bluuebunny/crossref_metadata_2025_split huggingface dataset:
Medial temporal contributions to learning, retrieval, and accuracy monitoring in verbal memory
Authors: Memel Molly B. , Casaletto Kaitlin B , Kramer Joel H. 
Published: December 2020

AbstractBackgroundVerbal memory profiles are commonly characterized as reflective of frontal or medial temporal dysfunction in clinical practice. Frontal‐subcortical patterns are marked by intrusion errors and impoverished recall that improves with cueing and recognition. However, retrieval deficits, intrusion errors, and impoverished learning are also seen in disorders affecting the medial temporal lobes (MTL), such as Alzheimer’s disease. The aim of the current study was to determine the relative contribution of prefrontal and MTL structural integrity to verbal memory patterns typically attributed to frontal or MTL dysfunction in a mixed neurodegenerative sample.Method1148 participants at the UCSF Memory and Aging Center completed the CVLT‐III‐Short Form, and an MRI (T1‐weighted) scan. Participants varied in neurodegenerative syndrome. 55 functionally intact older adults were included for comparison. MRI analyses focused on a priori regions of interest including dorsolateral prefrontal cortex (DLPFC) and MTL regions (Hippocampus, Parahippocampal Gyrus, and Entorhinal Cortex). Linear regression models assessed the relative contribution of DLPFC and MTL volumes to six CVLT metrics of interest: 1. Benefit from multiple learning trials 2. Learning Slope 3. Cued Recall Gains 4. Total Intrusions 5. Recognition Gains 6. Response Bias.ResultsAlthough participants with smaller DLPFC volumes exhibited a greater benefit from recognition, as would be expected based on commonly characterized frontally‐mediated retrieval deficits, DLPFC volume was not associated with benefit from cueing, intrusions, or response bias. In contrast, patients with smaller MTL volumes benefited less from cued recall and recognition, and the relative contribution of MTL volume was 1.5‐2 times larger than DLPFC. Furthermore, only MTL volume was associated with intrusion errors and benefit from multiple learning trials. Performance was not associated with either region of interest in the control group.ConclusionWhile the current findings support the association between retrieval deficits and prefrontal integrity, they highlight the prominent contribution of MTL to commonly characterized frontal memory deficits, including improvements with repetition, cueing, and recognition. When interpreting verbal memory patterns in neurodegenerative samples, consideration of both PFC and MTL integrity is warranted.
Real‐time prediction of working memory performance: A machine learning‐based approach towards dementia prevention
Authors: Mirjalili Mina , Zomorrodi Reza , Hill Sean , Daskalakis Zafiris J , Rajji Tarek K 
Published: December 2020

AbstractBackgroundMCI is a clinical state that typically precedes Alzheimer’s dementia (AD). Working memory deficits are common in MCI and affect routine activities. Thus, developing an intervention that enhances working memory could enhance day‐to‐day function in these patients and, in turn, prevention progression to dementia. Towards this goal, a model that predicts individual‐specific working memory performance in this population could be instrumental for personalized interventions. Electroencephalography (EEG) captures the time dimension of cognitive events that happen during working memory performance and could predict individual‐specific performance. EEG predictive markers can then be targeted by interventions to enhance performance.MethodWe propose a single‐trial classification process that predicts individuals’ responses i.e. target correct (TC) vs. target noncorrect (TNC) responses during a working memory task, N‐back. We applied this process to EEG data of 15 healthy participants (mean age (SD) = 29.8 (7.6)) while performing the 3‐back task. We used event related (de‐)synchronization (ERD/ERS) from EEG signals 600 milliseconds prior to stimulus presentation as input features to a support vector machine classifier. To avoid overfitting of the model, we applied recursive feature elimination and cross validation to the first two‐thirds of the task. A trained classifier was then tested on the last third of the session. Non‐parametric permutation testing was used to ensure that the extracted pattern is associated with the original data rather than a random pattern.ResultOur model identified the brain regions where ERD/ERS predicted each individual’s working memory performance. Mean (SD) prediction accuracy across 15 participants was 70.1% (5.9). Accuracy was significantly above chance in 12 out of the 15 participants. The total number of the predictive EEG features across all participants ranged between 4 and 9. The mode was 6. As an example, in one participant, we achieved 69.2% accuracy based on 6 features: decreased parietal theta ERS; increased prefrontal theta ERS; decreased right temporal and occipital gamma ERS; and increased frontal and right temporal alpha ERD.ConclusionThis pilot study could lead to a machine‐learning based approach to increase the efficacy of personalized AD preventative interventions by individualizing the targets for these interventions.
Association of G protein‐coupled receptor kinases with tau pathology in Alzheimer's disease
Authors: Guimaraes Thais Rafael , Swanson Eric , Kofler Julia , Thathiah Amantha 
Published: December 2020

AbstractBackgroundAlzheimer's Disease (AD) is characterized by pathological aggregation and accumulation of hyperphosphorylated microtubule‐associated protein tau1 in intracellular neurofibrillary tangles (NFTs)2,3. Phosphorylation is a vital cellular process associated with protein homeostasis and disease4. Tau, for instance, has more than 80 putative phosphorylation sites, which regulate both physiological and pathological tau functions1. Although several tau kinases have been identified to play causative roles in AD tau pathogenesis1,5, kinase‐targeted therapies for AD have been unsuccessful thus far6. Interestingly, the kinases responsible for several putative tau phosphorylation sites remain unknown7. G protein‐coupled receptor kinases (GRKs) are a family of seven kinases (GRKs 1‐7) that are implicated in numerous peripheral and brain pathologies8,9, including a cursory association of GRKs 2 and 5 with AD10. Nevertheless, a comprehensive characterization of the expression and distribution of GRKs in the non‐demented and AD human brain has not been previously performed. We hypothesize that establishment of the GRK profile and pattern in the human brain may provide insight into the putative involvement of GRKs in tau pathobiology in AD.MethodWe performed immunohistochemical and biochemical analysis of the four ubiquitously expressed GRKs (i.e., GRKs 2, 3, 5, and 6) in relation to the expression and accumulation of tau in postmortem human hippocampal tissue from control subjects and AD patients.ResultWestern blot analysis indicates that GRK levels are similar in control and AD brains. However, a region‐specific immunohistochemical analysis reveals that all four GRKs are decreased in the CA1 of the AD hippocampus, one of the most vulnerable regions to AD pathology11,12. Interestingly, the GRKs differentially co‐localize within total and phosphorylated tau NFT pathology. Additionally, all GRKs tend to positively correlate with soluble tau levels in the AD brain. Finally, GRKs 3 and 5 display a remarkable co‐localization with late‐stage NFTs in the AD brain.ConclusionCollectively, our findings show that the GRKs associate with tau pathology in AD brains, suggesting that GRKs may regulate tau phosphorylation, solubility, and aggregation in AD. These results provide a foundation for future mechanistic studies addressing the putative role of GRKs in tau physiology and pathology.
Endoplasmic reticulum aggregation act as a nucleation site for autophagosome formation in an amyloid‐β model of Alzheimer’s disease
Authors: Chang Raymond Chuen‐Chung , Ho Janice Yuen Shan , Yeung Sherry Sin Hang 
Published: December 2020

AbstractBackgroundAutophagy via formation of the autophagosome is a major cellular degradation pathway for long‐lived proteins and organelles. Dysfunction in autophagic processes are prominently linked to neurodegenerative disorders associated with an aggregation of misfolded protein. However, the underlying cellular mechanisms of how amyloid‐β (Aβ) promotes autophagy in Alzheimer’s Disease remains elusive.MethodTo investigate this, primary culture rat hippocampal neurons were transfected with GFP‐KDEL construct at DIV5 and treated with 15 µM ABO at DIV7. Either an AMPKα activator (1 mM AICAR) or inhibitor (10 µM Dorsomorphin) was applied at timed 2, 8, 24 h intervals. Cells were fixed and analysed using confocal imaging and biochemical data.ResultAβ‐induced autophagy was shown to begin from recruitment of ULK‐1 via an AMPK‐dependent pathway to the endoplasmic reticulum (ER). Pharmacological inhibition of AMPKα by Dorsomorphin in Aβ‐treated primary hippocampal neurons demonstrated reduced recruitment of ULK‐1 to the ER, while AMPKα activation by AICAR resulted in increased ULK‐1 recruitment to the ER. Live cell confocal imaging demonstrated intracellular interactions between ULK‐1 and the Atg14L‐Beclin1‐Vps34 complex. There were visible aggregation and ubiquitination on the ER promoting the formation of omegasomes and ultimately kick‐starting the autophagic pathway. In parallel, p62 was also found to translocate to ER aggregation sites after Aβ treatment aside from its known roles in protein shuttling towards mature autophagosomes.ConclusionThis study demonstrates that Aβ‐induced autophagy is an AMPK‐dependent process and begins with recruitment and aggregation of important proteins such as ULK‐1 and PI3K‐III complex to the ER thereby pushing off the formation of mature autophagosomes.
The role of automatic habit in physical activity behaviours in older people: A new target for lifestyle interventions for dementia risk reduction?
Authors: Andrews Sophie C , Parekh Dinaz , Brady Brooke , Delbaere Kim , Killcross Simon , Anstey Kaarin J 
Published: December 2020

AbstractBackgroundPhysical inactivity is a key risk factor for dementia, yet physical inactivity is common in older adults. Increasing physical activity levels in this population is an urgent health priority. Automatic, context‐dependent habits may play an important role in physical activity behaviour. This study aimed to investigate the relationship between physical activity behaviours and their automaticity in older people.Method123 community dwelling Australians aged over 65 years (M=72.2; 81 women), recruited from participant registries, local hospital noticeboards and community groups, completed an online questionnaire. Current physical activity levels were measured using the Incidental and Planned Exercise Questionnaire, and automaticity of those physical activity behaviours were measured using the Self‐Report Habit Automaticity Index. Participants also reported demographic information, falls and medical history, and current mood symptoms.ResultParticipants reported an average of 2.28 hours planned walking (SD=2.33), 5.81 hours planned moderate/vigorous exercise (SD=4.02), and 20.5 hours incidental activity (SD=15.52) per week. Multiple regression analyses revealed that after controlling for age, gender, BMI and depression symptoms, higher automaticity scores were associated with more hours per week of planned walking (p=.012), moderate/vigorous exercise (p=.038), and incidental activity (p=.017).ConclusionIn a sample of active older Australians, participants who engaged in higher levels of physical activity reported their activity to be more automatic than those reporting lower levels of activity, regardless of the type of physical activity engaged in. Supporting older people to make their physical activity more habitual could therefore be an effective approach to increase levels of physical activity in this population.
Global response to the provision of dementia information and support during the COVID‐19 crisis
Authors: Lynch Chris , Weidner Wendy S 
Published: December 2020

AbstractBackgroundDementia and COVID‐19 share the same key risk factor ‐ age. As the world reacted to the pandemic it became evident that people living with dementia were an exceptionally high‐risk group; disruption to the diagnosis pathway, provision of post diagnostic support, interruptions to research and trials. Alzheimer's Disease International responded quickly to support our global network of 102 associations, many challenged with having to re‐invent their services, including withdrawal of face‐to‐face support & confronting income crises; plus providing timely information, support and advocacy interventions to partners.MethodEarly 2020 ADI engaged our global associations to gauge the concern around COVID‐19, with insight from our member association in China. Regular contact with the WHO and our international partners gave us impetus to adapt our programme of work.ResultADI produced an online COVID‐19 resource; a go‐to for information, advice, experience and learning. A key resource, an advisory video from Prof. Huali Wang, China, offering health and care advice ‐ subsequently translated into a number of co‐authored articles in The Lancet; followed by a paper on 'Difficult decisions about hospital admission and triage' Through series of global webinars ADI provided up to the minute experience & information focussing on key areas ‐ care homes; the scarcity of resources; life/ deaths decision making and the rights of people with dementia to treatment. Future gazing sessions followed to ascertain the impact of COVID‐19 on the diagnosis pathway, national plans, trials and on prevalence rates. Thorough our engagement with the WHO, ADI contributed to the creation of an inter‐agency mental health and psychosocial support resource and participated in the Civil Society Working Group on NCDs. Media engagement brought vital attention and coverage to dementia, through titles including BBC World & Futures, The Economist, The Telegraph.ConclusionTimely responses, interventions and the provision of COVID‐19 resources has enabled our global associations to adapt their operations to better respond to the crisis and to review operational and policy strategies. Through partnership working, timely sharing of information and advice, we have facilitated a strong reaction and positive response throughout the dementia sector to this extraordinary period.
Analytical characteristics of the updated elecsys Abeta42 Gen 2 assay, including comparisons with the Gen 1 assay
Authors: Blennow Kaj , Zetterberg Henrik , Rutz Sandra , Wittig Martina , Manuilova Ekaterina , Logan Chad , Bauer Ekaterina , Stomrud Erik 
Published: December 2020

AbstractBackgroundCerebrospinal fluid (CSF) biomarker amyloid‐β1–42 (Abeta42), quantified using the Elecsys® Abeta42 (Gen 1) immunoassay, supports diagnosis of Alzheimer’s disease. Compared with Gen1, the updated assay Elecsys Abeta42 CSF II (Gen2) has a higher threshold for biotin interference, extended measuring range, and is re‐standardised according to certified reference Abeta42 peptide ERM‐DA480/‐481/‐482. The new Routine‐Use (RU) pre‐analytical protocol will be introduced with the Gen2 assay (reported separately). Here, we present the analytical performance of the Gen2 assay, including comparisons with Gen1.MethodAnalytical performance experiments were conducted on cobas e 601 analysers. Precision was investigated according to Clinical and Laboratory Standards Institute EP05‐A3 (21‐day experiment) using seven native and two control samples. For lot and instrument comparisons (cobas e 801 vs e 601), 125 native CSF sample pools were measured in one run. Gen1 and Gen2 were compared in two method comparison (MC) studies: in‐house study: 103 frozen CSF samples were measured in one run; external study (Pre‐analytical study 2): CSF samples from 24 patients with suspected normal pressure hydrocephalus were prospectively collected according to the RU, Roche Trial and BioFINDER protocols. MC was based on mean concentrations obtained from 3–4 aliquots per patient. Aliquot‐aliquot variability was compared for each protocol. MC analyses included calculation of Pearson’s correlation (r) and Passing‐Bablok regression fit.ResultPrecision analysis provided within‐run variability of <6% and intermediate precision of <8% for all samples. Measurements of three lots were highly correlated (r=1.00) with bias <5.2%, within the clinically relevant range. Measurements on cobas e 601 and e 801 analysers were highly correlated (r=0.995) and regression analysis yielded a slope of 0.941. Gen1 and Gen2 were strongly correlated in both MC studies (in‐house: r=0.999; external: r=0.990). Slope estimates were 0.75 and 0.79 in the in‐house and external studies, respectively (Figure). Aliquot‐aliquot variability was similar for Gen1 and Gen2 assays within each protocol and lower in the RU versus the Roche Trial protocols (Table).ConclusionThe Abeta42 Gen2 assay strongly correlated with the Gen1 assay. High precision and low variability between lots and analysers showed the Gen2 assay provided additional benefits over Gen1 without compromising technical performance.
Association of sera levels of anti‐pemphigoid autoantibody (BP 180) with AD: A pilot case‐control study
Authors: Salama Mohamed , Shalash Ali 
Published: December 2020

AbstractBackgroundBullous pemphigoid (BP) is a common dermatological disease affecting the aging population. Previous research showed potential cross‐talks between BP patients and those with neurodegenerative diseases e.g. dementia. The present study assessed serum levels of autoantibodies (AIAs) against pemphigoid in a sample of Alzheimer's disease (AD) as well as Parkinson's disease (PD) patients compared to matched healthy controls.MethodTwenty‐five PD patients were compared to fifteen AD patients and matched ten controls. All patients were evaluated clinically and their sera were collected to estimate levels of AIAs against pemphigoid. PD stages were considered clinically using UPDRS subscales, Hoehn and Yahr scale, and Schwab and England scales, while AD patients were evaluated using MoCA scale.ResultThe results showed a significant elevation in BP 180 AIAs in AD patients (37.5%) compared to PD patients (14%) and controls (10%).ConclusionThe present findings highlight the possible role of cross‐reactivity between the skin and brain antigens in developing AD.
Reminiscence therapy using virtual reality technology affects cognitive function and morale of elderly with dementia
Authors: Tominari Maho , Uozumi Ryuji , Becker Carl , Kinoshita Ayae 
Published: December 2020

AbstractBackgroundJapan already confronts a super‐aged society in which the number of dementia patients is increasing drastically. We need to improve care methods to meet the needs of elderly dementia patients. Thus, we developed a novel reminiscence therapy care program using a virtual reality (VR) tool for elderly people with mild dementia; then we evaluated the effect in comparison to the conventional reminiscence therapy.MethodWe measured 52 people with mild cognitive impairment using the Mini‐Mental State Examination, Revised PGC Morale Scale, Multidimensional Observation Scale for Elderly Subjects, Trail Making Tests A and B, and Word Fluency Test before and after 8 weeks of reminiscence therapy. We randomly assigned them to reminisce with either conventional still photos or VR panoramas. We compared their results using t‐tests.ResultThe scores of MMSE totals showed improvement for both groups, but it did not achieve the primary objective. The considerable improvement was seen only in the VR panoramas group. The PGC morale scale scores rose considerably higher in the VR panoramas group than in the still photo group. No definite differences were observed in other scales, neither between the two groups nor before and after the intervention.ConclusionReminiscence therapy produced cognitive improvement regardless of whether still photos or VR panoramas were used as stimuli. However, reminiscence therapy with VR panoramas produced greater improvement in participants’ morale, which may enhance patients’ well‐being.
Combined low plasma Aβ42/Aβ40 ratio and high neurofilament light chain levels are associated with both cognitive and physical function declines over time in non‐dementia older adults with memory complaints
Authors: He Lingxiao , Barreto Philipe de Souto , Nguyen Andrew D , Morley John E , Li Yan , Bateman Randall J , Vellas Bruno ,   the MAPT/DSA Group
Published: December 2020

AbstractBackgroundAlthough brain amyloid deposition (Aβ) and plasma neurofilament light chain (NfL) are associated with cognitive decline, associations of combined plasma Aβ and NfL profiles with cognitive and physical functions in older adults remain unknown. The current study aimed to investigate prospective associations of combined plasma Aβ+ and NfL+ profiles with cognitive and physical functions in older adults.MethodPlasma Aβ and NfL levels, cognitive and physical function data (n=452 participants) collected from the Multidomain Alzheimer’s Preventive Trial (MAPT, www.clinicaltrials.gov [NCT00672685]) were used in this study. The MAPT recruited 1680 non‐dementia older adults with memory complaints for a 3‐year intervention, followed by a 2‐year observational follow‐up. Cognitive function was evaluated as mini mental state examination and composite cognitive score (CCS, a mean Z‐score combining four cognitive tests). Physical function was evaluated as gait speed (4‐m usual‐pace walk test) and chair‐stand time (5‐time maximal chair‐stand test). Cognitive and physical function data measured at the moment and after blood Aβ and NfL tests were used for analysis. Participants with plasma Aβ42/Aβ40 ratios lower than 0.107 and NfL levels greater than 93.04 pg/ml were classified as Aβ+ and NfL+. Multivariable regressions and mixed effects linear models were used.ResultAt the cross‐sectional level, no significant association was found between Aβ+NfL+ and cognitive or physical function. Evaluating longitudinal changes, participants with Aβ+NfL+ had more decline in the CCS and gait speed over time, compared to the other participants. After adjusting for APOE ɛ4 genotype, Aβ+NfL+ was associated with greater decline only in CCS.ConclusionCombined low plasma Aβ42/Aβ40 ratio and high plasma NfL level was associated with greater declines in cognition and gait speed over time, providing further evidence of the links between cognitive and physical function.