bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anticholinergic burden and cognitive performance: Cross‐sectional results from the ELSA–Brasil study
Authors: Medeiros dos Santos Adriana Nancy , Brunoni Andre R , Goulart Alessandra C , Viana Maria Carmen , Benseñor Isabela , Lotufo Paulo , Suemoto Claudia Kimie 
Published: December 2021

AbstractBackgroundThe use of multiple drugs with anticholinergic properties is common in older adults and it may lead to cumulative anticholinergic toxicity and increase the risk of cognitive impairment. We investigated the association between the Anticholinergic Cognitive Burden scale (ACB) and cognitive performance among middle‐aged and older Brazilian adults (35‐74 years).MethodIn this cross‐sectional analysis of the Brazilian Longitudinal Study of Adult Health (ELSA‐Brasil), 13,065 participants were included (mean age = 51. ± 8.9 years old, 55% female, 53% white). Anticholinergic Cognitive Burden (ACB) was calculated according to the medications in use. We investigated the association of ACB with a global cognitive z‐score and memory, verbal fluency (VF), and Trail Making Test z‐scores, using multiple linear regression models adjusted for sociodemographic and clinical variables.Result16% of the sample had an ACB score >0. ACB was associated with worse cognitive performance on the memory (β= ‐0.022, 95% Cl= ‐0.045, 0.001, p=0.056) and in the trail making test (β= ‐0.021, 95% Cl= ‐0.043, 0.000, p=0.054) after adjustment for confoundersConclusionAnticholinergic burden was related to worse cognitive performance on the memory and trail making test in Brazilian participants.
Lower motor function prior to the Covid‐19‐imposed lockdown predicts emotional distress in older adults with T2D
Authors: Benari Ori , Ravona‐Springer Ramit , Almog Ganit , Yore Iscka , Zadok Maya , Lin Hung‐Mo , Ouyang Yuxia , Livny Abigail , Beeri Michal Schnaider 
Published: December 2021

AbstractBackgroundType 2 diabetes (T2D) is associated with accelerated cognitive decline and increased dementia risk. Lockdowns imposed due to the Covid‐19 outbreak led to unprecedented changes in the life of older adults. However, little is known about emotional distress consequences. We assessed associations of grey matter (GM) volumes (N=179), cognitive and motor functions (N=403) with emotional distress of older adults with T2D from the Israel Diabetes and Cognitive Decline Study (IDCD).MethodsDuring the first Covid‐19‐related lockdown in Israel, we applied a phone questionnaire, which included information about anxiety (“Over the last two weeks, how much have you been bothered by Feeling anxious or nervous?”; Anxiety levels now compared to before Covid‐19), depression (“Over the last two weeks, how much have you been bothered by feeling sad, down, or uninterested in life?”; sad feelings now compared to before Covid‐19), general well‐being (“How are you feeling in general?”), optimism towards the future (“Are you optimistic towards the future?”). Grey matter (GM) volumes (measured by high resolution T1‐weighted MRI), cognitive (a global measure summarizing 14 cognitive tests) and motor function (gait speed and grip strength), are routinely assessed by the IDCD study. Spearman correlation adjusting for age, sex, education, HbA1c and duration of T2D (as well as TICV for the GM analyses) examined associations of GM, cognitive and motor functions with emotional distress measures.ResultsThe sample averaged 72 years of age (SD=4.4), and 14 years of education (SD=3.5); 40.9% were female. Lower grip strength prior to lockdown was associated with increased sadness (r=‐0.21, p<0.001) and anxiety (r=‐.011, p=0.020), less optimism (r=0.10, p=0.042) and lower general feeling (r=0.17, p=0.0005). Slower gait speed was associated with increased sadness (r=0.13, p=0.005). Lower GM was associated with greater anxiety during the lockdown (r=‐0.19, p=0.011) and compared to before Covid‐19 (r=‐0.19, p=0.012). Global cognition was not associated with any of the emotional distress measures.ConclusionsMotor function, but not cognitive function, were associated with lockdown imposed emotional distress in older adults with T2D. These associations point to the importance of good motor function and physical conditioning in emotional well‐being related to acute stress related to stay‐at‐home‐orders.
Associations of fully automated Elecsys CSF and novel plasma biomarkers with Alzheimer's disease neuropathology
Authors: Grothe Michel J. , Moscoso Alexis , Ashton Nicholas J , Zetterberg Henrik , Blennow Kaj , Schöll Michael 
Published: December 2021

AbstractBackgroundThe development of fully automated analysis platforms for cerebrospinal fluid (CSF) biomarkers of Alzheimer’s disease (AD) and recent advances in blood‐derived biomarkers signify major steps towards a widespread clinical use of fluid‐based biomarkers. We aimed to study AD CSF biomarkers analyzed by fully automated Elecsys immunoassays in comparison to neuropathologic gold standards, and compare their accuracy to plasma phosphorylated tau (p‐tau181) and neurofilament light (NfL) measured using novel Simoa assays.MethodWe compared ante‐mortem Elecsys‐derived CSF biomarkers to standardised post‐mortem assessments of AD and non‐AD neuropathologic changes in 45 participants from the Alzheimer’s Disease Neuroimaging Initiative autopsy cohort. In a subset of 26 participants, we also analyzed ante‐mortem levels of plasma p‐tau181 and NfL. Reference biomarker values were obtained from 146 amyloid‐PET‐negative healthy controls (HC)([18F]Florbetapir‐PET <12 Centiloids).ResultAll CSF biomarkers clearly distinguished pathology‐confirmed AD dementia patients (N=27) from HC (AUCs=0.86‐1.00). CSF total‐tau (t‐tau), p‐tau181, and their ratios with Aβ1‐42, also accurately distinguished pathology‐confirmed AD from non‐AD dementia (N=8; AUCs=0.94‐0.97)(Fig. 1). In pathology‐specific analyses, intermediate‐to‐high Thal amyloid phases were best detected by CSF Aβ1‐42 (AUC[95% CI]=0.91[0.81‐1]), while intermediate‐to‐high CERAD neuritic plaques and Braak tau stages were best detected by CSF p‐tau181 (AUC=0.89[0.79‐0.99] and 0.88[0.77‐0.99], respectively)(Fig. 2). Optimal Elecsys CSF biomarker cut‐offs were derived at 1097/229/19 pg/ml for Aβ1‐42, t‐tau, and p‐tau181. In the plasma subsample, both plasma p‐tau181 (AUC=0.91[0.86‐0.96]) and NfL (AUC=0.93[0.87‐0.99]) accurately distinguished pathology‐confirmed AD (N=14) from HC. However, only p‐tau181 distinguished AD from non‐AD dementia cases (N=4; AUC=0.96[0.88‐1.00])(Fig. 1), and showed a similar, though weaker, pathologic specificity for neuritic plaques (AUC=0.75[0.52‐0.98]) and Braak stage (AUC=0.71[0.44‐0.98]) as CSF p‐tau181. No CSF or plasma biomarker was sensitive to the presence of Lewy body or TDP‐43 pathology, but Elecsys CSF Aβ1‐42 levels detected the presence of cerebral amyloid angiopathy (AUC=0.84[0.73‐0.96]).ConclusionWe demonstrate for the first time that the fully automated Elecsys CSF biomarkers detect AD neuropathologic changes with very high discriminative accuracy in vivo, and we report corresponding pathology‐based cut‐offs for these standardized biomarker measurements. Preliminary findings in a smaller subsample also support the use of plasma p‐tau181 as an easily accessible and scalable biomarker of AD pathology.
Fighting social isolation of vulnerable people with dementia through remote group meetings: An experience report
Authors: Alves Emily Viega , de Abreu Elisabeth Araujo , Beber Bárbara Costa , Brandao Lenisa 
Published: December 2021

AbstractProject DescriptionWith the COVID‐19 pandemic (WHO, 2020), social distancing became a crucial means to prevent further spread of the disease (Wendy et al, 2020). This raises concerns for dementia care (Wang et al, 2020), as social distancing leads to reduced cognitive stimulation, exercise, social networking and leisure activities (Brown et al, 2020). Active participation in art has shown positive impacts on the psychosocial wellbeing of stroke survivors (Morris et al, 2019). Additionally, engaging with humor potentially improves the memory, communication and self‐esteem of people with dementia (PWD) (Stevens, 2012). This study aims at reporting an innovative, interdisciplinary remote intervention targeted at groups of PWD and stroke survivors during the COVID‐19 pandemic. These were part of the university community outreach program Playful Living, which aims at promoting digital inclusion, quality of life and equity through artistic group activities. The project began in 2020 and consists of weekly group meetings through online platforms, with different creative practices happening each week. These include dance, gastronomy, storytelling and clowning. There are 32 participants: 13 PWD, 14 stroke survivors and 5 older adults with no diagnosis of neurological conditions. All participants were selected considering social vulnerability determinants: income, race, gender and educational background. Participants were divided into four groups, each with a fixed team (students of Speech Therapy, Psychology, Dance and Dramatic Arts) and moving members. So far, seven meetings took place. The activities have provided different opportunities for sharing memories, experiencing and expressing emotions through art. Participants reported looking forward to the meetings, with increasing participation and bonding. A major concern has been digital inclusion: stable internet access, camera and microphone management. Those aspects directly affect participants' ability to engage in group dynamics and potentially impact their self‐esteem and well‐being. However, improvements are observed on a daily basis, thanks to the combined efforts of team members and caregivers. The project has provided participants with means for self‐expression and social interaction in a safe environment. Perceived difficulties thus far point toward the need for continued efforts in terms of social and digital inclusion for this population currently and beyond the pandemic setting.
The development of a national evaluation framework for the First Link® program across Canada
Authors: Whate Alexandra , Kernoghan Alison , Elliott Jacobi , Stolee Paul , Sivananthan Saskia 
Published: December 2021

AbstractIn Canada, the Alzheimer Society’s First Link® program connects people living with dementia and their caregivers to the information, supports and services they need as early as possible and throughout the progression of the disease. Since its launch in 2002, First Link® has been implemented in all provincial societies across Canada. We have developed a national evaluation framework to guide the Alzheimer Society to gather data to assess First Link’s® impact on the health system. This work has been conducted with active engagement and consultation with the Alzheimer Society, persons living with dementia and their caregivers and other health system stakeholders. We have also received guidance from a national project advisory committee of stakeholders. A contribution analysis lens was used to understand how the First Link® program may contribute to health system outcomes. First, we assessed the current state of the First Link® program across Canada and developed a theory of change. Key informant interviews with First Link® staff, clients and community referral partners, as well as those without direct experience with the First Link® program, were used to gather evidence to build upon and test the theory of change. We then mapped all available and potential data sources to the theory of change to develop a draft evaluation framework with indicators that show program impact. The draft evaluation framework will be presented to stakeholders for feedback and tested and revised in a rapid cycle evaluation at a representative group of Alzheimer Society pilot sites. The outcomes of this initiative will provide data to support the Alzheimer Societies’ efforts to build a national case for ongoing, sustainable funding for First Link®.
Dementia‐inclusive radio series ‘Talkin’ About Neurodegeneration'—A look under the dementia umbrella and a follow‐on series to award‐winning ‘Voyage Around My Brain’ on NearFM
Authors: Meenan Karen Patricia 
Published: December 2021

AbstractBackground‘Talkin’ About Neurodegeneration’ a ground‐breaking radio series sharing voices of Brain Health Experts, with people living with different neurodegenerative diseases, their caregivers and other experts working in the arts – a four‐way conversation about living with dementia. The aim is to spotlight lesser‐known diseases in particular LBD which is the most common dementia that nobody knows about and educate listeners that Alzheimer’s Disease is not the only one associated with dementia. Radio producer, researcher, broadcaster and GBHI Fellow, Karen Meenan was awarded CRAOL National Gold Award for ‘Voyage Around My Brain’ which introduced listeners to people living with dementia, their caregivers and Brain Health Experts from GBHI over 17 weeks with 50+ guests, half of whom were living with dementia. CRAOL stated ‘congratulations for sharing the voices of people living with dementia, we need to hear these stories, great twist to have experts on the same programme’. Listenership on NearFM on Monday 7‐8pm has almost doubled v same period last year with regular emails saying how listeners enjoy learning new aspects about dementia. ‘Thank you for this programme, I look forward to it eagerly each week’ ‘My Dad has Parkinson’s disease, I didn’t realise that dancing was an important part of his care, thanks for letting me know’ ‘Thanks for the spotlight on insomnia, I have had trouble sleeping for years, I’m going to put into practice some of the suggestions by your guests last week’ … as samples of the correspondence. ‘Talkin’ About Neurodegeneration’ will tell the story of these diseases in an engaging, educational and entertaining way – how did Lewy Body Dementia get its name, how is Huntington’s disease in South Africa traced back to one individual, why is dancing good for people living with Parkinson’s disease and how can reminiscence theatre spark memories for people living with Alzheimer’s Disease. Karen Meenan is designing and building a new website for people in Ireland living with Lewy Body Disease – there is nothing in place for these estimated 6,000 people at present. ‘Talkin’ About Neurodegeneration’ is a component of this new website. This is her GBHI Pilot Project.
Establishment of updated biomarker cut‐off values for the second‐generation Elecsys β‐amyloid(1–42), pTau and tTau CSF immunoassays
Authors: Hansson Oskar , Rutz Sandra , Corradini Veronika , Manuilova Ekaterina , Logan Chad , Blennow Kaj 
Published: December 2021

AbstractBackgroundCompared with the first‐generation (Gen1), second‐generation (Gen2) Elecsys® cerebrospinal fluid (CSF) immunoassays (currently under development, Roche Diagnostics International Ltd) for detection of β‐amyloid(1–42) (Abeta42), phospho‐tau(181P) (pTau) and total‐tau (tTau) have higher thresholds for biotin interference. Abeta42 Gen2 is re‐standardized to Abeta42 certified reference materials ERM‐DA480/IFCC, ERM‐DA481/IFCC and ERM‐DA482/IFCC and has an extended measurement range. Additionally, the newly developed pre‐analytical ‘Routine‐Use’ protocol provides more reliable analyte recovery for Abeta42 against comparators (Hansson et al., Alzheimers Dement. 2020;16(S3):e047394). Here, we establish adjusted cut‐off values for concordance of Abeta42, pTau/Abeta42 and tTau/Abeta42 Gen2 results with amyloid‐PET based on those previously established for Gen1, accounting for different pre‐analytical protocols.MethodCSF samples from 26 patients with normal pressure hydrocephalus were collected per the Routine‐Use protocol for fresh CSF (n=3 aliquots/patient) and two clinical trial protocols (BioFINDER and Roche‐Trial) for frozen CSF (<–60°C; n=4 aliquots/patient). Abeta42, pTau and tTau were quantified using Elecsys Gen1/Gen2 immunoassays (cobas e 601 analyzer; Roche Diagnostics International Ltd). Bias at medical decision point was estimated for comparison of Gen1 and Gen2 immunoassays (Roche‐Trial protocol) by weighted‐Deming regression. Original cut‐off values were determined in the BioFINDER cohort using Gen1 immunoassays (Hansson et al.). Adjusted cut‐off values for Gen2 immunoassays with both Routine‐Use and Roche‐Trial protocols were determined. Concentration bias between Routine‐Use and Roche‐Trial protocols was also investigated, measured using Gen2 immunoassays. Mean percentage differences provided estimates of overall bias between protocols and protocol‐assay combinations.ResultNo clinically meaningful differences between assay generations and pre‐analytical protocols were obtained for pTau or tTau. Bias at medical decision point for Abeta42 Gen2 immunoassay versus Gen1 was –20% (95% confidence interval [CI]: –22%, –18%). Bias between concentrations of Abeta42 measured using BioFINDER/Gen1 versus Routine‐Use/Gen2 was –6.3% (95% CI: –8.7%, –3.9%). Cut‐off values for Routine‐Use/Gen2 were adjusted based on this result (). Bias between Routine‐Use versus Roche‐Trial protocols for Abeta42 Gen2 was –22% (95% CI: –24%, –19%). Cut‐off values for Roche‐Trial/Gen2 were adjusted based on this result.ConclusionElecsys CSF Abeta42 results were independently affected by immunoassay generation and pre‐analytical protocol, while tau results were unaffected. Appropriate adjusted cut‐off values have been established.
The impact of the COVID‐19 pandemic on cognitive health
Authors: Brooker Helen , Hayman Vincent , Aarsland Dag , Creese Byron , Ballard Clive , Corbett Anne 
Published: December 2021

AbstractBackgroundThe COVID‐19 pandemic has presented an extraordinary and unprecedented challenge to individuals, society and governments. Aside from the direct clinical impacts of COVID‐19, the social restrictions are likely to have had considerable impacts on cognitive and mental health. Understanding these trends will be critical to improve future responses to outbreaks and to improve the treatment and care provided to individuals affected.MethodPROTECT is an innovative online study (www.protect.org.uk) in adults aged 50 and over in the UK, Participants complete annual cognitive assessment and health measures including the PHQ‐9 and GAD‐7. Participants were divided into three cohorts (Normal Cognition, Stage 2 Early AD and Stage 3 Early AD, based on the FDA framework) using baseline data from the cognitive assessment battery. This analysis utilised data from a total of 5301 participants followed annually over the last 5 years, including the year of the COVID‐19 pandemic. It also utilises the newly published FLAME composite cognitive measure that has shown sensitivity to cognitive decline.ResultIn the participants with worsening PHQ‐9 and GAD‐7 scores between 2019 and 2020 (63%), composite measures of Speed [Stage 2: p=0.008, d=0.27; Stage 3: p=0.0006, d=0.17], and accuracy of Attention [Stage 2: p=0.004, d=0.11; Stage 3: p=0.0016, d=0.21], Memory [Stage 2: p=0.0011, d=0.3; Stage 3: p=0.0009, d=0.22] and Executive Function [p=0.08], as well as the composite FLAME measure [p=0.0014, d=0.28], showed a larger decline over the last 12 months compared to the prior assessment period. Whilst no significant increase in the rate of decline was seen in people without worsening of depression or anxiety.ConclusionThe pandemic has had a detectable and significant detrimental impact on key aspects of cognitive health in adults over 50, including adults with early cognitive impairment (stage 2 and 3 pre‐clinical AD in the FDA framework) mediated predominantly through worsening of mental health.
Piloting an innovative knowledge translation and exchange (KTE) approach on educational resources for caregivers
Authors: Malvern Riley , Sivananthan Saskia , Christie Nathan 
Published: December 2021

AbstractBackgroundKnowledge translation and exchange (KTE) is about moving knowledge into practice, involving stakeholders in an ongoing iterative process. The Alzheimer Society of Canada (ASC) approaches KTE by emphasizing ongoing collaborations with our primary audiences: people with lived experience of dementia, healthcare providers, and researchers. Knowing that people have diverse learning styles and preferences for accessing information, ASC is diversifying the range of educational resources that are currently provided through a traditional medium (i.e., printed information sheets) to a multimedia range of KTE tools that can better meet the needs of our audiences. Beginning with a pilot project that explored the practical application of KTE to a key education resource, ASC has developed an operational process with the involvement of stakeholders to help our audiences access and benefit from the information they need in a manner that accommodates them.MethodA resource for the KTE pilot project was chosen based on a data driven approach to assess need and impact (i.e., number of website views, downloads, printed resource orders and feedback from stakeholders). Using ASC’s KTE framework and the results of an environmental scan that identified KTE approaches used by other organizations, the team operationalized the KTE framework through a focus on four dimensions: 1) audiences, 2) information channels, 3) feasibility and 4) accessibility of the resource. Key stakeholders, including Alzheimer Society support staff and family caregivers, collaborated with ASC on the development of the tools through focus groups.ResultAn infographic and a small video series on practical communication tips for caregivers were created. These KTE tools will support caregivers in staying connected to the person living with dementia at all stages of the disease; as the information is broad and digestible, it can be used by other audiences, such as healthcare providers.ConclusionThe KTE pilot project is a stepping‐stone to establish a more integrative KTE approach to ASC’s educational resources. The process established through this project will ensure that those who turn to ASC for information can find reliable, up‐to‐date and evidence‐based content through a variety of tools that are engaging, easy to understand and accessible.
Neuroanatomical substrates of attention processing speed in early dementia with Lewy bodies (DLB): A white‐matter voxel‐based morphometry and diffusion tensor imaging study
Authors: Botzung Anne , Mondino Mary , Noblet Vincent , Philippi Nathalie , Blanc Frédéric 
Published: December 2021

AbstractBackgroundBased on a previous study (Botzung et al., 2019) that revealed the importance of grey matter (GM) integrity in the striatum for attention processing speed, the purpose of this study was now to examine, in early DLB patients, the relationship between impaired attentional speed performances and white matter changes.MethodWe administered the Trail Making Test A (TMTA) to 73 prodromal to moderate DLB patients (mean MMSE = 26.4) and 30 control subjects (mean MMSE = 28.9) to assess attention processing speed. Three‐dimensional (3D) MRI and Diffusion‐weighted images (DTI) were acquired for all participants and correlational analyses were performed in the patient group using WM‐VBM, fractional anisotropy (FA) and mean diffusivity (MD).ResultBehavioral results showed significantly impaired performances in patients in comparison to control subjects (p = .004). In addition, correlational analyses using WM‐VBM revealed negative WM correlations in the anterior corpus callosum and in the anterior cingulum (p < .05 FDR). Using DTI (p < .05 FDR), correlated with TMTA scores, we found reduced FA in bilateral frontal and posterior regions, and increased MD in bilateral anterior and posterior networks.ConclusionWM‐VBM analysis revealed the involvement of anterior corpus callosum and cingulum, which could indicate a disruption of the loops connecting striatal regions and the prefrontal cortex. Changes in both FA and MD also correlate with impaired attentional speed: further DTI analyses are still ongoing to question the degree of which white matter tracts are disrupted between the striatum and cortical anterior and posterior networks, respectively.