bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trends in dementia consultations in two psychiatric hospitals in Mexico City: 2010‐2018
Authors: Astudillo‐Garcia Claudia I , Jaime Beatriz Paulina Vázquez , Ávila Xiasú García , Austria‐Corrales Fernando , Velásquez José Javier Mendoza 
Published: December 2020

AbstractBackgroundThe analysis of the information about the use of health services is a key input for understanding infrastructure and planning requirements, as well as for contributing to the identification of deficiencies and opportunities aimed at improving the provision of services. Dementia is a condition that is increasing in Mexico; however, the health system lacks long‐term care services, being psychiatric hospitals one of the main centers for providing services to the population affected by this disease. That is why this research aims to identify trends in dementia care for adults over 60 years who were attended in two psychiatric hospitals in Mexico City between 2010–2018.MethodWe used records of the psychiatric hospitals "Fray Bernardino Álvarez" and "Samuel Ramírez Moreno", during the period 2010‐2018. The annual proportion of first and subsequent consultations for dementia (according to ICD‐10, code F00) in both men and women was estimated. The Joinpoint Trend Analysis Software version 4.1.0 was used to explore the change in time trends of care. Trend changes are presented as Annual Percent Change (APC) and was considered statistically significant when p<0.05.ResultOn average, both psychiatric hospitals recorded 9000 dementia consultations per year. Statistically significant increases are observed by sex. Among women, first‐time consultations were recorded with a 16.8% (CI: 5.5‐29.4) and subsequent consultations (APC: 13.4%, CI: 6.2‐21.2). And in men it is only significant in subsequent consultations (APC: 19.5%, CI: 6.6‐34.1).ConclusionThe number of hospital consultations for dementia has increased significantly; however, the health system in Mexico is limited in resources and infrastructure that could guarantee long‐term care services, so it should restructure services and promote other instances that would allow for quality care to be provided to people affected by the disease, as well as their caregivers.
Discovery of SLC16A9 and SLC22A1 as regulators of acylcarnitines associated with Alzheimer’s disease
Authors: Horgusluoglu‐Moloch Emrin , Arnold Matthias , Kaddurah‐Daouk Rima F. , Zhang Bin 
Published: December 2020

AbstractBackgroundPropionylcarnitine (C3) as short‐chain acylcarnitine is highly associated with brain volume changes and cognitive impairment in symptomatic stages of Alzheimer’s Disease (AD), and the lower concentration of C3 level is associated with cerebrospinal fluid amyloid‐beta level in AD (Varma, Vijay et al. 2018). However, the genetic mechanism and key biological pathways underlying changes in propionylcarnitine in AD remain unclear. To better understand the key drivers and biological pathways underlying changes in propionylcarnitine in AD, we performed a genome‐wide association study (GWAS) of propionylcarnitine using Alzheimer’s Disease Neuroimaging Initiative (ADNI) Cohort.MethodGWAS for propionylcarnitine from Non‐Hispanic Caucasian participants in the ADNI cohort (328 controls, 84 significant memory concern, 712 mild cognitive impairment, and 276 AD) was performed using an additive model with a linear association analysis for quantitative traits in Plink v1.90. Age, gender, education, body mass index (BMI), medication history, cohort, and diagnosis status were used as a covariate. A summary p‐value for each gene (including ± 5kb) was calculated from GWAS results using GATES (Li, Gui et al. 2011). For the pathway analysis of GWAS results, the Molecular Signatures Database was used to identify biological pathways representing the enrichment of association in the GWAS. False discovery rate (FDR) P < 0.05 was considered to identify significant pathways.ResultWe identified nine SNPs resides in SLC16A9 (a carnitine efflux transporter) gene, and four SNPs reside in SLC22A1 (related to acylcarnitine efflux) gene (Table 1; Figure 1). Analysis of the genotyping level of the most significant SNP (rs1171616) shows that the participants carrying at least one copy of the minor allele (N = 560; GT/GG genotype) have less C3 metabolite level in the blood compared to those without minor allele (N = 828; TT genotype) (Figure 2A). Participants with two minor alleles have worse episodic memory scores (Figure 2B and 2C). Enrichment pathway analysis with C3 associated genes (nominal p‐value < 0.05) revealed that the immune system, Alzheimer’s Disease, mitochondrion, neurogenesis, metabolic process, and enzyme binding are among the pathways enriched for the genes from the gene‐based association analysis (Table 2).ConclusionSLC16A9 and SLC22A1 are potential regulators of acylcarnitine levels associated with AD.
Effect of Alzheimer’s disease‐related β‐amyloid peptide conformations in transgenic mouse models of β‐amyloidosis
Authors: Célestine Marina , Jacquier‐Sarlin Muriel , Borel Eve , Herard Anne‐Sophie , Buisson Alain , Dhenain Marc 
Published: December 2020

AbstractBackgroundAlzheimer’s disease (AD) brain dysfunctions are not exclusively related to amyloid plaques occurence, but are thought to start much earlier, presumably due to soluble pathological forms of b‐amyloid peptide (Aβ). Indeed Aβ oligomers induce synaptic dysfunctions that cause cognitive decline, exacerbate tau pathology[1] and influence neuronal networks[2]. Although mutation‐induced phenotypes are identified in AD patients, the in vivo effects of different Aβ variants are poorly understood. Here we characterized the effects of different Aβ variants in a transgenic mouse model to provide deeper insight of transconformational processes and the subsequent alterations. Deciphering Ab profiles would help in developing new diagnostic and therapeutic approaches.MethodWe developed well‐characterized amyloid variants: Aβ1‐42, Aβ bearing the icelandic mutation (A2T), Aβ bearing the Osaka mutation (E22D[1]) and Aβ bearing the mutation F19S/L34P. First, these variants were overexpressed in cortical neuron cultures. Then, two‐month‐old APP/PS1dE9 mice were inoculated with these variants in the dentate gyrus (n = 5/per group). We assessed Aβ oligomerization profiles, cerebral amyloid load and synaptic health in neuron and mouse (4 months post‐inoculation) models by biochemistry and histology.ResultThe different amyloid forms exhibit distinct aggregation profiles and synaptotoxicity in vitro (Figure 1). They did not have the same effect on mouse survival. Osaka‐Aβ induced the highest mortality. Then, we focused on the local reorganization of amyloid. Osaka‐Aβ led to increased 6‐mer and 12‐mer amyloid forms at inoculation site (Figure 2) but also at distance in the cortex. This suggests that Aβ variants differently modulate Aβ metabolism and aggregation. Amyloid plaque assessment showed an Osaka‐Aβ‐induced increase in amyloid load in the hippocampus (Figure 3) and its connected regions.ConclusionA single inoculation of different Aβ variants in APP/PS1dE9 mice expressing wild‐type Aβ is sufficient to differentially modulate Aβ metabolism, amyloid load and mouse mortality. This suggests that Aβ variants differentially interact with the biochemical/biophysical cerebral environments to differentially induce toxic downstream events that are crucial for better AD physiopathology understanding. References: (1) Delacourte et al., Experimental Gerontology, 2002. (2) Bero et al., Journal of Neuroscience, 2012. (3) Tomiyama et al., Ann Neurol, 2008.
IGF‐I modulates sleep patterns through orexinergic neurons: Role in aging
Authors: Zegarra‐Valdivia Jonathan Adrian , Pignatelli Jaime , de Sevilla Maria Estrella Fernández , Munive Victor , Martinez‐Rachadell Laura , Nuñez Angel , Torres‐Alemán Ignacio 
Published: December 2020

AbstractBackgroundAging and dementia are related to sleep and circadian disturbances. These disturbances are attributed to neurodegeneration of brain networks involved in sleep. On the other hand, increasing evidence supports the notion that Alzheimer’s disease (AD), a condition that presents heterogeneous pathological disturbances, including sleep regulation, is also associated with perturbed metabolic function affecting insulin‐like growth factor I (IGF‐I). Moreover, metabolic alterations are commonly associated with sleep disturbances. In this work we took advantage of a very specific group of cells ‐ orexinergic neurons ‐ that are involved in sleep/circadian regulation, to study how IGF‐I may modulate their activity, as well as its role in sleep regulation through aging.MethodWe use electrophysiology, optogenetic, and immunofluorescence techniques. Transgenic mice without IGF‐I Receptor in orexinergic neurons (Firoc mice) and C57 animals (young vs old mice) were used.ResultWe found reduce C‐fos expression in orexin neurons after IGF‐I injection (ip). As well as diminish response to local and systemic IGF‐I in electrophysiology experiments in Firoc mice, determined by the responses of PeF neurons to locus coeruleus (LC) stimulation. We also found perturbations in sleep and lower levels of orexin in Firoc hypothalamus. To confirm the participation of IGF‐I modulation of orexinergic neurons, we optogenetically identify orexin neurons using a mouse expressing channelrhodopsin (ChR) specifically in these cells and inject IGF‐I locally. These results suggest that IGF‐I modulates orexinergic function. Then, we use elderly C57 mice to check if orexinergic neurons respond normally to IGF‐I. We found a reduce orexinergic neurons response to IGF‐I in electrophysiology experiments.ConclusionThese initial results reinforce recent observations that IGF‐I act as a peripheral circadian marker and modulates sleep through orexin neurons, and suggests that sleep disturbances in the elderly may be related to altered brain IGF‐I input to orexin neurons.
Real‐world site experiences with a recruitment‐related registry: An exploration of Alzheimer’s disease prevention research recruitment
Authors: Bardach Shoshana H , Langbaum Jessica B , Jicha Gregory A 
Published: December 2020

AbstractBackgroundRegistries have been proposed as a novel way to identify accelerate recruitment for Alzheimer’s disease prevention clinical trials. However, the role of registries in real‐world clinical settings remains largely unknown. Registry enrollment involves a combination of local site promotion of the registry as well as social media and advertising efforts to encourage participation. This manuscript explores one site’s experience with GeneMatch, a novel genetic registry for Alzheimer’s disease research.MethodReferrals from GeneMatch to the site were tracked to understand the demographics of those referred and ultimate research enrollment decisions. Using the site’s existing recruitment database, referrals were cross‐referenced for prior research contact, to better understand the role of GeneMatch in the context of existing recruitment efforts.ResultThere were a total of 86 GeneMatch referrals to the site, which ultimately resulting in 54 individuals coming into the site to pursue research involvement further. The majority of referrals (52/86, 60.47%) did not have prior contact with the site about recruitment interest, and having such contact did not predict likelihood of ultimately signing a research consent.ConclusionGeneMatch helped identify new individuals for participation in AD prevention studies. These results highlight the value of continuing local site‐level efforts while also taking advantage of registries to enhance research recruitment. Ongoing efforts to develop novel strategies for outreach and engagement are still needed.
Synapse disruption by Alzheimer’s Aβ/APP
Authors: Gouras Gunnar K. , Martinsson Isak 
Published: December 2020

AbstractBackgroundSynapse loss is known as the best brain correlate of cognitive decline in AD, while numerous lines of evidence support that Aβ/APP are involved in the disease. We previously reported that with AD pathogenesis soluble Aβ42 accumulates in late endosomes near synaptic terminals where it then aggregates and disrupts synapses. Based on these studies our modified amyloid hypothesis views intra‐neuritic Aβ as initiating a cascade that after synaptic degeneration via prion‐like extracellular Aβ propagation perpetuates the pathological process. This scenario illuminates the Aβ‐tau anatomical disconnect, since vulnerable projection neurons with early Aβ accumulation later develop tangles at their cell soma but plaques in their terminal fields. Here we set out to better understand the effects of early Aβ accumulation on synapses using live cell calcium imaging in cultured primary neurons.MethodPrimary cortical/hippocampal neurons are obtained from APP/PS1 mutant transgenic and wild‐type mice. We previously reported that primary AD transgenic neurons show progressive Aβ accumulation and AD‐like synapse alterations. After live cell calcium imaging of neurons with Fluo‐4, neurons are fixed and immuno‐labeled with markers for inhibitory or excitatory cells. In addition, viral constructs harboring fluorescent tags (e.g. TdTomato) and promoters to label excitatory or inhibitory neurons are used to measure calcium oscillations directly in different types of neurons during live imaging.ResultBy live cell imaging primary neurons from AD transgenic compared to wild‐type mice showed hyperactivity consistent with prior in vivo work. Calcium oscillations were increased in both frequency and amplitude in the AD transgenic neurons.ConclusionSynapses are increasingly viewed as vulnerable early sites in AD. Here we show evidence for neuronal hyperactivity related to Aβ/APP and aim to dissect the neuron subtype vulnerability of these early Aβ‐induced synaptic alterations.
Longitudinal changes in sedentary behavior, physical activity and aerobic fitness over 5 years in a cohort at risk for Alzheimer’s disease
Authors: Dougherty Ryan J , Mergen Brandon , Lose Sarah , Gaitán Julian M , Okonkwo Ozioma C , Cook Dane B 
Published: December 2020

AbstractBackgroundLow levels of physical activity and aerobic fitness are established modifiable risk factors for Alzheimer’s disease and all‐cause mortality. Work from our group and others has demonstrated significant and positive cross‐sectional relationships between physical activity, aerobic fitness and indicators of brain health (e.g. biomarkers of AD, cognition). The aims of the current study were to determine 5‐year changes in sedentary behavior, physical activity and aerobic fitness in adults at risk for Alzheimer’s disease.MethodThis study enrolled fifty‐seven cognitively unimpaired adults from the Wisconsin Registry for Alzheimer’s Prevention. Participants completed 7 days of physical activity monitoring via accelerometry and a maximal exercise test at two time‐points – 5 years apart. Based on current physical activity guidelines, our chosen measures were time spent engaged in sedentary behavior and moderate‐to‐vigorous physical activity. Aerobic fitness was defined as the highest oxygen consumption (VO2peak, mL/kg/min) value recorded during the final stage of the maximal exercise test when standardized criteria were met. A repeated measures model was used to investigate whether sedentary behavior, physical activity, and aerobic fitness changed over a 5‐year period. Cohen’s d effect sizes and bivariate correlations were used to explore the magnitude of these changes and their relationships with age.ResultAt baseline, participants (mean age at baseline 63.81±6.1) spent 77.86±8.11 hours/week sedentary, engaged in 10.34±4.26 hours/week of physical activity and displayed an aerobic fitness level of 28.26 ±0.99 mL/kg/min. At follow‐up (mean age at follow‐up 68.52±6.1), we observed non‐significant increases in sedentary behavior 2.1% (d=.2; p=.09), and significant declines in physical activity 12.3% (d=.3; p=.01) and aerobic fitness 14.2% (d=1.2; p<.001). Age was negatively associated with 5‐year change in physical activity (r=‐.31; p=.02) but not sedentary behavior (p=.19) or aerobic fitness (p=.80).ConclusionThis study found that physical activity and aerobic fitness significantly declined over a 5‐year period in adults at risk for Alzheimer’s disease, and this decline may accelerate with advancing age. Strategies aimed at promoting physical activity and aerobic fitness (e.g. exercise training) in mid‐late adulthood are warranted. Future studies are needed to test whether changes in sedentary behavior, physical activity, and aerobic fitness are related to brain and cognitive health.
Public policies to support dementia caregivers
Authors: Bangerter Lauren , Kaskie Brian , Dawson Walter D 
Published: December 2020

AbstractBackgroundFamily caregivers are major providers of long‐term care and support for family members with Alzheimer’s disease and related dementias (ADRD). Caregiving for a person with ADRD is a demanding role that is linked to physical, emotional, relational, and financial burden. Ensuring that ADRD caregivers are adequately supported is rapidly becoming a cornerstone of successful public health policy agendas in the United States.MethodWe conducted a review of publicly available legislation and policy briefs to identify federal policies that support ADRD caregivers, both directly and indirectly.ResultFederal policies for caregivers have evolved and increased over time, most notably through the National Family Caregiver Support Program, part of the Older Americans Act. The passage of recent legislation (e.g., the RAISE Caregiver Act and the BOLD Infrastructure for Alzheimer’s Act) indicate a pattern of targeted investment in supporting ADRD caregivers.ConclusionGerontology research and public policy can and should intersect in order to optimize the effectiveness of policy efforts to support ADRD caregivers.
Associations of vitamin B12 status with cognitive domain performance in cognitively healthy older adults
Authors: de Jager Celeste A , Nalder Liam , Zheng Bang , Chiandet Giulia , Middleton Lefkos T 
Published: December 2020

AbstractBackgroundIncreasing longevity worldwide has resulted in an unprecedented high burden of dementia. Several lines of research have implicated factors affecting B‐vitamin status among risk factors for cognitive decline and dementia. We aimed to determine the prevalence of vitamin B12 deficiency among cognitively healthy volunteers from the Cognitive Health in Ageing Register: Investigational, Observational, and Trial Studies in Dementia Research: Prospective Readiness cOhort (CHARIOT:PRO) SubStudy (CPRO‐SS) and also, to explore associations with cognitive performance at screening.MethodThis analysis includes data from cognitively healthy volunteers (n=1946) aged 60‐85 years who underwent, as part of screening, Repeatable Battery for Neuropsychological Status (RBANS), vitamin B12 and folate measures. Levels of B12 biomarkers, homocysteine and methylmalonic acid, were assayed for those with low vitamin B12 (<133 pmol/L); high levels indicating severe B12 deficiency. Gender‐specific linear regression models were computed for associations of B vitamin biomarkers and BMI with RBANS domain indices and individual tests, controlling for confounders. Regression by B12 status group (normal, deficient, severely deficient) for RBANS associations were analysed for all participants.ResultVitamin B12 deficiency (<148 pmol/L) was detected in 17.2% of the cohort; folate <10nmol/L in 1%. Low vitamin B12 was associated with subtle deficits in immediate and delayed memory test scores (p<0.03) in men. Elevated folate was associated with poorer Attention index in men (β ‐0.12; p=0.019), and individual subtests in men and women (p<0.03). High BMI was associated with poorer Attention and Visuospatial indices and subtests in men and women (P<0.05), but no interaction with B12 was detected (p>0.05). Regression by B12 status group revealed deficits in Attention (β ‐6.46; p=0.004) for B12 Deficient, and Immediate Memory (β ‐2.99; p=0.019) for Severely Deficient (with elevated homocysteine and/or methylmalonic acid and/or low folate), relative to the Normal group.ConclusionThis study highlights subtle domain‐specific cognitive deficits that varied between men and women, with evidence of graded cognitive deterioration with increasing severity of vitamin B12 deficiency. High BMI had negative effects on attention and visuospatial skills in this cohort. These results will be discussed in the context of clinical trials for prevention of AD and therapeutic strategies for subgroups.
Predicting progression in subjective cognitive decline (SCD) using a machine learning (ML) approach: The role of the complaint’s severity
Authors: Felpete Alba , Valladares‐Rodríguez Sonia , Mallo Sabela C. , Lojo‐Seoane Cristina , Facal David , Belleville Sylvie , Juncos‐Rabadán Onésimo , Pereiro Arturo X. 
Published: December 2020

AbstractBackgroundPresence of significant subjective complaints about cognition (SCD) is considered the first behavioral manifestation of Alzheimer disease (AD). However, SCD has not yet overcome the challenge of becoming a reliable preclinical AD marker. Severity indices were proposed to improve the accuracy of complaints when predicting the risk of AD (Jessen et al., 2010).Our aim was to compare the predictive accuracy of ML algorithms using a more (95%ile) or less (5%ile) restrictive cut‐off point in severity of complaints for classification in Low (LSC) and High (HSC) subjective complaints groups.MethodOne hundred and ninety‐nine participants from the Compostela Aging Study (ComPAS) were identified at baseline as SCDs and completed three follow‐up measurements (54‐72 months). Considering their total scores in the Subjective Memory Questionnaire, participants were classified as LSC and HSC following using two distinct cut‐off points: complaint scores above or below than 5%ile vs 95%ile. Participants were labeled as ‘worsening’ or ‘stable’ based on their progression or not to MCI or AD. ML classifier algorithms (Random Forest, Support Vector Machine, Extra Tree) were applied to forty‐one measures (socio‐demographic, time, health, cognitive, behavioral, cognitive reserve) collected at baseline.ResultsThe best performing model was the Random Forest (95%ile: PPV =.87; Sensibility =.92; Specificity =.38; 5%ile: PPV =.66; Sensibility=.61; Specificity =.51). The confusion matrix (Figure 1) showed that: a) both, the more (95%ile) and the less (5%ile) restrictive criteria mostly classified the HSC‐stable participants as LSC‐stable; and b) criterion 5%ile, but not 95%ile, was able to differentially identify progressors based on their complaints. Episodic memory, executive functions, depression, cognitive reserve and progression timing measures assume the highest levels of importance in the ML algorithm that differentially predicts the progression of SCD to MCI and AD according to the level of complaints.ConclusionsFor both the criteria, algorithms failed to successfully identify stable SCD participants. The less restrictive criterion resulted in a better classification than the more lenient one to differentially identify LSC and HSC participants who get worse. Cognitive, affective, cognitive reserve and progression timing were the more prominent variables in conforming the predictive algorithm.