bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immigration and Cognitive Change after age 90: findings from the LifeAfter90 Study
Authors: Meunier Claire C. , Corrada Maria M. , Gilsanz Paola , Kawas Claudia H. , Mungas Dan M. , DeCarli Charles S. , Meyer Oanh L. , Whitmer Rachel A. 
Published: December 2022

AbstractBackgroundPrior studies have suggested immigration may be associated with different cognitive decline; however, this has not been explored in those aged 90+ years. This study examined the association between United States (US) born vs non‐US born and cognitive decline in a diverse cohort of oldest‐old.MethodWe followed 641 participants of the LifeAfter90 study, an ongoing cohort study to evaluate aging and incident dementia in individuals aged 90+ recruited from Kaiser Permanente Northern California. Verbal episodic memory (VEM), semantic memory (SM), and executive function (EF) were measured using the Spanish and English Neuropsychological Assessment Scale every six months and domain‐specific scores were z‐scored to baseline. Self‐reported birthplace was collected at baseline or visit 2 (if previously not asked due to changes in the survey). Linear mixed models with random intercepts and slopes were adjusted for baseline age, gender, race/ethnicity, education, years since baseline, and practice effects.ResultThe sample was comprised of 60% women, 30% White, 18% Latino, 22% African American, 22% Asian, and 8% multiracial individuals (Table 1). Nineteen percent (n = 123) of the participants was born outside of the US, of those, 74% identified as Asian or Latino. Average baseline age was 93 years without differences between US‐born and non‐US born participants. Participants were followed for up to 7 waves (3.5 years with a mean of 2 visits). At baseline, participants born outside of the US had lower EF z‐scores (β = ‐0.39; 95% CI:‐0.57,‐0.21) and lower SM z‐scores (β = ‐0.69; 95% CI:‐0.87,‐0.51) than US‐born counterparts after adjustments (Table 2, Model 3). Participants had similar rates of cognitive change in the EF and VEM domains over the 7 waves. Participants born outside the US had a faster rate of decline in SM (β = ‐0.14; 95% CI:‐0.26,‐0.03) after adjusting for covariates.ConclusionIn oldest‐old individuals, we found that those born outside of the US had lower baseline EF and SM; a faster rate of decline in SM and a similar, though not quite significant, effect on VEM decline. Further comprehensive data on immigration, such as age of immigration and educational opportunities, may help explain the relationship between cognitive function and immigration
Awareness Creation of Neurotoxins‐induced Wallerian‐type degeneration causing brain Acetylcholine‐imbalance and frank Alzheimer disease
Authors: Olughor Vincent Oghenekevbe 
Published: December 2022

AbstractBackgroundPresence Environmentally Mediated Intellectual Decline Neurotoxins ('presence‐EMIDN') threats from 'bounded', 'unbounded' and 'pervasive' sources puts everyone at risk of developing neurodegenerative diseases (eg. Alzheimer) once specific lipophilic‐neurotoxins breach the blood‐brain and nose‐brain barriers to reach the brain and build up to harmful thresholds. Such neurotoxins exist; how they provoke Wallerian‐type degeneration to cause FAD have been threaded together from experimental evidenced‐based reviews. My intent/interest is to create awareness and establish the aetiology for FAD, which has remained idiopathic since 1906, when the German Neurologist, Alois Alzheimer, discovered the disease.MethodThrough threaded literature reviews from multiple sourcesResultsMany neurotoxins produce Wallerian‐type degeneration: organophosphorus compounds (DFP, TOCP), acrylamide, n‐hexane and some of its metabolites. Wallerian‐type degeneration have been demonstrated in animals: hens, cats, rats, rabbits. Changes during Wallerian‐type degeneration can be grouped into two (Histopathological and Biochemical): it describes the cascade of events taking place in the distal part of an axon that has been cut or crushed. The histopathological changes occur in stages in the following order of succession: stage a: primary degeneration of axon followed by secondary degeneration of myelin in these order: axon swelling; axon disintegration; loss of normal myelin structures with swelling; tumefaction; and breakdown of myelin sheaths; followed by stage b: Cellular proliferation; and then stage c: Fibrosis. The biochemical changes result from liberations of normal biochemical constituents of axon and myelin. There is specifically a decrease in the CNS neurotransmitter's Acetylcholine content, in stage a (causing deficiency‐imbalance), increase in collagen in stage c, and other stage b changes.ConclusionThere are evidences showing that symptoms of FAD is due to 'Acetylcholine deficiency‐imbalance in the brain' where it exercises Excitatory and Inhibitory effects which progressively kick‐starts FAD with fatalities after 5 years. Establishing this aetiology brings vistas of new hope/challenges for possible therapeutic interventions developments.
Myeloid cell bioenergetics regulate cognitive function in aging
Authors: Andreasson Katrin I. , Minhas Paras Singh , Wang Congcong 
Published: December 2022

AbstractBackgroundA hallmark of aging is the appearance of sustained pro‐inflammatory responses and reduced clearance of pathogenic materials. Systemically, aging is accompanied by a skewing of the immune system towards the myeloid cell lineage and an increase in circulating pro‐ inflammatory factors. In the aging brain, functional degradation of microglia leads to the accumulation of neurotoxic misfolded proteins, a loss of trophic factors that support neurons, and a failure to maintain a homeostatic microenvironment. However, the underlying mechanisms that initiate and sustain maladaptive inflammation with aging are not well defined.MethodTo maintain homeostatic responses, immune cells require robust glycolytic and mitochondrial metabolism to meet demand for energy and biosynthetic precursors. In this study, we investigated metabolic and immune effects of inflammatory prostaglandin E2 (PGE2) signaling in age‐associated inflammation and cognitive decline.ResultWe demonstrate that PGE2 signaling via its EP2 receptor suppresses healthy peripheral myeloid and microglial cell glucose metabolism by driving sequestration of glucose into glycogen through the AKT/GSK3ß/GYS1 pathway and away from generation of ATP. This energy‐deficient state in turn promotes maladaptive, neurotoxic immune responses in vivo. Using genetic and pharmacological modeling, we demonstrate that inhibition of EP2 signaling restores youthful myeloid bioenergetics and immune responses and rescues synaptic mitochondrial function, hippocampal plasticity and spatial memory.ConclusionInhibition of EP2‐dependent disruption of myeloid metabolism may represent a new approach to disorders of aging, with greater specificity than the use of non‐steroidal anti‐inflammatory drugs that target COX‐2 and COX‐1 and suppress both beneficial and toxic prostaglandin signaling pathways.
The Impact of COVID‐19 on Family Dementia Caregivers: Insights from a Memory Clinic in Germany
Authors: Klein Olga A. , Karras Antonia , Teipel Stefan , Hoffmann Wolfgang , Kilimann Ingo ,   DZNE GAIN research group
Published: December 2022

AbstractBackgroundFamily dementia caregiving is associated with a high burden on the caregiving relatives. With the worldwide spread of coronavirus SARS‐CoV‐2, new stress factors were added for both the caregivers and the PwD, as they had to further limit their social contacts due to statutory restrictions and they belong to the groups of people with a higher risk of a severe COVID‐19 disease course. Our aim was therefore, to investigate the impact of the COVID‐19 pandemic on the care situation and well‐being of family dementia caregivers.MethodSemi‐structured telephone interviews with family dementia caregivers (n = 20) were conducted, recorded, transcribed and analysed thematically. This study was embedded within a larger randomised controlled trial (RCT) assessing the effectiveness of a digitally supported care management programme.ResultNegative consequences reported were a decrease in support for caregiving responsibilities, adverse consequences for the PwD, and problems in connection with organising a COVID‐19 vaccination. New care requirements included the responsibility to ensure that the PwD complies with the corona security measures as well as the additional care tasks for the family caregivers that could no longer be guaranteed by third parties. Positive changes that were highlighted by some participants were that they had more time for their care responsibilities due to fewer visits from family or friends and as well as reduced perceived stress for the PwD. For the majority of participants, the impact was primarily reduced by the persistence of private and professional support services and their own coping strategies.ConclusionDespite some negative consequences, the results showed that the COVID‐19 pandemic had little overall impact on the caregiving situation of family dementia caregivers. These were surprising results as they stand in contrast to previous research findings. The overall low impact reported could be due to several factors. The interviews took place around the time of the second lockdown in Germany, which was generally described as a “light version” with back‐up measurements in place ensuring healthcare services operating almost as usual. In addition, an already restricted lifestyle as well as the fact that some caregivers received a care management programme at the time could have mitigated the impact.
Meta‐Analysis of Animal Fluency Performance in Amnestic Mild Cognitive Impairment and Cognitively Unimpaired Older Adults.
Authors: Sharma Vivek Attri , Malek‐Ahmadi Michael H. 
Published: December 2022

AbstractBackgroundAnimal fluency is a commonly used neuropsychological measure that is used in the diagnosis of mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Although most individuals with MCI have clinically normal scores on this test, several studies have shown the MCI individuals’ performance is significantly lower than that of cognitively unimpaired (CU) individuals. The aim of this meta‐analysis will be to characterize the effect size of animal fluency performance differences between MCI and CU individuals.MethodLiterature search with search terms used were: “animal fluency and mild cognitive impairment”, “semantic fluency and mild cognitive impairment”, “category fluency and mild cognitive impairment”. Data was extracted only from studies that met the following criteria: 1. It was to be an observational study (interventional studies were excluded; 2. Peterson criteria was used for diagnosis of the MCI individuals; 3. The study had raw data available animal fluency performance. Both the standardized mean difference (SMD) and the raw mean difference (RMD) were derived from random effects analyses. Demographically adjusted z‐scores for Animal fluency performance for the MCI groups were obtained to determine normative performance.ResultTwenty studies were included in the analysis. The SMD for animal fluency performance between CU and MCI was 0.89 (95% confidence interval: [0.73; 1.04], p<0.001), I^2 = 68.6% [50.2%; 80.2%], which reflects a large effect size with moderate heterogeneity. The RMD was ‐4.09 [‐4.78; ‐3.40], p<0.001 indicating that MCI individuals generated significantly fewer animals than CU individuals. The mean z‐score for MCI groups’ animal fluency scores was z = ‐0.75 indicating performance in the Low Average range.ConclusionThis study found a large effect size for differences on animal fluency performance between MCI and CU individuals. On average, the MCI groups’ normative performance did not fall into the Impaired range indicating that there are important sub‐clinical differences on animal fluency performance between CU and MCI individuals. These findings are relevant to the use of composite efficacy measures for AD prevention trials. Specifically, the inclusion of animal fluency in these composite scores may help increase their sensitivity to change and yield greater statistical power for these trials.
The Impact of COVID‐19 on Family Dementia Caregivers in Vietnam ‐ Insights from A Memory Clinic in Ho Chi Minh City
Authors: Tam Pham Thi Thanh , Nam Vu Hai , Huong Tran Thi Thu , Liem Do Thanh , Luu Phan Thi , Thang Tran Cong , Weschke Sarah , Kilimann Ingo , Klein Olga A. 
Published: December 2022

AbstractBackgroundThe COVID‐19 pandemic has unprecedented consequences on stress, isolation, and financial well‐being for family caregivers of people with dementia globally. In Vietnam, soaring COVID‐19 cases have led to widespread social distancing, isolation, and quarantine orders from the government. To date, limited evidence exists about the situation of persons with dementia and their family caregivers during the pandemic in Vietnam.ObjectivesThe study aimed to provide insights into the impact of the COVID‐19 pandemic on family caregivers of people with dementia.MethodsMixed methods were used, and data collection took place in two rounds. In the first round during the first wave of infections at Ho Chi Minh City, semi‐structured interviews with caregivers and health care workers (n = 16) were conducted and analysed thematically. In the second round, this data will be complemented with survey data from family caregivers of people with dementia (n = 30). The survey includes a combination of closed‐ and open‐ended questions on the impact of the pandemic on the caregivers’ health and caregiving responsibilities.ResultsResults of the first round of data collection showed a high impact of the pandemic on caregivers resulting in negative psychosocial and emotional consequences of caregivers such as worry, stress, frustration as well as restrictions in time and place. Caregivers had reduced access to counselling services needed. At the same time, treatment services for people with dementia were reduced or even halted. The results from the survey will give additional insights into the impact of the COVID‐19 pandemic on family caregivers of people with dementia, including their challenges and concerns. These results will help to adapt counselling and treatment services for dementia family caregivers and will be presented in detail.ConclusionThe study will lead to a better understanding of the impact of the COVID‐19 pandemic on family caregivers of people with dementia and will facilitate the adaptation of the existing as well as integration of new topics into our caregiver counselling program. Additionally, the development of (digital) self‐help groups for caregivers could be another option to prevent disruption of the health care system and to ensure ongoing service provision despite pandemic‐related restrictions.
Altered L‐carnitine and acylcarnitine profiles in APOE e4 carriers with Alzheimer’s disease reflect impaired fatty acid oxidation.
Authors: Abdullah Laila 
Published: December 2022

AbstractBackgroundAbnormal lipid metabolism is now considered one of the key biological features of Alzheimer’s disease (AD). The L‐carnitine system plays an important role in lipid metabolism, particularly fatty acid (FA) transport and metabolism in mitochondria. Blood and tissue acylcarnitine accumulation reflects incomplete fatty acid beta‐oxidation (FAO), corresponding with insulin resistance, oxidative stress and inflammation. We hypothesized that changes in blood and brain markers of the L‐carnitine system would indicate dysfunctional FAO in aging e4 carriers, thereby influencing AD pathogenesis.MethodPlasma and brain L‐carnitine, L‐carnitine metabolites and acylcarnitine were analyzed in controls and patients with early or moderate AD stratified by APOE genotypes. The L‐carnitine system was examined over a range of ages (10 to 50 weeks) in plasma and brains from transgenic mice expressing different human APOE isoforms and EFAD mice with human APOE and 5 x AD mutations.ResultAmong e4 carriers, plasma L‐carnitine decreased, but its metabolite, Trimethylamine N‐oxide, increased in patients with early or moderate AD. Among non‐e4 carriers these changes are detected only in moderate AD patients. Among e4 carriers, plasma long chain acylcarnitines (LCA) and very‐LCA (VLCA) were lowest in moderate AD patients. In e4 carriers, plasma acylcarnitines correlated with cerebrovascular, amyloid and tau pathologies. Whereas in e2 carriers, both brain and plasma acylcarnitines were correlated with amyloid, tau and cerebrovascular pathologies. In APOE4‐TR mice, medium chain acylcarnitines (MCA) and LCA decreased with age within the cerebrovasculature. Parenchymal acylcarnitines increased at an earlier age (25 weeks) among APOE4‐TR mice compared to mice with other APOE genotypes (50 weeks).ConclusionThese data suggest that among e4 carriers, the L‐carnitine system‐mediated FAO is dysregulated early in the disease process of AD. Age‐dependent decreases in MCA and LCA in the cerebrovasculature in APOE4‐TR compared to APOE3‐TR mice indicate FAO deficits at an earlier age in APOE4‐TR. Understanding the role of APOE4 in impaired FAO with age in relation to the L‐carnitine system is required for developing novel preventative/therapeutic strategies for AD.
Pathological tau interactors and their role in propagation and neurodegeneration
Authors: Martínez Pablo , Patel Henika , You Yanwen , Garfe Nur Jury , Perkins Abigail , You Yingjian , Huang Xiaoqing , Dutta Sayan , Wijeratne Aruna , Redding Javier , Mosley Amber L. , Rochet Chris , Zhang Jie , Troncoso Juan C , Reeves Cristian A Lasagna 
Published: December 2022

AbstractBackgroundTau aggregates are critical pathological features of Alzheimer’s disease (AD) and other tauopathies. An important focus of research has been to understand the pathological tau propagation in AD patient brains that follow neuronal networks. Despite the knowledge acquired, the cellular mechanism involved in tau propagation and seeding are still unclear. Unfortunately, the nature of the tau species involved in the spreading and the precise seeding/template remains unknown. Despite this uncertainty, some studies suggest that a high molecular weight tau (HMW‐tau) is the form of tau involved in trans‐synaptic propagation. It remains unresolved whether these HMW‐tau particles are made exclusively of tau or contain other constituents such as proteins necessary for propagation.Method3‐months‐old PS19 mice (n=3). TBS‐soluble PS19 brain extracts were passed through a Size Exclusion Chromatography (SEC) column. We then measured the tau seeding activity of each SEC‐fraction using a well‐described bio sensor cell line that relies on flow cytometry detection of FRET signal. To identify other constituents or interactors of this tau‐ seed, we IP human tau using the HT7 antibody from the fraction with highest tau seeding activity and subjected it to TMT‐tag quantitative Mass Spectrometry. Through quantitative Mass Spectrometry, we were able to identify the protein‐interactome of the tau‐ seed and the interactome of monomeric tau isolated from the same brains.ResultWe determined that tau from fraction‐9 (F9) forms an HMW‐tau complex in vivo (>2,000KDa) with the strongest seeding activity. Interestingly, the tau present in F9 is less than 4.4% of the total tau in the brain of PS19 mice and adopt a protofibrillar morphology. Bioinformatics from both interactomes revealed an enrichment of a specific set of proteins in the tau‐seed in comparison with monomeric tau.ConclusionHMW‐Tau, which represent the 4% of total tau in PS19 brains, has the highest seeding activity. The protein interactome of this HMW‐tau also differs from the monomeric tau interactome.
Investigating the use of an autonomous robot assistant to improve the wellbeing of institutionalized older adults in Armenia
Authors: Mahakian Jane 
Published: December 2022

AbstractBackgroundResearchers investigated the use of an emotional support robot to improve the well‐being of institutionalized older adults in Armenia. The autonomous assistant called Robin the Robot assessed the cognitive and psychosocial needs of elders in a nursing home in Armenia. Robin the Robot is a semi‐autonomous robot that interprets facial expressions and conversational contextual clues to understand emotions from individuals, and then uses artificial intelligence to guide its responses and develop a therapeutic interaction with patientsMethodThe twelve‐week study was a randomized control trial of using Robin the Robot as an intervention to improve well‐being of older individuals in long‐term nursing care facilities in Armenia. Upon enrollment, participants completed a brief demographics interview. Evaluation of study participants, both pre and post‐test included: the International Short‐Form of the Positive and Negative Affect Schedule (I‐PANAS‐SF)2; Montreal Cognitive Assessment (MoCA)8 and the Geriatric Anxiety Scale (GAS‐10)9 and Geriatric Depression Scale (GDS)10,11ResultThe results of the study revealed Robin the Robot’s interventions improved the elder’s cognitive functioning. On the Montreal Cognitive Assessment test (MoCA), the elder’s score improved an average of 3.29 points per person. Their word recall had the largest numerical improvement. On the Geriatric Depression Test, Geriatric Anxiety Test and the PANAS Test (positive and negative affect test) there were no significant differences between the pre and post intervention, although a slight improvement on the Geriatric Depression Test, however no statistical difference.ConclusionThe use of emotional support robots improved memory and cognitive functions of the elders, as well as slight improvement in mood. This project made a significant contribution in improving health outcomes for the elderly, bringing more attention to nursing facilities, and contributing to research on health and prevention.
Characterisation of D409V/WT mice as a novel dementia model
Authors: Sander Millie , Brown Jonathan T , Ballard Clive G , Lunnon Katie 
Published: December 2022

AbstractBackgroundAlzheimer’s disease (AD) and dementia with Lewy bodies (DLB) share various pathological and symptomatic traits. Such overlap complicates diagnosis, ultimately impacting the level of care and treatment options available to patients. The development of novel models to further understand DLB is therefore imperative. Recent research indicates mice with heterozygous mutations (D409V/WT) in the GBA gene to be a viable option, presenting DLB‐associated characteristics such as age‐related cognitive decline, an increase in monomeric α‐synuclein deposition and cholinergic dysfunction (Clarke et al., 2019).MethodsTo further characterise D409V/WT mice, we looked at measures of brain atrophy, patterns of neuronal firing, and transcriptomic changes. Global brain atrophy was assessed using six different measures surrounding cortical thickness and ventricle size from cresyl violet stained coronal sections. Neuronal activity in the medial septum was recorded through a series of multi‐electrode array (MEA) studies, and RNA was extracted from the same region in order to investigate transcriptional changes. All studies used WT littermates as controls.ResultsAt 12 months of age, D409V/WT mice exhibited both ventricle enlargement and cortical thinning when compared with WT controls. All six measures used were significant at the p < 0.05 level. Neuronal firing appeared to be disrupted among D409V/WT mice compared to WT controls, but this was not found to be significant. Further analysis is currently being undertaken to determine the effects of both cell and slice variation upon these results. We anticipate all further MEA analysis, and transcriptomic analysis to be complete by 31st May 2022.ConclusionsThese findings support D409V/WT mice to be a candidate model for DLB. Following further characterisation, we suggest this model may be useful in better understanding DLB and developing novel diagnostic tools.