. These findings could be due to ApoE essential role in circulation lipoprotein metabolism and key role in regulation of cholesterol impacting synaptic function maintenance; e4 allele carriers usually demonstrate higher dysfunction. Follow‐up analyses are required to substantiate current preliminary findings.
Elevation of membralin can improve the cognitive decline in 5xFAD mice
Authors: Jiang LuLin , Myers Stephanie , Shah Palak , Huang Huijie , Huang Timothy , Kaufman Randal J. 
Published: December 2022

AbstractBackgroundAlzheimer’s Disease (AD) is the most prominent neurodegenerative dementia in the aging human population, with pathological hallmarks that include deposition of extracellular β‐amyloid (Aβ) plaques and intracellular neurofibrillary tangles (NFTs). Aging is one of the largest risk factors for developing AD. Disturbed protein homeostasis is associated with the aging process. However, the cell‐type‐specific contribution of disturbed protein homeostasis to the aging process and AD progression is unclear. Our previous works identified a novel Endoplasmic‐Reticulum‐Associated Degradation (ERAD) component, membralin/TMEM259, which can mediate the turnover of nicastrin protein, consequently affect gamma‐secretase complex formation and activity. Knockdown membralin in an AD mouse model (TgCRND8) exaggerated beta‐amyloid‐associated neuronal damage. Moreover, selective deletion of membralin in astrocytes decreased excitatory amino acid transporter 2 (EAAT2) expression and induced neuroinflammation. Therefore, we hypothesized that elevation of membralin would improve beta‐amyloid‐associated cognitive decline and alleviate neuroinflammation.MethodTo investigate this, we generated a transgenic mouse line carrying the membralin gene, which expression was driven by a Prion promoter, and crossed this mouse line with 5XFAD mice. We performed behavioral studies using the Barnes Maze, Morris Water Maze, and Fear Conditioning tests on the 6‐month‐old animals. Biochemical and pathological analyses were used to determine the load of beta‐amyloid accumulation and neuroinflammation phenotype.ResultElevation of membralin improved spatial learning and memory in 5xFAD mice. Abeta 42 and Abeta 40 levels significantly reversely correlated with the membralin protein level. The abeta plaques appeared to be compact, and there were more microglia associated with the abeta plaques in the membralin transgenic animals crossed with the 5xFAD animals.ConclusionOverall, this suggests that elevation of membralin improves beta‐amyloid‐associated cognitive decline. And this could be partially from the effects of membralin in regulating neuroinflammation. Modulation of glial ER homeostasis could be a promising target to regulate neuroinflammation for AD therapy.
Strategies for diverse participant recruitment to a preclinical Alzheimer’s Disease prevention trial: The AHEAD study
Authors: Molina‐Henry Doris P. , Grill Joshua , Sperling Reisa A. , Aisen Paul , Clanton Taylor , Devins Theresa , Dhadda Shobha , Glover Crystal M , Irizarry Michael C , Johnson Keith A. , Kirn Dylan , Kramer Lynn D , Shum Leona K , Zhou Jin , Raman Rema 
Published: December 2022

AbstractBackgroundImproving the demographic diversity of clinical trial participants, including preclinical Alzheimer’s disease (AD) trial participants, is a scientific, social, and ethical imperative.MethodThe AHEAD Study is an ongoing preclinical AD trial evaluating the efficacy of lecanemab (BAN2401) in biological and cognitive disease progression in cognitively unimpaired biomarker eligible individuals ages 55‐80. The study has an overall goal of at least 15% randomizations from underrepresented populations. The AHEAD Recruitment and Retention Workgroup designed a comprehensive and collaborative recruitment plan tailored to increase diverse participation.ResultRecruitment strategies spanned central infrastructure and national initiatives, existing trial ready cohorts, enhanced site engagement, community outreach, and whenever possible, implementation of evidence‐based tactics. Central infrastructure includes a national call center, a study website with capacity for prescreening and site referral, including priority flags for underrepresented groups at the pre‐screener level; establishment of a website dedicated to Spanish speakers; and implementation of blood‐based screening across all sites and targeted communities. Site engagement approaches include disbursement of specialized funding to support local recruitment efforts tailored to diverse populations and the development of partnerships with community organizations or across sites within a region. Outreach activities, at the national, regional, and local level, include earned media and social media campaigns and award‐winning plays and videos surrounding themes of participation of diverse groups in clinical trials. Throughout, additional funding opportunities enable testing of innovative approaches and novel partnerships for recruitment of underrepresented groups at individual sites. Evaluation and additional support of these initiatives will be based on number of underrepresented participants pre‐screened, screened, and randomized in the study.ConclusionFocused, multipronged approaches and sustainable partnerships with demographically diverse communities are required to promote the participation of underrepresented groups into preclinical AD trials like AHEAD. Our initiatives demonstrate the commitment to increase recruitment of underrepresented groups by supporting successful efforts centrally, at the site‐level and the participant level using a combination of traditional and modern recruitment approaches.
Impact of the COVID‐19 Pandemic on Dementia Caregivers in the South US
Authors: Starks Takiyah D. , Lloyd Shawnta' , Caban‐Holt Allison M , Clark Jarrel , Byrd Goldie S. 
Published: December 2022

AbstractBackgroundCompared to their non‐caregiving peers, caregivers of persons with dementia (PWD) endure higher psychological distress, social isolation and increased morbidity and disability. Stress and isolation experienced by caregivers during the COVID‐19 pandemic have added to caregiver burden and worsened health. The objective of this study was to obtain a greater understanding of the health and needs of informal caregivers of PWD during the COVID‐19 pandemic.MethodUsing a cross‐sectional questionnaire, we attained demographic data, characteristics of caregiving during the COVID‐19 pandemic, mental health status, COVID‐19 testing and illness, and protective measures taken to prevent infection with COVID‐19 among caregivers of PWD. From March 2021 to August 2021, respondents were recruited through the Maya Angelou Center for Health Equity’s Alzheimer’s disease (AD) registry. Descriptive statistics (frequency and proportions) of demographic, caregiving, health, and COVID‐19 related data for caregivers of PWD was conducted using SAS® software version 9.4.ResultA total of 274 caregivers of PWD participated in the study. More than half of caregivers were women (56.57%), and approximately 73% of caregivers were married. The racial composition of the majority of caregivers included African American (44.16%), Non‐Hispanic White (26.64%), and Native American (20.44%). Most caregivers were providing care for parents (59.86%) or a partner (21.17%). Nearly 46% of caregivers reported experiencing stress, but not being burnt out. Almost 47% of caregivers reported high psychological distress during the COVID‐19 pandemic. In addition to caregiving stressors due to the COVID‐19 pandemic, caregivers also experienced behavioral changes in their household; more than half of caregivers experienced increased interpersonal conflict with loved ones, friends, or co‐workers. The top 3 needs reported during the COVID‐19 pandemic included support with caregiving, medical care, and food.ConclusionApproximately half of caregivers of PWD experienced stress and psychological distress during the COVID‐19 pandemic. In addition to the stress of caregiving, caregivers lacked support for necessary medical services and social needs. The data collected from caregivers during the COVID‐19 pandemic will be used to develop recommendations to support informal caregivers during emergency situations.
Prevalence of neuropsychiatric symptoms is greater in early‐ than late‐onset Alzheimer’s disease
Authors: Polsinelli Angelina J , Salazaar Krystal , Lane Kathleen A. , Gao Sujuan , Apostolova Liana G. 
Published: December 2022

AbstractBackgroundNeuropsychiatric symptoms (NPS) present early in the disease course of Alzheimer’s disease (AD), increase in severity over time, and significantly affect patient and family quality of life. However, less clear is whether NPS may be more prevalent in early‐onset AD (EOAD) compared to late‐onset AD (LOAD).MethodData were obtained from the National Alzheimer’s Coordinating Center database. Baseline data from two groups – those with AD and those with a CDR of 0 at all visits (i.e., cognitively unimpaired [CU]) – were used for this analysis. Baseline was defined as the first time the individual was diagnosed with impaired cognition (AD) or the first evaluation (CU). Participants who completed the Neuropsychiatric Inventory Questionnaire were included. Participants who had additional neurological, systemic, psychiatric, or medical disease that could have significantly contributed to cognitive impairment were excluded. The AD group was divided into EOAD (< 65) or LOAD (≥65). The CU group was divided into early CU (< 65) or late CU (≥65) groups by age at evaluation.Multiple logistic regression models were run for each NPS to examine its association with symptom onset (early or late), AD vs. CU, and onset*ADvsCU. All models were adjusted for sex, education, and disease severity (CDR‐SB). To explore the potential for medications to mask group differences, exploratory models were also run for each NPI symptom adjusting for psychotropic medication use.ResultEOAD had higher rates of NPS than LOAD in almost all symptom categories (Figure 1). EOAD had significantly higher rates of elation, nighttime behavior and appetite/eating problems than LOAD relative to their CU age groups (p< 0.05). Younger age (age < 65) was associated with significantly higher prevalence of depression, anxiety, irritability, apathy, agitation, motor disturbance, and disinhibition (Table 1). Including medication use in these models did not change significance of results except for agitation (Table 1).ConclusionEOAD is associated with greater NPS burden than LOAD, and psychotropic medication use does not mitigate this association. Greater NPS load may significantly increase caregiver burden in this group. Future explorations will compare the association between disease progression and NPS severity in EOAD and LOAD.
Prevalence of Dementia and Mild Cognitive Impairment in the United States: Findings from the Health and Retirement Study (HRS) Harmonized Cognitive Assessment Protocol (HCAP) Project
Authors: Manly Jennifer J , Jones Richard N , Langa Kenneth M , Ryan Lindsay H , Levine Deborah A , McCammon Ryan , Heeringa Steven G , Weir David R 
Published: December 2022

AbstractBackgroundNationally representative data are critical for understanding the causes, costs and consequences of dementia and MCI in the US and can better inform policies aimed at reducing their impact on patients, families, and public programs. Because research on dementia is often based on highly selected samples of older adults who are disproportionately White, college‐educated, and high‐income, the nationally representative Health and Retirement Study (HRS) has become an essential resource for US population‐level information on dementia prevalence and incidence. However, the original HRS substudy providing dementia diagnostic information was fielded more than 20 years ago. We developed the Harmonized Cognitive Assessment Protocol (HCAP) to provide national estimates of the prevalence of MCI and dementia in the US and to examine differences by age, race and ethnicity, and gender.MethodA random sample of 3,496 HRS participants age 65+ completed a comprehensive neuropsychological test battery and a standard informant interview. Dementia and MCI were classified using an algorithm based on standard diagnostic criteria and comparing test performance to a robust normative sample. National prevalence was estimated using population weights.ResultA total of 393 (9.8%) individuals [mean (SD) age, 82.3 (7.4); 243 women (62%) and 150 men (38%)] were classified as having dementia, and 804 (22%) individuals were classified as having MCI [mean (SD) age, 76.8 (7.8) years, 243 women (62%) and 150 men (38%)]. People with dementia and MCI were more likely to be older, had fewer years of school, and were more likely to be non‐Hispanic Black or Hispanic than non‐Hispanic White. No differences in prevalence were found between women and men.ConclusionUsing a comprehensive, harmonized neuropsychological test battery and large substudy sample to derive national estimates, we found the prevalence of dementia and MCI among people age 65 and older was similar to that of other Western countries. Cognitive impairment is common among older adults, and shows significant patterning along racial, ethnic, and socioeconomic lines. Updated dementia prevalence estimates for the United States from 2016 show that the disproportionate burden of dementia and MCI among Black and Hispanic older adults and people with lower educational attainment persists.