bluuebunny/crossref_metadata_2025_split huggingface dataset:
African American Dementia Caregivers’ Perspectives on and Appraisal of Stress Associated with the Caregiving Role: A Qualitative Study
Authors: Block Laura M , Cotton Quinton , Seyyedmirza Paria , Chang Juliet , Gilmore‐Bykovskyi Andrea L 
Published: December 2022

AbstractBackgroundAfrican Americans are disproportionately impacted by Alzheimer’s disease and related dementias (ADRD), with family members providing the majority of support and care. Dementia caregivers often face high levels of stress and burden which contribute to poor physical and psychological health outcomes. African American dementia caregivers often face greater risk for stress and burden with discrepant evidence on whether this leads to worse outcomes compared to counterparts. Yet African American dementia caregivers remain under‐included in research designed to understand and ameliorate the stress and burden of caregiving. Our study aimed to understand African American dementia caregivers’ perspectives and appraisal of stressors surrounding caregiving and stressful events, such as hospitalization of the person with ADRD.MethodsWe harnessed qualitative interview data from the Stakeholders Understanding of Prevention Protection and Opportunities to Reduce HospiTalizations (SUPPORT) Study, a multi‐site study designed to determine family caregiver perspectives surrounding hospitalizations for people with ADRD residing in highly disadvantaged neighborhoods. Data from 30 dementia caregivers who self‐identified as African American were analyzed using thematic analysis.ResultsAll participants described the presence of stressors and stressful events related to their life broadly and to dementia caregiving more specifically. However, there was great variation in the described degree of stressors in caregiver’s daily life. Caregivers experiencing a greater number, more recent, and more acute stressors described greater burden in their daily life. Long‐standing stressors, such as family conflict and financial hardship, sometimes ‘resurfaced’ with the proximity and role changes brought on by caregiving. Other individual and situational factors, such as one’s own health or status as a ‘sandwich caregiver,’ or the habits and preferences of the person with ADRD, could serve as contributors to overall stress. Few caregivers related stressors to long‐term outcomes, though some described strategies to seek formal mental health counseling.ConclusionsAfrican American dementia caregivers described a variety of acute and ongoing stressors that related not only to caregiving for the person with ADRD but also the caregiver’s personal health and their broader familial and neighborhood context, signaling the need for adaptive caregiver support interventions capable of addressing intervention targets across various stressors.
Different associations of varying types of Vitamin E and cognitive function in older adults with or without APOE Ɛ4 allele
Authors: Liu Xiaoran , Beck Todd , Dhana Klodian , Evans Denis A , Rajan Kumar B 
Published: December 2022

AbstractBackgroundDifferent forms of vitamin E may have a different association with cognitive function, which might vary by the APOE E4 allele status. We aim to examine vitamin E from different sources and in varying forms and their relation to cognitive decline among those with and without the APOE E4 allele.MethodsWe included 2,014 participants from the Chicago Health and Aging Project (62% African Americans, 63% female). Global cognition was assessed using a composite score of episodic memory, perceptual speed, and the MMSE. Diet was assessed by a 139‐item FFQ. APOE genotype was assessed by hME Sequenom mass‐array platform. Mixed models were adjusted for age, sex, education, smoking status, calorie intake, alcohol consumption, use of supplements, time since baseline, and the interaction term of time with each covariate.ResultsA higher dietary vitamin E was associated with slower cognitive decline. Those in the highest quintile of dietary vitamin E intake had 28% slower cognitive decline than the lowest quintile (β = 0.014, p = 0.02). A higher intake of dietary αlpha‐tocopherol was associated with slower cognitive decline in participants with APOE E4 allele, but not among those without. In participants with APOE E4 allele and in the highest quintile of alpha‐tocopherol intake had a 16.4% slower rate of global cognitive decline than those in the lowest quintile (β = 0.015, p = 0.0015). A higher intake of delta‐tocopherol was associated with a slower decline in individuals without the APOE E4 allele only. Among those without the APOE E4 allele and in the highest quintile, the rate of global cognitive decline was slower by 22% than the lowest quintile (β = 0.012, p = 0.0014). We found no significant associations between beta‐ and gamma‐tocopherol intakes and cognitive decline among those with and without the APOE E4 allele.ConclusionOur study found a positive association of alpha‐tocopherol with cognitive decline among those with the APOE E4 allele and delta‐tocopherol with the decline in those without the APOE E4 allele. Our findings suggest that different forms of vitamin E might have a different association with cognitive decline in older adults depending on their APOE E4 allele status.
Screening for MCI in the Swedish H70 Birth Cohort Study using digital automatic speech biomarker tests for cognition and a machine Learning classifier
Authors: Skoog Johan , Mallick Elisa , Bodin Timothy Hadarsson , Mina Mario , Linz Nicklas , Tröger Johannes , Skoog Ingmar 
Published: December 2022

AbstractBackgroundEven if classic neuropsychological tests often have excellent psychometric properties to detect Mild Cognitive Impairment (MCI), they are not suitable for cost‐effective low‐burden screening at scale. Speech‐based digital biomarkers can be deployed in a highly automated fashion. We present the results of an MCI screening algorithm based on a digital Speech Biomarker for Cognition (SB‐C) in the Swedish H70 birth cohort study.MethodWe used a sample from the Swedish H70 Birth Cohort study (N = 404; 356 cognitively healthy (HC), 48 MCI). We automatically extract the SB‐C score and its subscores (executive function, memory, semantic memory, processing speed) from SVF and RAVLT speech recordings using ki:elements’ proprietary speech analysis pipeline including automatic speech recognition and feature extraction. We performed (1) inferential statistics comparing MCI and HC group based on the biomarker scores and (2) built a machine learning model to screen for MCI. For (1) we performed a non‐parametric Kruskal‐Wallis test to compare SB‐C scores of both HC and MCI groups to check for general feasibility. For (2), we trained a support vector machine model with class weights and leave‐one‐out cross validation to classify between MCI and HC using the SB‐C scores as input (overall score and the subscores).ResultThere was a group difference for the SB‐C aggregated cognition score between the groups (HC > MCI; χ2 = 45.9 (1), p <0.001; Figure 1), and also for the subscores (Table 2). To classify between MCI and HC, using a feature selection method, the best model was found for all the five biomarker scores selected with an Area Under Curve of 0.77 (Figure 2), a specificity of 0.77 and a sensitivity of 0.76 (Table 3).ConclusionWe found that a machine learning‐based screening algorithm based on the SB‐C can detect probable MCI patients in representative population sample of older people using a speech biomarker read‐out.
Development of a Telehealth Intervention for People with Dementia: ROAD MAP (Recovery‐Oriented Approach to Dementia through Meaningful Activity Participation)
Authors: Garcia Lesley 
Published: December 2022

AbstractBackgroundGiven the success of recovery approaches for people living enduring mental illness who nevertheless experience the outcome of personal recovery despite ongoing clinical symptoms it is appropriate to consider applying this model to dementia. Additionally, telemedicine is increasingly seen as an effective and efficient means of health care delivery among this population (Rice et al., 2021). Leamy and colleagues identified the elements of CHIME (connectedness, hope and optimism, identity, meaning in life and empowerment) as the key features of successful recovery‐oriented approaches (Leamy et al., 2011). This research is postulating that enhancing CHIME in people with mild dementia through the use of a web‐based self‐management intervention tool will have health‐promoting outcomes for both the person living with mild dementia and their carer.MethodThe research design used in this intervention development process is participatory design (Young et al., 2020) based on systematic reviews, Agilie methodology in line with current best practice guidance on research with and for people living with dementia (Gove et al., 2018). Specifically, the intervention co‐design process will follow the guidance (Cathain et al., 2019) on the development and reporting (Duncan et al., 2020) of complex healthcare interventions.ResultThe development of a novel telehealth intervention that enhance markers of personal recovery, defined as CHIME, in people with mild dementia.ConclusionIt is intended that this systematic development process will enhance knowledge of the methodology of development of useful and acceptable telehealth tools for people living with this condition. Involvement of stakeholders in the co‐development process will be invaluable with regard to usability and acceptability, and hopefully limit wasting of research resources as a consequence.
Proposal of a stepwise approach for CSF biomarkers testing for Alzheimer's Disease in middle‐ and low‐income countries
Authors: Bicalho Maria Aparecida Camargos , Hansen Erika de Oliveira , Dias Natália Silva , Miranda Millena Figueiredo , Miranda Mariana Figueiredo , Costa Giulia , Barbosa Izabela , Burgos Ivonne Carolina Bolaños , Romano‐Silva Marco Aurelo , Viana Bernardo de Mattos 
Published: December 2022

AbstractBackgroundThe incidence and prevalence of dementia are increasing, mainly in low‐ and middle‐income countries. Alzheimer's disease (AD) accounts for the majority of cases. Thus, cost‐effective techniques with lower cost are necessary for scaling up the number of tested individuals in these countries for research and clinical use. Luminex (Millipore xMap®) is a semi‐automated test that can analyze CSF biomarkers with a cost per sample of one fourth of ELISA’s kits.MethodWe performed a cross‐sectional, case‐control study. After consent, 35 older adults were submitted to clinical and neuropsychological assessment, and then to a lumbar puncture. Based on clinical and neuropsychological assessment, seven patients had a diagnosis of AD’s dementia (McKhann criteria), 17 of amnestic mild cognitive impairment (MCI) (DSM‐5 criteria) and 11 without objective cognitive impairment. CSF biomarkers concentrations were measured by INNOTEST® (ELISA) and Millipore xMap®. Both techniques were compared and the accuracy of the latter was assessed.ResultMillipore xMap® measurements showed a robust accuracy for all biomarkers, with AUC of 0.808 for t‐Tau, 0.935 for p‐Tau and 0.952 for Aβ42 compared to ELISA as the reference test. The Aβ42 showed a great sensibility (100%) and the ratio p‐tau/Aβ42 a good specificity (0,944). So, we propose a stepwise approach for the diagnosis of AD based on CSF biomarkers. A patient with a cognitive assessment suggestive of AD (MCI or initial dementia) could be initially assessed for CSF biomarkers with a more affordable test, such as Luminex. If there is a need of a confirmation due low pretest probability or the need of a more specific test for a high‐cost treatment, researchers and clinicians could order an ELISA test in the same CSF sample or additional molecular neuroimaging techniques. For patients with a high pretest probability, Luminex has excellent accuracy and can define biological diagnosis.ConclusionThe use of Millipore xMap® as the first step in a stepwise approach for the assessment of suspected AD in middle‐ and low‐income countries cases is promising, considering its accuracy and lower cost per sample. Still, the implementation of the proposed approach in this study should be replicated in larger and different samples.
Diagnostic Utility of Brain MRI Volumetry in Comparing Traumatic Brain Injury, Alzheimer Disease and Behavioral Variant Frontotemporal Dementia
Authors: Raji Cyrus A. , Meysami Somayeh , Porter Verna R. , Merrill David A. , Mendez Mario F. 
Published: December 2022

AbstractBackgroundApplication of brain MRI with volumetric quantification can improve delineation of various neurocognitive disorders.MethodWe utilized 136 participants from previously defined cohorts of traumatic brain injury (TBI; n=40) [1], early (EOAD; n=45) and late onset Alzheimer disease (LOAD; n=31) [2] as well as of behavioral variant frontotemporal dementia (bvFTD; n=20). Participants had brain MRI including 3D T1 sequences amendable to volumetric quantification. Scans were analyzed with an FDA cleared software program, Neuroreader[3] to measure regional brain volumes. At the time of analysis, Mini‐Mental State Exam (MMSE) scores were available on majority of participants (n=125). One‐way ANOVA compared mean age, MMSE, and brain volumes across all four groups with Bonferroni correction for multiple comparisons. All brain volumes were corrected for total intracranial volume (TIV). Discriminant analysis was done with leave‐one‐out cross validation on measured brain volumes to determine diagnostic delineation across groups. Automated linear regression identified predictive features from these quantified structures.ResultParticipant demographics and MMSE scores are shown in Table 1. With respect to age, LOAD was the oldest compared to other groups (p<.001). There were no statistically significant differences in sex (p=.58) with women comprising 54.4% of the entire sample. EOAD and LOAD had the lowest MMSE scores compared to TBI (p=.04 for EOAD and p=.01 for LOAD). Regional volume difference across groups showed lowest hippocampal volumes in LOAD (p=.005), low white matter volume in TBI (p=.007), lower parietal lobe volumes in EOAD (p<.01), and lower frontal lobe volumes in bvFTD (p<.001). Regional volume differences resulted in a correct classification of 89%, 79.4% after cross validation. Predictive features included caudate, amygdala, frontal, parietal, temporal lobar and total white matter volumes.ConclusionWe identified the diagnostic utility of regional volumetric differences across multiple neurodegenerative and non‐neurodegenerative disorders. The lower parietal lobe volumes in EOAD and lower hippocampal volumes in LOAD and well as frontal atrophy of bvFTD reflect the known anatomical distribution of pathology in those conditions[4]. The white matter volume loss in TBI is a previously demonstrated feature of that condition[5]. Brain MRI volumetry may therefore be beneficial in clinical practice.
The relationship of soluble p‐tau isoforms with brain amyloid and tau deposition in sporadic AD
Authors: Barthélemy Nicolas R. , Saef Benjamin A. , Li Yan , Gordon Brian A. , He Yingxin , Horie Kanta , Sato Chihiro , Ovod Vitaliy , Benzinger Tammie L.S. , Morris John C. , Bateman Randall J. , Schindler Suzanne E. 
Published: December 2022

AbstractBackgroundHyperphosphorylated tau isoforms (p‐tau) in cerebrospinal fluid (CSF) and plasma represent promising measures to monitor Alzheimer disease (AD) pathological changes. Brain amyloid deposition precedes tau aggregation and associated clinical decline by two decades. Several CSF and plasma p‐tau isoforms have been described as potential surrogates for tau Positron Emission Tomography (PET) imaging, but p‐tau isoforms have a strong association with amyloid PET, and increase without tau pathology. In this study, we investigated the relationship between multiple CSF p‐tau isoforms and brain imaging measures in the Knight ADRC cohort.MethodWe analyzed 10 p‐tau isoforms by mass spectrometry in 1932 CSF samples (1173 participants). Associated data includes 1250 amyloid PET and 442 tau PET scans, as well as CSF Aβ42/Aβ40 by immunoassay for all samples. We measured phosphorylation occupancies (ptau/tau) at T111, T153, T175, T181, S199, S202, T205, S208, T217 and T231, together with corresponding p‐tau and tau concentrations. We compared the accuracy of CSF p‐tau isoforms in predicting amyloid PET and tau PET status stratified according to amyloid PET, tau PET and/or Clinical Dementia Rating (CDR) status.ResultsPT217/T217 best‐predicted abnormal amyloid PET (AUROC=0.980) or CSF Aβ42/Aβ40 (AUC=0.954). PT217/T217 predicted brain amyloidosis in asymptomatic and symptomatic participants with similar accuracy (AUC=0.979 and 0.986 respectively) and was correlated with amyloid PET centiloid and CSF Aβ42/Aβ40 (Spearman R=0.73 and ‐0.76, p<0.0001). Notably, the correlation between pT217/T217 and amyloid PET centiloid was higher in amyloid PET(+)/tau PET(‐) compared to amyloid PET(+)/tau‐PET(+) (R=0.77, p<0.0001 versus 0.16, p=0.007). PT205/T205 and pT217/T217 better predicted tau PET positivity in amyloid PET(+)positive participants (AUC=0.908 and 0.866). These markers were also associated with tau PET signal in tau PET(+) participants (R=0.53 and 0.55 p<0.0001). Other p‐tau isoforms also predicted amyloidosis, except for T175, S199, S202 and T205. Only pT205/T205 and pT217/T217 were correlated with tau‐PET in tau PET(+) participants.ConclusionThese results suggest that tau hyperphosphorylation, notably at T217, is more strongly associated with brain amyloid burden than tau deposition in tau PET(‐) individuals. After tau PET becomes positive, p‐tau217 and p‐tau205 are correlated with tau burden. Soluble p‐tau are markers of both amyloid and tau aggregation in the AD brain.
Therapeutic Efficacy of the Murine Precursor to PBD‐C06: a Novel CDC‐Mutant Anti‐pGlu3Aβ mAb
Authors: Bathini Praveen , Grenon Martine , Papavergi Maria‐Giusy , Price Brittani R. , Schroeder Maren K. , Kleinschmidt Martin , Rahfeld Jens‐Ulrich , Schilling Stephan , Lemere Cynthia A. 
Published: December 2022

AbstractBackgroundPyroglutamate‐3Aβ (pGlu3Aβ) is a toxic N‐terminally truncated and modified form of Aβ that leads to faster aggregation and seeding of plaques, making it an important target in Alzheimer’s disease. Anti‐amyloid antibodies, e.g., bapineuzumab, are associated with Amyloid‐Related Imaging Abnormalities (ARIA) involving vasogenic edema and microhemorrhages in AD patients, especially in ApoE4 carriers. Previously, we demonstrated reductions in plaques and cognitive deficits using an anti‐pGlu3Ab mAb, 07/2a. Here, we tested a novel CDC‐mutant version (07/2a‐k, murine precursor to PBD‐C06) to avoid C1q activation to reduce vascular‐related inflammation associated with anti‐amyloid antibodies.MethodTo estimate an effective therapeutic dose, 12 mo‐old APP/PS1dE9 mice were treated weekly (i.p.) for 5 weeks with 150, 300 or 600 µg 07/2a‐k or IgG2a (n=10‐12/group). General Ab and pGlu3Aβ levels were quantified by ELISA and immunohistochemistry. Next, 16 mo‐old APP/PS1dE9; hApoE4 mice were treated weekly (i.p.) for 15 weeks with 350 µg of 07/2a‐k, 3D6‐L (a murine analog of bapineuzumab), or IgG2a, while hApoE4 mice were treated with PBS (n=10‐13 mice/group). Subsequently, cognitive testing was performed over 3 weeks using the Spatial Novelty Y Maze (SNYM), Novel Object Recognition (NOR), and the Barnes Maze followed by euthanasia.ResultFive weekly treatments with 07/2a‐k in the dosing study did not alter general and pGlu3 Aβ biochemical levels; however, hippocampal pGlu3Aβ plaques were significantly reduced (300 µg, p<0.0005; 600 µg, p<0.005). In the therapeutic study, 3D6‐L reduced Aβx‐42 levels (p<0.009) by ELISA but not Abx‐40 levels. 07/2a‐k did not significantly alter Aβx‐42 or Abx‐40 levels. Both antibodies improved performance in the NOR test (07/2a‐k, p<0.05; 3D6‐L, p=0.05) and showed a non‐significant trend for improvement in the SNYM and Barnes maze compared to IgG2a controls. Macro‐hemorrhages were visible in 33% of 3D6‐L treated mice but not in 07/2a‐k treated mice.ConclusionTreatment with the 3D6‐L mAb, a murine analog of bapineuzumab, lowered cerebral Aβ levels and improved cognition but induced macro‐hemorrhages in aged APP/PS1dE9;hApoE4 mice, while treatment with 07/2a‐k, the precursor to PBD‐C06, did not alter general Ab levels but improved cognition in the absence of macro‐hemorrhages. Further analyses are underway to quantify cerebral pGlu3Ab levels, plaques, CAA, microhemorrhages and gliosis. (NIH 1RF1AG058657‐CAL)
Screening for Memory Concerns at the Well‐Woman Visit
Authors: Joyce Jillian L. , Caes Dorota , Chapman Silvia , Gottesman Reena T. , Haque Hoosna , Manly Jennifer J , Waltrip Leah H. , Rizer Sandra , Marder Karen , Rosser Mary L. , Cosentino Stephanie 
Published: December 2022

AbstractBackgroundRoutine healthcare visits offer the opportunity to screen older adults for cognitive changes that accompany the earliest clinical stages of Alzheimer’s disease (AD) including Mild Cognitive Impairment (MCI) and Subjective Cognitive Decline (SCD). It is well‐established that women are at increased risk for AD and that many women see their gynecologist as their primary care doctor. Given this unique relationship, the Women’s Preventive Services Initiative and the American College of Obstetrics and Gynecology now advocate for integrated care of women at all ages. Memory screening of older women should be paramount in this effort. Research is needed to determine which screening tools are most effective and practical. Here we assess the feasibility and utility of a subjective memory screener at the well‐woman visit.MethodWomen aged 60 and above completed a 5‐item screener at their well‐woman visit at the Columbia University Integrated Women’s Health Center (Table 1). Women who endorsed any item were considered to have a positive screen and were given the option to pursue clinical evaluation for memory concerns through the Division of Aging and Dementia.ResultOnly 8 of 354 women declined to complete the screener. Of the completed screeners, 16% (n = 56) were positive. The most frequently endorsed item was difficulty with memory or thinking compared to others the same age (8%, n = 28) (See Table 1). 44% (n = 24) of women with positive screens pursued referral, and six have been seen to date. One woman was diagnosed with MCI. Clinical impressions of the remainder were unremarkable. All six cases had family history of dementia or memory problems.ConclusionThe well‐woman visit provides a key opportunity to routinely screen older women for early indicators of AD and treatable causes of cognitive impairment. Preliminary results support the feasibility and value of such screening as part of a comprehensive well‐woman program. Early identification of women experiencing SCD will enable investigation into the cause of their memory concerns, and longitudinal monitoring of cognitive change. Future work should evaluate the added value of an objective cognitive screen to complement SCD screening and identify women who may benefit from further evaluation.