bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell‐type‐specific and sex‐dependent changes in the chromatin accessibility landscape in late‐onset Alzheimer’s disease brains
Authors: Chiba‐Falek Ornit , Barrera Julio , Song Lingyun , Safi Alexias , Yu Young Jun , Garrett Melanie , Gamache Julia , Chipman Danielle , Ashley‐Koch Allison , Crawford Gregory 
Published: December 2020

AbstractBackgroundDecoding the genetic mechanisms of late‐onset Alzheimer’s disease (LOAD) is a major challenge in the post‐GWAS era, since the majority of the LOAD associated SNPs are in noncoding regions. Noncoding disease‐associated loci have been shown to be enriched for regulatory elements in tissues and cells relevant to the disease. Thus, post‐GWAS research requires an in‐depth characterization of cell‐type‐specific DNA regulatory elements and gene expression patterns.MethodsWe conducted ATAC‐seq profiling using NeuN sorted‐nuclei from 40 frozen brain tissues to determine LOAD‐specific changes in chromatin accessibility landscape in a cell‐type specific manner. We complemented these experiments by generating single‐nuclei(sn)RNA‐seq data from a subset group of the same brain samples.ResultsThe study has five major findings for the field of LOAD epigenetics. First, we generated a map of LOAD‐associated cell‐type specific chromatin accessibility sites. Second, we identified 211 LOAD‐specific differential chromatin accessibility sites in neuronal‐nuclei. Third, we provided a catalogue of 842 female‐specific disease‐associated chromatin accessibility sites in non‐neuronal cells. Forth, we showed that the LOAD‐associated cell‐type‐specific changes in chromatin accessibility overlapped with ∼25% of the LOAD‐GWAS regions. Thus, suggesting a noncoding regulatory mechanism, namely chromatin accessibility, by which several LOAD‐GWAS loci may exert their pathogenic effect. Fifth, we functionally validated the ATAC‐seq findings using snRNA‐seq datasets. Data integration identified overlaps between the LOAD‐specific ATAC‐seq signals with the transcriptome profiles of known and new LOAD loci and demonstrated that LOAD‐associated changes in chromatin accessibility can result in gene dysregulation.ConclusionTo our knowledge, this study represents the first and most comprehensive systematic interrogation of the chromatin accessibility landscape in LOAD and the functional effect on gene dysregulation. Moreover, the outcomes unveiled how cell‐type‐specific and sex‐dependent alterations in chromatin structure and transcription programs are associated with LOAD. These findings enhance the interpretation of LOAD‐GWAS discoveries towards translating association to causation, provide potential pathomechanisms, and suggest novel LOAD‐loci. Furthermore, our results convey mechanistic insights into sex differences in LOAD risk and clinicopathology.
Memory palaces to improve quality of life in Alzheimer's disease
Authors: Bormans Kasper ,   Leuven School for Mass Communication Research
Published: December 2020

AbstractBackgroundDementia is the problem of the future in health care. Dementia is hard for the person living with it, but even more burdensome for his/her environment. The conversational dialogue seems to decline. Dementia is more than memory‐loss, there is also communication‐loss. The primary objective is to examine whether the addition of (augmented) reality to communication strategies can reconnect subjects in the early phase of Alzheimer's Disease (AD) with their caregivers and family members. The secondary objective includes a follow‐up on quality of life (QOL‐AD), feelings of depression (GDS 15) and connectedness (QCPR) of subjects in the early phase of AD and their significant others.MethodWe have developed a mobile health‐application (MemoryHome) which allows caregivers to construct virtual scale models of the residential settings / at home situation. These models function as memory palaces in which photos of significant others are connected to the architectural, spatial environment. It is a visual‐audio‐guide through a well‐known environment and subjects in the early phase of AD can make this walk together with a caregiver or a family member.ResultOur intervention is non‐pharmacological, rather inexpensive, patient‐friendly, unconventional and easy to combine with regular treatment of Alzheimer’s disease. Data were collected in two different environments: in homecare and residential settings. Results showed a modest but positive relation with quality of life, connectedness between caregivers and their family members and the absence of feelings of geriatric depression.ConclusionThe mobile application MemoryHome is a convenient instrument to reinforce the dialogue that seemed to diminish between patients and their environment.The application allows participants to independently improve the recall and recognition of familiar faces.
Cognitive reserve and resilience: Possible mechanisms of dementia prevention
Authors: Livingston Gill , Selbaek Geir , Rockwood Kenneth , Huntley Jonathan D , Sommerlad Andrew , Mukadam Naaheed 
Published: December 2020

AbstractBackgroundPredictions about future dementia prevalence vary but usually suggest large increases in numbers of people with dementia as the population ages. However, in some countries, for example, the US, UK and Netherlands, while overall numbers of people with dementia are growing as predicted, the age‐specific incidence rates of dementia have decreased substantially. This is probably due to educational, socio‐economic, health and lifestyle changes.MethodWe reviewed known risk factors listed in the 2017 Lancet commission: education, hypertension, hearing impairment, smoking, obesity, depression, exercise, diabetes and social contact; literature about cognitive reserve and considered effective interventions for these risks.ResultCognitive reserve is the brain resilience which allows for cognition maintenance despite neuropathological damage. Early, mid and late life factors are all important. Early‐life factors, such as education, are important for cognitive reserve and those with more education build greater cognitive reserve. Lifelong higher educational attainment also reduces dementia risk. Cognitive reserve is not static and is affected by a number of factors. Quantifying it uses proxy measures such as education, residual approaches (the variance of cognition not explained by demographic variables and brain measures) or identifying underlying brain functional. People in more cognitively demanding jobs tend to show less cognitive deterioration before, and sometimes after retirement than those in less demanding jobs. Hypertension and obesity in mid‐life are risk factors for dementia, as is hearing impairment. More frequent social contacts at age 60 years is associated with lower dementia risk over 15 years of follow‐up. Smoking in late life increases the risk of dementia. In later life people’s physical health may moderate the susceptibility to neuropathology. Those who are frail may develop Alzheimer’s disease with a lesser burden of neuropathology. Older people otherwise in good physical health can sustain a higher burden of neuropathology without cognitive impairment. There are however relatively few evidence based interventions and we will discuss what interventions we found in systematic review and what developments are still needed.ConclusionThere are clinically and economically effective interventions. It is important to consider the stage of the life course when thinking about possible effective interventions to prevent dementia.
Amyloid, pTau, NfL, and GFAP as biomarkers for Alzheimer’s disease
Authors: Thijssen Elisabeth H. , Verberk Inge M.W. , Stoops Erik , Boxer Adam L. , Teunissen Charlotte E. 
Published: December 2020

AbstractBackgroundAlzheimer's disease (AD) is a multifactorial disease, with ongoing amyloid and tau accumulation, axonal damage and astrocytosis. Blood‐based biomarkers reflecting these processes are potentially valuable for patient selection for clinical trials, for monitoring disease progression and treatment effects, and for the differential diagnosis of AD. Several studies have shown that plasma amyloid beta (Abeta) 42 and 40 concentrations, phosphorylated tau (pTau) at amino acid 181 or 217, neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) are changed in AD. Therefore, our studies are driven by the idea that combination of several markers will provide a more complete picture of the full complexity of AD.MethodThe results presented were obtained in several retrospective clinical cohort studies in memory clinics. Plasma Abeta 42 and 40, GFAP, and NfL were measured with Simoa technology, using homebrew assays (Amyblood, ADx), and commercial kits (Quanterix). pTau181 and 217 were measured using MSD technology with Lilly antibodies. Based on positive Amyblood and GFAP results, a novel 4‐plex assay was developed (AUMC, Quanterix, ADx). Results will be presented on the use pTau217 and of the measurement of combinations of Abeta isoforms, GFAP, and NfL for differential diagnosis of AD, Lewy body dementia, and Frontotemporal lobar degeneration (FTLD).ResultThe plasma markers are analyzed in over 1100 subjects. The Abeta 42/40 ratio decreased 1.2 fold in cases in the AD spectrum with a positive amyloid‐PET status, compared to amyloid negative cases. pTau181 concentrations were increased 2.4 fold in cases with tau accumulation measured with FTP‐PET, and pTau181 was increased 2.3 fold in AD compared to FTLD. NfL was increased 1.4‐2.3 fold in AD and FTLD patients compared to controls. GFAP levels were increased 1.8 fold in amyloid‐PET cases. Combining GFAP and the Abeta 42/40 ratio together with APOE e4 carriership resulted in an AUC of 88% differentiating amyloid‐PET positive from negative cases.ConclusionIndividual blood‐based biomarkers reflect different physiological processes in the brain. Creating a panel of t markers could provide a more complete picture of ongoing pathological processes and likely increases diagnostic accuracy to be suitable for blood‐based screening of AD and enable personalized medicine.
Optimizing meaningful engagement among persons living with dementia through sensitivity to differing situations and realities
Authors: Kemp Candace Lynn , Epps Fayron , Bender Alexis A , Hill Andrea M , Ciofi Joy , Duong Stephen , Manley Pamela R 
Published: December 2020

AbstractBackgroundMeaningful engagement is a critical dimension of quality of life and quality of care for persons living with dementia and an area highlighted in recent Alzheimer’s Association Dementia Care Practice Recommendations. Defined broadly as participation in an activity, including the “the act of being occupied or involved in an external stimulus,” engagement has implications for well‐being, mental health, and cognitive and physical function and shows promise as a non‐pharmacological strategy for addressing anxiety, depression, and behavioral expressions. Across long‐term care settings, including assisted living, meaningful engagement among persons with dementia represents a significant challenge. This poster presents findings from our ongoing 5‐year study conducted in the United States and funded by the National Institute on Aging (R01AG062310). The overall goal of the study is to identify best care practices aimed at recognizing, creating, and maintaining optimal meaningful engagement opportunities for persons with dementia that enhance their quality of life. Guided by grounded theory methods, our research involves: participant observation; formal and informal interviewing with residents, assisted living staff, family and friends, and others involved in residents’ daily lives and routines. Here, we report on analysis of data collected over a one‐year period in 4 diverse care settings. As expected, residents’ meaningful engagement experiences were highly variable. Residents’ cognitive and physical function also varied widely and typically fluctuated over time, influencing meaningful engagement opportunities. Awareness of and sensitivity to residents differing situations and for some, differing realities, were essential to optimizing meaningful engagement experiences among this heterogeneous and dynamic population. Care partners, including care staff and families and friends, who met residents “where they’re at” had more success collaborating with them to create positive engagement experiences compared to those who did not. We offer data‐driven recommendations for research and practice including the need to emphasize and promote person‐ and relationship‐centered care.
Vitamin deficiencies in geriatric memory patients
Authors: Przybelski Anna Gabriel , Vogt Nicholas M , Bendlin Barbara B , Przybelski Robert J 
Published: December 2020

AbstractIntroductionAging is the primary risk factor for dementia, and vitamin deficiencies are common in geriatric patients. Vitamins B12 and folate are commonly checked in memory patients, but other CNS‐significant vitamins such as B6 (pyridoxine), B1 (thiamine), and vitamin D are not. The purpose of this study was to determine prevalence of deficiencies of these vitamins in geriatric memory patients.MethodsAll new patients presenting to a university geriatrics memory clinic were assessed for vitamin B1, B6, B12, and vitamin D (total 25‐OHD) levels on the day of their first visit unless these studies were done in the prior 6 months or their health system required laboratory tests be done only through their primary care provider. Laboratory tests were performed through the university laboratory routine methods. No fasting or other special arrangements were made for the tests. Only test results obtained at the first visit, with neuropsychological evaluation were evaluated. A retrospective review of the medical records from the most recent 12 months provided the data presented here. Deficiency thresholds used for the study were: B1 <70 nmol/L, B6 <30 nmol/L, B12 <300 pg/mL, and D <30 ng/nL.ResultsRecords from 203 patients were reviewed; 189 had at one or more vitamin level obtained at the first visit. Of those patients, 68 (40%) had at least one vitamin deficiency; 35 (19%) had two deficiencies, 7 (3%) had three deficiencies, and 1 patient was deficient in all four. The number of patients that had a particular vitamin level done and the number with a deficiency are shown in the table.DiscussionAlmost half of the geriatric patients were deficient in at least one vitamin. Vitamins B6 and D were the most common deficiencies, yet these are not routinely tested in memory patients. The commonly tested B12 showed a deficiency rate of only 16% compared to 37% and 33% for vitamins B6 and D respectively. Treating these vitamin deficiencies that can affect cognition will enhance function and increase the likelihood of effective medical treatment and successful research studies.
Why do we need an Asian brain template in clinical trials of Alzheimer's disease? A comparative study of brain structures between Asian vs Caucasian brains
Authors: Kang Dong Woo , Lee Chang Uk , Lim Hyun Kook 
Published: December 2020

AbstractBackgroundThere is a recognized need for the creation of ethnic‐specific brain templates of cognitively normal older adults for the purpose of evaluating structural and functional brain imaging data in the normal aging process and neurodegenerative disease including Alzheimer’s disease. However, previous studies of racial difference in cortical thickness of cognitively normal older adults have been restricted to small sample size and have not adequately controlled biases. We aimed to compare cerebral cortical thickness between cognitively normal older adults of East Asians and of Caucasians adjusting for age, gender, education.MethodWe evaluated the brain cortical thickness by using FreeSurfer on standard T1‐weighted images of cognitively normal older adults in East Asians [n= 321 (60’s = 166, 70’s = 155)] and Caucasians [n= 282 (60’s = 111, 70’s = 171)], and examined the difference in cortical thickness between two races by whole brain analysis (ANCOVA adjusting age, education, MMSE scores, corrected p < 0.05, FDR correction).ResultEast Asians were shown to have a higher cortical thickness in bilateral superior frontal, lateral and medial orbitofrontal, middle temporal, left superior parietal, right inferior parietal, and inferior temporal cortex and lower cortical thickness in bilateral parahippocampus, postcentral, lateral occipital, left transverse temporal, lingual, precuneus, right superior temporal, fusiform cortex than Caucasians. Additionally, interactions between age and race had an impact on cortical thickness in right superior frontal cortex.ConclusionThe findings indicated that there was a significant difference in cortical thickness between cognitively healthy elderly in East Asians and in Caucasians according to the brain regions. The findings could contribute to a better understanding of the race‐specific structural change in the normal aging and provide an importance of an ethnic‐specific template for evaluating the structural and functional brain imaging in the healthy aging and neurodegenerative disease including Alzheimer’s disease.
Drug repurposing for Alzheimer’s disease: Selective serotonin reuptake inhibitors
Authors: Rao Praveen P. Nekkar , Tin Gary , Mohamed Tarek , Shakeri Arash , Pham Amy Trinh 
Published: December 2020

AbstractBackgroundAlzheimer’s disease (AD) is a devastating neurodegenerative disorder which affects more than 50 million people across the globe. Unfortunately, the current pharmacotherapy options are very limited and provide only symptomatic relief. Several drug discovery efforts to treat AD have failed in the clinical trials which is a setback in discovering novel anti‐AD therapies. Considering the cost, time and risks involved in bringing a new drug from the bench‐to‐bedside, drug repurposing or discovering novel therapeutic indications for drugs already in the market is an attractive alternative to find novel AD therapies. Targeting the amyloid (Aβ) cascade event in AD is one of the several potential targets to develop novel anti‐AD agents. Our studies looked at the possibility of repurposing marketed selective serotonin reuptake inhibitors (SSRIs) fluvoxamine, fluoxetine, paroxetine, sertraline and escitalopram in AD and investigated their anti‐Aβ aggregation properties.MethodExperiments conducted include fluorescence aggregation kinetics using the dye thioflavin T (ThT), determining Aβ morphology in the presence and absence of SSRIs by transmission electron microscopy (TEM) and computational modeling using the software Discovery Studio Structure‐Based‐Design.ResultThese experiments demonstrated that among the SSRIs tested, paroxetine in particular was able to prevent the aggregation of both Aβ40 and Aβ42 peptides. Computational studies were used to understand the interactions of paroxetine with Aβ40 and Aβ42 oligomer and fibrils models.ConclusionThese studies suggest that the antidepressant paroxetine has the potential to target the amyloid cascade in AD. Further studies are required to determine the suitability of repurposing paroxetine to treat AD.
Association of the motoric cognitive risk syndrome with levels of perceived social support
Authors: Felix Nicole , Ayers Emmeline , Verghese Joe , Blumen Helena M 
Published: December 2020

AbstractBackgroundThe Motoric Cognitive Risk (MCR) Syndrome is a pre‐dementia syndrome characterized by slow gait and cognitive complaints that predicts dementia. It remains unclear whether decreased levels of social support predict MCR. Our goal is to assess the risk of developing MCR as a function of varying levels of self‐reported social support in the categories of: (a) emotional/information support (b) tangible support (c) affectionate support and (d) positive social interactions.MethodsOur prospective cohort study sampled male and female older adults between 65 and 96 years old, with a mean age of 77, and with no MCR or dementia at baseline. We calculated MCR incidence based on participants’ levels of perceived social support with adjustments for age, sex, race/ethnicity, years of education, global health score, geriatric depression scale score, and marital status. Cox regression analyses were used to estimate hazard ratios with 95% confidence intervals across a one to seven‐year time span and a median follow‐up time of 2.5 years.ResultsThirty‐eight participants (9.8%) developed MCR. Increased tangible support decreased the risk of MCR by 30.9% [aHR:0.691, 95% CI (.523‐.915), p=0.010]. A higher overall social support score also decreased the risk of MCR by 33.8% [aHR: 0.662, 95% CI (.456‐.962), p=0.031]. The other categories of social support as well as the Social Network Index (SNI) scores were not significantly associated with a decreased risk of MCR (p>.05).ConclusionsIncreased social support, especially tangible support, may prove protective against MCR, dementia and other forms of cognitive decline.
Dementia prevalence in Torres Strait communities
Authors: Strivens Edward , Russell Sarah G , Quigley Rachel , Sagigi Betty , Miller Gavin 
Published: December 2020

AbstractBackgroundDementia prevalence in Aboriginal communities is amongst the highest in the world, with rates up to three to five times higher than the wider Australian community being reported. Risk factors identified included age, male gender, lack of formal education, smoking, stroke, epilepsy, head injury, poor mobility, falls, and incontinence. However, Australia has two culturally distinct Indigenous populations, and it is not known if Torres Strait Islander peoples, who comprise 10% of all Indigenous Australians, share this increased risk of dementia. The aim of this study was to assess dementia prevalence in the Torres Strait and investigate factors associated with dementia risk.MethodA total of 322 residents living in the Torres Strait in Far North Queensland (94% Indigenous) participated in a comprehensive diagnostic Geriatrician assessment. Mean age of the sample was 64.58 (SD11.2, range 41‐93) and 37.3% were male. All had some formal education (30.6% primary school only). Using consensus diagnosis, participants were diagnosed with dementia, cognitive impairment no dementia or normal cognition according to DSM IV criteria.ResultsConsistent with findings in Aboriginal communities, the prevalence of dementia in the sample was 2.94 times higher than the wider Australian population. Over 14% of the sample were diagnosed with dementia and a further 21% with Cognitive Impairment No Dementia. Preliminary results showed that age, education, hypertension, heart disease, chronic kidney disease, previous stroke, falls risk and pain were associated with dementia in this sample.ConclusionTorres Strait Islander peoples share an increased risk of dementia seen in Aboriginal Australians compared to the wider community but have a distinct pattern of risk factors. This highlights the need for tailored interventions to address this increased dementia risk for different Indigenous communities.