bluuebunny/crossref_metadata_2025_split huggingface dataset:
Faster rates of tau accumulation in FTP‐PET in females relative to males, and a cross‐sectional influence on faster cognitive decline: Preliminary findings from HABS and ADNI
Authors: Buckley Rachel F. , Properzi Michael J. , Schultz Aaron P. , Scott Matthew R. , Jacobs Heidi I.L. , Farrell Michelle E. , Kirn Dylan , Hanseeuw Bernard J. , Amariglio Rebecca , Rentz Dorene , Johnson Keith A. , Sperling Reisa A. 
Published: December 2020

AbstractBackgroundClinically normal older females exhibit higher cross‐sectional 18F‐Flortaucipir (FTP)‐PET signal, but not Aβ‐PET, than males, particularly in temporal regions. What remains unclear is the extent to which these findings represent a real biological phenomenon as opposed to a methodological bias. Here, we explored sex differences in longitudinal tau accumulation, and how contemporaneous rates of FTP‐PET, Aβ‐PET and cognitive change may be modified by sex.MethodWe examined 128 clinically‐normal participants from the Harvard Aging Brain Study (HABS; 60% Female, Age=75(6.6)years) with at least two time‐points of contemporaneous FTP‐PET, PiB‐PET and cognition. Also, 153 ADNI participants with at least two time‐points of FTP‐PET (nCN=94/nMCI=59; 50% Female, Age=73(6.4)years), and with prospective longitudinal AV45‐PET and cognition (n=131). Mean follow up was 3.3yrs (range=1.2‐6.2yrs) and 1.4yrs (range=0.6‐3.3yrs), respectively. For FTP‐PET we exclusively examined the inferior temporal lobe (non‐partial volume corrected, cerebellar greyreference), for Aβ‐PET we used the PiB summary measure in HABS (cerebellar greyreference) and the AV‐45 summary measure in ADNI (whole cerebellumreference). For cognition, we used the Preclinical Alzheimer Cognitive Composite (PACC). We examined relationships between contemporaneous longitudinal FTP‐PET, Aβ‐PET, and cognitive performance using linear mixed models, adjusting for age, years of education and random intercept.ResultIn HABS, females exhibited faster rates of FTP‐PET accumulation than males, but only with increasing rates of Aβ‐PET accumulation (t=1.93, p=0.003; see Figure 1A). In ADNI, females exhibited faster rates of FTP‐PET accumulation, not moderated by Aβ‐PETchange (t=2.92, p=0.004; see Figure 1B). Sex did not moderate the relationship between FTP‐PET and PACC change in HABS or ADNI (see Figure 2.). We did, however, find that females with higher baseline FTP‐PET resulted in faster PACC decline than men in only clinically‐normal individuals in both cohorts (t=‐1.86ADNI,‐2.72HABS, p∼0.02; see Figure 3.).ConclusionThese findings support a female susceptibility to tau as a biological phenomenon of accelerated tau accumulation in AD‐vulnerable regions. A lack of an association between changing tau and changing cognition remains to be understood. It is possible that our models are picking up more on the ‘severity of burden’ (e.g. baseline tau) to influence faster rates of decline in females, rather than dynamic change per se.
Clinical assessment of sleep disorders in elders with Alzheimer’s disease and their relationship with intracranial pressure using a non‐invasive method
Authors: Ribeiro Estela B , Ramos Caio Freitas , Vale Francisco Assis Carvalho , Frigieri Gustavo 
Published: December 2020

AbstractBackgroundLiterature establishes that sleep disorders (SD) possess strong correlations with Alzheimer’s Disease (AD) derivations and the more resources are found to perform assessments, the better and earlier diagnoses can be performed. Thus, allowing early interventions that could improve the quality of life of the person with AD. This study aims at verifying whether there are alterations in the intracranial pressure (ICP) of elder patients with AD and SD when compared to elders patients with AD but without SD.MethodThe sample was obtained in the Ambulatory of Cognitive‐Behavioural Neurology (ANEC) at UFSCar, in partnership with BrainCare® company, which developed a new method for non‐invasive intracranial pressure measurement.ResultMost of the sample was composed of females. The most frequent CDR was 3 in the AD Group, indicating a more advanced dementia stage. When analyzing the full group, without subdivisions, a correlation between T2/T1 (p=0,01/ρ=‐0,42) was verified as dimensions that assessed night behavior. More specifically, when the elders were questioned about awakening several times at night and if they had the habit of rising up during the night (p=0,04/ρ=‐0,36). No correlations were found between the ICP assessments and other variables of this study. However, when the subjects were subdivided into patients with SD or without SD, the results were different compared to the general assessment.ConclusionDue to the novelty of this study, it was not possible to discuss the findings with previous literature. Nevertheless, the study presents a limitation related to the size of the sample; a widening of the sample size would possibly have led to different findings. Although no difference between patients with AD and TS was found in the assessment of the ICP morphology, there was a difference between the groups with AD and without AD. Similar studies should consider expansion and evaluation within different contexts.
Association between cerebral amyloid accumulation and synaptic density in Alzheimer’s disease: A multitracer PET study
Authors: O'Dell Ryan S. , Mecca Adam P. , Chen Ming‐Kai , Godek Tyler A. , Harris Joanna E. , Bartlett Hugh H. , Banks Emmie R. , Kominek Victoria L. , Zhao Wenzhen , Naganawa Mika , Toyonaga Takuya , Lu Yihuan , Nabulsi Nabeel B. , Ropchan Jim R , Ye Yunpeng , Vander Wyk Brent C. , Varma Pradeep , Arnsten Amy F.T. , Huang Yiyun , Carson Richard E. , van Dyck Christopher H. 
Published: December 2020

AbstractBackgroundSynaptic loss is an early pathology in Alzheimer’s disease (AD) and the major structural correlate of cognitive impairment. We have recently demonstrated extensive synaptic loss in medial temporal and neocortical brain regions of participants with AD. In this study, we further investigate the association of global and local amyloid burden with synaptic density in AD using [11C]UCB‐J PET.Method[11C]UCB‐J and [11C]PiB binding were measured in 38 participants with AD and 19 cognitively normal participants aged 55‐85 years. For [11C]PiB analysis, parametric images of binding potential (BPND
) were generated using SRTM2 with cerebellum as a reference region and converted to distribution volume ratios (DVR). For [11C]UCB‐J, BPND
was computed using SRTM2 with a shrunken centrum semiovale reference region and converted to DVR with a cerebellum reference region.ResultThe AD group showed significant widespread reductions in cortical and subcortical synaptic density, most pronounced in medial temporal lobe, and significantly elevated cortical amyloid in regions commonly affected by AD pathology (Figure 1). Among pooled participants (n=57), higher global amyloid burden was associated with lower synaptic density in the majority of regions. Significant negative associations between local amyloid and SV2A were also observed across the majority of cortical regions in the pooled sample (lateral temporal, prefrontal, posterior cingulate/precuneus, lateral parietal, and lateral occipital; r=‐0.29 to ‐0.48, p<0.05) with the exception of medial temporal (r=‐0.18, p=0.17), anterior cingulate (r=‐0.19, p=0.15), and pericentral (r=‐0.23, p=0.08) cortices (Figure 2). These significant associations between either global or regional amyloid and SV2A were not observed in analyses restricted to the AD group, in both an region‐ or surface‐based analysis (Figure 3).ConclusionUsing [11C]UCB‐J PET, widespread reductions of synaptic density were observed in AD participants. Cortical regions associated with the least accumulation of fibrillar amyloid (medial temporal lobe) were associated with the most pronounced reductions in synaptic density. Significant negative associations between both global and local amyloid and synaptic density in the pooled sample were driven by group differences, and not significant within the AD group alone. Our findings are consistent with postmortem studies describing the patterns of fibrillar amyloid burden and synaptic loss in AD.
Patient engagement in research on dementia: Perceptions from researchers in a multidisciplinary research consortium
Authors: Bethell Jennifer , Chertkow Howard , Sivananthan Saskia , McGilton Katherine S 
Published: December 2020

AbstractBackgroundPatient ‘engagement’ or ‘involvement’ in health research refers to including people with lived experience (i.e. individuals with personal experience of a health issue and their friends, family and caregivers) in the research process – not as study subjects, but as collaborators in planning, conducting and communicating research. Patient engagement is being advanced by researchers, funding organisations, advocacy groups and others on both moral and methodological grounds. Although patient engagement in research on dementia is not new, it is becoming more common. Still, there are unresolved questions of how to incorporate, evaluate and adapt engagement activities for different types of research.MethodWe are reporting results of a survey of researchers who are members of the Canadian Consortium on Neurodegeneration in Aging (CCNA), conducted to understand their perceptions of engaging people with lived experience of dementia in research.ResultThere were 84 responses (27% response rate). Respondents included biomedical (n=10; 12%), clinical (n=35; 42%), health services (n=27; 32%) and social/cultural/environmental/population health (n=12; 14%) researchers. Overall, almost all (n=78; 93%) agreed that people with lived experience of dementia can contribute meaningfully to the research process. Nearly two thirds of respondents (n=54; 64%) indicated their research already included engagement activities and the most frequently reported motivations were to increase the quality and relevance of the research and empower people who have lived experience of dementia. They reported engagement activities took place most often in the context of knowledge translation, priority setting and study recruitment. Of those who indicated no current engagement activities (n=30; 36%), most were interested in opportunities for engagement and, for those who were not interested, the most common reason reported was that it was not relevant to their area of research. Limitations to these results include the low response rate that likely introduced some selection bias; researchers with an interest in engagement may have been more likely to respond.ConclusionMany CCNA researchers working in the area of dementia are engaging people with lived experience in their research. These data will be used to describe how researcher knowledge, attitudes and activities differ according to type of research.
Glyphosate‐based herbicide alters brain amino acid metabolism without affecting blood‐brain barrier integrity
Authors: Limberger Christian , Ferreira Pamela C.L. , Fontella Fernanda U. , Oliveira Ana Cristina Laydner Joly , Salles Giovanna Bortoluzzi , Souza Diogo O. , Zimmer Eduardo R. , de Souza Débora Guerini 
Published: December 2020

AbstractBackgroundGlyphosate‐based herbicides (GBH) are the most widely used pesticides, mainly due to their use in genetically modified crops. Lately, GBH induced‐neurotoxic effects are gaining attention since they are potential risk factors for developing neurodegenerative diseases, including Alzheimer’s disease (AD). It has been shown that GBH exposure is associated to brain glutamatergic excitotoxicity ‐ a key pathological feature in AD, which may cause blood‐brain barrier (BBB) breakdown. In addition, the activity of some urea cycle enzymes and arginine downstream metabolites seem to be altered in AD patient brains. Based on that, we aimed at evaluating central and peripheral effects of GBH acute exposure.MethodGBH was administered into adult male Wistar rats (90 day‐old, n = 14) in a single oral dose (400 mg/kg). The AA and albumin levels in CSF were assessed by High‐Performance Liquid Chromatography in control conditions and 3, 24 and 48 h after administration. Serum urea content was measured by colorimetric assay. L‐[3H]glutamate uptake and AA release were measured in tissue slices of parietal cortex, hippocampus and striatum to better understand alterations in 3 h (n = 8).ResultCSF levels of excitatory AA aspartate and glutamate, as well as ornithine ‐ a downstream arginine metabolite ‐ were elevated 3 h after GBH exposure (Figures 1A, 1D). Accordingly, high levels of ornithine were released from slices of all brain regions in the same time point (Figure 1B). We did not observe changes in serum urea, CSF albumin levels (Figure 1C) and L‐[3H]glutamate uptake.ConclusionWe hypothesize that GBH directly affects brain AA metabolism regardless of its effects in the periphery, since we observed changes in CSF AA levels independently of BBB breakdown. Additionally, no changes in serum urea were observed, which points to a normal function of the urea cycle and a higher production/release of ornithine from brain cells. This suggests a potential unbalance in excitatory amino acids and arginine downstream metabolism as an effect of GBH exposure, which could contribute to GBH‐induced neurotoxicity. This work is in progress and we intend to characterize GBH long‐term exposure effects and its possible contribution to the pathogenesis and/or progression of AD.
Virtual navigation and scene exploration in early Alzheimer's disease
Authors: Parizkova Martina , Kalinova Jana , Vyhnalek Martin , Hort Jakub , Wiener Jan , Laczó Jan 
Published: December 2020

AbstractBackgroundSpatial navigation deficits are present early in Alzheimer´s disease (AD) and could thus serve as an early cognitive marker of the disease. AD patients were shown to have altered scene exploration during spatial navigation as they overlook objects of interest. We aimed to evaluate the potential of a virtual spatial navigation task and eye‐tracking assessment to identify individuals with early AD and to differentiate them from those with cognitive deficit of other etiology.Methods48 participants: amnestic mild cognitive impairment (aMCI) with positive AD‐biomarkers (aMCI due to AD, n=14), aMCI with negative biomarkers (aMCI AD‐negative, n=8), mild AD dementia (n=9) and cognitively normal (CN) older adults (n=17) underwent clinical and neuropsychological evaluation, MRI brain scan, amyloid PET imaging, cerebrospinal fluid biomarker assessment and spatial navigation testing in a virtual realistic‐looking “Intersections” test. The test consisted of three tasks: i) egocentric “route repetition”, where participants repeated the route through a virtual city, ii) allocentric “route retracing”, where participants indicated their way back, and iii) allocentric “different approach direction” combined with eye‐tracking, where participants indicated their original position from a different perspective at each intersection with two same and two unique houses. Number of fixations and length of fixation of unique houses were analyzed.ResultsThe aMCI due to AD and mild AD dementia groups had lower scores in the egocentric “route repetition” and allocentric “route retracing” tasks compared to the CN (p<0.012) and aMCI AD‐negative (p<0.007) groups. There were no differences between the CN and aMCI AD‐negative groups in these tasks. The AD dementia group had lower scores in the allocentric “different approach direction” task compared to the CN group (p=0.027). Duration and number of fixations of unique landmarks in the “different approach direction” was similar across all groups that demonstrated higher number and longer duration of fixations regardless of the task performance (p<0.001).ConclusionThe egocentric and allocentric tasks from the virtual “Intersection” test reliably detect spatial navigation impairment typical for early stages of AD. Spatial navigation unlike scene exploration can differentiate individuals with aMCI due to AD from those with non‐AD etiology.
Associations between subjective cognitive decline (SCD) diagnosis and severity with plasma tau and NfL levels using SIMOA technology
Authors: Azad Dishari Zaman , Debure Ludovic , Vedvyas Alok , Osorio Ricardo S , Masurkar Arjun V , Wisniewski Thomas , Shao Yongzhao 
Published: December 2020

AbstractBackgroundSubjective cognitive decline (SCD) is thought to be a preclinical stage of Alzheimer’s disease (AD) and is based largely on subjective report data in the context of normal neuropsychological functioning. There is, however, an unclear relationship between SCD and potential plasma markers along the AD spectrum.Method213 older adults (53 cognitively normal, [NL], 52 SCD, 54 mild cognitive impairment [MCI] and 54 AD), mean age 74.9±9.6, completed the UDS 3.0 battery, the Global Deterioration Scale (GDS) and a blood draw. Plasma levels of Aβ40, Aβ42, neurofilament light (NfL) and tau were measured using ultra‐sensitive, single‐molecule array (SIMOA) technology.ResultPlasma NfL levels were high in MCI patients and higher still in those with AD over cognitively unimpaired people (NL and SCD) (F(2,198)=22, p<.001) before and after correction for age, sex and apoE4 status. Both plasma tau and Aβ42 levels were higher in SCD over NL subjects (F(1,95)=7.8 and F(1,96)=6.5; both p<0.05). Importantly, plasma tau but not Aβ42, Aβ42/ Aβ40 ratio or NfL was correlated with self‐reported Cognitive Change Index (CCI) scores both in the overall sample (r154=2.4, p<0.01) and in the NL and SCD only (r89=2.15, p<0.5).ConclusionPlasma NfL is a potential biomarker of cognitive decline to MCI and AD, while plasma tau may have higher discriminatory value in the preclinical stages of the disease and is associated with SCD.
Association of depression and diabetes mellitus with processing speed, inhibitory control and cognitive flexibility in older adults with mild cognitive impairment
Authors: Costa Mônica Vieira , de Paula Jonas Jardim , Ávila Rafaela , Pires Lívia Rabelo , Cintra Marco Túlio , Dias Raphael Figueiredo , Bicalho Maria Aparecida 
Published: December 2020

AbstractBackgroundDepression and diabetes mellitus (DM) are associated with an increased risk for dementia and mild cognitive impairment (MCI). Subcortical anatomical changes associated with processing speed impairment are shared by both DM subtypes. This profile is similar for depression, a condition in which processing speed and executive functions mediate deficits in other domains. Thus, the aim of this work is to investigate the interaction between diabetes and depression with executive functions and processing speed on older adults with mild cognitive impairment.Method76 elderly people aged 60 to 96 years (M=75, SD=7.5) from UFMG outpatient clinic for older adults on Instituto Jenny de Andrade Faria participated in the study, predominantly low formal education (M=4, SD=4.5), 23 with significative depressive symptoms, 21 with diabetes mellitus, and 7 with both conditions. Multivariate analysis of variance was used (with cognitive variables as dependent, depression and diabetes as factors and age and education as covariates). Statistical method used was GLM and post‐hoc LSD analysis (Fisher's least significant difference). The level of significance adopted was 0.05. Processing speed, inhibitory control and cognitive flexibility were the study dependent variables, measured by the Five Digit Test.ResultDiabetes is associated with processing speed impairment (F =5,505; p =0,022; partial η2 = 0,073) and depression symptoms with decrease in inhibitory control (F =6,467; p =0,013; partial η2 = 0,085). The interaction between two conditions is associated with poorer performance in inhibitory control (F =6,423; p =0,014; partial η2 = 0,084).ConclusionSubcortical anatomical changes associated with processing speed impairment are shared by depression and diabetes mellitus. But when two conditions are compared on a similar group of older adults with mild cognitive impairment, executive functions decline is more expressive than processing speed on patients with depression. These results corroborate those found in the literature, where the cognitive decline in patients with depression is mediated by executive functions and on diabetes by processing speed.
Obstructive sleep apnea is associated with depressive symptoms among patients with mild cognitive impairment
Authors: Chou Mei‐Chuan , Chen Shiou‐Lan , Hsu Chung‐Yao , Ke Liang‐Yin , Tsai Ming‐Hsien , Chen Sharon Chia‐Ju , Chen Chu‐Huang , Lai Chiou‐Lian , Liu Ching‐Kuan 
Published: December 2020

AbstractBackgroundObstructive sleep apnea (OSA) is increasingly recognized as a modifiable risk factor of cognitive decline and dementia. However, the impacts of OSA on mood among patients with mild cognitive impairment (MCI) have remained rarely explored. The aim of this study was to investigate whether OSA is associated with depressive symptoms among patients with MCI.MethodThe diagnosis of MCI was based on the criteria proposed by Peterson in 2004 after a series of comprehensive work‐up. The over‐night polysomnography (PSG) was performed in hospital for the diagnosis of OSA and the patients with AHI of 10/hour or higher were eligible for enrollment in the OSA group. The group for comparison was composed of the patients without OSA (AHI < 5/hour) by over‐night PSG and the patients with low risk of OSA defined by Berlin Questionnaire. The Center for Epidemiologic Studies Depression Scale (CESD) was administered for assessing depressive symptoms and the Cognitive Abilities Screening Instrument (CASI) with derived Mini‐Mental State Examination (MMSE) score was used for assessing cognitive function. Apolipoprotein E (APOE) genotyping was done in each subject.ResultThe study sample was composed of 68 MCI patients (age: 67.5 ± 8.83 years; female: 46.8%). As compared to the MCI patients without OSA or with low risk of OSA (n=14), the MCI patients with OSA (AHI ≥ 10/ hour; n=54) had higher CESD score ( 15.8 ± 10.6 versus 7.1 ± 1.9 ; P = 0.011). In the multivariate analysis, the association remained significant after adjusting the confounding factors including age, gender, education years, baseline CASI score, BMI and APOE epsilon 4 genotyping status. (β = 5.54; 95 % CI: 0.63– 10.45, p = 0.028).ConclusionThe results of this cross‐sectional study suggest that obstructive sleep apnea is independently associated with depressive symptoms among patients with MCI. The long‐term effects of OSA on the mood among MCI patients warrant longitudinal studies. Our results probably set the horizon for the basic researches for the delineation of pathological mechanisms underlying the association between OSA and depression among MCI patients.