bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk factors and association of cognitive impairment among older adults with concurrent vision and hearing impairment: A scoping study
Authors: Jaiswal Atul , Gupta Shikha , Santhakumaran Sangeetha , Holzhey Peter , Aubin Gabrielle , Dumassais Shirley , Wittich Walter 
Published: December 2021

AbstractBackgroundThe concurrent loss of vision and hearing, termed dual sensory impairment (DSI), can have a significant impact on one’s functioning. Evidence is emerging on the prevalence of DSI in the older population, including those with cognitive impairment (CI). In the context of an ageing population with increasing prevalence of DSI, we aimed to synthesize existing evidence on the association of CI with DSI and identify risk factors for the development of CI in older adults with DSI, establishing its relevance to primary prevention.MethodThe scoping review was performed using Arskey and O’Malley’s framework (2005). In June 2020, eleven scientific databases (CINAHL, Embase, Global Health, Mednar, OAIster, OpenGrey, PsycEXTRA, PsycINFO, PubMed, Web of Science, and WorldWideScience) were searched using index terms and keywords relating to CI and DSI. To be included, studies had to be empirical, peer‐reviewed, had older adults with DSI as the focal population, and have explored the concept of CI as an impairment of one or more cognitive domains, such as memory, attention, or executive functions. The screening of the retrieved studies was completed using Covidence, and relevant data were extracted using an a priori data extraction tool.ResultOut of 11,595 identified sources, 56 articles were included. Twelve studies reported the prevalence of CI in older adults with DSI, while 20 reported risk factors for CI in older adults that could be applied to older adults with DSI as well, such as depression, hearing impairment, and social isolation. Thirteen studies presented DSI alone as a risk factor for CI in older people. Seven studies reported other risk factors for CI in older adults with DSI, such as non‐sensory comorbidities, illiteracy, physical inactivity, and gender.ConclusionOur review indicates that further population‐based longitudinal research is needed to explore the association between CI and DSI and identify whether there are risk factors that are unique for CI among older adults with DSI. With the prevalence of DSI increasing in the older population, robust evidence is needed to inform the recommendations regarding screening, assessment and management of CI in older adults with DSI.
Identifying amine fragments as potential inhibitors of acetylcholinesterase and butyrylcholinesterase through in silico analysis and validation through in vitro enzyme inhibition analysis
Authors: Kandasamy Saravanan , Loganathan Chitra , Sakayanathan Penislusshiyan , Subramani Karthikeyan , Marimuthu Dinesh Kumar , Ravichandran Saravanan , Sivalingam Vignesh , Thayumanavan Palvannan 
Published: December 2021

AbstractBackgroundThe cholinesterases [ChEs; acetylcholinesterase (AChE) and butyrylcholinesterase (BChE)] which are involved in cholinergic neurotransmission are target for drug development against cognitive dysfunction in Alzheimer’s disease. The search for novel ChEs inhibitors with improved biological profiles continues to be of great interest. Currently know inhibitors of ChEs such as galatamine, tacrine, donepezil and rivastigmine are amine‐based compound. Keeping this view, in the present study virtual screening was carried out to identify the potential amine fragment that interacted with the ChEs in in silico. The selected molecules were analyzed by molecular docking and molecular dynamics simulation. The best interacted molecule in in silico was further characterized for its inhibition against AChE and BChE in in vitro.MethodHigh Throughput Virtual Screening (HTVS) of various amine fragments was carried out in Schrödinger suite. Identified top ten molecules were subjected to molecular docking analysis using Induced Fit Docking (IFD) module. Molecular dynamics (MD) simulation of top three scored compounds were carried out to understand the stability of the interaction with ChEs. In silico quantum crystallography studies was done to understand the involvement of functional group in the interaction with ChEs. In vitro inhibition and kinetic analysis of these compounds against ChEs was performed to determine the inhibitory constant and type of inhibition.ResultAmong the amine compounds screened, three compounds 2‐aminoquinoline (2AQ), 2‐aminobenzimidazole (2AB) and 2‐amino‐1‐methylbenzimidazole (2AMB) was identified to interact with ChEs with lowest docking score. Further MD simulation confirmed the stable binding of these compounds in the active site of the ChEs. Topological and electrostatic properties of intermolecular interactions between these compounds with ChEs showed that amine group played important role in interacting with protein structure. These amine compounds inhibited the BChE and different molecular forms of AChE at micromolar concentration. Kinetic analysis revealed the mixed‐type of inhibition.ConclusionAmine fragments screened for interaction with ChEs in in silico. Three compounds (2AQ, 2AB and 2AMB) showed better interaction in molecular docking and molecular dynamics analysis. These compounds showed inhibition against ChEs in in vitro.
Association of pulmonary function with cognitive trajectories and structural brain differences: A population‐based cohort study
Authors: Wang Jiao , Song Ruixue , Qi Xiuying , Ma Jun , Bennett David A. , Xu Weili 
Published: December 2021

AbstractBackgroundThe relation of poor pulmonary function (PF) to cognitive trajectories and the mechanisms behind the relation remains unclear. We aimed to investigate the association of poor PF with cognitive decline in different domains and structural brain volumes.MethodWithin Rush Memory and Aging Project, 1377 dementia‐free subjects were followed up to 21 years. PF was assessed with a composite score (tertiled as the lowest, middle, and highest) based on peak expiratory flow, forced expiratory volume in 1 second, and forced vital capacity measured at baseline. Episodic memory, semantic memory, working memory, visuospatial ability, and perceptual speed were assessed annually constructed from 19 cognitive tests. A sub‐sample of the participants (n=373) underwent brain magnetic resonance imaging (MRI), and total, regional brain (white matter, gray matter) and white matter hyperintensities volumes were assessed. Data were analyzed using linear mixed‐effect models and linear regression models.ResultAt baseline, the PF score was ranged from ‐2.36 to 3.47. In multi‐adjusted mixed‐effect model, compared with the highest PF, the lowest PF was related to decline in global cognition (β=‐0.039, 95% CI: ‐0.054 to ‐0.024), episodic memory (β= ‐0.053, 95% CI: ‐0.072 to ‐0.033), semantic memory (β= ‐0.032, 95% CI: ‐0.048 to ‐0.015), working memory (β= ‐0.028, 95%CI: ‐0.041 to ‐0.014), visuospatial ability (β= ‐0.027, 95% CI: ‐0.042 to ‐0.013), and perceptual speed (β= ‐0.038, 95% CI: ‐0.053 to ‐0.022). In MRI data analysis, the lowest PF was associated with smaller volumes of total brain (β= ‐29.61, 95% CI: ‐45.25 to ‐13.98), white matter (β= ‐12.62, 95% CI: ‐23.56 to ‐1.68), and gray matter (β= ‐16.95, 95% CI: ‐28.93 to ‐4.96), but greater white matter hyperintensities (β= 0.214, 95% CI: 0.094 to 0.334), compared to the highest PF.ConclusionLow PF accelerates cognitive decline in global cognition, episodic memory, working memory, semantic memory, visuospatial ability and perceptual speed. Neurodegeneration and vascular lesions in the brain may underlie the association of PF with cognitive decline.
The relationship of regional abdominal adiposity and adiposity‐related factors with cognitive functioning among middle‐aged individuals at high Alzheimer’s dementia risk
Authors: Boccara Ethel , Golan Sapir , Ravona‐Springer Ramit , Inbar Yael , Yore Iscka , Heymann Anthony , Beeri Michal Schnaider 
Published: December 2021

AbstractBackgroundObesity in midlife has been consistently associated with late‐life cognitive decline and Alzheimer’s dementia (AD). Obesity is typically assessed by body mass index (BMI) rather than specific anatomical location of stored excess fat. These fat depots can affect the secretion of adipose‐related factors that in turn may affect AD risk. In this study we examined whether regional abdominal adiposity and adiposity‐related secreted factors are related to cognition in middle‐aged adults at high AD risk due to a parental history of AD.MethodParticipants were from The Israel Registry for Alzheimer’s Prevention (IRAP) study following middle‐aged offspring of Late‐Onset AD patients (N=390). To date, 46 participants who have complete cognitive assessment (summarized as global cognition and four cognitive domains—episodic memory, executive functions, language and working memory) have also been scanned for hepatic and pancreatic adiposity, and abdominal adipose tissue (AAT) via magnetic resonance imaging (MRI). Adiposity‐related factors primarily secreted by the liver (PAI‐1), visceral fat (TNF‐α), and the pancreas (PYY) were quantified by MILLIPLEX® MAP for 26 participants. Linear regressions examined the association of regional fat and adiposity‐related factors with cognition adjusting for age, sex, education, and BMI.ResultParticipants (52% women) averaged 51.5 (SD=5.5) years of age, 17.3 (SD=2.1) years of education. Higher AAT was associated with lower global cognition (r=‐0.347, p=0.024), executive function (r=‐0.471, p=0.024) and approached significance for language (r=‐0.301, p=0.053). Higher hepatic fat was associated with lower executive functions (r=‐0.334, p=0.031) and the association of higher pancreatic fat with poorer executive function approached significance (r=‐0.273, p=0.081). All three adipose‐related secreted factors were associated with lower executive functions (PAI1 (r=‐0.635, p=0.003), TNF‐α (r=‐0.478, p=0.033) and PYY (r=‐0.420, p=0.065)) but not with global cognition or other cognitive domains.ConclusionHigher regional abdominal adiposity and related secreted factors were associated with poorer cognitive functions, especially executive functions, already in midlife, in asymptomatic individuals enriched for AD risk, and regardless of global body fat measured by BMI. By AAIC 2021, we anticipate 100 IRAP participants will be assessed for regional abdominal adiposity and adipose‐related factors. Targeting regional adiposity is expected to prevent or delay cognitive decline, and ultimately AD.
Disparities in dementia and AD biomarkers in the ARIC study: The important contribution of social determinants of health
Authors: Gottesman Rebecca F. , Schneider Andrea L.C. , Rawlings Andreea , Power Melinda C. , Walker Keenan A. , Wruck Lisa , Wong Dean F. , Jack Clifford R. , Knopman David S. , Mosley Thomas H. 
Published: December 2021

AbstractBackgroundDementia disproportionately impacts people of color in the U.S.. Whether these disparities are due to differences in vascular risk factors, cognitive reserve, or AD pathophysiology remains unclear.MethodBlack and White participants from four U.S. communities were recruited into the Atherosclerosis Risk in Communities (ARIC) study at ages 45‐64. Vascular risk factors were evaluated in midlife and at multiple visits over 30+ years, as were markers of cognitive reserve, with expert classification of dementia. In participants with brain MRI, brain volumes were evaluated in association with dementia. In nondemented participants in the ARIC‐PET ancillary study, florbetapir PET scans were used to quantify brain cortical amyloid; differences in levels by race, vascular risk factors, and white matter hyperintensities (WMH) were evaluated.ResultIn 15744 ARIC participants, dementia was more common in Black vs White participants. Although midlife vascular risk factors were related to dementia, the impact of these risk factors on dementia risk and cortical volumes didn’t differ by race. Lower education was nonsignificantly more strongly associated with dementia in Blacks vs Whites, and an APOE e4 allele was more strongly associated with dementia in Whites. In ARIC‐PET (N=322), vascular risk factors from midlife were associated with PET amyloid, without similar associations for late‐life risk factors; these associations did not significantly differ by race. WMH volume was more strongly associated (cross‐sectionally) with PET amyloid in Blacks vs Whites, but differences were not statistically significantly different. Finally, Blacks had an over two‐fold increased odds of elevated florbetapir PET vs Whites, independent of vascular risk factors, demographics, WMH volume, cognitive status, and APOE genotype.ConclusionConsideration of racial disparities in dementia should consider vascular risk, cognitive reserve, and social determinants of health, across the life course. Vascular risk factors do not appear to differentially impact dementia risk or brain amyloid in Blacks vs Whites, but the greater prevalence of these risk factors in Blacks must be considered. Although the A/T/N framework may clarify underlying biology contributing to Alzheimer’s disease, inclusion of these additional factors is needed to understand and reduce racial disparities in dementia rates.
Cognitive decline related to substance consumption in a Colombian kindred with familial Alzheimer's disease: A retrospective cohort study
Authors: Ramos‐Perez Claudia Patricia , Villalba Arvey Camilo , Garcia Jenny , Lanata Serggio , Lopez Hugo Elias , Aguirre‐Acevedo Daniel C , Lopera Francisco 
Published: December 2021

AbstractBackgroundSubstance use is a presumed risk factor for Alzheimer's Disease (AD). So, it would be essential to evaluate it in people who already have a high risk of dementia. Neuroscience Group of Antioquia, GNA, is a research group from Medellin, Colombia, which studies Presenilin 1 (PS1) E280A mutation carriers. These carriers will course four stages of AD: 1) asymptomatic Pre‐Mild Cognitive Impairment (Pre‐MCI), 2) symptomatic pre‐MCI, 3) MCI; and 4) Dementia. Substance consumption could modify age‐at‐onset of those stages, but this association has not been deeply explored.MethodWe performed a retrospective cohort study with 163 subjects enrolled between January 25, 2019, and April 29, 2020. Of those participants, 69 (42.3%) were non‐carriers, and 94 (57.7%) were carriers. A psychiatrist interviewed the subjects through the "CACoS" questionnaire, an instrument specifically designed for this research. The subjects' cognitive information included CERAD test battery, MMSE, CDR, and a subjective memory complaints checklist. We analyzed the relationship between the onset of AD stages and substance consumption through a time‐to‐event analysis (survival analysis and Cox proportional hazards regression).ResultFor dementia onset, there was an association with less than one time per month of alcohol consumption in the last year (HR 0.42, CI 0.18‐0.96). For MCI onset, there was a relationship with less than one time per month of alcohol consumption in the last year (HR 0.39, CI 0.17‐0.91), and also with consumption of 5 to 11 drinks per day of consumption in the previous twelve months (HR 0.12, CI 0.01‐0.99). For pre‐MCI onset, there was a relationship with daily coffee consumption throughout life (HR 2.37, CI 1.07‐5.25).ConclusionA low frequency of alcohol consumption could be protective against MCI and dementia, but coffee was associated with Pre‐MCI acceleration. It would be critical to continue exploring these substances' role as modifiable risk factors soon.
An investigation into the association between diet and dementia risk
Authors: Dobreva Ivelina , Mukadam Naaheed , Solmi Francesca 
Published: December 2021

AbstractBackgroundThe number of people living with dementia is rising. It is estimated that by 2030, the total number of people with dementia would reach 82 million. By 2050, the number would increase to 152 million. Modifiable risk factors are gaining increasing attention as means of prevention or delaying of the disease. A number of those factors relate to diet, however specific patient guidance has not been established due to inconsistent evidence, heterogeneity of samples, small effect and sample sizes.We aimed to use a large sample with long follow up times to clarify links between dietary factors and dementia. We use data from the UK Biobank cohort [enrolment from years 2006‐ 2010] on dietary patterns and registered dementia cases to establish an association between diet and dementia risk.We investigate the association between adherence to the Mediterranean diet, as well as specific aspects such as vegetarianism and high versus low fat which could have an impact on dementia risk.This will help in establishing specific guidance for reduction in dementia risk.MethodWe will combine variables to form quantiles of low, medium and high adherence to the Mediterranean diet. We will also classify people into those adhering to a vegetarian/non‐vegetarian diet and those eating a low versus high fat diet. We will summarise characteristics of the sample and compare those developing and not developing dementia. Dementia diagnosis will be determined from self‐report and recorded diagnoses in electronic health records. We will conduct a Cox regression to investigate the effect of dietary factors on dementia risk, adjusting forage, sex, education, physical activity and cardiovascular risk factors.ResultResults will be presented in the form of summary tables as well as results of Cox regression models. We will examine which dietary factors have the biggest impact on dementia risk and, if supported by the evidence, we will provide suggestions as to how to reduce dementia risk through dietary adjustments.ConclusionThis project examines association between diet and dementia risk.
Anticipatory cue‐related alpha desynchronization reflects top‐down disinhibitory control during verbal working memory task
Authors: Mirjalili Mina , Zomorrodi Reza , Daskalakis Zafiris J. , Hill Sean , Rajji Tarek K. 
Published: December 2021

AbstractBackgroundWorking memory deficits are common in mild cognitive impairment (MCI) and cause troubles in routine activities. Frontal theta event‐related synchronization (ERS) and parietal alpha event‐related desynchronization (ERD) are known to be associated with working memory capacity. However, their association with working memory performance, including at the trial‐by‐trial level, has yet to be determined.Method54 healthy adults (mean age (SD) = 28.4 (7.4)) completed the N‐back working memory task at three conditions (N = 1, 2, and 3). Single‐trial ERS/ERD was measured during N‐back and in response to an anticipatory cue at the beginning of each trial. Anticipatory cue‐related power changes at the trial level were used to assess neural oscillation before target correct (TC) and target non‐correct (TNC) responses.Result2‐way ANOVA showed significant effect of response type (p=0.01) and interaction between N‐back condition and response type (p=0.03) on alpha ERD. Post‐hoc comparisons revealed less alpha ERD in TC vs. TNC responses during 2‐ and 3‐back conditions (p’s < 0.02), and less alpha ERD in TC trials of 2‐ and 3‐back compared to 1‐back condition (p’s < 0.001). Finally, no significant effect was observed in theta band.ConclusionGiven that alpha ERD has been associated with top‐down disinhibitory control, our findings suggest that less anticipatory disinhibition prior to the processing of a working memory item of information promotes correct processing and high‐capacity working memory
Blood‐based multi‐omic signatures of blood‐brain barrier impairment and CSF‐defined Alzheimer disease in older adults
Authors: Clark Christopher , Bowman Gene L. , Dayon Loic , Raymond Frederic , Wojcik Jerome , Konz Tobias , Rezzi Serge , Masoodi Mojgan , Descombes Patrick , Popp Julius 
Published: December 2021

AbstractBackgroundBlood‐brain barrier (BBB) breakdown and accummulation of Alzheimer disease (AD) pathology are risk factors for age‐related dementia. However, both require either lumbar puncture or advanced neuroimaging for detection that are not widely available. Less invasive ways to detect these risk factors early on could permit more targeted therapies for prevention. Multiple‐level molecular biomarker approaches (e.g., ‘multiomics’) may identify candidates for diagnostic development and help initiate earlier risk factor modificaion. We deployed multi‐omics spanning plasma or serum of non‐coding RNAs, proteins, and lipids to comprehensive nutrient biomarkers to distinguish BBB impairment and CSF defined AD pathology in older adults.MethodCSF albumin index ≥ 9.0 indicated BBB impairment. CSF p‐tau181/abeta42 ratio > 0.0779 indicated AD pathology. miRNAs were measured with the HTG EdgeSeq technology; inflammatory biomarkers with MesoScale sandwich immunoassays; mass spectrometry was used for proteomics, lipidomics, metabolomics, measurements of amino acids, hydro‐and liposoluble vitamins, fatty acids, and minerals; mass spectrometry was coupled to liquid, supercritical fluid or gas chromatography where needed. LASSO logistic regression models selected multi‐omic signatures that best classified BBB impairment and AD pathology using formal diagnostic accuracy and area under the curve (AUC) statistical criteria.ResultCross‐sectional analysis was conducted in 120 subjects with a mean age of 70 years, 64% were female and the mean MMSE was 27. Prevalence of BBB impairment and AD pathology was recorded in 13.5% and 35%, respectively. A blood‐based multi‐omic signature, including 1 amino acid , 1 cholesterol ester, 1 mineral, 1 pro‐inflammatory cytokine, 3 proteins and 4 miRNAs produced a diagnostic accuracy of 93% for BBB impairment (AUC of 0.96 with 95% confidence interval (CI) of 0.91‐0.99; Figure 1). Another blood‐based multi‐omic signature, including 2 amino acids, ethanolamine and a phospholipid , 2 minerals, 3 inflammatory‐specific markers, 4 other proteins, 1 miRNA , APOE4 genotype and age diagnosed AD pathology with 86% accuracy and generated an AUC of 0.92 (95% CI of 0.86‐0.96; Figure 2)ConclusionWe identified distinct blood‐based signatures of BBB impairment and CSF biomarkers of AD pathology in a cohort of predominantly non‐demented older adults using pre‐specified outcome criteria. Multi‐omic approaches in blood can provide novel insights into mechanism and improve detection of underlying risk factors for age‐related dementia.