bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advanced glycation end products, their receptor and the risk of dementia in the general population: A prospective cohort study
Authors: Chen Jinluan , Mooldijk Sanne S. , Licher Silvan , Waqaz Komal , Ikram M. Kamran , Uitterlinden André G. , Zillikens M. Carola 
Published: December 2020

AbstractBackgroundAdvanced glycation end products (AGEs) and their receptor (RAGE) are implicated in the pathophysiology of dementia and potentially underlie the relation between diabetes and neurodegeneration. We determined the link between two proteins involved in the AGE‐RAGE system, namely Extracellular Newly identified RAGE binding protein (EN‐RAGE) and the soluble form of RAGE (sRAGE), and dementia prevalence and incidence. Additionally, we assessed the association between skin auto fluorescence (SAF), a proxy for AGEs tissue accumulation, and cognition.MethodWithin the prospective Rotterdam Study, plasma EN‐RAGE and sRAGE were measured in 1208 participants (mean age 74.1 (standard deviation (SD) 7.7); 57.5% women). Participants were categorized into tertiles, to compare participants with high, intermediate and low concentrations, with the lowest tertile as the reference. Associations of SAF, measured in 3009 participants (mean age 72.3 (SD 9.4); 56.4% women), and cognition were assessed using linear models. We adjusted for age, sex, diabetes, APOE ε4 carrier status and other potential confounders, including cardiovascular risk factors, and additionally stratified by sex and APOE ε4 status.ResultParticipants with higher EN‐RAGE and lower sRAGE levels were more likely to have dementia (adjusted odds ratio (OR); 3.64 [95% confidence interval 1.56‐8.50] and OR 0.39 [0.17‐0.83], for high level compared to low level). During follow‐up (median 12.4 years), 161 participants developed dementia, of whom 130 Alzheimer’s disease (AD). Higher EN‐RAGE was non‐significantly associated with higher risk of dementia during the first years of follow‐up (adjusted hazard ratio (HR); 1.48 [0.52‐4.25] after 4 years of follow‐up), while a lower risk was found over the entire follow‐up duration (HR 0.65 [0.42‐1.01]) (Figure 1). Higher SAF was associated with lower global cognitive function (adjusted difference in z score per SAF standard deviation (SD); 0.07 [0.04‐0.11]). This effect was stronger for carriers of the APOE ε4 allele (0.15 [0.07‐0.22]).ConclusionOur results indicate involvement of the AGE‐RAGE system in the pathophysiology of dementia, independent of the history of diabetes, showing involvement of EN‐RAGE and sRAGE, and of SAF in cognitive functioning. These associations were stronger for APOE ε4 carriers, suggesting a combined role of AGEs and APOE in neurodegeneration.
The influence of antipsychotics and antidepressants on people with dementia in Northern Ireland: A retrospective analysis
Authors: McMichael Alan J , Zafeiridi Evi , Passmore Anthony Peter , McGuinness Bernadette 
Published: December 2020

AbstractBackgroundDementia is a term used to describe a broad group of conditions that affect the brain and causes a progressive cognitive decline in the ability to think, learn and remember. People with dementia may be prescribed medications such as antipsychotics and antidepressants to help deal with their symptoms. Little is known about the rate of which these drugs are prescribed in Northern Ireland and whether such drugs influence mortality rates among people with dementia.MethodUsing data from the Honest Broker Service, which holds information on approximately 13,000 people with dementia in Northern Ireland we aim to assess the number of people with dementia who are currently being prescribed antidepressants and antipsychotics and determine whether or not such medications influence mortality rates. In addition we also aim to explore what demographic characteristics influence the liklihood of whether a person with dementia will be prescribed antipsychotics and / or antidepressants. Data will be ready for analysis in February 2020.ResultBy conducting a retrospective analysis on national datasets, we aim to determine whether antipsychotics and antidepressants influence mortality rates in people with dementia and investigate what demographic parameters inConclusionGiven the questionable benefits of antipsychotics in particular for treating people with dementia, these results have the potential to provide valuable information to clinicians and the carers of people with dementia.
The association between low social support and risk of cognitive impairment is partially mediated by neuroanatomic biomarkers of Alzheimer’s disease
Authors: Petkus Andrew J , Gruenewald Tara L , Wang Xinhui , Younan Diana , Espeland Mark A , Widaman Keith F , Gatz Margaret , Rapp Stephen R , Shadyab Aladdin H , Lockhart Samuel N , Flores Melissa , Kroenke Candyce H , Tindle Hilary , Masaki Kamal , Chen Jiu‐Chiuan 
Published: December 2020

AbstractBackgroundSocial relationships with less support are linked to greater risk of developing Alzheimer’s disease (AD) and other dementias. Despite growing evidence of this link, to our knowledge, no studies have examined neuropathological processes through which low social support may affect risk of cognitive impairment. We used data from the Women’s Health Initiative Memory Study (WHIMS)‐MRI Study to examine whether neuroanatomical characteristics indicative of AD risk and cerebrovascular diseases underlie the greater risk of cognitive impairment or dementia over time in those with less supportive social relationships.MethodParticipants included 989 women (aged 73‐87 years) from the WHIMS‐MRI study who completed the Medical Outcomes Study Social Support Scale, assessing perceived emotional, tangible, and affectionate support, in 2004‐05. Structural brain scans were performed in 2005‐06 to assess small‐vessel ischemic disease (SVID) volume and determine AD pattern similarity scores (AD‐PS), a brain‐MRI measured neuroanatomical biomarker reflecting diffuse gray matter atrophy in brain regions vulnerable to AD neuropathologies, developed by supervised machine learning and validated with AD Neuroimaging Initiative data. Annual WHIMS follow‐ups included extensive neuropsychological assessments to ascertain centrally‐adjudicated incident cases of mild cognitive impairment (MCI) or all‐cause dementia. Structural equation models were used to assess the association between social support and risk of MCI/dementia (diagnosis data available through June 2018), and whether the association was mediated by global SVID volumes or AD‐PS scores. Models were adjusted for depressive symptoms, demographic, lifestyle, and clinical covariates.ResultLow social support was associated with higher MCI/dementia risk (hazard ratio= 1.23 per 1‐SD; 95% CI: 1.07, 1.44) and also with higher AD‐PS scores (β=.067; 95% CI: .01, .12), but not SVID volume. Higher AD‐PS score accounted for 18.6% (95% CI: 4%, 43%) of the total effect of low social support on risk of MCI/dementia (Figure 1). Higher SVID only accounted for 1.9% (95% CI: ‐1.5%, 8.8%) of the total effect.ConclusionOur study illustrates an association between low social support and higher MCI/dementia risk among older women, which was partly mediated by gray matter atrophy indicative of higher AD risk. Findings also suggest less of a role of cerebrovascular disease in mediating these associations.
Implementation of a targeted screening program for Alzheimer's disease risk in a primary care setting
Authors: Korthauer Laura E , Denby Charles , Molina David , Wanjiku Janet , Daiello Lori A , Drake Jonathan D , Grill Josh D , Ott Brian R 
Published: December 2020

AbstractBackgroundPrimary care providers (PCPs) are well‐positioned to promote early detection of cognitive impairment, yet the value of comprehensive screening of Alzheimer’s disease (AD) risk factors has received limited attention. The goal of this pilot study was to evaluate the feasibility of implementing a population health approach to screening for cognitive and genetic risk for AD in a primary care setting.MethodPCPs (N=6) referred patients with a family history of AD or memory complaints (N=94) to the Rhode Island Alzheimer’s Disease Prevention Registry for apolipoprotein E (ApoE) genotyping and a telephone‐based cognitive screen (Minnesota Cognitive Acuity Screen). PCPs informed patients of testing results (ApoE status, cognitive screening diagnosis) and counseled them about risk factor modification. The impact on patients’ understanding of their AD risk and providers’ care management was subsequently assessed via surveys.ResultTwenty‐three participants (31%) had probable mild cognitive impairment; 30 participants (35%) had one or two ε4 alleles. More cognitively normal (93%) than MCI patients (50%) correctly recalled their cognitive screening results (p=.003). Compared to cognitively normal patients, MCI patients correctly reported a higher likelihood of developing AD (p<.001). More ApoE non‐ε4 carriers (100%) than ε4 carriers (80%) correctly recalled their genetic test results (p<.001); both groups correctly reported that the ε4 allele confers greater AD risk. PCPs reported recommending lifestyle changes (e.g., diet, exercise, cognitive stimulation) to 99% of patients, but only 27% of patients reported that this recommendation was made. However, patients who recalled being given a lifestyle recommendation were significantly more likely to have enacted a lifestyle change (OR=7.2; p=.01) than those who did not recall this recommendation. Each PCP reported that the program was a valuable addition to their practice and benefitted their care management. Psychological distress was reported in <5% of participants (1 MCI‐positive, 3 ε4‐positive individuals).ConclusionGiven the increasing focus on cognitive health in aging, population health initiatives delivered in primary care are needed to offer guidance to at‐risk patients. Implementing a cognitive and genetic screening program for AD risk in a primary care setting is feasible and may provide added value to PCPs in advising patients about risk factor modification.
The role of sleep apnea in APOE‐Alzheimer's disease pathway
Authors: Hegde Krupa N , Ding Xiuhua , Gardner Marylin 
Published: December 2020

AbstractBackgroundPrevious studies have shown contradictory findings on if the APOE gene is associated with sleep apnea. Thus, the goal of this study is to examine the relationship between the APOE gene and sleep apnea and investigate whether levels of amyloid beta in cerebrospinal fluid (CSF) depend on sleep apnea and/or APOE gene.MethodData was obtained from the National Alzheimer’s Coordinating Center (NACC). We restricted participants to those who were enrolled at or after 2015 due to availabilities of sleep apnea measurements and with normal cognition status at enrollment. CSF sample data for a subset of these participants were merged to initial visit data by subject ID and year of visit. Logistic regression was used to investigate the association between sleep apnea and APOE and backward elimination was used to identify a final model. T‐tests were used to compare the mean levels of CSF amyloid beta between APOE gene groups and between sleep apnea groups, respectively.ResultOf a total of 1630 subjects identified to meet criteria, 3.83% participants had sleep apnea and are APOE ε4 carriers, 26.87% did not have sleep apnea and are APOE ε4 carriers, 9.88% had sleep apnea and are APOE ε4 non‐carriers, 59.45% did not have sleep apnea and are APOE ε4 non‐carriers. Logistic regression showed that sleep apnea was not significantly associated with APOE gene after adjusting age, gender and BMI. The mean levels of CSF amyloid beta among APOE ε4 carriers (mean± SD: 414.7±241.7) were lower than APOE ε4 non‐carriers (mean± SD: 500.9±150.5), and the mean levels of CSF amyloid beta among sleep apnea subjects (mean± SD: 434.6±90.1) were lower than subjects without sleep apnea (mean± SD: 504.9±194.3). However, the differences were not statistically significant.ConclusionIn this study, sleep apnea was not significantly associated with APOE in the NACC sample and the mean levels of CSF amyloid beta did not depend on sleep apnea or APOE gene in cognitively normal subjects.
Alzheimer’s disease‐related sex differences in insulin sensitivity, glucose metabolism, and spatial memory
Authors: Findley Caleigh A. , Sime Lindsey N. , McFadden Samuel , Hascup Kevin N. , Bartke Andrzej , Hascup Erin R. 
Published: December 2020

AbstractBackgroundWomen are at higher risk for developing Alzheimer’s disease (AD), comprising two‐thirds of AD patients. In this study, we aimed to characterize AD‐related sex differences in insulin sensitivity, glucose tolerance, and spatial learning and memory in male and female APPNL‐F/NL‐F mice, a model of AD, and normal aging C57BL/6 mice.MethodMale and female C57BL/6J and APPNL‐F/NL‐F mice underwent data collection at 6 months of age. Insulin and glucose tolerance testing (ITT, GTT) were performed to examine metabolic function, followed by Morris water maze (MWM) to determine cognitive ability.ResultPreliminary ITT data (area under the curve for percent change from baseline) indicate that male APPNL‐F/NL‐F mice (n=9; 10,260 ± 679) tended to be less insulin sensitive than genotype‐matched females (n=5; 7,900 ± 494). There were no sex differences observed for C57BL/6 mice and no genotype differences. GTT results support a trend of female C57BL/6 mice (n=7; 9975 ± 1,517) having impaired glucose metabolism compared to genotype‐matched males (n=5; 7,083 ± 584). No sex differences were observed for APPNL‐F/NL‐F mice. Of note, APPNL‐F/NL‐F (n=9; 9,211 ± 1,391) males tended to have impaired glucose metabolism compared to C57BL/6 males. For MWM, female mice tended to have impaired long‐term memory recall as supported by cumulative distance measures (C57BL/6J n=7, 15.24 ± 1.73; APPNL‐F/NL‐F n= 5, 15.61 ± 2.38) and annulus 40 entries normalized for distance swam (C57BL/6J n=7, 0.4833 ± 0.0485; APPNL‐F/NL‐F n=5, 0.4542 ± 0.1174) compared to genotype‐matched males (C57BL/6 n=5, 12.11 ± 1.20; APPNL‐F/NL‐F n=9, 12.03 ± 1.86) (C57BL/6J n=5, 0.6732 ± 0.1128; APPNL‐F/NL‐F n=9, 0.6534 ± 0.1150).ConclusionPreliminary results support insulin insensitivity in male APPNL‐F/NL‐F mice compared to genotype‐matched females and impaired glucose metabolism compared to C57BL/6 males, a potential early indication of AD pathology. Female mice from both genotypes had impaired long‐term memory retrieval compared to genotype‐matched males, possibly providing an insight into female AD pathology. Collectively, these preliminary findings support potential sex differences for insulin sensitivity and long‐term spatial memory in AD pathology. Studies to further elucidate sex differences in AD disease progression are ongoing. This research was supported by the NIH and SIUSOM.
Effects of a multi‐session cognitive training combined with brain stimulation on age‐associated cognitive decline
Authors: Thams Friederike , Antonenko Daria , Li Shu‐Chen , Flöel Agnes 
Published: December 2020

AbstractBackgroundResearch on non‐invasive methods of modulating age‐associated cognitive decline has yielded promising results. Current evidence shows that transcranial direct current stimulation (tDCS), if administered with concurrent cognitive training, may successfully modulate cognitive performance. In the TrainStim‐Cog trial, we investigated in healthy older adults if longer‐term training combined with tDCS, versus sham, would lead to higher increases in performance on the trained tasks, and to larger transfer to non‐trained domains. Moreover, we aimed to elucidate neural mechanisms underlying these effects.MethodFifty‐six participants (20 men; mean age / SD = 69.8 / 4.0 yrs) underwent nine sessions of cognitive training over a period of three weeks with concurrent administration of either tDCS stimulation over 20 min (1mA current) or sham stimulation. The cognitive training consisted of two tasks targeting executive functions: a letter‐updating task was used to train working memory updating and, reward‐based decision‐making was trained with a three‐stage Markov decision‐making task. Prior to the intervention and immediately after the intervention, performance on training and transfer tasks was assessed and neural correlates were recorded using structural, functional and diffusion tensor MRI.ResultAt the time of submitting this abstract, assessment of primary endpoint has just been completed; data base lock, and unblinding of intervention type will be conducted in February 2020. The trial has been registered at clinicaltrials.gov (ID NCT03838211), the study protocol of the trial has been published (Antonenko et al., 2019, Frontiers in Aging Neuroscience), and a statistical analysis plan has been uploaded at clinicaltrials.gov. Results of the analyses will be presented at the AAIC conference.ConclusionOur results will determine if a 3‐week combined cognitive training and tDCS approach may not only enhance trained functions, but also transfer to non‐trained tasks. Moreover, we will determine if effects are sustained over longer periods of time, and we will aim to identify predictors of response to the intervention on the individual level. Thus, our trial will hopefully contribute to the development of non‐medical interventions in the field of age‐associated cognitive decline.
Development and evaluation of 0.5 mm isotropic resolution T1‐weighted and DTI templates of the older adult brain
Authors: Niaz Mohammad Rakeen , Ridwan Abdur Raquib , Wu Yingjuan , Qi Xiaoxiao , Zhang Shengwei , Bennett David A , Arfanakis Konstantinos 
Published: December 2020

AbstractBackgroundHuman brain MRI templates with low spatial resolution lack important fine details due to partial volume effects. The purpose of this work was to introduce a novel approach for high‐resolution template construction based on principles of super‐resolution, and using this technique, to develop high‐resolution T1‐weighted and DTI templates of the older adult brain.MethodT1‐weighted (222 images,1mm isotropic) and DTI (202 images,2mm isotropic) brain MRI data from non‐demented older adults (65‐95 age‐range, male:female=1:1) participating in the Memory and Aging Project were used in this work (Fig.1). The raw images were spatially normalized in a 0.5mm isotropic resolution space using conventional template building methods. The resulting non‐linear deformations were utilized to map the signals from raw space to exact physical locations in the 0.5mm template space, minimizing interpolations that occur in conventional template‐building method. The final signal in a 0.5mm isotropic voxel in template space was calculated as the weighted average of all signals included in that voxel using a Gaussian kernel. The new T1‐weighted template, MIITRA_0.5mm_T1, was compared to MCALT_0.5mm, ICBM2009b_0.5mm, Colin27_0.5mm, and MIITRA_1mm_T1 (Fig.2A). The new DTI template, MIITRA_0.5mm_DTI, was compared to ICBM81, NTU, IIT_v5.0, EVE, and IXI (Fig.4A). The templates were evaluated in terms of image quality and spatial normalization accuracy achieved when used as references for alignment of MRI data from a large number of older adults.ResultFine structures were resolved in MIITRA_0.5mm_T1 in contrast to MCALT_0.5mm and MIITRA_1mm_T1 (Fig.2B). Visual inspection revealed atypical brain features in the cortex of MCALT_0.5mm (red circles). MIITRA_0.5mm_T1 has higher image sharpness (Fig.3A) and allowed higher inter‐subject spatial normalization accuracy of older adult T1‐weighted data (Fig.3B,C,D) compared to other templates. Fine white matter structures such as the anterior commissure, posterior commissure, inter‐thalamic adhesion and optic chiasm were clearly resolved in MIITRA_0.5mm_DTI (Fig.4B), in contrast to other DTI templates. MIITRA_0.5mm_DTI exhibits higher image sharpness (Fig.5A) and allowed higher inter‐subject spatial normalization accuracy of older adult DTI data (Fig.5B,C,D,E,F) compared to other templates.ConclusionMIITRA_0.5mm_T1 and MIITRA_0.5mm_DTI are high‐quality, high‐resolution templates of the older adult brain and allow higher spatial normalization accuracy of older adult data compared to other available templates.
Atrial fibrillation and the interaction with stroke in relation to white matter lesion volumes: A population‐based study in 70‐year‐olds
Authors: Rydén Lina , Sacuiu Simona , Wetterberg Hanna , Najar Jenna , Zettergren Anna , Kern Silke , Pereira Joana B , Wahlund Lars‐Olof , Westman Eric , Skoog Ingmar 
Published: December 2020

AbstractBackgroundAtrial fibrillation (Afib) increases the risk of stroke and dementia. However, the mechanisms underlying the association between Afib and dementia in the absence of manifest stroke are not that well understood. The aim of this study is to investigate the association between Afib and white matter lesion (WML) volumes in a population‐based sample of 70‐year‐olds.MethodData were obtained from the Gothenburg H70 birth cohort studies (H70). In 2014, 1203 participants were examined (response rate: 72%) and a subsample (n=791) underwent structural MRI using a fluid‐attenuated inversion recovery (FLAIR) sequence. WML volumes were measured on FLAIR images using the Lesion Segmentation Tool (LST) and subsequently log transformed for further statistical analyses. Afib was diagnosed through self‐report, ECG, and hospital register. Stroke was diagnosed through self‐report, proxy‐report, hospital register, and large infarctions (>15mm) on brain‐MRI. Linear regression was used to analyze the association between Afib and WML volumes, while adjusting for potential confounders.ResultAfter excluding individuals with neurodegenerative diseases, valvular heart diseases, and incorrect WML segmentation, 779 individuals remained for statistical analyses. Of these, 65 individuals (8.3%) had Afib. Individuals with a history of Afib had larger WML volumes than individuals without Afib after adjusting for total intracranial volume and sex. However, after additional adjustments for cardiovascular and metabolic diseases, smoking, alcohol risk‐consumption, education and stroke, this association was no longer seen (β 0.1 (95% CI ‐0.2‐0.3); p=0.697). A significant interaction was found between Afib and stroke (p<0.001) regarding the association with WML volume. Therefore, we stratified the material by stroke and found that Afib was associated with increased WML volumes in individuals with stroke (β 1.1 (95% CI 0.0‐2.2); p=0.047) but not in those without.ConclusionThis study suggests that Afib is associated with larger WML volumes in individuals with stroke but not in those without.