bluuebunny/crossref_metadata_2025_split huggingface dataset:
Describing trends in the quality of health care and services for men and women living with dementia
Authors: Bui Tammy X , Arsenault‐Lapierre Genevieve , Sourial Nadia , Godard‐Sebillotte Claire , Rochette Louis , Vedel Isabelle 
Published: December 2020

AbstractBackgroundAs the Canadian population ages, challenges have emerged with the quality and healthcare utilization of services for persons living with dementia (PWD). These challenges may be exacerbated when we consider the sex inequalities. A disconcerting trend in sex differences has arisen among older adult women, where they are more disadvantaged compared to older men when seeking and receiving treatment. The aims of this study are to describe the quality of dementia care and healthcare utilization among PWD by sex.MethodsThe study will employ a repeated annual cross‐sectional cohort design over 15 years using linked administrative databases to examine health service use data. All incident cases of dementia in community‐dwelling persons aged 65 and over occurring between April 1st and March 31st for each year will be included. Dementia diagnosis will be ascertained using a validated algorithm. Quality of care indicators include: most regularly seen doctor (Overall UPC index), hospitalization for ambulatory care sensitive conditions, continuity of care (Bice‐Boxeman index), degree of coordination (30‐day hospital readmission). Healthcare utilization indicators include: emergency department visits, hospitalizations, alternate level of care, visits to primary care physicians and cognition specialists, long‐term care admission and mortality. Data will be stratified by sex.Results237,259 people (62.7% women) were included in the analyses. Variations over time and between men and women are observed in healthcare utilization indicators including emergency department visits, hospitalizations, alternate level of care, visits to primary care physicians and cognition specialists, long‐term care admission and mortality. For each indicator, graphs will be presented with an annual rate, adjusted for age and follow‐up time in the study.ConclusionAddressing the knowledge gap in the quality of care and healthcare utilization in PWD by sex is essential to inform decision‐makers for the implementation of adequate policies to promote equity in dementia care and ultimately improve the health among men and women living with dementia.
RNA aptamers that recognize amyloid β oligomers in AppNL‐G‐F/NL‐G‐F mice as a model of arctic Alzheimer disease
Authors: Murakami Kazuma , Obata Yayoi , Kawase Taiji , Hirose Kenji , Izuo Naotaka , Shimizu Takahiko , Irie Kazuhiro 
Published: December 2020

AbstractBackgroundRNA aptamers have garnered attention for diagnostic applications due to their ability to recognize diverse targets. Oligomers of Aβ42 are among the most difficult molecules for aptamer recognition because they are prone to aggregate in heterogenous forms. In addition to designing haptens for in vitro selection of aptamers, the difficulties involved in determining their effect on Aβ42 oligomerization impede aptamer research. We previously developed three RNA aptamers (E22P‐AbD4, ‐AbD31, and ‐AbD43) with high affinity for protofibrils (PFs) derived from a toxic Aβ42 dimer (Murakami, K. et al., J. Biol. Chem.
2020, 295, 4870–4880). In this study, these aptamers were further validated for specificity to oligomers using ion‐mobility mass spectrometry and a knock‐in AppNL‐G‐F/NL‐G‐F
mouse harboring the Arctic mutation (E22G‐Aβ).MethodThe ability to inhibit oligomer formation of Aβ42 was evaluated by ion mobility‐mass spectrometry, which can avoid the disruption of non‐covalent interactions among Aβ oligomers without using organic solvents, leading to observation of the near‐native status of oligomers in the presence of aggregation inhibitors. The immunostaining of Aβ oligomers in the brain was carried out using a knock‐in AppNL‐G‐F/NL‐G‐F
mouse that is prone to induce PF formation as a Arctic AD model, provided by Dr. Saido (RIKEN). The prediction of G‐quadruplex was estimated based on quadruplex‐forming G‐rich sequences (QGRS) Mapper.ResultRNA aptamers recognized diffuse aggregates, which likely originated from PFs in a knock‐in AppNL‐G‐F/NL‐G‐F
mouse in addition to a PS2Tg2576 mouse. E22P‐AbD43 formed the adducts with Aβ42 monomer and dimer, leading to suppression of further oligomerization. In particular, the G‐quadruplex structure might be relevant to the binding of the aptamers (E22P‐AbD4 and ‐AbD31) to oligomers.ConclusionThe current data support the utility of these RNA aptamers as a promising diagnostic tool for AD research.
Relationship of parieto‐occipital brain energy phosphate metabolism and cognition using 31P MRS at 7TESLA in preclinical stages of Alzheimer’s disease
Authors: Das Namrata 
Published: December 2020

AbstractBackgroundNeuroenergetics, a study of brain energy metabolism (BEM), may uncover cues for early disease biomarkers that potentially trigger downstream neuropathological changes in amnestic mild cognitive impairment (aMCI), a transitory stage of Alzheimer’s disease (AD). Advancements in brain imaging modalities, such as in vivo 31phosphorus magnetic resonance spectroscopy (31P MRS) at higher magnetic strength, offer promising platforms to measure energy and membrane phospholipid metabolites, a window to understand BEM. The primary goal was to quantify distinct features of phosphorus metabolites in parieto‐occipital lobes using 31P MRS at 7Tesla in aMCI. Another objective was to examine the clinical significance of the metabolites to brain‐behavior relationships. Specifically, we examined the correspondence across BEM and membrane phospholipid indices in parieto‐occipital regions of the brain with cognitive performance‐ executive functions (EF), memory, attention, and visuospatial skills.Methods19 aMCI participants enrolled in the study. Each participant completed a cognitive assessment and a scan using partial volume‐coil 31P MRS over parieto‐occipital lobes at 7Tesla. BEM indices were measured using three energy indicators: energy reserve (PCr/t‐ATP), energy consumption (intracellular_Pi/t‐ATP), and metabolic state (PCr/intracellular_Pi) along with regulatory co‐factors of BEM‐intracellular Mg2+ and pH; whereas the ratio of phosphomonoesters (PMEs) to phosphodiesters (PDEs) represented membrane phospholipid indicator.Results
31P MRS data over parieto‐occipital lobes showed thirteen well‐resolved peaks of the energy and membrane phospholipid metabolites at 7Tesla. The higher BEM indices were associated with lower cognitive performance of memory [(energy reserve indicator: CVLT p=0.004), (metabolic state indicator: CVLT p=0.007)], executive function [(metabolic state indicator: TOSL (p=0.044)], and attention [(pH: selective auditory task, p=0.044)]. The finding of higher brain energy indices in the parieto‐occipital lobes associated with lower cognition may represent compensatory hypermetabolism during the early stages of brain disturbances in aMCI.ConclusionThe critical contribution of this work was to develop and test a methodology to quantify neurometabolic markers of energy and membrane phospholipid metabolites at 7Tesla in aMCI. Additionally, the study findings implicated the role of BEM as an early neurometabolic marker of brain changes linked to cognitive decline in the preclinical stages of AD.
Transcranial detection of tauopathy in vivo in P301L mice with high‐resolution large‐field multifocal illumination fluorescence microscopy
Authors: Ni Ruiqing , Chen Zhenyue , Gerez Juan A , Shi Gloria , Zhou Quanyu , Riek Roland , Nilsson K Peter R , Razansky Daniel , Klohs Jan 
Published: December 2020

AbstractBackgroundTau abnormal aggregates have been visualized in‐vivo using intravital microscopy techniques with high resolution, but are limited to a small field‐of‐view and depth. Here, we report a new method for the transcranial detection of tau deposits accross the brain with 6 μm resolution.MethodIn vitro Thioflavin T fluorescence assay was performed to screen fluorescence imaging probes that bind to tau fibrils. P301L (Thy1.2) mouse models of frontal temporal lobe dementia with four repeat tau and non‐transgenic littermates were imaged in vivo using a novel large‐field multifocal illumination (LMI) fluorescence microscopy technique using luminescent conjugated oligothiophenes h‐FTAA. Immunohistochemical staining were performed on P301L mouse brain tissue sections using anti‐phosphorylated tau antibodies AT8 and AT100.ResultIn vitro Thioflavin T fluorescence assay and LMI imaging shows that h‐FTAA bind to recombinant full‐length tau fibrils. In vivo LMI imaging using h‐FTAA showed higher retention in the cortex of P301L mice at 10 month‐of‐age compared to age‐matched non‐transgenic littermates. Immunohistochemical staining on P301L mouse brain tissue sections showed co‐localization of h‐FTAA with anti‐phosphorylated tau antibodies AT8 and AT100, thus verifying the specificity of the probe to tauopathy in P301L mice.ConclusionWe demonstrate a new in vivo high‐resolution imaging platform for detection of tauopathy in murine models of frontal temporal lobe tauopathy.
Microglial senescence: The missing link between hypertension and neurodegeneration?
Authors: Al‐Shama Rushd , Naessens Daphne MP , van Bavel Ed , Bakker Erik NTP 
Published: December 2020

AbstractBackgroundHypertension is a major risk factor for dementia. Hypertension is associated with neuroinflammation and neurodegeneration, however, the exact link is unclear. Microglia can undergo senescence, resulting in primed and dystrophic cells that can contribute to the development of Alzheimer’s disease. We hypothesized that microglia are affected by cumulative hypertensive brain injury and reflect an ongoing inflammatory and neurodegenerative pathology.MethodAn in‐depth immunohistochemical analysis of microglia was done on the brains of Spontaneously Hypertensive Rats (SHR) and their genetic controls, Wistar Kyoto rats (WKY); n=5 each. The number of cells and morphological features, such as size, number of branches, and branch length, were measured. We qualitatively assessed microglia for the presence of characteristic dystrophic cells then performed fractal analysis on individual cells to quantitate their morphologies.ResultSHR microglia were more numerous and exhibited signs consistent with senescence and priming, with shorter, fewer branches and the sizes of their cell bodies were larger and more heterogeneous (p<0.05). In SHR, 2.91% of microglia were dystrophic as compared to 0.32% in WKY (p=0.01). Using fractal analysis, we confirmed the presence of dystrophic cells and distinctly characterized them against ramified cells based on 3 main characteristics: complexity, shape, and branching.ConclusionMicroglial senescence, an indicator of neuroinflammation and neurodegenerative pathology, is associated with hypertension. It could thus serve as a therapeutic target and may help identify novel biomarkers. Moreover, fractal analysis is a useful tool to quantify meaningful subtleties.
Hypertension produces a cumulative negative effect on cognition independently of diabetes in late life
Authors: Moll Allison C. , Woodard John L. 
Published: December 2020

AbstractBackgroundHypertension impacts approximately 33% of US adults broadly, and specifically 65% of persons over 60 years of age. Previous research has shown that hypertension produces damage in cerebral blood vessels, leading to neuropathological changes and possibly promoting Alzheimer’s disease pathology. Hypertension is often comorbid with diabetes mellitus (DM). While most studies show an association of hypertension and DM with worse cognition, the time course of emerging cognitive deficits related to hypertension in late‐life is less clear. This study contrasted older adults with and without self‐reported hypertension and diabetes at two time points in late‐life (MBaseline age
=64.3 years, SD1
=0.7; MFollow‐up age
=71.2 years, SD2
=0.9), separated by approximately seven years.MethodsParticipants included 4,594 1957 high school graduates from the Wisconsin Longitudinal Study, a publicly available database that includes high school graduates who were followed longitudinally until 2011. Cognitive, demographic, and health variables from the 2003‐2005 (baseline) and 2011 (follow‐up) waves were used. Cognitive assessment included Letter Fluency, Category Fluency, Digit Ordering, Similarities, and Immediate and Delayed Recall of a 10‐word list. Bayesian independent t‐tests examined the effect of self‐reported hypertension on cognition at baseline and follow‐up, as well as the effect of self‐reported hypertension on cognition in persons with and without diabetes.ResultsSelf‐reported hypertension over seven years was associated with worse Digit Ordering and Letter and Category Fluency performance at follow‐up, relative to persons without self‐reported hypertension. No baseline cognitive differences were observed between groups. Participants with self‐reported hypertension showed greater decline in Letter Fluency and Digit Ordering compared to persons without self‐reported hypertension. Diabetes negatively impacted cognition at baseline, follow‐up, and over the seven‐years. However, the negative effect of hypertension on cognition was still present in the absence of diabetes.ConclusionsWhile no cognitive differences between persons with and without hypertension in their mid‐60s were observed, cognitive decline in persons with self‐reported hypertension was observed over seven years. These findings suggest a cumulative negative impact of hypertension on cognition, particularly in late‐life, exclusively on measures of executive functioning rather than on episodic memory measures. Additionally, the effects of hypertension on cognition were independent of the cognitive effects of diabetes.
The impacts of Chinese cultural adherence to filial piety on the dementia care decision processes in East Asian communities
Authors: Kuo Ching‐Yi 
Published: December 2020

AbstractObjectivesDeveloping knowledge of Chinese cultural adherence to filial piety helps understand Dementia in the Asian Pacific Regions regarding its dementia care practices and medical system cluster around filial piety.BackgroundChinese filial piety has been deeply rooted in East Asian culture for over five thousand years, affecting life choices, including medical treatments decisions and end‐of‐life care decisions for family members. Regardless of their level of westernization, Chinese filial piety continues to play a key role in determining timely diagnosis, and institutionalization of a person with dementia. As characterized by collectivism, filial piety also explicitly directs informal caregivers' careers paths, mental health, and physical health, especially for females. Consequently, dementia care practices and medical system in East Asian communities cluster around the level of practice of filial piety, which directly affects dementia care decision making processes as well as the welfare of a person with dementia and costs to society.MethodsA systematic literature review for the previous decade on filial piety will be employed. Implications: Through developing knowledge of underlying cultural adherence to dementia care practices in East Asian communities, government, social policies, and professionals across the fields as a whole can develop a better supportive environment for persons with dementia and their caregivers.
Fear of memory decline predicts lower quality of life and increased memory failures in older adults: Preliminary findings from a novel fear‐avoidance of memory decline scale
Authors: Farina Francesca R , Bennett Marc P , Griffith James W , Lenaert Bert 
Published: December 2020

AbstractBackgroundEvidence concerning the impact of dementia‐related fear on health‐related outcomes is limited. Our aim was to determine the relationship between fear of dementia, quality of life and subjective memory in older adults using a novel scale to measure fear of memory decline (FAM scale).MethodSixty‐seven older adults (59‐81 years) completed a 23‐item self‐report scale designed to capture experiential, cognitive and behavioral components of fear of memory decline. Memory performance was assessed using the Wechsler Memory Scale (WMS‐IV) and the Memory Failures Scale (MFS). General anxiety was assessed using the Depression, Anxiety and Stress Scales (DASS) and the Geriatric Anxiety Inventory (GAI). Quality of life was assessed using the Older Person’s Quality of Life scale (OPQOL‐35).ResultThe FAM scale demonstrated strong internal consistency (α=.82) and concurrent validity (r=.47 with GAI scores). Three latent factors were observed, which were: (1) fear‐avoidance, (2) problematic beliefs and (3) resilience. After adjusting for age, education, objective memory performance and general anxiety, higher fear‐avoidance predicted lower quality of life (p=.021) and increased memory failures (p=.022).ConclusionIncreased fear of memory decline predicts lower quality of life and subjective memory failures in healthy older adults. Based on these findings, we propose a preliminary fear‐avoidance model that explains the development and maintenance of dementia‐related functional disability in terms of psychological processes.
Variability in tau‐atrophy relationships reveals underlying phenotypes in individuals on the Alzheimer’s disease continuum
Authors: Das Sandhitsu R , Xie Long , McCollum Lauren , de Flores Robin , Irwin David J , Nasrallah Ilya M , Dickerson Brad C , Yushkevich Paul , Wolk David A ,   Alzheimer's Disease Neuroimaging Initiative
Published: December 2020

AbstractBackgroundTau neurofibrillary tangles (T) are thought to be the primary driver of downstream neurodegeneration (N) and subsequent cognitive impairment in AD. However, there is substantial variability in the T‐N relationship – manifested in higher or lower atrophy than expected for the level of tau in a given brain region. We quantitatively describe and categorize source(s) of variability using region‐based measures of T and N to gain insight into underlying modulatory factors, including polypathology.MethodRegional cortical thickness and 18F‐Flortaucipir SUVR were computed in 108 gray matter ROIs from cognitively‐impaired, amyloid‐positive individuals (n=137) in ADNI. ROI‐specific residuals from a robust linear fit between SUVR and cortical thickness were computed. Using a threshold of +/‐ 1.5 standard deviation (S.D.), ROIs were categorized into “positive”, “negative”, or “neutral” residual (Fig 1). The residual signs for all ROIs were used in a hierarchical clustering framework to partition the dataset.ResultSix groups appear to represent different phenotypes summarized in Table 1. Overall, the groups differed in age, burden of white matter hyperintensity (WMH), clinical status, and MMSE. However, they did not differ in tau burden in key brain ROIs (e.g. inferotemporal cortex, precuneus, angular gyrus). Group 1 is largest, consisting of individuals with low residuals described as having a canonical “T‐N” relationship. Group 2 has significantly higher temporolimbic atrophy relative to tau with many cases having a pattern of atrophy suggestive of TDP‐43 copathology. Group 3 appears to be a resilient phenotype with less atrophy relative to tau in lateral cortical regions. Group 4 is similar to Group 2 with high temporal atrophy, but also more diffuse atrophy. Group 5 also displays resilience, particularly in the temporal lobe. Group 6 shows widespread higher atrophy relative to tau, has the lowest MMSE and highest WMH.ConclusionWe demonstrate that a measure of deviation from a normative relationship between tau burden and neurodegeneration across brain regions in individuals on the AD continuum captures variability due to multiple underlying factors, and can reveal phenotypes, which if validated, may be helpful for identifying possible contributors to neurodegeneration in addition to tau, which may ultimately be useful for cohort selection in clinical trials.
Is the engagement in social and cognitive type of leisure activities protective against dementia risk? Evidence from the English Longitudinal Study of Ageing
Authors: Almeida‐Meza Pamela , Steptoe Andrew , Cadar Dorina 
Published: December 2020

AbstractBackgroundStudies have suggested that mentally stimulating activities and a socially engaged lifestyle have protective effects for dementia prevention; however, it is unclear which activities are more beneficial. This study aimed to investigate the role of cognitive and social type of leisure activities in relation to dementia incidence over a 15‐year follow up.MethodsThe analytical sample was comprised of 8,205 participants aged 50 years and older from the English Longitudinal Study of Ageing, who joined the study at wave 1 (2002‐2003), or at waves 3 (2006‐2007), or 4 (2008‐2009). Dementia was ascertained at every wave up to wave 8 (2016‐2017). Leisure activities were grouped into 6 cognitive activities (e.g. attending art classes) and 7 social activities (e.g. meeting with friends). Cox proportional hazard regression models were used to estimate the hazard ratios (HR) of dementia in relation to engagement in cognitive and social type of leisure activities. The models were adjusted for sex, marital status, education, wealth, physical health and health behaviours. A sensitivity analysis was carried out for a sub‐sample of 5,056 participants with APOEe4 data.ResultsDuring the follow‐up period, 413 (mean age 74) participants developed dementia. We found that with every additional cognitive activity, the hazard of dementia decreased by 11% (HR 0.89, 95% CI 0.82‐0.97, p=0.013), while for every additional social activity the hazard of dementia decreased by 8% (HR 0.92, 95% CI 0.85‐0.99, p=0.035). The association between social activities and dementia was maintained even after additional adjustment for APOEe4 (HR 0.90, 95% CI 0.81‐0.99, p=0.047), but not the association with cognitive activities. Individual analyses for each leisure item showed a significant independent association for reading the newspaper (HR 0.79, 95% CI 0.64‐0.97, p=0.029), having hobbies (HR 0.74, 95% CI 0.58‐0.93, p=0.012), and being a member of sports clubs (HR 0.71, 95% CI 0.52‐0.97, p=0.033).ConclusionsEngagement in various cognitive and social type of leisure activities was found to be protective against dementia risk. Noticeable effects were observed for reading the newspaper, having hobbies and being a member of sports club. Interventions to engage adults in opportunities for cognitive and social leisure participation are warranted.