bluuebunny/crossref_metadata_2025_split huggingface dataset:
Minority Stress, Caregiving Experiences, and Health of Bi+ Informal Caregivers of People with Alzheimer’s Disease and Related Dementias
Authors: Kittle Krystal R. , Cicero Ethan C. , Pelkmans Jordan , Flatt Jason D. , Anderson Joel G 
Published: January 2025

AbstractBackgroundBi+ people, those with non‐monosexual identities (e.g., bisexual, pansexual, sexually fluid) are more likely to experience poor physical and mental health compared with monosexual minority (i.e., gay[G], lesbian[L]) people. These poor health outcomes stem from minority stress related to their sexual minority status (e.g., discrimination, victimization). Due to minority and caregiver stress, LGB+ people providing care to someone with ADRD are more likely to have worse health than their straight counterparts. Little is known about how minority and caregiver stress affect the health of bi+ ADRD caregivers versus monosexual minority ADRD caregivers.MethodCross‐sectional survey data from a non‐probabilistic sample of sexual minority ADRD caregivers (bi+, n = 125; gay/lesbian, n = 161) were used to examine associations between minority stress (discrimination, victimization, microaggressions, perceived stress), caregiver stress (caring for spouse/partner, respite use, distress from care recipient’s neuropsychiatric symptoms, care recipient’s level of independence) on overall self‐rated health and if these associations differed among bi+ and monosexual minority ADRD caregivers. Multivariable regression, adjusting for demographic characteristics, was used to investigate if sexual orientation (bi+ vs. gay/lesbian) moderated the association between minority/caregiver stress variables and health.ResultAll minority stressors and two caregiving stressors (caring for spouse, care recipient’s level of independence) were associated with overall health. In our adjusted model, three variables (lifetime victimization, day‐to‐day discrimination, caring for spouse/partner) moderated the association between sexual orientation and overall health. As lifetime victimization scores increased, bi+ overall health decreased while monosexual minority overall health increased (B = ‐0.56; 95% CI = 1.06,0.05; p = 0.03). Caring for a spouse/partner, protective for both groups (B = 5.11; 95%CI = 3.04,7.17; p<0.001), had a greater effect on health for monosexual minorities (B = ‐4.26; 95% CI = ‐7.49,‐1.03; p<0.001). Higher day‐to‐day discrimination scores predicted worse health for both groups (B = ‐0.61; 95% CI = ‐0.91,‐0.32; p<0.001), but the magnitude was greater for monosexual minorities (B = 0.41; 95% CI = 0.01,0.80; p = 0.044).ConclusionThe effects of lifetime victimization, day‐to‐day discrimination, and caring for one’s spouse/partner on health differ significantly dependent on being bi+ or gay/lesbian. Qualitative inquiries may help illuminate the underlying mechanisms for this phenomenon, informing interventions and policy development aimed at supporting the health and well‐being of bi+ ADRD caregivers.
Relationships between Diabetes, Vitamin D Status, Neuropsychological Functioning, and Hispanic Ethnicity in Older Rural West Texans: A Project FRONTIER Study
Authors: McCready Riley , Morris Claudia , Antwi‐Adjei Philip , Pourghaed Mohammad , Ramirez‐Velandia Felipe , Kopel Jonathan , Culberson John , Ashworth Gabriela , Singer Jonathan , Molinar‐Lopez Veronica , Sabbagh Marwan N. , Neugebauer Volker , Decourt Boris , Lawrence J. Josh 
Published: January 2025

AbstractBackgroundDiabetes, a chronic metabolic disease leading to damage to multiple organs and the nervous system, is associated with cognitive decline. Moreover, Vitamin D (VD) insufficiency/deficiency is implicated as a risk factor for diabetes. However, the specifics of the relationships between these variables remain unclear. Previous studies also have suggested that Hispanic individuals have a higher risk of VD deficiency, diabetes, and cognitive decline. We aimed to determine associations between VD level, diabetes, cognitive functioning, and Hispanic ethnicity (HE) amongst a sample of aging, rural West Texans from Project FRONTIER (PF; Facing Rural Obstacles to Health Care Now Through Intervention, Education, and Research).MethodData were obtained from a cohort of 292 PF participants (mean age 62.6±11.8, 70.5% female, 40.1% HE). We examined relationships between consensus diabetes diagnosis, blood‐based diabetes‐related biomarkers, VD level, Repeatable Assessment for Neuropsychological Status (RBANS) total score, and HE status. Logistic and linear regression analyses were performed on binary and continuous variables, respectively. We utilized Spearman correlation for bivariate comparisons and Mann‐Whitney U tests for between‐group comparisons.ResultRegression analyses indicated significant negative associations between VD and HbA1c (p=0.0004), fasting blood glucose (p=0.0003), and consensus diabetes diagnosis (p=0.0060). Regression analyses also indicated significant negative associations between overall cognitive functioning and HbA1c (p=0.0282) and consensus diabetes diagnosis (p<0.0001). A significant positive correlation emerged between VD levels and overall cognitive functioning score (p=0.0439). HE was associated with significantly lower VD levels (p<0.0001), higher HbA1c (p=0.0003), and higher fasting blood glucose levels (p=0.0011) compared to non‐HE participants. HE was associated with lower overall cognitive functioning scores (p<0.0001), indicating greater cognitive impairment.ConclusionOur results suggest that, in a rural West Texas cohort, HE is associated with lower VD levels, higher levels of diabetic indicators, and greater levels of cognitive impairment. These disparities are important to consider when investigating areas to improve healthcare in West Texas. Further investigation is necessary to elucidate the connection between VD, diabetes, and cognitive decline in minority, rural populations.
Early life factors and dementia risk: A study of adverse childhood experiences and later‐life cognition and behavior
Authors: Mudalige Dinithi M , Guan Dylan X. , Smith Eric E. , Ismail Zahinoor 
Published: January 2025

AbstractBackgroundOf the 12 modifiable dementia risk factors established by the Lancet Commission, only one addresses early life. However, the brain is highly plastic in early life. Adverse childhood experiences (ACE)–physical, emotional, and sexual abuse and neglect–can result in long‐term reductions in brain volume. These alterations increase susceptibility to neurodegenerative diseases like Alzheimer’s disease. We investigated associations between the severity of ACE and cognitive and behavioral risk for dementia, operationalized as later‐life cognitive impairment and mild behavioral impairment (MBI), respectively.MethodData were from the Canadian Platform for Research Online to Investigate Health, Quality of Life, Cognition, Behavior, Function, and Caregiving in Aging (CAN‐PROTECT) study. Measures included the Childhood Trauma Screener (for ACE), neuropsychological tests (objective cognition), Everyday Cognition (ECog)‐II (subjective cognition), and the MBI Checklist (MBI‐C, later‐life behavioral changes). Linear regressions modeled associations between ACE severity and neuropsychological test scores. Multivariable negative binomial regressions (zero‐inflated, if appropriate) modeled associations between ACE severity and ECog‐II and MBI‐C scores. Models adjusted for age, sex, education, and ethnocultural origin. Clinical diagnosis of depression and/or anxiety were explored as covariates and mediators of the observed associations.ResultParticipants (n = 1102) were 64.6 (SD = 7.3) years old; 883 (80.1%) were female, 290 (26.3%) had a bachelor’s degree or equivalent, and 939 (85.2%) were of European origins. Every 1 standard deviation (SD) increase in ACE score was associated with worse performance on Trail Making B (b = 0.10, 95%CI:0.05–0.16), Switching Stroop (b = ‐0.08, 95%CI:‐0.14—0.03), Paired Associates Learning (b = ‐0.08, 95%CI:‐0.13—0.02), and Digit Span (b = ‐0.08, 95%CI:‐0.14—0.02). Every 1 SD increase in ACE score was associated with higher ECog‐II (b = 1.1, 95%CI:1.0‐1.1, p = 0.007) and MBI‐C (b = 1.2, 95%CI:1.1–1.3, p<0.001) scores, not mediated by previous psychiatric history (ECog II p = 0.16; MBI‐C p = 0.13).ConclusionGreater ACE severity predicted more later‐life cognitive and behavioral symptoms, representing higher dementia risk, not mediated by psychiatric history. These findings extend the public health importance of ACE to brain aging and emphasize the importance of incorporating early‐life risk factors into dementia risk assessment. ACE are potential targets for risk reduction and identify persons who should be screened for cognitive and behavioral risk markers.
Which Nursing Homes Received Paycheck Protection Program Funding?
Authors: Coe Norma , Sun Chuxuan , Travers Jasmine , Chen Kevin , Burke Robert , Pogorzelska‐Maziarz Monika , Castle Nicholas , Falvey Jason 
Published: January 2025

AbstractBackgroundNearly 90% of nursing homes in the US experienced severe staffing shortages during COVID‐19, which disproportionately affected over 50% of nursing home residents living with Alzheimer’s Disease and Related Dementia (ADRD). One major federal policy to support the maintenance of staffing levels during the COVID‐19 pandemic was the Paycheck Protection Program (PPP), a $75 billion program that provided loans to small businesses, including nursing homes. Loans were forgivable if at least 60 percent of the loan was spent on payroll providing an incentive to apply resources toward staffing. This paper examines the organizational and staffing characteristics of nursing homes that received PPP loans, including the prevalence of residents living with ADRD and Serious Mental Illness (SMI).MethodWe examine a national cohort of non‐VA nursing homes eligible for PPP funding. We compare those who received a PPP loan to nursing homes that did not receive a PPP loan. PPP loan receipt was captured in the US Small Business Administration (SBA) PPP data from April 2020 to June 2021. We primarily use datasets from 2019 to examine baseline characteristics, including Nursing Home Compare data, the Minimum Dataset (MDS), LTC Focus, and the Payroll‐Based Journal data.Result3,536 nursing homes received a PPP loan in any of the three rounds; 9,943 eligible nursing homes never received a PPP loan.More than 50% of nursing home residents were living with ADRD, and nearly 1 in 3 had a serious mental illness. These rates were slightly higher among facilities receiving PPP loans.Staffing in 2019 was inferior in nursing homes receiving PPP loans than those who did not on all measures: lower‐star ratings on both quality and staffing measures, higher turnover rates at the RN (9.7% vs. 9.0%), LPN (11.2% vs. 10.3%), and CNA levels (11.4% vs. 11.0%). COVID‐19 affected PPP‐receiving nursing homes more in terms of confirmed cases (522 vs. 511), resident deaths (107 vs. 97), and staffing shortages (22% vs. 18%).ConclusionThis first‐ever direct federal funding effort to support nursing home staff during a pandemic appears to have supported the most vulnerable nursing homes.
Elucidation of tRNA‐Derived Fragments in Alzheimer’s Disease: Cell‐Type Implication for New Biomarkers and Regulators
Authors: Rippee‐Brooks Meagan D , Vedder Hannah , Wu Wenzhe , Dong Jianli , Pappolla Miguel A , Fang Xiang , Bao Xiaoyong 
Published: January 2025

AbstractBackgroundAlzheimer’s disease (AD), the most common type of dementia, affects at least twenty‐four million people globally, yet, the causation, mechanisms of progression, and therapeutic strategies remain elusive. Currently, tRNA‐derived RNA fragments (tRFs), a family of recently discovered small non‐coding RNAs (sncRNAs), have surfaced as promising biomarkers for many diseases, including AD. Our work revealed that several AD‐impacted tRFs in human hippocampus, CSF, and serum.MethodHerein, we further characterized the expression of tRFs in AD through elucidating exactly which cell types of the brain contribute to the higher expression of tRFs, using human induced pluripotent stem cells (iPSCs)‐derived cells. We further delve into the identification of tRFs, commonly affected by emerging SARS‐CoV‐2 infection and AD, for a future study on the influence of SARS‐CoV‐2 infection on AD.ResultOur results indicate that neurons derived from AD iPSC have significantly enhanced tRF expression than neurons derived from healthy adult donor. The impacted tRFs include tRFs derived from the 5’‐end of mature tRNA encoding ProAGG (tRF5‐ProAGG), GluCTC (tRF5‐GluCTC), and GlyGCC (tRF5‐GlyGCC). Such a difference did not show in iPSC‐derived astrocytes. Interestingly, among AD‐impacted tRFs in neurons, two of them are also inducible by SARS‐CoV‐2 infection.ConclusiontRF5‐ProAGG, ‐GluCTC, and ‐GlyGCC continue to show the potential as AD biomarkers originating from neurons from within the brain. Commonly impacted tRFs by SARS‐CoV‐2 and AD, combined with our recently published data showing the impact of tRF5 on the regulation of genes important for neuronal functions, implicates SARS‐CoV‐2’s influence on AD.
Persistent functional impairments in cognitively normal older adults and risk of cognitive decline and dementia
Authors: Ghahremani Maryam , Ismail Zahinoor 
Published: January 2025

AbstractBackgroundMaintaining functional independence is an essential aspect of healthy aging. In fact, functional dependence to perform activities of daily living (ADL) is a fundamental part of a dementia diagnosis. Newer diagnostic criteria for MCI also consider functional impairments (FI) but not to the extent of compromising functional independence. Therefore, accurate characterization of FI across the cognitive spectrum could help identify individuals who may be at a greater risk of cognitive decline and dementia, thereby improving treatment strategies. Here, we explored the utility of capturing persistent FI, in contrast to transient FI, to identify a higher‐risk group for cognitive decline and dementia.MethodData from cognitively normal (CN) older adults from the National Alzheimer’s Coordinating Center were analyzed. From the Functional Activities Questionnaire four items were used (assembling tax records, paying bills, shopping alone, and traveling). Persistent FI was operationalized as FI present at more than two‐thirds of all study visits (TTV) prior to cognitive decline and dementia. The two comparator groups either had transient FI not meeting TTV criteria or no FI in advance of cognitive decline and dementia. Kaplan‐Meier survival curves were generated for all FI groups. Cox proportional hazard models compared incidence rates for cognitive decline and dementia across FI groups, adjusted for age, sex, education, race, APOE‐e4 status, and presence of subjective cognitive decline and neuropsychiatric symptoms.ResultsThe CN sample comprised 1,612 Persistent‐FI (age = 77.3±9.7; 61.7% female), 3,195 Transient‐FI (age = 72.9±8.8; 63.7% female), and 7,284 No‐FI participants (age = 69.7±8.4; 66.0% female) (Table 1). Persons with persistent FI had lower survival (p<0.0001) and a 3.89‐fold greater incidence rate for cognitive decline and dementia compared to No‐FI (CI:3.45‐4.38, p<0.001); persons with transient FI had a 2.04‐fold greater incidence rate than No‐FI (CI:1.84‐2.27, p<0.001) (Figure 1).ConclusionsCN older adults with persistent FI had greater incidence of cognitive decline and dementia than transient FI or no FI. Operationalizing FI‐related risk based on the persistence of functional impairments improves the prognostication of cognitive decline and dementia and allows for the identification of individuals who are at a greater risk in the absence of objective cognitive impairments.
Association Between MIND Diet Score and Cortical Thickness in an Aging Population
Authors: Dempsey Desarae A. , Apostolova Liana G. , Brosch Jared R. , Clark David G. , Farlow Martin R. , Mathew Sunu , Unverzagt Frederick , Wang Sophia , Gao Sujuan , Clark Daniel , Saykin Andrew J. , Risacher Shannon L. 
Published: January 2025

AbstractBackgroundThe Mediterranean diet has been associated with decreased brain atrophy (Staubo et al. 2016,Alz&Dem), but the MIND (Mediterranean‐Dietary Approaches to Stop Hypertension (DASH) Intervention for Neurodegenerative Delay) diet, designed for dementia prevention (Morris et al. 2015, Alz&Dem), remains underexplored for its impact on brain atrophy. We investigated the MIND diet’s association with cortical thickness (CT) in the Indiana Alzheimer’s Disease Research Center (IADRC) sample.Methods134 participants (49 CN, 45 SCD, 30 MCI, 10 AD/other) completed a self‐report MIND diet questionnaire at the IADRC, which was coded into high, medium, or low intake groups for each food (5 ‘unhealthy’ food groups were reverse scored) and completed an MRI scan on a 3T scanner. The cortical surface was parcellated using FreeSurfer v6. We selected two regions of interest (ROIs) reflecting AD‐associated neurodegeneration: temporal and global CT. We examined the association of MIND diet scores (0‐15) and food groups with CT using regression models adjusted for age, sex, race, education, and diagnosis.ResultsHigher MIND diet scores were associated with greater mean temporal CT (r = 0.269, p = 0.002) and greater mean global CT (r = 0.230, p = 0.008). In multivariable‐adjusted models, the association persisted for temporal but not global CT. Among the 15 food components, greater olive oil (r = 0.034, p<0.001), fish (r = 0.181, p = 0.040), beans (r = 0.237, p = 0.008), and nuts (r = 0.214, p = 0.014), and reduced fast food intake (r = 0.188, p = 0.035) were significantly associated with temporal CT. These associations, except for nuts, remained significant in multivariable‐adjusted models, with an additional relationship found for chicken (r = 0.189, p = 0.038). Among the 15 food components, greater olive oil (r = 0.243, p = 0.008), and beans (0.180, p = 0.044), and reduced fast food (r = 0.212, p = 0.017) were significantly associated with global CT. Only reduced fast food retained significance in the multivariable‐adjusted models.ConclusionsGreater adherence to the MIND diet was associated with greater CT in both global and temporal regions. Specific components, including increased olive oil, beans, nuts, fish, and reduced fast food, showed significant associations with CT, suggesting elements within the diet driving this association. These findings highlight the potential neuroprotective effects of the MIND diet, emphasizing the importance of dietary patterns in preserving brain health during aging.
Blood‐brain barrier breakdown and abnormal brain microstructure in older adults with COVID‐19‐related cognitive impairment are modified by sex and APOE4
Authors: Reas Emilie T. , Alderson‐Myers Austin T , Solders Seraphina K. , Shen Qian , Wang Xin , Rivera Charlotte S. , Banks Sarah , Graves Jennifer 
Published: January 2025

AbstractBackgroundPersistent neurological symptoms including cognitive impairment can follow SARS‐CoV‐2 infection, a condition termed neurological post‐acute sequelae of COVID‐19 (Neuro‐PASC). Structural brain differences have been observed in individuals with Neuro‐PASC, raising concern that COVID‐19 may promote age‐related neurodegeneration. However, the mechanisms by which COVID‐19 impairs cognition and its impact on brain aging, remain poorly characterized. Blood‐brain barrier (BBB) dysfunction has been observed in Alzheimer’s disease and has been hypothesized to contribute to Neuro‐PASC, implicating potential acceleration of Alzheimer’s disease pathogenesis by COVID‐19. The present study evaluated BBB permeability and brain microstructure among older adults with Neuro‐PASC, along with modification by sex and APOE4, risk factors for Alzheimer’s disease that have also been associated with COVID‐19 outcomes.MethodOlder adults (50‐90 years; 54% women) with (N=16) or without (N=43) Neuro‐PASC underwent neuropsychological testing as well as multi‐shell diffusion MRI and dynamic contrast‐enhanced MRI to measure restriction spectrum imaging (RSI) metrics of brain microstructure and BBB permeability in subcortical, white matter, and gray matter regions of interest. ANCOVA compared cognitive and MRI measures between Neuro‐PASC and healthy controls, and models were repeated assessing interactions with sex or APOE4. Partial correlations examined associations between brain microstructure and BBB permeability. Models were adjusted for age and sex, with further adjustment for education for cognitive scores, and for MRI software for RSI measures.ResultNeuro‐PASC participants had worse episodic memory performance, higher white matter BBB permeability, and lower neurite density and hindered diffusion than controls. APOE4 carriers demonstrated more pronounced PASC‐related cognitive impairment and microstructural abnormalities than non‐carriers. PASC‐related BBB leakage was stronger among men, whereas women showed stronger PASC‐related increases in free water and decreases in restricted diffusion. Among Neuro‐PASC, but not controls, hippocampal BBB permeability correlated with greater hippocampal free water.ConclusionOlder adults with persistent COVID‐19‐related neurological complaints demonstrate objective cognitive impairment accompanied by BBB dysfunction and microstructural brain abnormalities. PASC‐related cognitive decline, BBB breakdown, and microstructural injury differ by sex and are magnified among APOE4 carriers. Longitudinal investigation is warranted to determine whether PASC heightens risk for Alzheimer’s disease by accelerating cerebrovascular and neurodegenerative changes, particularly among high‐risk populations.
Poor sleep is adversely associated with MRI markers of AD‐specific neurodegeneration
Authors: Shi Hui , Archer Derek B. , Perry Arden , Pechman Kimberly R. , Shashikumar Niranjana , Landman Bennett A. , Hohman Timothy J. , Jefferson Angela L. , Full Kelsie M 
Published: January 2025

AbstractBackgroundPoor sleep has emerged as a potentially modifiable risk factor for Alzheimer’s disease (AD) and related dementias (ADRD). Few previous studies have incorporated objectively‐measured sleep and structural neuroimaging to understand if poor sleep relates to changes in brain structure. In a cohort of older adults, we investigated actigraphy‐measured sleep health and associations with well‐established magnetic resonance imaging (MRI) markers of AD‐specific neurodegeneration.MethodParticipants from the Vanderbilt Memory and Aging Project (n=390, Mean age: 69.5± 9.3 year; 47.4% women) wore ActiGraph GT9X accelerometers on their wrist daily for 10 days. Data were processed to estimate sleep regularity, wake after sleep onset (WASO), average awakening length, sleep fragmentation index, sleep timing, and sleep duration. 3T brain MRI was used to quantify hippocampal volume and to estimate the McEvoy AD signature (calculated according to published guidelines). We used cross‐sectional multivariate linear regression to assess the associations between individual sleep measures and neuroimaging markers. Models adjusted for age, sex, race, education, APOE‐ε4 status, cognitive status, sleep medication use, body mass, index, physical activity, depressive symptoms, and cardiovascular risk. For sleep timing and duration, quadratic terms were added in regression models. Models examining the total hippocampal volume also adjusted for intracranial volume.ResultIn the fully adjusted models, we found abnormal sleep duration (β = ‐2.35, 95% CI = ‐4.58, ‐0.11) and greater sleep irregularity (β = ‐0.34, 95% CI = ‐0.62, ‐0.07) were associated with lower AD signature values. Additionally, greater sleep irregularity (β = ‐262.36; 95% CI = ‐451.71, ‐73.00), greater WASO (β = ‐2.76; 95% CI = ‐5.30, ‐0.21) and greater average awakening length (β = ‐74.20; 95% CI = ‐128.47, ‐19.94) were associated with lower hippocampal volumes.ConclusionOur results suggest that several measures of poor sleep, including greater sleep irregularity, wake time, and sleep fragmentation, are cross‐sectionally linked to smaller hippocampal volume and smaller brain volumes in regions most affected by AD neuropathology. Longitudinal studies are needed to clarify if poor sleep contributes to brain atrophy over time.