bluuebunny/crossref_metadata_2025_split huggingface dataset:
Providers’ perceptions of the role played by living alone in providing services to diverse patients with cognitive impairment in the US
Authors: Portacolone Elena 
Published: December 2023

AbstractBackgroundThe potential moderating role of living alone in either facilitating or hampering access to services to older adults with cognitive impairment is largely unknown. Given the estimated 4.3 million older adults from diverse racial/ethnic backgrounds who are living alone with cognitive impairment in the United States, it is critical to understand directly from providers of healthcare and social services whether living alone creates barriers to supportive services for racially/ethnically diverse patients with cognitive impairment. The objective of this study was to identify the potential moderating role of living alone in the use of healthcare and social services for patients with cognitive impairment by eliciting providers’ perceptions of caring for diverse patients with cognitive impairment living alone, in comparison to counterparts living with others.MethodThis qualitative study used semi‐structured interviews conducted between March 2021 and June 2022 with purposively sampled providers of services to diverse patients with cognitive impairment in Michigan, California, and Texas. An inductive content analysis was used to analyze the data.ResultThe majority of the 76 interviewed providers belonged to communities of color and cared for racially/ethnically diverse patients with cognitive impairment. Providers included physicians, nurses, social workers, home care aides, for a total of 20 professions. Providers elucidated specific factors that made serving people living alone with cognitive impairment (PLACI) more challenging, as well as specific factors that increased their concerns when serving PLACI, including a crisis‐dominated healthcare system. Providers also elucidated reasons for systematic unmet needs of PLACI for essential healthcare and social services, such as policies limiting access to home‐care aides.ConclusionThe vast majority of providers underscored the critical, yet understudied, role of living alone in moderating access to essential healthcare and social services among patients with cognitive impairment. Findings suggest that living arrangement are a social determinant to health among patients with cognitive impairment because patients with cognitive impairment who live alone are more likely to experience gaps in services because they are more challenging to serve than counterparts living with others and the healthcare system is not designed to address these challenges.
Testing a Faith‐based Model to Increase Alzheimer’s Disease Knowledge, Detection and Management in a Rural, Racially/Ethnically Diverse Farmworker Community
Authors: Wiese Lisa Ann Kirk , Lingler Jennifer H , Williams Ishan Canty , Schoenberg Nancy E , Williams Christine Lynn , Holt Janet , Galvin James E 
Published: December 2023

AbstractBackgroundRural and racially/ethnically diverse residents face multiple disparities that may increase Alzheimer’s disease and related disorder (ADRD) risk, including less formal education, less access to health care information, delayed disease detection, and challenges with management (Liu et al., 2022). Health‐promoting behaviors may reduce ADRD risk in the presence of these and other factors, e.g., environmental exposures (Peritogiannis et al., 2022; Livingston et al., 2020). We hypothesized that providing ADRD‐related education would increase disease knowledge, cognitive screening behaviors, dementia detection, and diagnosis rates in multiculturally diverse field workers in the Lake Okeechobee region of South Florida.MethodSchoenberg’s (2009) Faith Moves Mountains framework guided this CBPR descriptive, quasi‐experimental study of 241 primarily African American and Afro‐Caribbeans ≥ age 50. Local church congregants were engaged as health educators and research assistants in recruiting, enrolling, surveying, and screening participants. The Basic Knowledge of Alzheimer’s Disease survey (Wiese et al., 2020) and brief Montreal Cognitive Assessment (MiniMoca) (Nasreddine, 2019) were administered at baseline and one year later. Persons scoring below the MiniMoca score cutoff of 12 were referred to providers for further assessment and potential diagnosis/treatment.ResultPositive screen rates were 45.6% at Time 1 and 51.2% at Time 2. Lower pretest BKAD scores [β = ‐0.14, t = ‐3.02, p = .002] and lower years of education [β = ‐0.07, t = ‐1.81, p = .04] were associated with higher referrals. Longer duration of rural residence [β = 0.02, t = 3.09, p = .001], and ethnicity predicted referrals: African American [β = 0.62, t = 3.48, p<.001] or Afro Caribbean [β = 1.04, t = 1.81, p = .04]. Self‐report by participants on follow‐up by the health educators revealed new ADRD diagnoses primarily among African American (47.2%), Afro‐Caribbean (36.1%), White (13.9%) rural residents; Hispanics comprised 2.8%. Rates of new treatments by ethnicity were similar (Table 1).ConclusionExtending Schoenberg’s successful “Faith Moves Mountains” approach beyond the Appalachian setting and chronic illnesses of cancer (2009), smoking cessation (2016), and diabetes (2017) was effective for increasing ADRD knowledge, detection, and management in a unique non‐White rural community. A larger, randomized controlled trial is needed to test if ADRD education among varied faith‐based settings increases health‐seeking behaviors among rural residents experiencing health inequities due to social and medical determinants of health.
Rural childhood residence, college education, and late‐life brain health
Authors: Peterson Rachel , George Kristen M , Maillard Pauline , Gilsanz Paola , Soh Yenee , Lor Yi , Corrada María M. M. , Decarli Charles , Barnes Lisa L. , Whitmer Rachel A. 
Published: December 2023

AbstractBackgroundRural communities tend to have higher prevalence of dementia risk factors including cardiovascular diseases and low education. Childhood rural residence has also been associated with worse late life cognition.1 It is unknown if these associations extend to neuroimaging markers of late life brain health.MethodKHANDLE and STAR are harmonized cohorts of racially/ethnically diverse long‐term Kaiser Permanente Northern California members. Regional brain volumes and white matter integrity were measured among a 25% random sample using 3T MRI. Stabilized inverse probability weights were estimated to account for imaging selection based on study, race/ethnicity, baseline age, sex/gender, and geographic region of birth. Rural residence was self‐reported using birth address or imputed from addresses at age 5 (n = 8) or age 10 (n = 1) when missing. MRI measures, except free water fraction and fractional anisotropy, were normalized on intracranial volume. All MRI measures were z standardized. Weighted general linear models tested associations between childhood rurality and MRI measures among those ages 65+. Exploratory models stratified analyses by college degree attainment.ResultCompared to the overall cohort, the imaging sample was slightly younger, had slightly higher educational attainment and was comprised of more males. Imaging participants with a rural childhood were about 1 year older (mean = 76, SD 6.0) and had about ½ year less education (mean = 14.5, SD = 2.4) than the imaging sample overall (Table 1). In weighted linear models (Table 2), childhood rurality was associated with smaller occipital cortex volumes (β = ‐0.25 95% CI = ‐0.50, ‐0.004). In models stratified by education, we observed a non‐significant trend of worse brain health among participants who were college‐educated with rural childhoods (vs. college educated without rural childhoods), that was not present among those without a college degree (Table 3).ConclusionWe observed limited effect of childhood rurality on MRI markers of brain health. Although under‐powered, our analyses suggest that among college educated older adults rural childhoods (vs. non‐rural) may have a negative impact on brain health.Reference:1. Peterson, et. al., (In press: 2023). Rural residence across the lifecourse and late‐life cognitive decline in KHANDLE: A causal inference study. Alzheimer’s and Dementia: Diagnosis, Assessment and Disease Monitoring. https://doi.org/10.1002/dad2.12399
APOE4 Carrier Status Modifies Alzheimer’s Disease Plasma Biomarker Concentrations in Healthy Adults Over 85 Years Old
Authors: Cooper Jennifer G , Ghodsi Mohammad , Stukas Sophie K , Leach Stephen , Brooks‐Wilson Angela , Wellington Cheryl L 
Published: December 2023

AbstractBackgroundMany blood‐based biomarkers have been thoroughly investigated in the context of Alzheimer’s disease (AD) and other dementias. However, few studies have examined these biomarkers in healthy seniors in the absence of dementia or other age associated morbidities. Investigating biomarkers in a healthy geriatric population allows for the identification of novel biological associations that might otherwise be masked by presence of disease. This study will investigate the effect of APOE genotype on plasma biomarkers of AD to determine whether carrying the APOE4 allele, which increases risk of AD, modifies biomarker concentrations in healthy seniors. Plasma biomarkers analyzed include: amyloid beta 42/40 (Aβ42/40), phosphorylated tau‐181 (p‐tau‐181), neurofilament light (NF‐L), and glial fibrillary acidic protein (GFAP).Methods370 plasma specimens from the Super Seniors study, which enrolled participants ≥85 years old who have never been diagnosed dementia, cancer, diabetes, cardiovascular or major pulmonary disease; were used. Biomarkers were analysed on the Quanterix Simoa HD‐X analyzer using commercial Neurology 4‐plex E and p‐tau‐181 assays. Group comparisons were performed using a Mann‐Whitney test for continuous variables and a Fisher’s exact test for categorical variables. The association between APOE genotype and biomarker concentration was analyzed using multivariable linear regression.Results80 (22%) participants were APOE4 carriers (E3E4 N = 71, E4E4 N = 3, E2E4 N = 6) and 290 (73%) were non‐carriers (E2E2 N = 3, E2E3 N = 58, E3E3 N = 229). No significant differences were found between APOE4 carriers and non‐carriers in age (p = 0.3215), sex (p>0.9999), or mini mental state exam scores (p = 0.1327). In APOE4 carriers, Aβ42/40 is lower (0.0596 vs 0.0618 pg/ml, p = 0.0462), and p‐tau‐181 (3.24 vs 2.78 pg/ml, p = 0.0069) and GFAP (196 vs 172 pg/ml, p = 0.0474) are higher than in non‐APOE4 carriers. NF‐L had no significant difference between carrier status (p = 0.1188). After adjusting for age and sex, p‐tau‐181 remains significantly associated with APOE4 carrier status (β = 0.066, p = 0.0112), while Aβ42/40 and GFAP no longer have significant associations.Conclusionsp‐tau‐181 concentration is associated with APOE4 genotype in healthy seniors, making it an important variable to account for in future analysis.
Astrocyte transcriptomic changes along the spatiotemporal progression of Alzheimer’s disease
Authors: Serrano‐Pozo Alberto , Li Zhaozhi , Woodbury Maya E. , Muñoz‐Castro Clara , Wachter Astrid , Jayakumar Rojashree , Bryant Annie G , Noori Ayush , Welikovitch Lindsay A. , Hu Miwei , Lin Gen , Pastika Timothy , Tamm Joseph A. , Abdourahman Aicha , Kwon Taekyung , Bennett Rachel E , Talanian Robert V. , Biber Knut , Karran Eric H , Hyman Bradley T. , Das Sudeshna 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) is defined by widespread accumulation of Ab plaques and phospho‐tau neurofibrillary tangles throughout the brain, with the latter following a stereotypical hierarchical spatiotemporal pattern along neural networks. These AD neuropathological changes are accompanied by a dramatic loss of synapses and neurons as well as prominent morphological and functional changes of astrocytes, collectively termed reactive astrogliosis. Astrocytes also play a critical role in maintaining brain homeostasis. However, their changes along the spatiotemporal progression of AD neuropathology remain largely unknown. To investigate these astrocyte changes, we performed single‐nucleus RNA‐sequencing on 5 brain regions along the stereotypical progression of AD neuropathology from 32 donors representing the entire normal aging‐severe AD spectrum.MethodNuclei were isolated from five brain areas of n = 32 donors with increasing AD neuropathology (total n = 160 samples). The five brain areas were chosen based on their hierarchical accumulation of tau pathology: entorhinal cortex (EC)> inferior temporal gyrus (BA20) > dorsolateral prefrontal cortex (BA46) > secondary visual cortex (V2 or BA18/19) > primary visual cortex (V1 or BA17). To enrich in astrocytic nuclei, NEUN+ and OLIG2+ nuclei were separated via FACS, whereas NEUN‐/OLIG2‐ nuclei (including astrocytes) were subjected to snRNA‐seq resulting in a transcriptomic dataset of 629,755 astrocyte nuclei, which were subsequently examined for common and region‐specific AD related changes.ResultWe discovered temporal gene‐expression‐trajectories with gene sets differentially activated at various disease stages. Surprisingly, a gene set enriched in proteostasis (genes encoding heat shock proteins) and energy metabolism (e.g., ATP synthases) was upregulated at late‐stage but unexpectedly returned to baseline levels at end‐stage, suggesting exhaustion of response in “burnt‐out” astrocytes. The spatial gene‐expression‐trajectories revealed that genes related to tripartite synapses (e.g., GLUL, GRIA2, NRXN1, SLC1A2) are dysregulated in parallel to the stereotypical progression of tangle pathology across regions. In addition, we identified substantial astrocyte heterogeneity across brain regions with a continuum from homeostatic to reactive cells through “intermediate” transitional states.ConclusionOur astrocyte snRNA‐seq dataset encompassing five regions of control and AD brains revealed distinct spatial and temporal gene trajectories, suggesting complex astrocytic dysfunction with AD progression.
ADNI4’s novel remote screening approach ‐ weighing priorities in participant selection
Authors: Miller Melanie Jayne , Weiner Michael S. W. , Nosheny Rachel L , Albala Bruce , Mindt Monica Rivera , Okonkwo Ozioma , Aisen Paul S. S , Petersen Ron , Shaw Leslie M. , Beckett Laurel , Harvey Danielle J. , Fristed Emil 
Published: December 2023

AbstractBackgroundThe Alzheimer’s Disease Neuroimaging Initiative (ADNI) is a longitudinal observational study of individuals across the dementia spectrum that validates biomarkers for clinical trials. The newest phase of the study, ADNI4, aims to substantially increase the inclusion of underrepresented populations to improve generalizability of ADNI results. Novel biomarkers, including a speech‐based cognitive assessment and blood‐based plasma biomarkers, are integrated into the study design as key participant screening measures.MethodTo help achieve recruitment goals, ADNI4 uses a new, multi‐phase approach to remotely enroll and screen participants. A large study cohort (aiming for 20,000+ participants) provide initial screening data via an online study platform including demographics, medical history related to study exclusionary criteria, and results from a speech‐based cognitive memory assessment (Novoic Ltd. Storyteller test) and a measure of subjective cognitive/functional decline (Everyday Cognition (ECog) 12‐item). Based on screening results, a subset of online study participants is referred to a Quest Diagnostics location to provide a blood sample for plasma biomarker analysis (aiming for 4,000+ participants). Finally, select participants are referred to ADNI clinical sites for in‐depth characterization (goal of up to 1,500 in‐clinic participants).ResultWe report ADNI’s initial approach for selecting participants from the online screening cohort to undergo plasma biomarker phenotyping, and subsequent selection to a clinical site. Participants from diverse demographic backgrounds (especially for race, ethnicity, and/or education) and those with a higher estimated likelihood of cognitive impairment are given priority in the referral selection process. Likelihood of cognitive impairment is assessed using results from subjective memory complaint questions, responses to the ECog 12‐item questionnaire, and the Novoic Storyteller results. Individuals with results showing high concordance across these measures are prioritized, as well as those who have subsequent plasma results indicating biomarker positivity.ConclusionWeighing the various study requirements and inclusivity goals increases the complexity of participant selection decision making, and is a time‐intensive process. As the ADNI study progresses we aim to automate the participant selection/referral process by developing algorithms that account and encode for changing study prioritizations and dynamics across numerous dimensions. Learnings from ADNI4’s new remote processes will help inform future clinical trial design.
CAN‐THUMBS UP: Recruitment in the Virtual Era
Authors: Nygaard Haakon B. , Slack Penelope , Feldman Howard H. , Chertkow Howard , Belleville Sylvie , Montero‐Odasso Manuel , Anderson Nicole D. , Bennett Daniel , Borrie Michael , Chan Senny , Jarrett Pamela , Lee Ashley , Lupo Jody‐Lynn , Matthews Genevieve , McGibbon Chris A , Revta Carolyn , Robillard Julie M. , Shadyab Alexandre , Shajan Sheetal 
Published: December 2023

AbstractBackgroundThe Brain Health Support Program (BHSP) of the CAN‐Thumbs Up Study is an online, interactive educational intervention designed to increase dementia literacy, self‐efficacy and address modifiable lifestyle risk factors. Recruiting for a virtual study presented both opportunities and challenges. This included the need to attract participants through means beyond referrals from medical clinics, as well as opportunities to reach geographically diverse Canadian population less feasible with in‐person evaluations.MethodsA comprehensive recruitment strategy for a virtual environment was implemented. A central website provided any interested candidate with study information, and a link to register and provide basic demographic information via a secure form. Potential participants were directed to the website via traditional recruitment through CCNA specialty clinics or existing cohorts, through geotargeting mailing to specific target populations throughout Canada, social medial advertising, partner organizations, and a coordinated National press release.ResultsThe study had an 8‐month open recruitment window. During this time 964 participants agreed to be contacted through our online portal. Of these, 18‐81 were consented to enroll in the study per month. A total of 7,569 geotargeted postcards were sent, with 153 individuals agreeing to be contacted for the study (2%). Social media advertising generated 974 clicks, with 6.8% subsequently agreeing to be contacted for more information. The majority of participants enrolled in the study came from existing clinical cohorts, CCNA clinical sites, and partner organizations. The recruitment cohort was from a diverse geographical location, 45% urban, 35% suburban, and 20% rural. Overall, the target cohort of 350 subjects was successfully enrolled by the end of the recruitment period.ConclusionRecruitment for the BHSP intervention demonstrates the value of relatively underutilized clinical trials recruitment strategies, such as geotargeted mailing, and social media advertising. We also show the value of a centralized web site for initial screening of interested participants. While traditional recruitment methods still directed the majority of participants to the recruitment website, geotargeted mailing, social advertising, partner organizations, and earned media can all be scaled up, and will likely play a major role in future recruitments efforts in the broader CAN‐Thumbs Up Study.
Olfaction and cognitive performance in early‐stage Parkinson’s disease
Authors: Serrano‐Rubio Luis Humberto , Young Vanessa M. , Velarde Angel G. , Gaona Carlos A. , Ramirez‐Castaneda Juan , Horn Sarah , Coss Pablo , Vaou Okeanis E. , Saklad Amy R. , Shipp Eric L. , Seshadri Sudha , Gonzalez David A. , Gonzales Mitzi M. 
Published: December 2023

AbstractBackgroundParkinson’s disease (PD) is a neurodegenerative disorder affecting 1% of the global population. While the core clinical symptoms of PD are bradykinesia, rigidity, and tremor, it is also often accompanied by non‐motor symptoms that reduce quality of life and increase health care costs. Of the non‐motor symptoms in PD, hyposmia is one of the most prevalent and often precedes clinical diagnosis by several years. In addition, hyposmia has been associated with accelerated disease progression. As individuals with PD are at elevated risk for dementia, the goal of this pilot study was to objectively evaluate the association between smell sensitivity and cognition in early‐stage PD.MethodParticipants with a clinical diagnosis of PD completed cognitive assessments of verbal and visual learning and memory, processing speed, attention, and executive function. Smell sensitivity was assessed using the University of Pennsylvania Smell Identification Test (UPSIT). Associations between cognitive performance and smell sensitivity were evaluated using partial correlations adjusting for age and education.ResultNineteen participants (mean age 69.4+7.9, 25% female) with early‐stage Parkinson’s disease (Hoehn and Yahr stage 1‐2) and free of dementia completed the UPSIT and cognitive assessments (see table 1 for sample characteristics). The average UPSIT score was 5.84+2.12 points and ranged from 2 to 10. Diminished olfactory sensitivity, assessed by the total correct score on the UPSIT, was associated with poorer visual learning (Brief Visual Memory Test Revised (BVMT‐R) immediate recall: r = 0.564, p = 0.18, Figure 1) and memory (BVMT‐R delayed recall: r = 0.610, p = 0.009, Figure 2).ConclusionIn the early‐stages of PD, diminished smell sensitivity was associated with poorer visual learning and memory, domains preferentially affected by the disease. The findings suggest that olfactory dysfunction may be a biomarker of cognitive decline. Larger, longitudinal studies will be important for evaluating the utility of olfactory function as a predictor of dementia risk in PD.