bluuebunny/crossref_metadata_2025_split huggingface dataset:
Virtual Cognitive Stimulation Therapy for dementia: The development, feasibility and initial outcomes of a global framework
Authors: Spector Aimee E , Perkins Luke , Fisher Emily , Felstead Cerne , Wong Gloria HY , Dai Ruizhi , Vaitheswaran Sridhar , Natarajan Nirupama , Venkatesan Shreenila , Mograbi Daniel C. , Ferri Cleusa P , Santos Raquel L , Stott Joshua 
Published: December 2023

AbstractBackgroundGroup Cognitive Stimulation Therapy (CST) is the most widely implemented post‐diagnostic intervention for dementia in the UK (Perkins et al, 2022). This presentation describes the development and initial testing of a virtual group Cognitive Stimulation Therapy (vCST) programme for people with dementia, developed as a result of services moving online during the COVID‐19 pandemic and a general increase in teletherapies.MethodThe vCST protocol was developed using the existing group CST manual, through stakeholder consultation with people living with dementia, caregivers, CST group facilitators and dementia service managers. This protocol was then field‐tested with ten groups of people living with dementia in the Brazil, China (Hong Kong), India, Ireland and the UK, and feedback on the protocol was gathered from 14 facilitators. Finally, the vCST programme was delivered to people with dementia in India (n = 15), Brazil (n = 44) and the UK (n = 24).ResultsField testing in five countries indicated acceptability to group facilitators and participants. Feedback from these groups was used to refine the developed protocol. Initial qualitative findings from the UK study and quantitative findings from India, Brazil and the UK will be presented, demonstrating the feasibility, acceptability and perceived benefits of these virtual groups.ConclusionThe final vCST protocol is proposed, including session materials for delivery of CST over video conferencing and a framework for offering CST virtually in global settings. vCST is an acceptable online intervention for many people living with dementia globally. We recommend that it is offered to those unable to access traditional in‐person CST, for example for health reasons and lack of transport or COVID‐19 restrictions. Many services have indicated plans to continue vCST long‐term, hence further research is needed to explore if participant outcomes are comparable to in‐person CST groups.Reference: Perkins, L., Fisher, E., Felstead, C., Rooney, C., Wong, G. H., Dai, R., … & Spector, A. (2022). Delivering Cognitive Stimulation Therapy (CST) Virtually: Developing and Field‐Testing a New Framework. Clinical Interventions in Aging, 17, 97.
Brain‐age prediction and its associations with glial and synaptic CSF markers
Authors: Cumplido‐Mayoral Irene , Milà‐Alomà Marta , Falcon Carles , Cacciaglia Raffaele , Minguillon Carolina , Fauria Karine , Molinuevo Jose Luis , Kollmorgen Gwendlyn , Suridjan Ivonne , Wild Norbert , Zetterberg Henrik , Blennow Kaj , Suarez‐Calvet Marc , Vilaplana Verónica , Gispert Juan Domingo 
Published: December 2023

AbstractBackgroundMRI‐derived brain‐age prediction is a promising biomarker of biological brain aging. Accelerated brain aging has been found in Alzheimer’s disease (AD) and other neurodegenerative diseases. However, no previous studies have investigated the relationship between specific pathophysiological pathways in AD and biological brain aging. Here, we studied whether glial activation and synaptic dysfunction are associated with biological brain aging in the earliest stages of the Alzheimer’s continuum.MethodWe included 418 cognitively unimpaired individuals (CU) from the ALFA+ study with available structural MRI, and CSF biomarkers of amyloid‐β (Aβ42/40) and tau pathology (p‐tau181), synaptic dysfunction (neurogranin, GAP43, SYT1, SNAP25), glial activation (sTREM2, YKL40, GFAP, interleukin‐6 and S100b) and α‐synuclein (Table 1). Aβ42/40, neurogranin and the glial activation biomarkers were measured using the Roche NeuroToolKit. We computed brain‐age delta as the difference between chronological and predicted brain‐age. The latter was estimated using a previously pretrained machine learning algorithm on cerebral morphological measurements on individuals from the UKBioBank cohort (N = 22.000). General linear modeling was used to test the associations between CSF biomarkers and brain‐age delta, adjusting by p‐tau, age, APOE status and sex. For the biomarkers whose associations were significant, we evaluated the interaction term “biomarker” × AT status while adjusting by age, APOE status and sex. AT staging was performed using pre‐established cut‐off values. We then used hippocampal volume as a marker of AD‐related neurodegeneration and repeated the same association studies with CSF biomarkers, adjusting by p‐tau, age, APOE status, sex and TIV.ResultBrain‐age delta was negatively associated with CSF sTREM2 (Padjusted<0.001), meaning that younger‐appearing brains showed higher levels of this biomarker (Table 1). None of the other biomarkers survived multiple comparisons. Hippocampal volume was not significantly associated with any of the CSF biomarkers (Table 2). There was no significant interaction between AT status and CSF sTREM2 for brain‐age delta, nor for hippocampal volume.ConclusionThese results showed that higher levels of CSF sTREM2 were associated with younger‐appearing brains in CU individuals independently of AT status, which might indicate a protective effect of this microglial phenotype in brain aging. This effect might not be AD‐related.
Relationship between white matter lesion coalescence and plasma cystatin C in an ethnically diverse population.
Authors: Sudre Carole H , James Sarah‐Naomi , Barnes Jo , Huang Felicia , Direk Kenan , Barkhof Frederik , Rolf Jäger H. , Chaturvedi Nishi , Hughes Alun D 
Published: December 2023

AbstractBackground: Brain and kidney share anatomical similarities in terms of the small vessels serving their irrigation. Previous work have shown associations between markers of cerebral small vessel disease (CSVD) e.g. white matter hyperintensities (WMH) and markers of renal function e.g. cystatin C. Few studies have however investigated the relationship between renal function and more detailed descriptions of lesion shape and distributionMethod768 individuals from the tri‐ethnic SABRE cohort underwent brain MRI including T1w and FLAIR sequences. WMH were automatically segmented and an overall measure of coalescence was derived from the lesion map ranging from 0 (only punctuate lesions) to 4 (high level of coalescence). Regional coalescence measures according to distance from the ventricles were further derived in 4 equidistant layers. Clinic blood samples were available for 731 individuals (45% female, mean age 71.3 (SD 6.4) years) including from 311 European; 172 African Caribbean; and 248 South Asian ethnicity. Blood measures include plasma cystatin C, a marker of glomerular filtration rate, white blood cell count (WBC) and HbA1c. Associations between cystatin C and coalescence score or lesion volume expressed as percentage of total intracranial volume were investigated using robust linear regression adjusting for age, ethnicity, sex, HbA1c and WBC; all factors known to be associated with cystatin C levels and WMH.ResultCystatin C was positively associated with male sex, WBC and HbA1c, and differed across ethnicities being highest in South Asians and lowest in African Caribbeans. After adjusting for potential confounders, cystatin C was positively associated with overall coalescence score (b = 0.026 [0.004;0.047], p = 0.018) despite unconvincing evidence of an association with overall lesion volume (b = 0.003 [‐0.0003; 0.007], p = 0.066). Associations between cystatin C and coalescence score were stronger in the South Asian group (b = 0.066 [0.027;0.105], p interaction = 0.001). Associations between cystatin C and coalescence score were similar across different layers.ConclusionShape patterns of WMH, rather than overall WMH volume, may provide a more sensitive measure to assess the relationship with markers of small vessel disease in the kidneys.
Brain‐age mediates the association between modifiable risk factors and cognitive decline early in the AD continuum
Authors: Cumplido‐Mayoral Irene , Brugulat‐Serrat Anna , Sánchez‐Benavides Gonzalo , Escalante Armand González , Anastasi Federica , Milà‐Alomà Marta , Falcon Carles , Shekari Mahnaz , Cacciaglia Raffaele , Minguillon Carolina , Fauria Karine , Molinuevo Jose Luis , Suarez‐Calvet Marc , Vilaplana Verónica , Gispert Juan Domingo ,   for the ALFA study
Published: December 2023

AbstractBackgroundNeuroimaging‐derived brain‐age is a useful biomarker to study the brain’s biological aging process. Brain‐age has shown cross‐sectional associations with cognitive function and modifiable risk factors for dementia. We aimed to study, in cognitively unimpaired (CU) individuals, the mediating role of brain‐age in the association between modifiable risk factors and cognitive changes, and the impact of AD pathology on this role.MethodWe included 416 CU individuals from the ALFA+ study with available structural MRI, measurements of the global cognitive Preclinical Alzheimer’s Cognitive Composite (PACC) (370 individuals had a follow‐up PACC assessment 3.28±0.27 years later), and lifestyle and cardiovascular risk factors assessments. We computed brain‐age delta as the difference between chronological and predicted brain‐age using a previously pre‐trained machine learning algorithm on structural MRI data. Partial Least Squares Path Modeling (PLS‐PM) was employed to investigate the mediation effect of brain‐age delta between a computed latent variable from modifiable risk factors (cardiovascular, mental health and mood, metabolic/endocrine disease history, and alcohol consumption factors; Table 1) and a latent variable from longitudinal PACC. Statistical bias adjustment was performed to control for the confounding effects of age and sex by using multiple linear regression. The analysis was performed on the whole sample (ALL) and after stratification by amyloid‐β (Aβ) status. Participants were classified as amyloid‐β positive (Aβ+) if CSF Aβ42/40<0.071 (Milà‐Alomà et al, 2020). Significance of mediation was examined by 95% confidence interval bootstrap.ResultThe effect of risk factors (latent risk) on longitudinal cognition (latent cognition) was partially mediated by brain‐age delta only in Aβ+ individuals (57.286%) (Figure 1C). Higher latent risk was associated with older brain‐age delta (p = 0.003) and older brain‐age delta was associated with worse latent cognition (p = 0.007). Conversely, the indirect effect was not significant in ALL nor in Aβ‐ individuals, where brain‐age delta was not significantly associated with latent cognition (Figure 1A‐B). Still, higher latent risk was associated with older brain‐age delta (ALL: p<0.001; Aβ‐: p = 0.004) and associated with worse latent cognition (ALL: p = 0.012, Aβ‐: p = 0.001).ConclusionIn CU individuals in the AD continuum, biological brain aging mediates the association between modifiable risk factors and cognitive decline.
Sleep disturbances, cortisol, and neuroimaging correlates among memory clinic patients
Authors: Sørensen Charlotte , Kåreholt Ingemar , Kalpouzos Grégoria , Udeh‐Momoh Chi T. , Holleman Jasper , Aspö Malin , Hagman Göran , Kivipelto Miia , Solomon Alina , Sindi Shireen 
Published: December 2023

AbstractBackgroundSleep disturbances are increasingly acknowledged as a preclinical marker for Alzheimer’s disease (AD), however, the mechanisms underlying the association between sleep disturbances and dementia remain unclear. Sleep disturbances may affect AD through brain morphology changes and vascular damage, as sleep disturbances are known to be linked with altered grey‐ and white‐matter integrity. Moreover, sleep and brain changes may be linked with cortisol levels. Sleep disturbances have been proposed to parallel cortisol dysregulation, and older individuals with preclinical AD have altered awakening cortisol, a feature that is intensified among people also suffering from sleep disturbances.MethodThe study is based on 146 memory clinic patients from the Karolinska University Hospital memory clinic (Sweden). Participants are in the age range 47‐86 years and diagnosed with either subjective cognitive impairment or mild cognitive impairment. Self‐reported sleep disturbances are measured by the Karolinska Sleep Questionnaire. Brain imaging (MRI or CT) was used to semi‐quantify brain atrophy using four visual rating scales: Medial Temporal Atrophy, Global Cortical Atrophy, Koedam (posterior brain atrophy) and Fazekas (white‐matter lesions) scales. Lastly, saliva cortisol has been sampled 6 times daily to measure diurnal cortisol patterns.ResultOrdinal logistic regressions show significant associations between sleep disturbances and brain parameters. Insufficient sleep (OR = 1.30, p = 0.048) is associated with greater odds of white‐matter lesions, and apnea (OR = 1.26, p = 0.036) and snoring (OR = 1.38, p = 0.045) are associated with greater odds of posterior brain atrophy. Increased daytime sleepiness is associated with both reduced awakening cortisol (β = ‐0.03, p = 0.025) and a flattened cortisol curve (β = ‐0.04, p = 0.019). Apnea is associated with reduced awakening cortisol (β = ‐0.06, p = 0.013). However, cortisol was not found to significantly interact with sleep in predicting brain outcomes.ConclusionThese results show that various sleep disturbance parameters (short sleep duration, apnea, and snoring) are associated with neuroimaging correlates, while daytime sleepiness and apnea are associated with markers of dysregulated cortisol patterns. The results suggest that neuroimaging correlates and cortisol measures may clarify the mechanisms underlying the associations between sleep disturbance and cognitive impairment, and the combination of objective sleep measures and neuroimaging markers in future studies may further reveal the mechanisms.
Implementation of MIND at Home Program for People Living with Dementia in Primary Care
Authors: Ciemins Elizabeth , Samus Quincy M 
Published: December 2023

AbstractBackgroundAs the U.S. population ages, the numbers of people living with dementia (PLWD) continues to grow. One way to improve care for PLWD is to work with their primary care practices to provide patient‐ and care partner‐centered, better quality of care at lower costs for their patients.MethodWe collaboratively implemented the MIND at Home Dementia Care Coordination Program into two large primary care clinics in two states, Iowa and California. The program pilot expanded the skills of existing primary care staff members to the level of Memory Care Coordinators (MCCs), who worked with larger primary care teams on combining the benefits of clinic‐based with home‐based services that support PLWD, their families, and care partners. The program targeted 150 PLWD for a 3‐month program implementation period. Program delivery included one home visit per month, a comprehensive needs assessment, and the subsequent development and implementation of an individualized care plan.ResultWe demonstrated the feasibility of implementing the MIND at Home program into primary care in a racially, ethnically, and geographically diverse population of PLWD to prepare for a larger study and provide qualitative and quantitative data on patient and provider acceptability of the program and early learnings about the program’s impact and barriers to implementation from the primary care practice perspective.ConclusionThis pilot study provides important information by determining the specific needs of patients in community‐based primary care and how creating tailored dementia‐focused care plans might improve communication and collaboration with primary care providers and their teams thereby reducing unnecessary hospitalizations and ER visits, reducing polypharmacy while increasing appropriate medication use, and improving care partners’ ability to provide needed support to PLWD.
Toward optimizing measurement of self‐perceived cognitive function ‐ a global expert survey on behalf of the SCD‐I Working Group
Authors: Butterbrod Elke , Rabin Laura , Tommet Douglas , Jones Richard N , Dubbelman Mark A. , Crane Paul K , Sikkes Sietske A.M. 
Published: December 2023

AbstractBackgroundAssessment of self‐perceived cognitive decline (SCD) is relevant in the context of Alzheimer’s disease and related disorders, but heterogeneity in measurement limits its interpretability and usability. Selection of optimal content for a questionnaire measuring SCD requires statistical information and expert opinion to ensure reliability as well as acceptability and feasibility. This study aims to survey experts about their perspectives on essential features of SCD measurement.MethodThe survey was distributed through the ISTAART Subjective Cognitive Decline PIA, International Neuropsychological Society’s Dementia Special Interest Group, and authors’ professional networks. Targeted experts included professionals working with older adults with SCD through research and/or clinical practice. Main topics were item content, item format, and questionnaire features. Topics were evaluated with multiple choice questions and open‐ended questions. Furthermore, experts were shown items from existing SCD questionnaires with relatively high information value as identified in a previous statistical harmonization effort using Item Response Theory analyses (see Rabin et al., 2021), and asked to select items they viewed as most relevant. Frequency analyses were performed.ResultNinety‐one experts (66% female) across four continents completed the questionnaire (Table 1). Thirty‐nine experts (43%) indicated routinely using an instrument to assess SCD (17 different instruments were mentioned). Seventy‐nine experts (87%) perceived a need for a harmonized SCD instrument. Whereas most experts (72%) responded that a questionnaire should measure both current ability and change in ability, views on the most relevant timeframe varied substantially (top choices: past year (33%) and past six months (25%)). Figure 1a and 1b show that items with the highest statistical information value were not necessarily selected as most relevant by experts. Preferred practical features of a questionnaire were availability of an informant version and coverage of multiple cognitive domains (chosen by 13% and 14% respectively). Preferred validation approaches were distinguishing psychiatric illness from neurodegenerative disorders and the correlation with neuropsychological test performance (both chosen by 20%).ConclusionDespite agreeing on the need for a harmonized SCD instrument, experts express varying views on optimal content, format, and validation approaches. The complementary information derived from statistical results and expert opinion can facilitate more comprehensive measurement of SCD.
Digitally interconnected tertiary old age mental healthcare services and primary healthcare services for seniors in remote areas in Greece: An exportable model?
Authors: Alexopoulos Panagiotis , Vorvolakos Theofanis , Kontogianni Evangelia , Tsibanis Konstantinos , Politis Antonios 
Published: December 2023

AbstractBackgroundEven though communities in remote areas across the globe age, old age mental healthcare services are mainly tertiary‐ or secondary hospital‐ based and subsequently not easily accessible by seniors with mental disorders living in such communities.MethodsThe INTegRated InterveNtion of pSychogerIatric Care (INTRINSIC) network embodies a model of digitally interconnected tertiary old age mental healthcare services and primary healthcare services for seniors in remote areas in Greece. It is coordinated by the Division of Old age mental health of the 1st Department of Psychiatry of the National and Kapodistrian University of Athens. INTRINSIC network is built around five pillars: The digital platform, bridging healthcare professionals, service users and communities; The old age mental health risk factor surveillance system, enabling the generation of a map of mental health problems of older adults living in each remote community and the initiation of the adequate treatment; the Modified Problem Adaptation Therapy (M‐PATH) intervention; Hearing and vision assessment and support of service users; and an advocacy body consisting of service users, their care partners and families and active members of the local communities. The initial, six‐month phase of INTRINSIC is funded by the Greek Ministry of Health.Results298 seniors living in remote areas of four different Nomenclature of Territorial Units for Statistics 2 (NUTS2) regions have been enrolled in INTRINSIC. They are on average 71.8 years old and 30.5% of them are males. Approximately 18% and 26% of INSTRINSIC service users suffer from depressive and anxiety symptoms, respectively; 62.3% complained about cognitive decline. Of note, only in 8% of service users the diagnosis of dementia had been established prior their enrolment, while 33.2% were treated with antidepressants.ConclusionBased on amplification of existing resources through the cooperation of tertiary‐ and primary healthcare professionals who share a vision of change, the INTRINSIC model offers a pragmatic opportunity to provide high quality old age healthcare services to seniors living in remote communities. The still ongoing collection and analyses of service users’ data may provide a solid foundation for INTRINSIC feasibility and sustainability
Motor neuron symptoms and pathology burden in de medulla oblongata of FTLD‐TDP brain donors
Authors: Scarioni Marta , de Koning Florianne , Gami‐Patel Priya , Fiondella Luigi , Timar Yannick , Rozemuller Annemieke J.M. , Hoozemans Jeroen , Aronica Eleonora , Raaphorst Joost , Pijnenburg Yolande A.L. , Dijkstra Anke A. 
Published: December 2023

AbstractBackgroundmotor neuron symptoms (MNS) are the hallmark of amyotrophic lateral sclerosis (ALS), which is clinically and pathologically related to frontotemporal dementia (FTD). Up to 20% of FTD patients are diagnosed with ALS (1). However, MNS are observed in a larger proportion of FTD patients (FTD‐MNS), which do not fulfill clinical diagnostic criteria for concomitant ALS (FTD‐ALS) (2). The burden of TDP‐43 pathology in the hypoglossal nucleus (HN) is higher in FTD‐ALS compared to pure FTD brain donors (3), but little is known about the distribution of TDP‐43 pathology in the medulla oblongata in FTD‐MNS.MethodMNS occurring at any disease stage were assessed from the records of FTLD‐TDP brain donors from the Netherlands Brain Bank (n = 38). The total amount of neurons and the percentage of neurons showing TDP‐43 pathology were counted in the HN, nucleus ambiguus (NA) and inferior olivary nucleus (ION). ANOVA was performed between pure FTD, FTD‐ALS, and FTD‐MNS.Resulta pure FTD syndrome was recorded in 12/38 FTLD‐TDP brain donors. A concomitant FTD‐ALS diagnosis had been established during life for 4/38 brain donors, while 16/38 had FTD‐MNS. The most common MNS were dysphagia (63%), spasticity (29%) and wasting (24%). A higher TDP‐43 burden in the HN and NA was observed in FTD‐ALS compared to FTD (p < 0.05). TDP‐43 burden in the HN and in the ION was significantly higher in FTD‐MNS compared to FTD brain donors (p < 0.05).ConclusionMNS are common in FTD, even in the absence of ALS. MNS in FTD are linked to TDP‐43 burden in the HN, NA and ION.References: 1) van Es et al, Lancet 2017 2) Burrell et al, Brain 2011 3) Halliday et al, J Neurol Sci 2016