bluuebunny/crossref_metadata_2025_split huggingface dataset:
Feasibility of implementing a standard cognitive assessment in Italian academic and non‐academic memory clinics
Authors: Grazia Alice , Cappa Stefano F , Marra Camillo , Agosta Federica , Caffarra Paolo , Galimberti Daniela , Bruni Amalia Cecilia , Ferrarese Carlo , Teipel Stefan , Boccardi Marina 
Published: December 2022

AbstractBackgroundA previous survey conducted among the European Alzheimer´s Disease Consortium (EADC) of academic memory clinics showed mild propensity (65%) towards implementing the clinician’s Uniform Dataset (cUDS), a standard cognitive assessment consistent with the US Uniform Dataset‐3rd, to diagnose mild cognitive impairment (MCI). Currently, in Italy translation and adaptations of the cUDS is in progress. Here, we evaluate the cUDS implementation feasibility in Italian academic and non‐academic settings.MethodThe 382 clinicians affiliated to the Italian Society of Neurology on Dementia (SINDem) were invited to complete the EADC online survey translated into Italian, investigating centers current practices, acceptability and feasibility of cUDS implementation. We used a mixed‐methods design to perform descriptive statistics, logistic regressions and qualitative analysis of clinicians' comments to investigate hurdles, facilitators and mechanisms impacting implementation.ResultSixty‐two clinicians participated from 14 of the 20 Italian regions. Response rates were unevenly distributed: 56% from Northern, 16% Central and 27% Southern regions (χ2(1) = 39, p = .0005). Centers were equally distributed among academic (48%) and non‐academic (52%) institutions(χ2(1) = 30, p = .899), had a variable yearly patient flow (M = 454;SD = 686) and mainly offered neurological (90%) and psychological (87%) services. 88% reported to use formal definitions for the diagnosis of MCI. 10% of academic and 30% of non‐academic clinicians reported full reimbursement of assessment. Fifty‐nine responders (95%) expressed willingness to implement cUDS. The most frequent facilitators were the availability of neuropsychologists(26%) and of tests' material(23%). 42% of non‐academic clinicians envisioned no specific barrier; 12% envisioned lack of neuropsychologists training, 12% cultural issues and 12% unavailability of local norms. 24% of academic clinicians identified time‐economic factors as barriers.ConclusionOur data showed very high acceptability for cUDS. Lower need of cross‐compatibility with previous standard might explain the higher acceptability in SINDem compared to EADC. Indeed, EADC clinicians are more reluctant due to the lack of compatibility and digital tools supporting harmonization with local datasets. Similar to EADC, SINDem academic clinicians reported the need for tests' material, but neuropsychologists’ training‐availability and finances were considered more important in Italy. Despite the small sample size, these results inform the design of future implementation in SINDem memory clinics.
Molecular and cellular responses to amyloid beta revealed from single cell analysis of surgical brain biopsies
Authors: Kamath Tushar , Gazestani Vahid , Dolan Michael John , Nadaf Naeem , Vanderburg Charles , Leinonen Ville , Macosko Evan 
Published: December 2022

AbstractBackgroundThe accumulation of amyloid beta is a diagnostic hallmark of Alzheimer’s disease. However, the cell types that are most sensitive to its accumulation, and the transcriptional pathways that are induced by amyloid beta in specific cell types, remain incompletely understood.MethodWe performed single nucleus RNAseq analysis (n = 1.1 million profiles) on frontal cortical biopsies (n = 58) from individuals undergoing shunt placement for idiopathic normal pressure hydrocephalus (iNPH). Of these 58 biopsies, 21 were positive of amyloid beta, and 8 were positive for both amyloid beta and hyperphosphorylated tau. We clustered the profiles into 92 distinct clusters, and performed an integrative analysis with 30 published human and mouse datasets. We tested for proportional loss or gain of specific populations in the presence of amyloid or amyloid + tau, and identified differentially expressed genes in each population.ResultsActivated microglial and astrocytic populations were proportionally over‐represented in the pathology‐containing biopsies. Compared with postmortem datasets, the biopsy‐derived profiles showed dramatically lower activation of immediate‐early gene signatures, suggesting stronger fidelity of measured transcriptional programs to the in vivo human cell states. Comparative analysis of microglial populations with published datasets of other diseases revealed transcriptional pathways specifically induced by amyloid accumulation. Specific subsets of layer 1 interneurons were under‐represented both in amyloid‐positive biopsies, and in published datasets generated from early (Braak stage < 4) postmortem tissue.ConclusionsThe use of fresh cortical biopsies enabled a faithful measurement and analysis of glial states induced by the accumulation of amyloid beta. Specific subsets of layer 1 interneurons are particularly sensitive to depletion by amyloid beta accumulation in frontal cortex.
Differential rates of internalisation and effects on reactivity of postmortem human tau in human astrocytes
Authors: Reid Matthew J , Noble Wendy , Perez‐Nievas Beatriz G. 
Published: December 2022

AbstractBackgroundHighly phosphorylated tau aggregates emerge in affected areas of human tauopathy brain as disease progresses as a result of prion‐like spread and/or replication of seeds. Evidence suggests that astrocytes may influence tau spread. However, the efficiency of uptake of disease‐associated tau species is not well defined, nor are the effects of tau uptake on astrocyte reactivity and function. We are investigating tau uptake in human astrocytes, and how resulting changes in their reactivity and functions affect their support for human neurons in vitro.MethodHuman iPSC‐derived astrocytes were established, and their gene and protein expression profiles characterised. Aggregated tau was isolated from human postmortem Alzheimer’s disease (AD) brain. AD brain tau and corresponding extracts from control (CTRL) human brain were spiked into iPSC‐astrocyte cultures and the efficiency of tau uptake was measured, in parallel with assessment of reactivity markers. Mechanisms of tau uptake and its intracellular processing were investigated. Astrocyte conditioned media was collected and applied to iPSC derived cortical neurons to determine the impact of tau‐induced astrocyte changes on measures of neuron health.ResultiPSC‐derived astrocytes express mature astrocyte markers. Aggregated tau from AD brain was readily internalised by these cells. Morphological, gene expression and protein expression changes were detected, suggesting that exposure to AD‐brain tau is sufficient to induce reactive response in these astrocytes. Variations in the rate and extent of uptake, and in markers of reactivity, were observed that reflect heterogeneity between different AD cases. Preliminary data indicates that cells may degrade internalised tau aggregates via lysosomal pathways and that tau‐induced astrocyte reactivity negatively impacts neuron health.ConclusionOur data shows that human astrocytes readily internalise AD brain‐derived tau aggregates, inducing changes in astrocyte reactivity and function, related to characteristics of the tau, that are detrimental to neurons. This supports an emerging body of evidence that astrocytic tau may influence neurodegeneration in AD.
Patient’s reaction to smartwatch based interventions in a controlled environment: preliminary results from the SAMi intervention study
Authors: Goerss Doreen , Köhler Stefanie , Rong Eleonora , Bieber Gerald , Teipel Stefan 
Published: December 2022

AbstractBackgroundAssistive technologies show promising features to support people with cognitive impairment in daily life, e.g. mobile sensors for falls detection or getting lost. On the other hand, smartwatches bear potential to not only monitor but also interact with the user. While sensor based monitoring in dementia care is already part of many projects, direct interaction of people with cognitive impairment with smartwatches is little investigated.MethodBased on qualitative studies, we designed interventions for a usual consumer smartwatch. We conceptualized two different tasks: A) drinking water and B) circling bells on a worksheet. Moreover, we implemented two different modes of intervention‐intensity affecting vibration patterns, alarm sounds, text sizes, display times or appearance of images and animations. We observed patients’ reactions to interventions A and B remotely via cameras. In case of failure, interventions were repeated up to three times. Here we present data of the interim analysis after completion of n=20 patients that were equally assigned either to mode 1 (regular interventions) or mode 2 (intensive interventions). In addition to observations, participants feedback was obtained with questionnaires. Patients were diagnosed with MCI (n=7) or dementia (n=13) in the local memory clinic.ResultWe found it feasible to study patient‐smartwatch‐interactions with a mixed methods approach. The majority of participants (n=18) were able to successfully complete at least one of two tasks, see Fig. 1. Circling bells (B) was completed only by 11 participants, while drinking water (A) was solved by 16 participants. The regular interventions were successful in 24%, the intensive interventions in 65%. Repetitions did not lead to an improvement of outcome in 13 cases, but in two cases. Reasons for insufficient task completion varied, e.g. patients showed unexpected reactions such as circling the picture on the smartwatch or doing arm circles. One patient fell asleep and did not react at all.ConclusionRemote observation of patients’ reaction to smartwatch based interventions is technically challenging but offers intriguing insights into human‐computer interaction. User‐centered design for patients with MCI or dementia differs from the approach for usual smartwatch users and needs to respect special needs and requirements.
Does adherence to the Mediterranean diet have differential effects on brain health for those living within and outside of the Mediterranean region?
Authors: Gregory Sarah , Ritchie Craig W. , Shannon Oliver , Stevenson Emma , Blennow Kaj , Muniz‐Terrera Graciela 
Published: December 2022

AbstractBackgroundThe Mediterranean diet (MedDiet) is a primarily plant‐based eating pattern. High adherence to a MedDiet has been associated with a 10‐40% lower incidence of dementia. There is limited evidence exploring associations between the MedDiet and Alzheimer’s disease (AD) pathology.MethodOur study explored cross‐sectional associations between MedDiet and AD outcomes in the European Prevention of Alzheimer’s Dementia Longitudinal Cohort Study (EPAD LCS), comparing effects between those living within and outside of the Mediterranean region. After deriving MEDAS scores, to quantify adherence to the MedDiet, we used linear regression analyses to test for associations between the MedDiet and hippocampal volume, white matter lesion volume (WMLV) cerebrospinal fluid Abeta 1‐42 and phosphorylated tau and cognition. Participants were categorised by Mediterranean or non‐Mediterranean region according to European Union classification.ResultWe included 1625 participants from the EPAD LCS baseline dataset, mean age 65.48 (±7.40) years, majority female (55.9%), majority with family history (66.3%) and minority APOEε4 carriers (39.0%). Mediterranean participants had higher MEDAS scores compared to non‐Mediterranean participants (7.44 (±1.60) vs 7.20 (±1.74), p = 0.007). Higher adherence to the MedDiet was associated with lower log WMLV in fully adjusted models (b: ‐0.06, standard error (SE): 0.02, p<0.001), indicating better brain health. Geographical region analysis found this effect only in Mediterranean participants (fully adjusted: b: ‐0.10, SE: 0.03, p<0.001). Exploratory analysis further showed this effect was only apparent in male, and not female, participants. For non‐Mediterranean participants, higher adherence to the MedDiet was associated with lower Four Mountains Test scores (fully adjusted: b: ‐0.25, SE: 0.08, p = 0.003), indicating poorer brain health. Analyses are corrected using the Benjamini‐Hochberg False Discovery Rate estimation.ConclusionOur findings suggest that adherence to the MedDiet is associated with better brain health in those living within, but not outside of, the Mediterranean region. One explanation may be a difference in the duration of exposure to this diet (i.e., life‐long versus later life adoption in Mediterranean vs. non‐Mediterranean regions). This study highlights the need to further explore who the MedDiet is particularly effective for with regard to brain health outcomes, to better inform public health campaigns and patient level interventions.
The Dynamic Impacts of Dementia on Preventive Care Utilization
Authors: Lin Zhuoer , Chen Xi 
Published: December 2022

AbstractBackgroundDementia can greatly affect individuals’ decision‐making and wellbeing; and impose substantial burdens on individuals, families, and society. Identifying earlier signals of dementia risk may offer people more time to prepare for the future, helping to delay the onset or slow the progression of dementia. However, lack of evidence documenting the impacts of dementia and its early signs on health care utilization largely limits our understanding of early presentation of the disorder. To fill the gap, this study investigates the short‐term and long‐term impacts of dementia on preventive care decisions, discovering early signs of the disorder and facilitating disease early diagnosis.MethodData were obtained from Health and Retirement Study, a nationally representative longitudinal study of Americans 50 or older. Individuals’ dementia status were assessed in 1995‐2018. 3,488 persons with incidence of dementia were identified and 22,619 consecutive person‐waves before and after the incidence of dementia were included. To quantify the short‐term effects of dementia, for each individual with an incidence of dementia, we examined the changes in preventive care utilization around the first occurrence of dementia relative to his/her own behaviors when he/she is non‐demented. To examine the long‐term effects of dementia, we further compared the dynamic changes of behavioral outcomes between individuals who developed dementia and those who never developed the disorder, covering up to 18 years before and 6 years after the incidence of dementia.ResultIncidental dementia was associated with significant reductions in preventive care utilization, including cholesterol test, flu shot, mammogram, and prostate test, relative to individuals’ own behaviors before the disorder. Moreover, the impact tended to increase over time, with significant larger effects in waves after the onset of dementia compared to incidental changes. Our long‐term dynamic estimation further corroborated the findings. In particular, consistent and growing declines were observed in preventive care utilization 4‐6 years before the incidence of dementia. The effects of dementia were strong and robust across types of preventive care, population groups, and model specifications.ConclusionOur findings highlight the salient impact of dementia risk on preventive care utilization, which may increase individuals’ vulnerability to health shocks, exacerbating the deterioration of cognitive function.
Impact of a smart‐clothes home nursing program in Taiwan during heightened COVID‐19 restrictions
Authors: Shyu Yea‐Ing L , Huang Huei‐Ling , Sung Ya‐Li , Lin Chung‐Chih 
Published: December 2022

AbstractBackgroundThe COVID‐19 pandemic has required restrictions of daily activities, which has been found to impact the lives of persons with dementia and their family caregivers, who have multiple care demands. The lack of relevant studies in Taiwan emphasized the need to explore the experiences of family caregivers of older persons with dementia faced with the intensified restrictions to control COVID‐19, and the impact of the availability of a smart‐clothes home nursing program.MethodThis qualitative study used semi‐structured interviews with family caregivers of older persons with dementia. Participants were recruited from dementia clinics of a medical center in northern Taiwan from a subset sample of a larger study on smart clothes assisted home nursing care. A total of 12 family caregivers who participated in the original study were interviewed during the follow‐up period; seven were caregivers of a person with dementia wearing a smart vest, which transmitted information to a home care nurse. Interviews were conducted by telephone because the conditions of the pandemic prevented face‐to‐face interviews. Recorded interviews were transcribed and analyzed using content analysis.ResultInterview data showed family caregivers’ felt the care recipient’s health was compromised and functional conditions intensified as Covid‐19‐related pandemic restrictions increased. Specific concerns included a lack social interactions, decreased daily activity levels, loss of interest and lack of motivation for activities, increased mood and behavioral problems, a decline in physical function and an increase in health problems. Family caregivers were also impacted by these restrictions, with significant increases in severity of caregiver role strain, including feeling trapped, a lack of in‐home support, profound powerlessness, and worries about the person with dementia contracting the coronavirus. The smart‐clothes assisted home nursing care program offered supplementary support to family caregivers by providing on‐time interactions, helping them manage health problems, enhancing predictability of the care recipient’s behaviors, and providing caregivers with emotional support.ConclusionThe findings of this study support alternative care such as implementation of technology‐assisted home health services to meet caregiver needs to facilitate family caregiving of persons with dementia during the necessary restrictions in activities during the COVID‐19 pandemic.
Exploring Traditional Healing and Medicine in Dementia Care for Indigenous Populations in North America, Australia, and New Zealand: A Policy Advocacy and Practice
Authors: Shrestha Hom Lal , McArthur Michael , Rowe Robyn L , Wabie Joey‐Lynn , Maar Marion , Walker Jennifer D 
Published: December 2022

AbstractBackgroundAccess to culturally‐safe dementia assessment, diagnosis, and care in Indigenous populations worldwide is an emerging challenge. In 2018, the World Health Organization recognized traditional healers as stakeholders in dementia care and prevention globally. Traditional healers contribute to dementia assessment, diagnosis, and care in unique ways, and play a catalytic role in the process of culturally‐safe dementia care planning and assessment with health care providers at the community level. The purpose of this scoping review was to understand the roles and experiences of traditional healers, to evaluate strategies for integration between Indigenous traditional healing and western dementia care approaches, and to examine the policy barriers and research gaps in North America, Australia, and New Zealand.MethodThe scoping review methodology used was the Joanna Briggs Institute (JBI) approach that included six steps: protocol development based on participants, content and context framework, development of a search strategy, selection of relevant studies, charting of relevant data, synthesis, and reporting of results, and conducting stakeholder consultation.ResultSearched English literature in select bibliographic databases, including CINAHL, EMBASE, Medline and PsycINFO. The initial search identified 516 papers published between 2000 and 2020 that met the search criteria. After 164 duplicates were removed, we screened 352 titles and abstracts, excluding the 209 that did not meet the inclusion criteria. The second stage review of 143 full‐text studies resulted in the further exclusion of 141 studies. Only two studies from Canada met all inclusion criteria for this study and explored the potential integration of traditional healing in dementia care and the roles, perceptions, and experiences of traditional healers.ConclusionThis study emphasizes the inclusion of traditional healers, knowledge‐holders, and Grandmother groups that can contribute to building an evidence‐based dementia care decision‐making process for Indigenous people with dementia. Integration of Indigenous traditional healing and medicine in dementia care is a path to culturally‐safe dementia care and assessment. diagnosis. The study has policy implications for health care provider education and advocacy needs to engage with traditional healers in dementia care. It recommends two community‐based models to establish culturally‐safe dementia care between traditional healers and healthcare providers in a seamless collaboration.
A 2‐year Choral Singing intervention with community‐dwelling older adults at risk of cognitive decline to improve bio‐psychological outcomes: An open‐label Randomized Controlled Trial
Authors: Ng Ted K.S. , Mahendran Rathi , Kua Ee‐Heok , Feng Lei 
Published: December 2022

AbstractBackgroundFew randomized controlled trials (RCTs) have investigated the effects of choral singing (CS) on community‐dwelling older adults at‐risk of cognitive decline. Specifically, scarce literature exists on the effects of CS on affective symptoms and other bio‐psychological risk factors of cognitive decline, including low‐grade inflammation and perceived stress. Extant interventional studies on CS lack robust RCT design incorporating an active control arm controlling for active components which are not intervention‐specific. Addressing these gaps in knowledge, we initiated the CS‐RCT and hypothesized that a 2‐year CS intervention with older adults at risk of cognitive decline will improve affective, i.e., depressive and anxiety, symptoms, high‐sensitivity c‐reactive protein (hs‐CRP) levels, and perceived stress.MethodConducting a parallel‐arm and open‐label RCT, we recruited 93 community‐dwelling older adults at‐risk of cognitive decline, i.e., self‐reported cognitive complaints, cognitive impairment based on neuropsychological test scores or had multiple medical risk factors of dementia. They were randomized into either the treatment arm, CS, or the active control arm, the health education program (HEP) matched with non‐intervention‐specific components. Both the CS and HEP arms involved weekly 1‐hour group sessions held continuously for two years in parallel. In this paper, we examined the a priori registered (ClinicalTrials.gov Identifier: NCT02919748) secondary outcomes of the RCT at baseline, 1‐year, and 2‐year time‐points. The outcomes were depressive and anxiety symptoms, hs‐CRP levels, and perceived stress, using the Geriatric Depression Scale‐15 (GDS‐15), Geriatric Anxiety Inventory‐20 (GAI‐20), commercial plasma hs‐CRP ELISA kit, and the perceived stress scale (PSS), correspondingly. Linear‐mixed models were used to examine the effect of CS on all measures using intention‐to‐treat. Benjamini‐Hochberg procedure was used to correct for multiple testing.ResultCompared to the HEP arm, CS participants experienced no significantly modified scores on GDS‐15, GAI‐20, plasma hs‐CRP levels, and PSS throughout the 2‐year intervention time‐points.ConclusionIn contrary to previous studies using passive controls, compared to HEP as an active comparator, CS did not improve affective symptoms and two other bio‐psychological risk factors of cognitive decline in at‐risk community‐dwelling older adults. Our findings highlight the critical importance of examining real‐world‐efficacy of a nonpharmacological intervention among a community‐based sample (Stage 3).