bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cognitive health disparities and COVID‐19 stress: Evidence from metro‐Detroit
Authors: Ajrouch Kristine J , Brauer Simon , Zahodne Laura B. , Antonucci Toni C 
Published: December 2023

AbstractBackgroundRacial/ethnic minority groups and those with lower socioeconomic status suffer greater prevalence of cognitive health problems. For example, older Black Americans are about twice as likely to develop ADRD as older Whites (Lennon et al., 2022). Rates of ADRD are unknown among Middle Eastern/Arab Americans (MENA). Throughout the COVID‐19 pandemic, racial/ethnic disparities existed such that COVID‐19 prevalence and mortality were greater among Black and MENA populations compared to Whites (Dallo et al., 2022). This paper characterizes COVID‐19 stress prevalence and cognitive health in metro‐Detroit among three racial‐ethnic groups.MethodIn the recently completed U.S.‐based Detroit Area Wellness Network – COVID‐19 Supplement (DAWN‐CS) project (N = 606), participants were recruited from an existing longitudinal cohort study (i.e., Social Relations Study; Antonucci & Akiyama, 1994), supplemented by address‐based and respondent‐driven sampling in order to obtain a racially/ethnically balanced sample of MENA, Black, and White older adults. Eligible persons (aged 65+) within screened households were selected with probability to allow appropriate inference to the target population. Inclusion criteria for DAWN‐CS were: age 65+, fluency in English or Arabic, and identifying as MENA, Black, or White. Psychosocial questionnaires and cognitive measures were administered via telephone. Global cognition was a composite score of episodic memory, language, attention, and working memory tests.ResultMENA older adults reported more COVID‐19 stress and demonstrated lower cognitive health than White older adults, aligning more with profiles observed among Black older adults. The influence of COVID‐19 stress did not vary by race‐ethnicity or predict cognitive health in the whole sample. COVID‐19 stress predicted better cognitive health only for Whites.ConclusionIncluding underrepresented populations in the study of stress and cognitive health advances science and addresses societal health in its entirety. Disaggregating MENA from Whites demonstrates an unrecognized disparity (MENA versus White older adults), and improves estimates of other disparities (Black versus White older adults). The benefit of stress on cognitive health for Whites reflect that stress may have health benefits when experienced in small doses.
12‐month cognitive outcome after acute geriatric TBI not associated with U.S. Military Veteran status
Authors: Kornblith Erica S , Huie Russell , Manly Geoffrey , Mukherjee Pratik , Yaffe Kristine , Tarapore Phiroz , Yuh Esther C. , Gardner Raquel C. 
Published: December 2023

AbstractBackgroundTraumatic brain injury (TBI) increases risk for cognitive decline and Alzheimer’s disease/related dementias (ADRD), and Veterans may be at increased risk of both TBI and cognitive decline due to combat/training related exposures and other risk factors. However, it is unknown whether older Veterans are more likely to experience a poor cognitive outcome after acute TBI compared to civilians.MethodWe examined 112 male Veterans and 320 male civilians (55+) who experienced an acute TBI and enrolled in Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK‐TBI). Data were collected at baseline (i.e., emergency room visit) on demographic and injury characteristics. Cognitive and TBI recovery data (i.e., Rivermead Postconcussive Questionnaire, Brief Symptom Inventory, Satisfaction with Life Scale, and Glascow Outcome Scale‐Extended) were collected at 2 weeks, 6 months, and 12 months. We calculated descriptive statistics and compared across Veterans and civilians. 12‐month cognitive outcome was defined as performance <9th percentile on 2+ cognitive tests, and/or decline from 2‐week or 6‐month score >90% reliable change index on two+ tests. We used propensity weighting to address missing cognitive outcome data and conducted a logistic regression analysis to examine association of Veteran status with classification of cognitive outcome.ResultVeterans were older and less likely to be Hispanic compared to civilians but did not differ on race, education, history of head injury, or injury severity. At 12 months post‐TBI, Veterans endorsed worse mood and satisfaction with life (p’s = 0.05), but these results were attenuated by adjustment for prior TBI and injury severity. In adjusted models Veterans did not differ from civilians on a measure of overall TBI outcome (p = 0.45) or postconcussive symptoms (p = 0.32). Moreover, there was no association between Veteran status and cognitive outcome (Wald chi square = 2.66, p = 0.45).ConclusionRisk of poor cognitive outcome following TBI does not differ between older male Veterans and civilians, and mood and life satisfaction outcomes were worse for Veterans but impacted by injury severity and prior head injury. These findings have implications for understanding risk for cognitive decline and ADRD among older men who experience an acute TBI as well as tailoring care, including provision of psychosocial support, for these patients.
Tau PET accumulation in Brodmann areas 35 and 36 is associated with individual differences in cognition in non‐demented older adults
Authors: Rani Nisha , Alm Kylie H. , Speck Caroline L , Soldan Anja , Pettigrew Corinne , Zhu Yuxin , Albert Marilyn S. , Bakker Arnold 
Published: December 2023

AbstractBackgroundMounting evidence indicates that tau accumulation in the entorhinal cortex (EC) occurs early in the course of Alzheimer’s disease (AD). Recent advances in automated segmentation methods allow for the investigation of smaller regions of the medial temporal lobes (MTL), including subregions of the EC. This study examined tau deposition in relation to individual differences in cognition among older adults, assessing whether MTL subregions explained a greater proportion of variance in cognition, when compared to standard labeling methods.MethodAnalyses included 91 BIOCARD study participants who were cognitively unimpaired (CU; n = 82) or had mild cognitive impairment (MCI; n = 9). Stepwise linear regressions were used to examine the contributions of regional tau burden to individual differences in the CDR sum of boxes (CDR‐SB), MMSE, and composite scores of global cognition and memory. Other model variables included amyloid burden, APOE4 status, sex, and education. Amyloid burden was assessed by 11C‐PiB and regional tau was assessed by 18F‐MK‐6240 PET. SUVR values representing tau accumulation were extracted using two MRI segmentation methods: (1) the FreeSurfer‐derived EC label, and (2) Automatic Segmentation of Hippocampal Subfields (ASHS)‐derived MTL subregions, including the EC and Brodmann areas 35 and 36 (Br35, Br36) defined in 1mm‐MNI space. Partial volume correction was applied to the motion‐corrected PET data.ResultTau burden in the right Br35, right Br36, and age were significant predictors of CDR‐SB scores, with the greatest proportion of variance explained when all three were included. The FreeSurfer‐labeled EC and other variables did not significantly contribute to the model. Right Br36 and age were significant predictors of MMSE while right Br36 and APOE4 status were significant predictors of the global cognition composite score, and right Br36 was a significant predictor of the memory composite score. Follow‐up analyses showed that addition of the FreeSurfer EC region did not significantly contribute to any of the models.ConclusionQuantifying tau burden in Br35 and Br36 better accounted for individual variability in cognition, when compared to standard EC labeling approaches. This suggests tau burden in these subregions may help identify CU and MCI individuals who are on a trajectory of decline due to AD.
Comparison of self‐similarity measures in FDG‐PET images and association with disease progression risk
Authors: Dicks Ellen , Barnard Leland R , Boeve Brad , Botha Hugo , Corriveau‐Lecavalier Nick , Graff‐Radford Jonathan , Gunter Jeffrey L. , Knopman David S. , Lee Jeyeon , Lowe Val J. , Schwarz Christopher G. , Senjem Matthew L. , Jack Clifford R. , Petersen Ronald C. , Jones David T. 
Published: December 2023

AbstractBackgroundDecreased image self‐similarity of repeated FDG‐PET scans has been suggested to indicate increased risk for disease progression. Here, we compared several self‐similarity measures based on conventionally used voxel‐ and ROI‐based approaches and those based on patterns of cortical metabolism.MethodFrom the MCSA/ADRC, we included 376 cognitively unimpaired (CU) individuals and those with a clinical diagnosis of MCI (n = 55) or AD (n = 20) who had two FDG‐PET images within 2‐3 years and clinical follow‐up available. We compared image self‐similarity for three approaches: voxel, ROI and “eigenbrain” (Fig.1). For the voxel approach, FDG‐PET images were normalized to template space, grey matter masked, and intensity normalized to the pons to create standard uptake value ratios (SUVR) for each voxel. From these images, mean SUVR were extracted for 122 ROIs (MCALT‐ADIR122) for the ROI approach. For the “eigenbrain” approach, the SUVR images were transformed to a latent space embedding composed of 253 components (“eigenbrains”) and reflecting metabolism patterns, that was generated in an independent sample of 7008 FDG‐PET images. For each approach, image self‐similarity between baseline and follow‐up values (voxel, ROI or eigenbrain) was determined using three metrics (Pearson correlation, cosine, Euclidean distance). We computed AUC to determine which approach and metric would best discriminate between groups. We used Cox regression analyses to assess whether the metrics could predict disease progression.ResultComparing each distance metric across approaches, AUC was highest in differentiating clinical diagnoses using self‐similarity measures based on eigenbrains, then voxels, then ROIs (e.g., Euclidean distance CU vs AD AUC eigenbrain: 0.86, voxel: 0.75, ROI: 0.71; Fig.1). Across all approaches, Euclidean distance always discriminated best between classes. Eigenbrain‐based Euclidean distance was associated with risk for progression to MCI in CU (HR [95%CI]: 1.25 [1.05, 1.49]), and eigenbrain‐based cosine and Euclidean distances were associated with risk for progression to AD in MCI (1.61 [1.1, 2.34] and 1.53 [1.01, 2.31], respectively), while we found no associations for voxel‐ or ROI‐based distance measures.ConclusionEigenbrain‐based measures outperformed other, more conventional approaches in discriminating clinical diagnoses, and were associated with risk for disease progression. Our results suggest that decreased self‐similarity in metabolism patterns informs on disease stage and prognosis.
Age‐Dependent Changes in Perineuronal Nets and Associated Parvalbumin Interneurons in the 5xFAD Amyloidosis Mouse Model
Authors: Nelson Ruth S , Rangaraju Srikant , Rayaprolu Sruti , Kumar Prateek , Espinosa‐Garcia Claudia , Xiao Hailian 
Published: December 2023

AbstractBackgroundPerineuronal nets (PNNs) are extracellular matrix structures that surround neurons and proximal dendrites and regulate synaptic transmission, plasticity, and several facets of memory. PNNs are commonly associated with parvalbumin‐positive (PV+) fast‐spiking interneurons which are hypothesized to play physiological roles in memory and cognition. Despite a growing literature related to PNNs and PV+ neurons’ roles in synaptic maintenance and memory, much remains unknown regarding how these structures are affected in neurodegenerative diseases such as Alzheimer’s Disease (AD). In this study, we used the 5xFAD amyloidosis mouse model to investigate how AD‐like pathology affects PNNs and PV+ neuronsMethodUsing immunofluorescence microscopy, we stained 5xFAD and Wild Type (WT) mice at 1.8, 3, 6, and 10 months of age. We stained for PV+ neurons (using anti‐PV antibody), PNNs (using a WFA antibody), and for Amyloid‐Beta (Aβ) plaques (using a 4G8 antibody). Images were then processed using ImageJ to quantify the presence of PV+ neurons, PNNs, and the association between them in several regions of interest across genotypes and age groups.ResultWe found that PNNs, but not PV+ neurons, are significantly depleted in the anterior cortex, posterior cortex, and subiculum of the 5XFAD mice in early amyloidosis (3‐6 month old 5XFAD mice). Furthermore, analyses investigating the co‐localization of PNNs and PV+ neurons in these regions found that PNNs were depleted surrounding PV+ neurons in an age‐dependent manner in the 5XFAD mice compared to WT. Specifically, in early amyloidosis (3‐6 months) there was a general depletion of PNNs, but in later amyloidosis (6 ‐10 months) the depletion of PNNs was preferentially surrounding PV+ neurons. Finally, assessing the relationship between Aβ plaque proximity and the co‐localization between PNNs and PV+ neurons revealed that PNNs closer to Aβ plaques were more likely to be associated with PV+ neuronsConclusionCollectively, these findings may indicate the time‐dependent impact of Aβ pathology on PNNs, both in general and specifically surrounding PV+ neurons. Our ongoing studies will further characterize PNN and PV changes across a wider age spectrum.
Combined Digital Clock Drawing Test and Delayed Word Recall and their relationship with PET Amyloid Biomarker Status in Cognitively Unimpaired Older Adults
Authors: Jannati Ali , Thompson Karl , Banks Russell E , Rentz Dorene M. , Johnson Keith A. , Sperling Reisa A. , Gomes‐Osman Joyce Rios , Showalter John , Tobyne Sean , Pascual‐Leone Alvaro 
Published: December 2023

AbstractBackgroundDCTclock™ is an AI‐enabled digital cognitive assessment (DCA) that strongly discriminates between cognitively impaired and unimpaired individuals (receiver operating area under‐the‐curve AUC = 0.89). Among cognitively unimpaired individuals, DCTclock predicts greater PET Aβ burden and shows stronger discrimination (Cohen’s d = 0.76) between Aβ± individuals than the Preclinical Alzheimer’s Cognitive Composite (d = 0.30) (Rentz et al., 2021). The Digital Clock and Recall (DCR™) was recently created by adding 3‐word delayed recall to DCTclock to assess verbal memory impairment – an early hallmark of Alzheimer’s disease. We assessed whether recreating the DCR with the 3‐word delayed recall from the Mini‐Mental State Examination (MMSE) and DCTclock would improve classification of Aβ PET biomarker status among cognitively unimpaired older adults.MethodDCTclock, MMSE (including delayed recall), and Aβ PET imaging data were collected from 159 cognitively unimpaired older adults in the Harvard Aging Brain Study (age = 78.6±5.9; 98 females; MMSE = 28.9±1.4). Logistic regression classifiers were trained to classify Aβ biomarker status and were assessed with standard metrics and AUC as compared to age‐ and MMSE‐only models.ResultThe best‐performing model classified biomarker status among cognitively unimpaired individuals with an AUC of 0.76 (sensitivity = 0.65, specificity = 0.73, accuracy = 0.71)‐outperforming age‐only and total MMSE‐only models (AUCs = 0.61). Recursive feature elimination identified spatial reasoning, average speed, maximum speed on Copy Clock, oscillatory motion on Command Clock, and delayed recall score as key features. DCTclock or recreated DCR summary scores alone classified biomarker status with AUCs of 0.72 and 0.74, respectively.ConclusionThe DCR, which combines DCTclock with delayed verbal recall, may offer a means to classify Aβ biomarker status among cognitively unimpaired individuals in as little as 3 minutes. Classification models trained on a subset of DCR features performed better than all other models, including traditional neuropsychological testing. These results reinforce the potential for DCR solutions to streamline cognitive testing in the clinic and accelerate diagnosis for individuals with early‐stage Alzheimer’s and other dementias. Future work will examine the best possible combination of additional tests to further increase classification accuracy.
Multifaceted approach to minority recruitment for participants in Alzheimer’s Disease research studies
Authors: Boegel Amy R , Wilson Blake , Mendenhall Laura , Newhouse Paul 
Published: December 2023

AbstractBackgroundAlzheimer’s Disease (AD) disproportionately affects Black and Hispanic adults as compared to white adults, yet 75% of those who participate in AD research are white (1,2,3). Without the full participation of under‐represented groups in clinical research studies and trials, researchers will have limited understanding of how potential treatments work in these communities (4,5).MethodThe study used an iterative, mixed methods approach to enhance the recruitment of URGs for AD research studies. These methods involved targeted direct mailing campaigns, advertising in minority specific media outlets (radio and newspaper), and URG‐specific email outreach. Each encounter offered an opportunity to address concerns and educate while also recruiting potential participants into AD research studies.Direct mailings were sent to 15,200 under‐represented people (URPs) within a 25‐mile radius of Vanderbilt University Medical Center (VUMC). The direct mailing contained a letter to the URP and a study brochure. Each mailing was in an envelope containing the official VUMC logo. Two weeks after the direct mailing, weekly emails were sent to URPs from the direct mailing list. If there was no response to the email, a second email was sent 4 weeks later. There was a total of 492 URPs that responded, a return of 3.2%. As the number of URPs reaching out from the direct mailing began to slow, additional URP specific advertisements were conducted in minority specific media outlets (radio and newspaper).ResultPreliminary results have shown that a mixed method approach has been successful in recruiting URGs. From August 2022 to April 2023 (8 months) from the direct mailing campaign, there were 93 URPs prescreened and 38 URPs that completed a screening visit. An additional 29 URPs were prescreened after the minority specific media outlets, and 5 were screened. In comparison, from 2017‐2021, only 18 URPs were prescreened and 6 enrolled into AD research studies.ConclusionOur findings show that, direct mailings campaigns can be a highly effective recruitment tool for URP recruitment into AD research studies. The success of the direct mailing campaign was enhanced by utilizing additional methods of contact with the targeted URPs.
Multilevel Racism and Discrimination and Cognitive Function and/or Cognitive Decline: A Systematic Review
Authors: Moody Danielle L. Beatty , Wright Regina Sims , Waldstein Shari R. , White Kellee , Taylor Antione D. , Maciver Peter , Tchangalova Nedelina , Pantesco Elizabeth J. 
Published: December 2023

AbstractBackgroundBlacks experience the greatest burden of racism and are twice as likely to have Alzheimer’s or other dementias as Whites in addition to higher rates of cognitive decline which acts as an early warning sign for these clinical outcomes (Discrimination in America Report, 2018; Alzheimer’s Disease Facts & Figures, 2023). Examining the levels, types, and forms of racism and discrimination associated with cognitive functioning and decline is essential to clarify mechanistic pathways and aid opportunities for intervening upon racially disparate burdens in cognitive impairment and Alzheimer’s trajectories. This systematic review aimed to establish (a) relations of racism and discrimination to cognitive function and decline, (b) characterize these differences across the levels, types, and forms of racism and discrimination, and (c) detail these linkages across a comprehensive battery of cognitive endpoints, among community‐dwelling, neurologically healthy Black adults aged 18 and older.MethodUsing the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses protocol 2,997 studies were identified from searches in CINAHL, PsycINFO, PubMed, and Web of Science published until April 7, 2023. We included original empirical articles that examined any form of racism and racial discrimination and cognitive functioning or decline across Blacks. These endpoints included Alzheimer’s disease; cognitive change, decline, function, impairment, performance; cognition; delayed recall, dementia; episodic or working memory; recall; neuropsychological performance; executive function; and fluency among others. Two reviewers independently screened full‐text articles.ResultWe will present ongoing results and discuss the current state of knowledge, quality of existing studies, biopsychosocial pathways and gaps in the literature.ConclusionWe will also highlight potentially key next steps.
Characterization of peripheral immune cell populations in stable and progressive Alzheimer’s disease
Authors: Loew Ethan B , Tracy Matthew , McCormick Beth , Haran John P 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) is the most common type of dementia which results in debilitating memory loss as the disease advances. In addition to the amyloid plaques, tau tangles, and neuronal inflammation characteristic of AD, there is strong evidence of dysregulation in the peripheral immune system, including decreased naïve T cells and increased memory T cells among older adults with AD. However, the involvement of the peripheral immune system in the neurodegenerative cascade leading to AD is poorly understood. Furthermore, among older adults with AD, some may experience rapid cognitive decline while others may maintain a stable cognitive status for years. It is currently unknown whether dysfunction in the peripheral immune system is associated with neuronal inflammation and cognitive decline.MethodIn our ongoing work, we are longitudinally characterizing resting peripheral immune system cells by flow cytometry and here present data from a subset of those with AD (n = 19) or no dementia (ND, n = 93) whom we have followed for >1 year.ResultWe have identified an increase in B cells (percent all lymphocytes, AD 6.4 (SD 8.6) vs ND 4.0 (SD 2.4) p = 0.031) and CD4+/CD62L+ naïve T cells (percent CD4+ lymphocytes, AD 33.4 (SD 18.4) vs ND 25.4 (SD 14.1) p = 0.034) among AD patients. Among the population of AD patients experiencing cognitive decline (n = 4) determined by increasing ADAS‐Cog score >6 points over one year compared to stable scores (n = 11), we have discovered a decrease in CD4+/CD62L+ naïve T cells (percent CD4+ lymphocytes, stable 33.9 (SD 14.5) vs declining 20.5 (SD 16.1) p = 0.049), increase in effector memory CD4+ T cells (percent CD4+ lymphocytes, stable 28.2 (SD 4.8) vs declining 47.0 (SD 6.5) p<0.001), and increase in B cells (percent all lymphocytes, stable 2.6 (SD 1.5) vs declining 5.3 (SD 1.8) p = 0.010), when compared to older adults with AD and stable cognitive status.ConclusionThis longitudinal clinical study identifies changes in resting peripheral B and T cell populations in AD patients and among AD patients with cognitive decline.