bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accountable care organizations and racial and ethnic disparities among patients with Alzheimer’s and related dementia diseases
Authors: Chen Jie 
Published: December 2020

AbstractBackgroundThe accountable care organization (ACO) is a new care coordination model and reimbursement mechanism that incentivizes providers to deliver high‐quality and well‐coordinated care. This study is the first to provide evidence on the ACOs enrollment and quality of enrolled ACOs among patients with ADRD, and evidence associated with racial disparities in quality of care for persons with ADRD.MethodOur study used 2017 Centers for Medicare and Medicaid Services Medicare inpatient claims data and Medicare Beneficiary Summary File. Our study focused on patients who had a diagnosis of ADRD. We further linked the CMS claims data with the 2017 MSSP ACO data to capture the patient’s participation of the ACO. The CMS ACO quality measures were used to examine the quality of the ACOs among those who enrolled in the ACOs. In this study, we examined four 4 ACO quality measures related to hospital care quality: risk standardized, all condition readmission (ACO 8), all‐cause unplanned admissions for patients with diabetes (ACO 36), heart failure (ACO 37), and multiple chronic conditions (ACO 38). Finally, we merged our data with the 2017 American Community Survey, Area Health Resource File, and the American Hospital Annual survey to capture the geographic and hospital characteristics.ResultsIn 2017, 37% of Medicare beneficiaries with ADRD were enrolled in the ACO. Substantial variation of the ACO participation by patients’ races and ethnicities was observed, ranging from 38% among the white to 14% among the Native ADRD patients. Regression results showed that compared to white, African American, Hispanic, Asian, and Native Medicare beneficiaries with ADRD were significantly less likely to enroll in the ACOs. Among those enrolled in the ACOs, we further observed ACO 8, ACO 36, ACO 37, ACO 38 were significantly higher, i.e. worse quality, among African American, Hispanic, and Native ADRD patients.ConclusionsResults suggested that policymakers should create incentives for minority‐serving providers to participate in ACOs and provide minority‐serving ACOs with structural assistance to ensure that they can successfully attain their performance goals.
Investigating Aβ plaque development using FTIR micro‐spectroscopy on native postmortem human brain tissue
Authors: Röhr Dominik , Boon Baayla D.C. , Großerüschkamp Frederik , Bouwman Femke , Hoozemans Jeroen J.M. , Rozemuller Annemieke J.M. , Gerwert Klaus Bernhard 
Published: December 2020

AbstractBackgroundFourier‐transform infrared microspectroscopy (FTIR) enables the resolution of various chemical compounds and the secondary structure of proteins in tissue sections1. We used FTIR to investigate Aβ plaques with regard to their supposed development process from diffuse to cored plaques. A central process in plaque formation is the misfolding of Aβ and its subsequent assembly into β‐pleated fibrils, which accumulate in amyloid deposits. Misfolded Aβ is believed be neurotoxic and to exhibit oxidative properties2. We aim to contribute to the understanding of mechanisms that lead to the emergence of Aβ plaques and processes that are associated with the characteristic plaque morphologies.MethodFTIR was performed on native human brain sections from AD cases (n = 7, plus 3 control cases). Subsequent immunohistochemical staining against Aβ was performed on the same tissue section. In cooperation with neuropathology experts we conducted a spectral analysis of specific plaque types (N = 167 plaques total), with annotations based on well‐described morphologies (diffuse, compact, classic cored).ResultWe observed increased contents of β‐sheet protein in different plaque types and interpret these findings with regards to proposed maturation sequences3. A red‐shift of the Amid 1 absorbance band suggests the formation of fibrils in plaques. Additionally, we investigated the lipid composition in different plaque types and compared these findings to previously described lipid alterations in AD brain4.ConclusionBy clarifying the relationship between Aβ fibrillation and different plaque types, we give evidence to hypotheses regarding plaque maturation. Our investigation of lipid alterations in plaques illuminate the neurotoxicity of Aβ and its relevance in AD pathology from a different angle. The capability to examine proteins and lipids simultaneously, marker‐free and under native conditions emphasize the research potential of vibrational spectroscopy in neurodegeneration5. References: (1) Kallenbach‐Thieltges, A. and Großerüschkamp, F.; et al., (2013) J. Biophotonics, 6, pp. 88‐100. (2) Butterfield, D. A.; Swomley, A. M. and Sultana, R., (2013) Redox Signal, 19, pp. 823‐835. (3) Thal, D.; et al. (2006) SAGE KE, 6, pp. 1‐9. (4) Prasad, M.; et al., (1998) Neurochem. Res., 23, pp. 81‐88. (5) Shahmoradian, S.H.; et al., (2019) Nat. Neurosci., 22, 1099‐1109.
In support of a national dementia plan: A follow‐up study for dementia incidence and risk profiling in Filipino homes
Authors: Dominguez Jacqueline C , Fowler Krizelle Cleo , De Guzman Ma Fe Payno 
Published: December 2020

AbstractBackgroundDementia is a growing public health priority. Alzheimer’s disease, the most common dementia subtype, is expected to hit 12 million seniors in Southeast Asia by 2050. In the Philippines, a baseline community study found a 10.6% prevalence. (Dominguez et al, 2018) Despite the results, a national dementia plan is yet to be developed. To support the initiative, the study quantifies the dementia incidence of community‐based seniors and determines its risk factors.MethodThis study employed a prospective cohort design, a continuation of the baseline (2009) Marikina Memory and Aging Project (MMAP) in Metro Manila. A total of 1,222 participants were seen to be eligible for follow‐up based on baseline cognition (normal or Cognitively‐Impaired‐Not‐Demented (CIND) status). For dementia incidence, person‐years were calculated. To determine the risk factors, Cox regression was used. Characteristics evaluated were demographics, medical history, and other factors (e.g. living arrangements and MCI status). All analyses were at 95% confidence level.ResultA total of 831 (60.8%) participants were reassessed and the most common reasons for exclusion were migration and unavailability of respondent. The mean follow‐up time for this study was 3.2 years. Incidence rate was at 16 (CI: 13 to 20) cases per 1,000 person‐years (pyr) with 17 (CI: 12 to 21) per 1,000 pyr for females while 14 (CI: 9 to 21) per 1,000 pyr for males. About 4 in every 5 incident cases were Alzheimer’s disease. Note that male seniors had longer years in education, more comorbidities, and more self‐reported alcohol abuse. On the other hand, female seniors experienced more depressive episodes and more of them reported living alone compared to males. Dementia incidence was significantly associated with MCI status and requiring living assistance (controlling for age, sex, and education). Specifically, having such characteristics doubled the risk of having the disease.ConclusionThe Philippines is projected to be one of the countries that would experience the consequences of the rise in dementia cases if left unprepared. The National Dementia Plan must then consider the current state of dementia in the country and the risk factors associated to it for better planning and disease management.
Social support moderates the influence of Alzheimer’s disease–related neurodegeneration on cognitive decline
Authors: Sung Kiyoung , Byun Min Soo , Yi Dahyun , Lee Jun Ho , Ko Kang , Sohn Bo Kyung , Kang Koung Mi , Sohn Chul‐Ho , Lee Dong Young 
Published: December 2020

AbstractBackgroundSocial support (SS) have been associated with decreased rate of cognitive decline in Alzheimer’s disease (AD). However, it is still unclear whether SS can moderate the influence of AD‐related neurodegeneration on cognitive decline. We aimed to test the hypothetical moderation effect of SS on the relationship between AD‐related brain atrophy and cognitive decline.MethodTotal 200 participants from the Korean Brain Aging Study for Early Diagnosis & Prediction of Alzheimer’s disease (KBASE), an ongoing prospective cohort study, were included for this analysis. Of the 200 participants, 130 were MCI and 70 were early AD. All participants underwent comprehensive clinical and neuropsychological assessment, multi‐modal neuroimaging including magnetic resonance imaging, and apolipoprotein E genotyping. AD‐signature cortical thickness (AD‐CT) was defined as a mean cortical thickness of several brain regions known to be sensitive to AD‐specific neurodegeneration. The Medical Outcome Study – Social Support Survey (MOS‐SSS), a 19‐iem brief, multi‐dimensional, self‐report social support survey, were administered to all participants to assess overall SS indices. Global cognitive performance was measured by the total score of the Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological test battery (CERAD‐TS).ResultThere was a significant interaction between AD‐CT and SS on CERAD‐TS. Subgroup analyses demonstrated that the association between AD‐CT and CERAD‐TS was weaker in high SS group than in low SS group.ConclusionOur results suggest that SS may delay the progression of cognitive decline by moderating the influence of AD‐related neurodegeneration.
Effects of candesartan vs. lisinopril on neurocognitive functioning in executive mild cognitive impairment: The CALIBREX trial
Authors: Hajjar Ihab , Okafor Maureen O. , McDaniel Darius , Obideen Malik , Dee Elizabeth , Shokouhi Mahsa , Quyyumi Arshed , Levey Allan I. , Goldstein Felicia C. 
Published: December 2020

AbstractBackgroundObservational studies suggest that angiotensin receptor blockers are associated with lower cognitive impairment. The CALIBREX (CAndesartan vs. LIsinopril effects on the BRain and Endothelial function in eXecutive MCI) trial aims to determine if this neurocognitive outcome in older adults with executive mild cognitive impairment (MCI) is due to blood pressure lowering effects or angiotensin receptors type 1 blockade.MethodA randomized, double‐blind, clinical trial on a sample of 176 participants 55 years or older with mild cognitive impairment (MCI) and hypertension. Individuals were withdrawn from prior antihypertensive therapy and randomized to escalating doses of oral candesartan (up to 32 mg once daily) or lisinopril (up to 40 mg once daily). Open‐label antihypertensive drug treatments were added as needed to achieve blood pressure <140/90 mmHg. Participants underwent neuropsychological assessments at baseline, 6 and 12 months. The primary outcome was executive function (Trail Making Test Parts A and B, TMT) and secondary outcomes were episodic memory (Hopkins Verbal Learning Test‐Revised, HVLT‐R) and neuroimaging evidence of microvascular brain injury reflected by white matter lesions (WML). Outcome analyses followed an intention‐to‐treat approach with linear mixed models adjusted for trial group assignment and the interaction between time (visits) and trial group assignment.ResultOf 176 randomized participants, 141 completed the trial (mean age=65 years; 55% women, 62% African Americans). Blood pressure control was equivalent for both groups but more participants withdrew from the lisinopril arm. At 12 months, the candesartan group had improved cognitive performance on TMT, B‐A (‐16.8 sec, 95% CI [‐30.3, ‐3.3]) while the lisinopril group had worse performance (11.5 sec [‐3.0, 26.0]; P‐value group*time=0.008). HVLT‐R delayed recall improved with candesartan by 1.0 (95% CI [0.3, 1.5]) whereas lisinopril improved by 0.3 (95% CI [‐0.3, 1.0]); P‐value group*time =0.026. There was no significant change in WML volume with candesartan (0.2 mm3, 95% CI [‐0.2, 0.7]) while the lisinopril group had a significant increase (0.9 mm3, 95% CI [0.4, 1.4]; P‐value group*time=0.06.ConclusionCandesartan demonstrates superior cognitive outcomes compared to lisinopril and may offer unique neurocognitive protection in older adults with executive MCI and hypertension.
Association of cognitive performance and psychological traits with diffusion‐weighted tract metrics in older adults with subjective cognitive decline and mild cognitive impairment
Authors: Wurdack Katharina , Schwarz Claudia , Benson Gloria , Horn Nora , Hayek Dayana , Köbe Theresa , Antonenko Daria , Wirth Miranka , Flöel Agnes 
Published: December 2020

AbstractBackgroundSubjective Cognitive Decline (SCD) may represent the earliest clinical manifestation of Alzheimer’s disease (AD) (Jessen et al. 2014). In individuals with SCD and mild cognitive impairment (MCI), changes in white matter (WM) microstructure have been shown using diffusion weighted (DW) imaging (Brueggen et al. 2019). However, it is unknown to which extent these alterations are associated with cognitive and psychological deficits. Thus, this study aims to investigate the relationship between WM tract metrics and cognitive performance as well as psychological traits in pre‐dementia stages of AD.MethodIn total, 88 patients with MCI, 90 individuals with SCD, and 47 healthy controls (mean age 69±7 years) underwent neuropsychological testing and DW magnetic resonance imaging. Selected questionnaires on stress coping, worry, and rumination were included to evaluate the psychological profile of SCD. Fractional Anisotropy (FA) and Mean Diffusivity (MD) from the DW images were obtained for selected WM tracts of interest using the TRACULA pipeline (Yendiki et al. 2011). Composite scores for memory and executive function were calculated. General linear models adjusted for age, sex, education, cardiovascular risk, and group membership were conducted. Due to the exploratory nature of this study, we did not correct for multiple testing.ResultAcross the entire study sample, higher memory performance was associated with DW parameters of the angular bundle of the cingulum (higher FA, p=0.004; lower MD, p=0.019). Higher FA of the anterior thalamic radiation (ATR) was related to a lower memory score (p=0.049). Higher executive function was related to DW metrics of the uncinate fasciculus (UNC) (higher FA, p=0.038; lower MD, p=0.034) and of the ATR (lower MD, p<0.001). Within SCD subjects, MD of the UNC was positively associated with positive stress coping strategies (p=0.005).ConclusionOur findings suggest that higher memory performance and executive functions are associated with favourable tract‐specific DW parameters in pre‐dementia stages of AD. The relationship of higher positive stress coping with WM microstructural alterations in SCD (i.e., increased MD of the UNC) might be explained by psychological compensatory mechanisms in the presence of early WM pathology. Further investigation is needed to elucidate possible clinical implications of these findings.
Alzheimer’s disease–related atrophy patterns in different definitons of subjective cognitive decline
Authors: Karakaşlı Ahmet Alp , Özkan Esra , Zorlu Nabi , Dogan Melike Karacam , Çap Duygu , Karaosmanoğlu Ayça , Karahan Sevilay , Saka Esen , Ayhan Yavuz 
Published: December 2020

AbstractBackgroundDifferent criteria sets were suggested for better operationalization of subjective cognitive decline. In this study, we aimed to assess structural neuroimaging biomarkers of AD in different definitions of SCD.MethodThe study was conducted at Hacettepe University, Turkey. 101 participants over 55 years of age, with memory complaints and no identifiable impairment in a valid cognitive screening test (Z scores>‐1.5 in the Modified Mini Mental Test 3MS) were included. We evaluated whether (i) using a scale (Subjective Memory Complaints Questionnaire‐SMCQ) rather than a single question assessing the subjective complaint; (ii) utilizing neuropsychological test data in addition to a screening test; (iii) evaluating SCD + criteria (additional qualitative features of the complaint) and (iv) the exclusion of comorbidities that may be associated with memory complaints; would be associated with increased atrophy in AD‐related areas. Three different cortical thickness and two cortical volume patterns based on previous research were determined as the dependent variables. MR images were obtained with a 1.5 Tesla MRI scanner. Cortical thickness and gray matter volumes were estimated using the FreeSurfer Software package version 6.0 on 3D T1‐weighted MRI scans (MP RAGE), in accordance with ADNI‐1 MRI acquisition protocol. The multivariate regression models were performed for evaluating the relationship of each independent variable.ResultResults suggested that age, sex, age of onset of memory complaints, depression or anxiety symptoms and vitamin B12 and vitamin D levels were associated with alterations in the structural markers of AD. Regarding different definitions of SCD; assessment of SCD + criteria, utilizing SMCQ, addition of neuropsychological test data and excluding individuals with comorbidities did not contribute to the validity of SCD in terms of the AD morphology.ConclusionOur findings indicate the importance of psychiatric evaluation in individuals with subjective memory complaints. The presence of depression and anxiety symptoms in a person with SCD may increase the likelihood of AD‐related brain morphological changes. Longitudinal studies, better assessment of the phenotype, inclusion of different diagnostic groups may help to refine the definition of SCD and the addition of criterion which may point to early morphological changes. This study has been funded by TUBITAK 214S048, Hacettepe THD‐2018‐17363.
Peripheral inflammation influences α‐synuclein toxicity and neuropathology in Parkinson’s disease models
Authors: Vitola Pietro , Balducci Claudia , Baroni Michela , Santamaria Giulia , Artioli Luisa , Castiglioni Marta , Caldinelli Laura , Pollegioni Loredano , Forloni Gianluigi 
Published: December 2020

AbstractBackgroundParkinson’s disease (PD) and its related disorders, including Lewy body dementia, are devastating progressive neurodegenerative pathologies arising from the interaction between environmental factors and genetic susceptibility. Since the discovery of α‐synuclein as the main constituent of Lewy bodies and neurites, and the identification of mutations in the gene encoding for the protein in familial form of PD, numerous efforts have been made to clarify the pathogenic role played by α‐synuclein. Oligomeric assemblies of α‐synuclein, originating from its aberrant aggregation, represent the most harmful species. Besides direct action on neurons, α‐synuclein oligomers may act through non‐cell‐autonomous pathways involving chronic and/or dysregulated activation of glial cells. Initially considered as a mere secondary phenomenon, inflammation is now viewed as the bridge between genetic susceptibility and environmental factors co‐fostering PD.MethodTo get direct insight on the role of neuroinflammation in influencing PD pathogenesis, we have developed a “double‐hit” in vivo approach, based on the peripheral administration of lipopolysaccharides (LPS) to C57 naïve mice, followed, one month later, by the intracerebroventricular injection of low dose of α‐synuclein oligomers characterized by atomic force microscopy. LPS was also injected to a‐synuclein A53T transgenic mice, motor and cognitive behavior was analyzed together with histopathological examinations in both models.ResultLPS induced a long‐lasting inflammatory response in the CNS, facilitating the detrimental activities of α‐synuclein oligomers: memory deficits and histopathological alterations. LPS‐activated microglia and astrocytes respond differently to the oligomers, with microglia further activated and acquiring a proinflammatory M1 phenotype, and astrocytes appearing atrophic. In addition, the peripheral administration of LPS in the A53T transgenic PD mouse model aggravated cognitive deficits, together with an increased microgliosis. Again, astrocytes responded differently from microglial cells to the double challenge presented by A53T genetic background and the treatment with LPS.ConclusionThe peripherally‐induced neuroinflammation potentiates the α‐synuclein oligomer actions and aggravates cognitive deficits in A53T mice. The management of both peripheral and central inflammation may offer a promising therapeutic approach to prevent or slow down some pathological aspects in α‐synucleinopathies.
Effect of APOE‐E4 gene dose on regional early neuroinflammation and beta‐amyloid deposition in cognitively normal elderly volunteers
Authors: Snellman Anniina , Ekblad Laura L. , Tuisku Jouni , Helin Semi , Bucci Marco , Karjalainen Tomi , Parkkola Riitta , Karrasch Mira , Rinne Juha O. 
Published: December 2020

AbstractBackgroundEpsilon 4 allele (E4) of APOE gene is an important genetic risk factor for late onset Alzheimer’s disease (AD). We investigated differences in regional neuroinflammation and beta‐amyloid (Aβ) deposition in vivo in cognitively normal homozygotic (Group 1: E4/E4) or heterozygotic (Group 2: E4/E3) carriers of the APOE*E4 allele in comparison to non‐carriers (Group 3: E3/E3), using [11C]PK11195 and [11C]PIB positron emission tomography (PET).Method60‐75‐year‐old participants with known APOE genotype were recruited via Auria Biobank (Turku, Finland). For this interim analysis, altogether 22 subjects with MMSE scores ≥ 26 were included (E4/E4 n=10; E4/E3 n=5; E3/E3 n=7). All participants underwent [11C]PIB PET, [11C]PK11195 PET, brain 3T‐MRI and neuropsychological testing. Tracer uptake was evaluated as standardized uptake value ratios (SUVR60‐90; [11C]PIB) or distribution volume ratios (DVR; [11C]PK11195) in a composite volume‐of‐interest (VOI) for Aβ deposition (including prefrontal cortex, precuneus, parietal cortex, anterior cingulate, posterior cingulate and lateral temporal cortex) and in medial temporal cortex for tau deposition. Analysis was performed using non‐parametric Kruskall‐Wallis and Spearman’s correlation tests.ResultDifferences between groups did not reach statistical significance yet in this interim analysis. However, a progressive increase in [11C]PIB uptake from E3/E3 (SUVR60‐90 1.8 ± 0.7) to E4/E3 (SUVR60‐90 2.0 ± 0.6) and E4/E4 (SUVR60‐90 2.4 ± 0.6) was already seen in the composite VOI including brain regions typical for early Aβ accumulation1 (Figure 1). CERAD total score had a fair negative correlation with [11C]PIB composite SUVR60‐90(rs= ‐0.48, p=0.023) in the whole population. In addition, a trend towards higher [11C]PK11195 uptake in E4/E4 (DVR 1.26 ± 0.08) compared to E3/E3 (DVR 1.18 ± 0.03) in the composite VOI was detected (p=0.07), but no correlation between [11C]PK11195 composite DVR and CERAD total score (rs= ‐0.13, p=0.58), or [11C]PIB SUVR (rs= ‐0.005, p=0.98) was found.ConclusionThe study is still ongoing; however, the interim data suggest that cognitively intact elderly APOE*E4 carriers have both higher Aβ deposition and higher level of activated glia in the brain regions typical for early AD pathology.