bluuebunny/crossref_metadata_2025_split huggingface dataset:
What patients and caregivers do with knowledge of Alzheimer’s disease CSF test results: Findings from the IMPACT‐AD BC study
Authors: Patel Khushbu Jayeshkumar , Yang David , Chambers Colleen , Feldman Howard H. , Hsiung Ging‐Yuek Robin , Nygaard Haakon B. , Best John R. , Dwosh Emily , Robillard Julie M. , DeMarco Mari L. 
Published: December 2022

AbstractBackgroundThe growing clinical use of the analysis of CSF amyloid‐beta peptides and tau proteins to assist in the diagnosis Alzheimer’s disease (AD) highlights an urgent need to understand the impact of this testing on patients, as well as their care partners. We aimed to address this knowledge gap by examining the perspectives of patients who underwent CSF AD biomarker testing as part of routine care, and a family member (‘care partner’).MethodWithin the ‘Investigating the Impact of Alzheimer’s Disease Diagnostics in British Columbia’ (IMPACT‐AD BC) study (NCT05002699), we conducted semi‐structured telephone interviews with patients that meet the appropriate use criteria for AD CSF biomarker testing and separate interviews with their care partner. A subset of patients (n=33) and care partners (n=31) were interviewed post‐CSF biomarker disclosure and again ∼5 months (median: 4.9 [4.2‐5.3]) after the initial interview. Thematic content analysis was performed to understand the impact of AD biomarker testing on health behaviors, financial and care planning decisions, and resources and support needs.ResultMost patients (94%) rated their decision to undergo testing as “easy”, with the remainder noting the decision was neither easy nor difficult. After result disclosure, a few patients (8%) reported feelings of concern, but the majority (80%) reported overall positive feelings from having more information about their brain health, certainty around their diagnosis, and the ability to plan ahead. Regarding actions patients planned to take after learning their test result, many expressed an intention to adopt or continue with healthy behaviors, such as exercise (42%). From the care partners’ perspective, many expressed relief at having more diagnostic certainty post‐disclosure, and that this information would help them plan for future care needs. Post‐disclosure, care partners also relayed an increased awareness of future caregiving responsibilities and the need or desire to connect with community resources to help navigate this new role. Additional analyses investigated responses based on patients’ amyloid status and disease severity.ConclusionIn summary, individuals undergoing AD CSF biomarker testing and their care partners found that CSF testing provided the information needed to help them make wellbeing decisions and plan their future.
Differential impact of APOE genetic variants on autosomal dominant‐ and sporadic‐ Alzheimer disease
Authors: McKay Nicole S. , Hobbs Diana A. , Doering Stephanie , Campbell Connor C. , Kwak Iris , Mei Bochun , Keefe Sarah J. , Flores Shaney , Hornbeck Russ C. , Chen Gengsheng , Renton Alan E. , Cruchaga Carlos , Bateman Randall J. , McDade Eric , Hassenstab Jason J. , Morris John C. , Gordon Brian A. , Benzinger Tammie L.S. ,   the Dominantly Inherited Alzheimer Network
Published: December 2022

AbstractBackgroundVariants in the apolipoprotein E (APOE) gene represent the greatest genetic risk factor for Alzheimer disease (AD). Carriers of the ε4 allele have an increased risk of developing AD pathology and a lower age of symptom onset. While prior work has focused on the sporadic form of AD, little is known about how the ε4 allele impacts AD‐specific pathology in autosomal dominant AD (ADAD).Method430 participants from the Charles and Joanne F. Knight Alzheimer Disease Research Center and 276 ADAD mutation‐carriers from the Dominantly Inherited Alzheimer Network, were included in these analyses. Participants were classified as ε4‐positive or ‐negative, and further grouped using Clinical Dementia Rating® (CDR®) scores as cognitively impaired or –unimpaired (Table 1). All participants completed magnetic resonance imaging (MRI), beta‐amyloid positron emission tomography (Ab‐PET), and cognitive testing within a 12‐month period.ResultUsing regression models, we replicated prior work demonstrating that the ε4 allele is associated with an increase in AD pathology measured by Ab‐PET and MRI in a sporadic AD cohort. Furthermore, the ε4 allele was also associated with a decline in cognitive performance. Follow‐up pairwise comparisons revealed that within the sporadic‐AD cohort, the influence of the ε4 allele was most pronounced in individuals who were cognitively impaired. In contrast, in a cohort of individuals possessing autosomal dominant mutations, the ε4 allele was not associated with increases in pathology measured by Ab‐PET and MRI, nor was it associated with a decrease in cognition (Table 1; Figure 1).ConclusionWe present quantitative evidence that the APOE‐ ε4 allele differentially impacts the pathology and cognitive outcomes of sporadic‐ and autosomal dominant AD. In those with sporadic AD, possession of at least one copy of the ε4 allele is associated with increased amyloid deposition and cortical thinning, as well as decreased cognition, particularly in individuals who are cognitively impaired. However, in ADAD mutation‐carriers, these same patterns are not evident. We propose that this is due to the overwhelming influence of the autosomal dominant genetic mutations that drive this unique and rare form of AD.
Childhood perceived financial status, current financial concerns, and late‐life cognition: Study of Healthy Aging in African Americans (STAR)
Authors: Gilsanz Paola , Soh Yenee , Malladi Pallavi , Barnes Lisa L. , Peterson Rachel L. , George Kristen M. , Mungas Dan M. , Whitmer Rachel A. 
Published: December 2022

AbstractBackgroundLow socioeconomic status in childhood has been associated with worse late‐life cognition. However, few studies have examined the association between perceived childhood financial status on late‐life cognition in this population.Method764 participants of the Study of Healthy Aging in African Americans (STAR), a cohort of Black Americans aged 50+ (mean age 62) reported their childhood financial status (response options: pretty well off (henceforth above average), about average (henceforth average) varied, or poor) and frequency of current financial concerns (coded as always/often, sometimes, never). Baseline executive function, semantic memory, and verbal episodic memory were assessed through the Spanish and English Neuropsychological Assessment Scales. Linear regression models estimated the associations of childhood financial status and current financial concerns with domain‐specific scores adjusting for age, sex, and education. Sensitivity analyses concurrently included childhood financial status and current financial concerns.ResultAmong participants, 68% were female, 28% reported poor childhood financial status, and 12% reported “always” or “often” having current financial concerns (Table 1). Compared to individuals reporting above average childhood finances, sematic memory scores were lower among those reporting average (β = ‐0.16; 95% CI: ‐0.32, 0.001; Figure 2), varied (β = ‐0.34; 95% CI: ‐0.61, ‐0.07), or poor childhood financial status (β = ‐0.20; 95% CI: ‐0.37, ‐0.03). There were no differences in executive function scores or verbal episodic memory scores by childhood financial status (Figures 1 and 3). Frequency of current financial concern was not associated with executive function, semantic memory, nor verbal episodic memory scores (Figures 1‐3). The association between childhood financial status and semantic memory scores persisted when additionally adjusted for frequency of current financial concerns. There were no associations between childhood financial status and current financial concerns with executive function or verbal episodic memory scores.ConclusionChildhood financial status was associated with lower semantic memory test performance, even after accounting for current financial concerns. Future studies including direct measurement of brain health (e.g. brain imaging) are needed to better illuminate associations between childhood socioeconomic status with late‐life brain health.
Dementia Spousal Caregiving
Authors: Johnson Florence U , Robinson‐Lane Sheria G , Veliz Philip 
Published: December 2022

AbstractIntroductionDementia family caregiving has been linked to depression, anxiety, insomnia, and other negative mental health symptoms, particularly among spousal caregivers who are most likely to have higher levels of caregiving hours. Further, depressive symptoms often present differently based on caregiver race and ethnicity. This study aimed to examine the association between spousal caregiving hours and self‐reported depressive symptoms as well as identify any racial/ethnic disparities in depression self‐reporting.MethodData was drawn from Wave 9 (2008) of the Health and Retirement Study and included 10,120 participants. Linear regression was used to evaluate the relationships between caregiving hours and depression symptoms. Further, a negative binomial model was used to test whether race/ ethnicity moderated the relationship between caregiving hours and self‐reported depressive symptoms.ResultsAs expected, self‐reported depressive symptoms increased as caregiving hours increased (1.65, SD = 2.02, p <0.01). Among the racial and ethnic groups evaluated, Latinx participants experienced the highest levels of depressive symptoms relative to caregiving hours.DiscussionDementia affects families. Care and consideration of the family are as important as the care of the individual affected by a dementia‐related diagnosis. Depression is a serious anticipated mental health outcome linked to dementia family caregiving responsibilities. As such, there is a need for increased culturally responsive professional screening and treatment for depression among family caregivers. Relatedly, primary care providers play an important role in identifying patients serving as family caregivers and offering necessary supports and referrals.
Altered Affect and Increased CLIP+ B cells in the Meningeal Lymphatics of 5xFAD mice are mitigated by antagonizing MHCII‐associated invariant chain (CLIP)
Authors: Iannucci Jaclyn , Beevers Samantha , Tobin Richard , Newell‐Rogers M. Karen , Shapiro Lee A. 
Published: December 2022

AbstractBackgroundDepression often occurs prior to Alzheimer’s disease (AD) and both depression and AD have been linked to immune mechanisms. A key role for activated B cells in AD pathogenesis was recently identified. The study found that B cell depletion reduced Aβ plaque accumulation, neuroinflammation, and behavioral deficits in three AD transgenic mouse models. Our work has shown that treatment with a peptide antagonist for Major histocompatibility complex class II (MHCII) invariant peptide (CLIP), a key component in the transition between innate and adaptive immunity, results in selective depletion of pro‐inflammatory, CLIP+ve B cells and neuroprotection. We hypothesized that selective depletion of CLIP+ve B cells in the 5xFAD model of AD would reduce depression‐associated behavioral deficits.Method11‐week‐old male WT and 5xFAD mice underwent social interaction and burrowing pre‐testing. 12‐week‐old mice were treated once with a competitive antagonist peptide (CAP) or vehicle, followed by social interaction and burrowing testing once a month for 5 months. 6 months post‐treatment, meningeal lymphatics were collected, stained, and analyzed flow cytometrically for markers of B cells (CD19), T cells (CD3), and CLIP.ResultAffective alterations were observed in 5xFAD mice as early as 11 weeks of age and persisted up to 9 months of age. CAP treatment in 5xFAD mice protected against an age‐associated decline in social interaction. At 9 months of age 5xFAD mice were found to have significantly more B cells and CLIP+ve B cells in the meningeal lymphatics when compared to age‐matched WT, and CLIP+ve B cells were significantly decreased by a single CAP injection at 3 months of age.ConclusionA key function of B cells is their role as antigen presenting cells (APCs). CLIP occupies the MHCII antigen binding groove until it is displaced by antigen to be presented to CD4+ T cells, marking the transition between an innate and an adaptive immune response. Our findings suggest that 5xFAD mice exhibit depression‐associated behavior by 11 weeks of age, that CLIP+ve cells are elevated in 5xFAD mice, and that antagonizing CLIP depletes these B cells and functionally protects mice genetically predisposed to AD.
Sexually‐dimorphic effects of C3aR1 disruption in a mouse model of Alzheimer’s disease
Authors: Quipildor Gabriela E. Farias , Audrain Mickael , Gandy Sam , Ehrlich Michelle E. , Salton Stephen 
Published: December 2022

AbstractBackgroundThe complement system can act as part of the innate immune system as well as the adaptive immune system. Complement activation in the brain has been shown to play a role in neurogenesis, synaptic pruning and plasticity. It has also been specifically involved in microglial function, since our group has previously shown that when the complement component 3a receptor 1 (C3aR1) is disrupted in mice, phagocytosis by primary microglia cells is impaired as compared to WT microglia. Therefore, it is hypothesized that complement might have neuroprotective effects early in life but neurotoxic effects later in life or within a disease context, such as during Alzheimer’s disease (AD) impeding to effectively clear hallmarks of the disease.MethodWe performed bulk RNA sequencing (RNAseq) analysis from cortex tissue of 8mo old male and female wild‐type, C3aR1 knock‐out (KO), 5xFAD and 5xFAD‐C3aR1 KO mice. We also performed Barnes Maze on these mice to assess spatial learning and memory, as well as biochemical assays to measure several AD markers.ResultData obtained from RNAseq analysis has shown a sexually‐dimorphic trend in various differentially‐expressed genes (DEGs). For instance, when comparing 5xFAD‐C3aR1 KO with 5xFAD mice, male mice show downregulated DEGs in axon guidance and calcium signaling pathways according to KEGG pathway terms, but this is not seen in females. Similarly, barnes maze has shown sexually‐dimorphic differences, with 5xFAD‐C3aR1 KO male mice showing improve memory and learning when compared to 5xFAD mice, and no differences are seen in female mice.ConclusionInterestingly, other studies in humans have shown increased complement proteins in the cerebrospinal fluid of men, compared to women, showing the importance of studying the complement system in both males and females. Assessing these sexually‐dimorphic differences in this AD mouse model is also important, given that generally not only female mice present more aggressive phenotypes of AD, but also AD in humans is more prevalent in women.
Characteristics and quantitative impact of off‐target skull binding in tau PET studies of Alzheimer disease
Authors: Flores Shaney , Chen Charles D. , Su Yi , Dincer Aylin , Keefe Sarah J. , Perez‐Carrillo Gloria Guzman , Hornbeck Russ C. , Goyal Manu S. , Vlassenko Andrei G. , Schwarz Sally , Nickels Michael L. , Wong Dean F , Tu Zhude , McConathy Jonathan , Morris John C. , Benzinger Tammie L.S. , Gordon Brian A. 
Published: December 2022

AbstractBackgroundBinding of 18F‐Flortaucipir (FTP) has qualitatively been noted in the skull. We investigate the characteristics of this off‐target signal, as well as its impact on regional PET analyses.MethodFTP tau PET, 18F‐Florbetapir (FBP) amyloid PET, head CT, and T1‐weighted MR images were acquired for 313 cognitively unimpaired and impaired older participants. A subset (n=152) also received a 11C‐PiB PET scan. Another subset (n=14) received longitudinal FTP scans. MR images were segmented into ROIs using FreeSurfer and a skull ROI for each participant was defined from the head CT after removing non‐skull bone and tissue. Standard uptake value ratios (SUVRs) were calculated for all ROIs. Skull binding was correlated across FTP, FBP, and PiB to determine if binding is radioisotope specific. Longitudinal persistence of FTP skull signal was tested in the subset with longitudinal data. Finally, participants were grouped by amyloid positivity based on FBP and linear models controlling for age and sex predicted regional non‐partial volume corrected (non‐PVC) and PVC SUVR from skull SUVR to assess the regional impact of skull signal.ResultFTP skull binding was significantly correlated with both FBP (ρ=0.48, p<0.001, Figure 1A) and PiB (ρ=0.34, p<0.001, Figure 1B), suggesting the binding is not due to tracer defluorination. In the longitudinal subset, baseline SUVR was significantly correlated with follow‐up SUVR (Figure 2). Higher skull SUVR resulted in erroneously elevated regional SUVRs for areas in the frontal, parietal, and temporal lobes in amyloid negative individuals. After applying PVC, only medial temporal, inferior parietal, and lateral occipital continued to show significant positive relationships with skull SUVR (Figure 3). Decreased skull bone density was significantly related to higher skull SUVR in women but not men (see Figure 4).ConclusionSkull signal from FTP is a stable, subject‐specific phenomenon that can persist across longitudinal visits and tracers. This off‐target signal can potentially bias quantitative PET measurements in AD tauopathy regions in amyloid negative but not positive individuals even after PVC is applied. The bone binding was overwhelmingly driven by women, suggesting at least some proportion of previously observed sex effects may be driven by bone uptake.
Not sexy enough: the uphill battle faced by non‐traditional treatments in the U.S. despite having the most compelling AD results to date
Authors: Hendrix Suzanne B. , Nicodemus‐Johnson Jessie , Hogan Nathaniel J. , Knowlton Newman , Hennessey Sean , Dickson Samuel P. 
Published: December 2022

AbstractBackgroundThe most followed investigational treatments for Alzheimer’s disease are small molecules (80/140 in development, 57%) and immunotherapies (32/140, 23%). These treatments have a clear regulatory path and are based on innovative scientific approaches that are generally patentable and marketable. The remaining 20% (28/140) of therapeutic approaches involve procedures, devices, supplements, combination treatments and others.MethodA literature review was performed for all interventions in phase 2 or later as listed on Alzforum.org for any stage of Alzheimer’s disease. Results were considered against the standard of the most progressive aspects of disease by either combining ADAS‐cog, ADCS‐ADL and a global outcome (CDR‐sb, CIBIC or CGIC) or assessing a progression composite such as ADCOMS. This was to ensure comparable results across studies and relevance to disease progression. The percent slowing versus placebo was compared.ResultOf the studies investigated, Souvenaid (mild cognitive impairment (MCI)) and AMBAR (mild‐to‐moderate) demonstrated the most compelling AD results to date. The Souvenaid results demonstrated a 36% slowing of progression over 24 months in MCI due to AD (ADCOMS). The AMBAR results (active vs control) demonstrated 59% slowing of progression over 14 months in Mild‐to‐Moderate AD (ADAS‐cog, ADCS‐ADL, and CDR‐sb+CGIC). Neither of these treatments have major side effects.ConclusionRegulatory approval increases visibility and availability of effective treatment to those suffering from AD. Unfortunately, no clear approval path is available for either of these promising treatments. If Souvenaid becomes available in the U.S., it will be considered one of many general supplements for cognitive health, despite the strong clinical trial data collected to a regulatory standard. Plasmapheresis is a procedure that is not subject to FDA regulation. The AMBAR treatment is available for other indications, and most plasmapheresis treatments are approved by payors if they are recommended by a plasmapheresis board, leading to a challenging regulatory path. Unless the regulatory playing field is leveled for non‐traditional treatments, the safest and most promising treatments may be overlooked in favor of sexier treatments like immunotherapies and small molecules.
Factors Associated with Cognitive Resilience in Persons Aged 80 and Older
Authors: Trammell Antoine R , Goldstein Felicia C , Parker Monica W , Hajjar Ihab 
Published: December 2022

AbstractBackgroundAfrican Americans (AA) have increased Alzheimer’s disease (AD) risk. Despite a high prevalence of risk factors for cognitive decline like vascular disease, data indicates that AA have a high degree of cognitive resilience, the ability to maintain normal cognitive functioning with aging. Most knowledge about cognitive resilience and SuperAgers (SA) is based on results from predominantly white samples. In a biracial sample, we investigated factors related to cognitive resilience in persons aged 80 and older.MethodData from the National Alzheimer’s Coordinating Center (NACC) through November 2020 was analyzed. NC was defined per global CDR score = 0 and SA by cognitive performance for episodic memory, executive function, naming, and phonemic fluency within 1 standard deviation of the mean or better. Using ANOVA or chi‐square, we compared demographic, medical, and lifestyle factors by race and cognition [normal cognition (NC) vs. SA]. Logistic regression evaluated factors related to cognitive group by race. The significance level for all tests was p < 0.05.ResultAA SA had more education years (15.3 vs. 13.9, p = .01), no alcohol abuse (11.7 vs. 1.4%, p<.01), and fewer lived alone (5.4 vs. 53.2%, p<.01) compared to NC. White SA had more education years (16.9 vs. 15.4, p<.01) and higher BMI (26.3 vs. 25.7, p = .03) compared to NC. In AA, regression showed that female sex (OR:3.12, 95% CI:1.19‐8.17) and no depression history (OR:7.46, 95% CI: 1.01‐55.1) were more likely to be SA. In whites, female sex (OR: 2.02, 95% CI: 1.56‐2.62) and no heart disease (OR:4.27, 95% CI:2.36‐7.72) were more likely to be SA.ConclusionIn persons of advanced age, factors associated with SA can vary with race. Prospective investigation with a diverse study sample is needed to investigate whether the findings are replicated.