bluuebunny/crossref_metadata_2025_split huggingface dataset:
Building a training program to diversify the academy and advance Alzheimer’s disease research
Authors: Ingram Lucy A , Ford Marvella E , Johnson Christiana , Ashford‐Carroll Brianna , McCollum Quentin , Chen Hongtu , Friedman Daniela B , Levkoff Sue E 
Published: December 2021

AbstractBackgroundAlzheimer’s disease and related dementias (ADRD) are at the forefront of the United States (US) public health agenda, with a disproportionate impact on racial/ethnic minorities. Aging scholars have called for prioritizing ADRD disparities research and addressing the systems that promote research as essential to achieving equity in healthy aging scholarship. In 2018, the National Institute on Aging (NIA)‐funded, Carolina Center on Alzheimer’s Disease and Minority Research (CCADMR) was founded to increase the diversity of the research workforce in population health and ADRD disparities. The CCADMR provides underrepresented minority (URM), junior/mid‐career faculty scientists with opportunities for pilot grant funding, mentorship by senior faculty, and health disparities‐focused training. We share evaluation findings from the training and mentorship components of the Center.MethodUsing a mixed methods approach, we analyzed data from quarterly scientist progress reports, interviews with mentors and scientists, and health disparities seminar evaluations.ResultNine scientists have been chosen as pilot project awardees since Center inception. They represent four academic institutions and have implemented disparities‐focused ADRD research ranging from estimating the prevalence of clusters of multi‐morbidity by ADRD type and race, to understanding the determinants of ADRD for African Americans to inform the development of a social robot to engage the community in ADRD‐related activities. Scientists have presented their research at aging and ADRD‐focused conferences, each with manuscripts currently under development. Qualitative interview data (N=9) show that mentors and scientists feel positively about the CCADMR, particularly the mentorship component. Junior scientists have a strong desire to advance their ADRD research, but they face challenges partly due to their institutions’ emphasis on diversity, which typically force them to assume additional responsibilities, leaving limited time for their research. Evaluation data show that nearly 85% of seminar attendees are greatly satisfied with the speakers and content. Since the conversion to virtual seminars due to the COVID‐19 pandemic, over 90% of attendees report being “very satisfied” with speakers and content.ConclusionWhile the evaluation of CCADMR outcomes is ongoing, our experience may be a practical resource for others developing interdisciplinary training programs to increase the pipeline of URM scientists conducting ADRD research.
Cardiometabolic disorders are associated with reduced cerebral perfusion and white matter microstructure
Authors: Lockhart Samuel N. , Hughes Tim M. , Suerken Cynthia , Jung Youngkyoo , Whitlow Christopher T. , Bateman James R. , Williams Benjamin J. , Espeland Mark A. , Sachs Bonnie C. , Hayden Kathleen M. , Baker Laura D. , Craft Suzanne 
Published: December 2021

AbstractBackgroundCardiometabolic disorders (hypertension and diabetes) often co‐occur and are considered key modifiable risk factors for Alzheimer’s disease and related disorders; yet, the extent to which they each affect brain structure and function is unclear. We examined their associations with neuroimaging biomarkers of white matter microstructure, cerebral perfusion, and cognitive function in a diverse cohort of older adults.MethodParticipants aged 50‐85 years enrolled in Wake Forest Alzheimer’s Disease Research Center’s Clinical Core between 2016‐2020 received clinical evaluation, oral glucose tolerance testing (OGTT), neuroimaging, cognitive testing, and adjudication for mild cognitive impairment (MCI) and dementia. 3T brain MRI included T1 (for gray/white matter segmentation, regional volumes/thicknesses); FLAIR for white matter hyperintensity volume (WMHv); arterial spin labeling for cerebral blood flow (CBF); diffusion tensor imaging (DTI) for fractional anisotropy (FA); and neurite orientation dispersion and density imaging (NODDI) for Free Water. Hypertension (HTN) was staged using seated blood pressure (BP) and medications. Hyperglycemia was staged using OGTT 120 minute glucose levels (OGTT120), hemoglobin A1c, and fasting glucose as available. Cardiometabolic status was categorized (HTN only, hyperglycemia only, hyperglycemia+HTN, neither). Multivariable linear regression modeled associations with neuroimaging measures adjusted for age, gender, and race.ResultMRI was available on 478 participants (35% MCI and 10% dementia) with mean age of 70±8 years, 74% with HTN, 61% with hyperglycemia (4% with non‐insulin treated diabetes), and 15% African‐Americans. The combination of hyperglycemia+HTN was associated with significantly higher NODDI Free Water and WMHv, lower FA, and lower gray matter perfusion, compared to neither factor (Table). Continuous levels of systolic BP and OGTT120 broadly correlated with WM microstructure, WMHv, and gray matter CBF (Figure). In adjusted models, systolic BP remained significantly associated with higher NODDI Free Water and WMHv, and CBF in gray and white matter. OGTT120 and WMHv remained significant in adjusted models. Cardiometabolic factors were not associated with gray matter macrostructure (e.g. volumes, temporal lobe cortical thickness) or cognitive status in this sample.ConclusionIn this deeply phenotyped and racially diverse sample, individual cardiometabolic factors and the co‐occurrence of disorders was associated with reduced cerebral gray matter perfusion and reduced white matter microstructure.
Prevalence of modifiable risk factors for Alzheimer’s disease and related dementias, and association with cognitive disability among transgender and gender non‐binary adults in the U.S.: BRFSS 2019
Authors: Lambrou Nickolas H , Norton Derek L , Gleason Carey E , Flatt Jason D 
Published: December 2021

AbstractBackgroundSubjective cognitive impairment (SCI) may represent an early sign of Alzheimer’s disease and related dementias (ADRD). Little is known about prevalence of SCI among people identifying as transgender men/women, or gender non‐binary (TNB). The Behavioral Risk Factor Surveillance System (BRFSS) defines cognitive disability as serious difficulty concentrating, remembering, or making decisions due to a health condition. Using report of cognitive disability as a surrogate for SCI, we aimed to: 1) characterize rates of morbidities considered modifiable risk factors for ADRD by gender identity, and 2) explore interactions between morbidities, cognitive disability and gender identity.MethodWe analyzed 2019 BRFSS data from 31 US states and Guam administering the optional sexual orientation and gender identity (SOGI) module. Chi‐squared tests characterized unadjusted associations between gender identity and health conditions (heart attack, stroke, diabetes, angina/coronary heart disease, and depression). Adjusted associations were investigated using logistic regression models. Models included cognitive disability as outcome, with gender identity, health condition, and age group as covariates, and interaction between gender identity and health condition. Likelihood ratio tests evaluated for interaction significance. Multiple correction controlled for false discovery rate at 5%.ResultOf respondents providing a gender identity (n=231,414), 955 identified as TNB. Rates of depression were significantly higher for TNB respondents (37%) compared to cisgender (i.e. non‐TNB) counterparts (19.2%). Additionally, reports of cognitive disability were significantly higher in TNB respondents (24.7%) compared to cisgender counterparts (10.5%). Adjusted odds of cognitive disability with depression were highest for transgender men (aOR=11.48; 95% CI=20.70‐6.37) and cisgender men (aOR=9.22; 95% CI=9.65‐8.81), followed by cisgender women (aOR=7.50; 95% CI=7.79‐7.23), transgender women (aOR=4.71; 95% CI=7.93‐2.79), and non‐binary respondents (aOR=3.48; 95% CI=6.44‐1.88). Overall, TNB respondents were younger, with most between ages 18‐44 years (48.3%), compared to cisgender counterparts (26.8%).ConclusionRates of depression and cognitive disability were significantly higher for TNB groups compared to cisgender counterparts. Interestingly, interaction analyses suggested that men, be it transgender or cisgender, demonstrated greatest cognitive disability associated with depression compared to other groups. Future directions include investigating psychosocial facets of gender identity and cognitive health, along with tailored interventions addressing modifiable risk factors and ADRD screening.
Iron intake, brain iron, and Alzheimer’s disease among community‐dwelling older adults
Authors: Agarwal Puja , Ayton Scott , Wang Yamin , Agrawal Sonal , Bennett David A , Barnes Lisa L , Leurgans Sue E , Bush Ashley I , Schneider Julie A 
Published: December 2021

AbstractBackgroundIron is an essential trace metal for brain health but maybe damaging when in excess, for example, through the regulated cell death program, ferroptosis. We earlier reported that higher brain iron levels are associated with faster cognitive decline and more neurofibrillary tangles, but the cause of iron elevation is unknown. This study investigates dietary and demographic factors associated with brain iron levels, Alzheimer’s Disease (AD) pathology, and cognitive decline.MethodThe study was conducted in 614 decedents (age‐at‐death:91.2±7.2years; education:14.6±3years;70% females) of the Rush Memory and Aging Project. AD pathology was assessed using standard criteria. Brain iron levels were evaluated in four brain regions (inferior temporal, mid frontal, and anterior cingulate cortices, and cerebellum) using Inductively Coupled Plasma Mass Spectrophotometry, and a composite mean z‐score was generated. Cognitive performance measured with 19 tests examined annually until death. Mean annual dietary iron intake was obtained from a validated food frequency questionnaire. Linear and logistic regression models with stepwise selection were used to investigate associations.ResultThe mean dietary iron intake (up to>10 years of follow‐up before death) was not associated with postmortem brain iron levels, cognitive decline, or global AD pathology. Age‐at‐death (β=‐0.01,p=0.001), sex (β=0.30,p<0.0001), smoking (β=‐0.20,p=0.0008), and APOE‐ε 4 status (β=1.65,p=0.01) were each associated with higher brain iron levels. Except for APOE‐ε 4 status, these associations were retained when further controlled for AD pathology. Among dietary factors, in the age‐adjusted model, total fat (β=0.007,p=0.04) was positively, and omega‐3 fat (β=‐0.18,p=0.001) was negatively associated with higher brain iron levels. However, with further adjustment for age, sex, smoking, and APO‐ε 4 status, only the omega‐3 association, was retained.ConclusionUnlike brain iron, dietary iron intake does not relate to AD pathology or cognitive decline. This may not be surprising since the blood‐brain barrier is relatively impermeable to fluctuations in blood iron levels. Brain iron accumulation in older adults relates to demographic factors independent of AD pathology. Overall, brain iron was not associated with dietary iron but was inversely associated with omega‐3 fats. Further studies on fat intake, dietary fat and iron interaction, and its relationship with brain measures are warranted.
Laser speckle‐based retinal imager as a potential screening tool for mild cognitive impairment
Authors: DeBuc Delia Cabrera , Kandukuri Jayanth , Sinha Avigyan , Lee Wen‐Hsiang , Crocco Elizabeth , Sapahia Rishav , Mendoza‐Santiesteban Carlos , Smiddy William E. , Garg Rajesh K. , Kostic Maja , Alfonso Michelle Marrero , Baumel Bernard , Rege Abhishek 
Published: December 2021

AbstractBackgroundAs the overall population's life expectancy rises, so does the prevalence of age‐related cognitive impairment (CI). Recent evidence has shown that cognitive impairment (CI) is not limited to the brain and affects the retina. In this study, we characterized dynamic retinal blood flow (RBF) patterns using the XyCAM RI (Vasoptic Medical, Inc.), a non‐invasive, laser speckle‐based retinal imager, in cognitively normal subjects (CN), patients with mild cognitive impairment (MCI), and individuals with diabetes mellitus (DM) including those with diabetic retinopathy (DR).MethodA total of thirty‐four individuals (68 eyes) were imaged using the XyCAM RI. Normal cognitive function was determined using neuropsychological tests. High frame‐rate (82 Hz) RBF data was acquired over six seconds from each eye. As described and defined in Fig. 1, various dynamic RBF metrics were computed from the shape of the temporal waveform of blood flow velocity indices (BFVi) averaged within multiple arterial and venous segments intersecting a circular track around the optic disc. One‐way ANOVA was used to compare group means (p<0.05).ResultsDynamic RBF metrics were computed using BFVi data from arterial and venous segments of 8 CN, 12 DM, 5DR, and 9 MCI eyes for comparison. Statistical comparisons (Table 1) confirmed significant differences between Dip BFVi in MCI vessels and CN/DR vessels but not DM vessels suggesting similar reduced RBF in both MCI and DM vessels. Compared with the Dip BFVi, no group‐wise differences were observed in Peak BFVi and Mean BFVi, suggesting the usefulness of assessing temporally‐resolved RBF data. A significantly higher arterial VRI (p < 0.002) and smaller venous VFI in MCI subjects demonstrated increased contractility compared to CN and DM subjects. The ANOVA test confirmed a statistically significant difference in the VFI of MCI subjects from each of the CN/DM/DR groups.ConclusionIndividuals with MCI have different RBF characteristics compared to CN and DM subjects. These results may be related to systemic changes in arterial stiffness and increased blood pressure, which have been correlated with a decline in cognition. Non‐invasive dynamic RBF metrics using the XyCAM RI should be further investigated as potential biomarkers for classifying individuals with MCI.
Plasma Aβ40, Aβ42 and Aβ‐clearance proteins as blood biomarkers for Alzheimer's disease, subjective cognitive decline, and MCI
Authors: Ito Hitomi , Shan Liu , Hata Naoko , Korenaga Tatsumi , Suzuki Hideaki , Meno Kohji , Takihara Takanobu , Akatsu Hiroyasu , Matsukawa Noriyuki , Asada Takashi , Arai Tetsuaki , Uchida Kazuhiko 
Published: December 2021

AbstractBackgroundFor early intervention and prevention of dementia, diagnostic biomarkers for MCI and preclinical Alzheimer's disease (AD) are important. amyloid β (Aβ) and tau are known as biomarkers for AD, and the CSF Aβ40 / Aβ42 ratio is clinically useful for diagnosis of AD. We have reported that three proteins in serum related to Aβ clearance: ApoA1, complement protein C3 and transthyretin (TTR) are useful as blood biomarkers for MCI (Triple marker). Plasma Aβ has been shown to correlate with amyloid PET, however, its clinical utility in MCI and AD diagnosis is unclear. Therefore, we investigated usefulness plasma Aβ in addition to the triple marker as blood test for MCI and AD. Here we analyzed plasma levels of Aβ40, Aβ42 and Triple marker in MCI and AD as diagnostic markers.MethodA total of 909 cases consisting of 354 non‐demented control (NDC), and 76 subjective cognitive decline (SCD), 312 MCI, and 167 AD diagnosed according to ADNI neuropsychological criteria were selected in the multicenter clinical study. The positron emission tomography (PET) using with [18F] Florbetapir was performed 24 APOE4‐carring SCD and MCI subjects. Plasma Aβ40, Aβ42 were measured by ELISA (EUROIMMUN, Lübeck). Plasma levels of ApoA1, TTR, complement C3 was measured as described previously (Liu et al., Alzheimer Dement (Amst) 2019).ResultPlasma ApoA1 and complement C3 levels were decreased in progression of the disease. Plasma Aβ40 / 42 ratio showed ROC AUC = 0.82 and 0.67 in AD vs. NDC and MCI vs. NDC, respectively. Combination of plasma levels of Aβ40 / 42 ratio and Triple marker (ApoA1, TTR, C3) showed AUC = 0.85 (80% sensitivity and 85% specificity) in AD vs. NDC and AUC = 0.76 (76% sensitivity and 70% specificity) in MCI vs. NDC. Aβ40 / 42 ratio and TTR were significantly decreased in amyloid‐positive subjects (SUVR≥1.10) compared to amyloid‐negative subjects (SUVR<1.10).ConclusionCombination of plasma Aβ40 / Aβ42 ratio and Triple marker is a useful blood test for not only AD but also the early stages of cognitive decline.
Cognitive correlations with amyloid, tau and neurodegeneration PET across the Alzheimer’s disease age spectrum
Authors: Tanner Jeremy A , Iaccarino Leonardo , Edwards Lauren , La Joie Renaud , Strom Amelia , Pham Julie Q. , Mellinger Taylor J. , Soleimani‐Meigooni David N. , Rosen Howard J. , Kramer Joel H , Miller Bruce L. , Rabinovici Gil D. 
Published: December 2021

AbstractBackgroundIn Alzheimer’s disease (AD), cognitive symptoms have varying associations with tau, amyloid and neurodegeneration. Patients with early‐onset AD (EOAD, age<65) have more non‐amnestic symptoms, greater AD pathological burden, and less co‐pathologies than late‐onset AD (LOAD, age≥65). It is unknown whether the association between cognitive symptoms and Alzheimer’s disease biomarkers differs with age, and this has implications for clinical trials. The goal of this study was (1) to evaluate the association between domain‐specific cognitive performance and PET‐based pathology in AD, and (2) to compare whether theses associations differ in EOAD versus LOAD.MethodAmyloid‐positive patients meeting criteria for mild cognitive impairment or AD dementia (Total n=71; EOAD n=33, mean age 58±4, MMSE 20±7, 61% female; LOAD n=38, mean age 74±6, MMSE 24±5, 45% female) underwent neuropsychological testing, 18F‐flortaucipir (FTP‐PET), 11C‐PIB‐PET (PIB‐PET), and a subset underwent 18F‐fluorodeoxyglucose‐PET (FDG‐PET, n=57). Composite scores were calculated for episodic memory, semantic memory, language, executive function and visuospatial domains. Voxelwise regressions (thresholded at uncorrected p<0.001 voxel‐level, FWE p<0.05 cluster‐level) evaluated PET/cognition correlations, and EOAD versus LOAD differences were tested with a PET*group interaction. Mediation analyses assessed direct and FDG‐PET‐mediated associations between FTP‐PET and cognitive performance in regions‐of‐interest based on the voxelwise regressions.ResultsFTP‐PET and FDG‐PET (lesser extent), but not PIB‐PET, showed significant domain‐specific voxelwise associations with cognitive performance that aligned with known brain‐behavior relationships (episodic memory/medial temporal lobe, semantic memory/anterior temporal, language/perisylvian, executive/frontal, visuospatial/occipital) (Figures 1‐3). There were no significant interactions between age and PET correlations across all modalities. Mediation analysis revealed that FDG‐PET mediated the relationship between FTP‐PET and cognition in all domains except episodic memory (Table 1). FTP‐PET also had a direct effect on executive function (p<0.001) and visuospatial (p=0.02) performance.ConclusionIn AD, cognitive performance correlated with tau and neurodegeneration, but not amyloid, in similar patterns across the age spectrum. The relationship between tau and cognition was in part mediated by glucose metabolism. These findings provide support for inclusion of EOAD patients in clinical trials, for tau PET as a biomarker that captures molecular specificity and aligns with clinical performance, and for the shared potential of disease‐modifying therapies across the AD age spectrum.
A randomised placebo‐controlled study on the effects of anthocyanins for maintaining cognitive functioning in individuals at increased risk for dementia
Authors: Khalifa Khadija Nasralla , Aarsland Dag 
Published: December 2021

AbstractBackgroundAnthocyanins are found in dark berries, that have antioxidant and anti‐inflammatory effects and can cross the blood‐brain barrier. This study aims to evaluate the safety and efficacy of anthocyanins in modifying key dementia‐related mechanisms and maintaining cognitive functioning in older people at risk for dementia.MethodWe conducted a 24‐week randomised, double‐blind, placebo‐controlled Phase II study. A total of 208 participants aged 60‐80 years with cardiometabolic disorders (n=143) or mild cognitive impairment (n=68), were randomised to either purified anthocyanins (Medox® capsules, 320mg/day) or placebo for 24 weeks. The primary outcome is the Quality of episodic memory score, a composite measure from the online cognitive test battery CogTrack®, administered monthly. Secondary outcomes include other cognitive scores, neuroimaging (MRI and FDG‐PET), blood and CSF biomarkers. Medication compliance was measured by counting returned capsules, and anthocyanin metabolite levels will be measured in serum and CSF. Longitudinal measures of Quality of episodic memory will be subject to Mixed Model for Repeated Measures ANCOVA. Cognitive data are currently being analysed but still blinded.ResultTreatment groups are shown in Table 1. Retention in the study was very good; only one participant discontinued the study due to adverse event (AE), diarrhoea, another four due to pre‐defined protocol deviation (Figure 1). AEs were reported in 34 participants, five of which were serious adverse event (hospitalisation for constipation, hypertension, MRI finding of acute ischemic stroke at final assessment, and two anginas). There were minor differences in the proportions of participants reporting AEs (18 vs 15%; p=0.58). There were no notable changes in safety blood tests and the medication compliance was high (median 98% of planned doses, IQR 93‐99%).ConclusionThis is one of the most ambitious trials of anthocyanins and cognitive impairment. Anthocyanin capsules were well‐tolerated and safe, with no significant differences in adverse events between the treatment groups. The analysis of the cognitive outcome measures is ongoing, and the results will be presented at the meeting. The study may contribute to further improvement of intervention strategies to prevent or delay the onset of dementia, including a potential decision to take anthocyanins toward phase III trials.