bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adaptation of an evidence‐based intervention for family carers of people living with dementia for delivery to UK‐based South Asian carers: Widening access to START (Strategies for Relatives)
Authors: Sommerlad Andrew , Amador Sarah , Mukadam Naaheed , Rapaport Penny , Lang Iain A , Livingston Gill 
Published: December 2020

AbstractBackgroundFamily members caring for a relative with dementia often become anxious or depressed. We developed START (STrAtegies for RelaTives) for family carers of relatives with dementia to promote helpful coping strategies. START is the first clinically‐ and cost‐effective intervention of its kind, and is currently delivered within UK National Health Service. However, barriers to delivery of START to South Asian carers include delayed presentation to health services, stigma, and language. In this study, we therefore aimed to widen access to START by adapting it for delivery to UK‐based South Asian family carers.MethodsIn Phase 1, we used the Cultural Treatment Adaptation Framework (CTAF) to guide data collection, through a semi‐structured interview guide. We interviewed 15 UK‐based South Asian carers about START and factors affecting its implementation to inform modifications. We transcribed interviews and researchers double‐coded them independently, using the CTAF to organise the findings.In Phase 2, we trained and supervised facilitators to deliver the adapted START intervention to South Asian family carers. In Phase 3, after START delivery, we used the i‐PARIHS framework to evaluate the implementation, through qualitative and quantitative interviews with all carers and qualitative interviews with facilitators.ResultsWe interviewed 15 South Asian carers in London and Bradford, UK. There were no changes to START’s core components. We incorporated cultural values and beliefs into the START intervention manual by modifying and adding in new examples and testimonials, and adding prompts. We also translated the manual into Urdu, a common South Asian language in the UK, and produced an audio version of the manual in Urdu. The project group met to agree on the modifications. The intervention was delivered to 13 family carers between January 2019 and January 2020 including 4 in Urdu and conducted interviews afterwards assessing satisfaction with the intervention and its effect on depression and quality of life.ConclusionsWe used multiple methodologies to identify barriers and facilitators to effective delivery of a psychosocial intervention for South Asian family carers based in the UK. We found that adaptations to the content and delivery of an intervention may improve its acceptability and efficacy.
A multicenter, randomized controlled feasibility trial for the programs of the SoUth Korea study to PrEvent cognitive impaiRment and protect BRAIN health through lifestyle intervention in at‐risk elderly people (SUPERBRAIN)
Authors: Choi Seong Hye , Jeong Jee Hyang , Moon So Young , Hong Chang Hyung , Na Hae Ri , Park Yoo Kyoung , Park Hee Kyung , Song Hong Sun , Lee Sun Min , Choi Muncheong , Park Kyung‐Won , Kim Byeong C , Cho Soo Hyun , Chun Buong‐O 
Published: December 2020

AbstractBackgroundMultidomain interventions can be useful for the prevention of dementia. We have developed the programs of SoUth Korea study to PrEvent cognitive impaiRment and protect BRAIN health through lifestyle intervention in at‐risk elderly people (SUPERBRAIN), which consists of a facility‐based (FMI) and a home‐based multidomain intervention (HMI) program suitable for elderly Koreans. This study aims to investigate the feasibility of the SUPERBRAIN programs before a large‐scale randomized controlled trial (RCT).MethodWe recruited 152 participants from eight centers, among those without dementia aged 60‐79 years with at least one modifiable dementia risk factor. They were randomly assigned: 51 to the FMI arm, 51 to the HMI arm, and 50 to the control arm. The 6‐month multidomain intervention consisted of: management of metabolic and vascular risk factors, cognitive training and social activity, physical exercise, nutritional guidance, and motivational enhancement programs. The intervention program is determined feasible if the following success criteria are met: 1) a minimum retention rate of 75% at week 24; 2) a minimum adherence to the intervention program of 75%; and 3) at least no difference from the control arm in the change of the total scale index score of the Repeatable Battery for the Assessment of Neuropsychological Status from baseline to study end. Main secondary outcomes are disability, depressive symptoms, quality of life, vascular risk factors, physical performance, nutritional assessment, and motivation questionnaire.ResultScreening began in May 2019 and was completed in August 2019. The intervention is ongoing as planned. There were no significant differences in the bassline age (71.7 ± 4.8 vs. 70.9 ± 4.9 vs. 70.7 ± 4.8 years, p = 0.57) and level of education (10.2 ± 4.8 vs. 9.9 ± 5.2 vs. 10.5 ± 4.8 years, p = 0.82) among the FMI, HMI, and control arms. The proportion of women did not differ in FMI, HMI and control arms (72.5% vs. 72.5% vs.78.0%, p = 0.77). The study will be completed in March 2020.ConclusionThis study will inform the applicability of these multidomain intervention programs in at‐risk elderly people and contribute to the success of a subsequent RCT.
Chronicity of amyloid: Methods for estimating amyloid onset and clinical research applications
Authors: Betthauser Tobey J. , Koscik Rebecca L. , Jonaitis Erin M. , Cody Karly Alex , Vasiljevic Eva , Erickson Claire M. , Mueller Kimberly D. , Clark Lindsay R. , Engelman Corinne D. , Stone Charles K. , Christian Bradley T. , Asthana Sanjay , Johnson Sterling C. 
Published: December 2020

AbstractBackgroundPrior works including our recent publication suggest amyloid PET levels provides information about the duration of amyloidosis exposure. This study compares two methods for modeling longitudinal amyloid trajectories and estimating the onset age of amyloid positivity (A+). Methods are applied to investigate similarities and differences across Apolipoprotein E (APOE) genotypes.MethodsTwo modeling strategies (iterative local linear approximation, ILLA; group‐based trajectory modeling, GBTM) were applied to [C‐11]PiB PET data acquired from the Wisconsin Alzheimer’s Disease Research Center and the Wisconsin Registry for Alzheimer’s Prevention (N=272). Amyloid burden was ascertained for each PiB scan by calculating a global mean distribution volume ratio (DVR). Annualized DVR rate vs. DVR was characterized in a subset with longitudinal data (n=179 from WRAP, baseline age mean±SD=61.0±6.2 years, 6.2±2.1 years follow‐up). This subset was used to train ILLA and GBTM models. Model performance was evaluated by aligning each person’s last scan to the modeled curve and calculating the explained variance in antecedent scans. Estimates of A+ age (EOA+) were compared across methods for APOE genotypes in all participants with high accumulation probabilities.ResultsΔDVR/yr was homogeneous for given levels of amyloid. Longitudinal DVR slopes were mostly constant and all were positive for DVR>1.2. ILLA and GBTM methods performed similarly with ILLA explaining slightly more variance in previous scans and having a shorter timeline compared to GBTM (Figure 1). EOA+ were similar across methods within APOE genotypes (ILLA 2.7±1.9 years >GBTM). Relative to APOE‐e3e3 carriers, e3e4 and e4e4 carriers had EOA+ 2.2 and 5.4 years earlier (Table 1). Accumulation rates were similar in APOE‐e4 carriers and non‐carriers (Figure 2).ConclusionsThese results suggest the chronic process of amyloid accumulation is remarkably similar between individuals. This homogeneity is amenable to modeling approaches that estimate age of A+ and thereby the duration of A+ exposure reflecting the chronicity of amyloidosis. Applying these concepts to APOE data indicated e4 carriers accumulate amyloid earlier rather than faster. These findings highlight how the combination of amyloid chronicity and A+ age concepts enable new lines of discovery related to AD risk and resilience. Future work will apply these methods to other cohorts.
Predictors of behavioral and psychological symptoms and caregiver burden in spousal caregivers of people with dementia: A longitudinal study
Authors: Lawlor Brian , Pertl Maria , Brennan Sabina , Robertson Ian H 
Published: December 2020

AbstractBackgroundAs the number of people with dementia and the demands on family caregivers continues to increase, it is important to understand the factors associated with increased burden in order to identify effective interventions that reduce burden and improve the quality of life for both the caregiver and the care‐recipient (C‐R).MethodWe examined the predictors of behavioral and psychological symptoms of dementia (BPSD) and caregiver burden in 253 spousal caregivers of people with dementia (mean age 69.64 +7.84; 64.8% female; mean length of caring 59.44 +39.29 months) followed up over 12 months.Result45% of spousal caregivers were experiencing moderate to severe burden levels at baseline as measured by the Zarit Burden Index. One‐year follow up data was available on 205 caregivers: 151 were still caring at home; 34 C‐Rs were in long‐term care; 20 C‐Rs were deceased. Among those who were still caring at home at follow‐up, caregiver depression, loneliness, anxiety and self‐efficacy for symptom management at baseline predicted BPSD severity at follow‐up, controlling for baseline BPSD severity, number of years providing care, the number of caregiving hours per day, and functional impairment. Baseline depression, loneliness, anxiety, self‐efficacy and BPSD severity also predicted caregiver burden at follow‐up. However, only BPSD severity predicted burden at follow‐up in a combined model, controlling for burden, number of years providing care, the number of caregiving hours per day, and functional impairment at baseline.ConclusionWhile the strongest predictor of caregiver burden is the severity of BPSD, the emotional health of caregivers may also contribute to greater BPSD severity over time. Targeting BPSD directly while at the same time addressing caregiver factors, such as depression, anxiety, loneliness and self‐efficacy for symptom management, has the potential to impact on the severity of BPSD and improve the quality of life of spousal carers of people with dementia.
Defining agitation, apathy and other psychiatric symptoms in cognitive impairment and dementia: Why we need to intervene
Authors: Sano Mary ,   International Psychogeriatric Association
Published: December 2020

AbstractBackgroundInternational Psychiatric Association (IPA) has a long history of defining and treating the behavioral and psychiatric symptoms that occur with cognitive impairment and dementia, including agitation and apathy. This presentation will describe the international and collaborative approach to creating definitions and diagnoses. Also a description of how these efforts have fostered trial design and can direct development of protocols with evidence‐ based selection of populations and meaningful outcomes.MethodThe methodology used by the IPA and other associations to characterize behavioral symptoms in aging and dementia begins with a review of the extant literature and the creation of a survey around the key elements of the diagnosis or definition of a given condition such as agitation or apathy. Elements of the definition are selected from the field and the surveys are disseminated via a link in an email. The email is distributed widely, to member of IPA and to its more than 20 different affiliates, which represent national organizations in geriatric psychiatry and allied fields. International working groups use the responses to formulate criteria that have meaning and importance to the largest number of stakeholders including, providers, regulators, researchers and patient advocates. The uptake of the criteria and their success in defining treatable conditions is monitored and in interactive process of updating the definitions to improve clinical utility is promoted.ResultThis approach has been used to create guidelines for defining agitation, apathy and psychosis. The presentation will include a review of the results of this process for agitation in which the publication of the provisional guidelines were followed by a notable increase in clinical trials and other research to address interventions and in work to improve outcome measures. Recent work in apathy has also provided support for selecting clinically relevant outcomes including measures of function, cognition and caregiver burden.ConclusionInternational collaboration to define psychiatric and behavioral symptoms associated with cognitive impairment can provide the stimulus to developing meaningful interventions.
The prognostic role of microglia and tau PET in Alzheimer’s disease
Authors: Malpetti Maura , Kievit Rogier A , Passamonti Luca , Jones P Simon , Tsvetanov Kamen A , Rittman Timothy , Mak Elijah , Nicastro Nicolas , Bevan‐Jones W Richard , Su Li , Hong Young T , Fryer Tim D , Aigbirho Franklin I , O'Brien John T , Rowe James B 
Published: December 2020

AbstractBackgroundNeuroinflammation is part of the pathophysiology of Alzheimer’s disease (AD), in addition to amyloid‐β plaques and tau neurofibrillary tangles. PET markers of microglial activation have indicated inflammation of temporo‐parietal regions, in proportion to disease severity. Here we test the prognostic value of [11C]PK11195 PET on longitudinal clinical decline in AD, alone and in combination with MRI and tau ([18F]AV‐1451) PET imaging.MethodTwenty‐six patients with Alzheimer’s dementia or amyloid‐positive Mild Cognitive Impairment, and 29 controls underwent multi‐modal assessment with [11C]PK11195 PET, [18F]AV‐1451 PET, structural MRI, and annual cognitively assessment with the Revised Addenbrooke's Cognitive Examination. Regional PET binding potentials and grey‐matter volumes from fifteen bilateral temporo‐parietal region were summarised by method‐specific Principal Component Analyses (PCAs). The rate of longitudinal cognitive decline was estimated using a Latent Growth Curve Model. The predictive value of PET and MRI on cognitive decline was tested with modality‐specific regression models, and a multi‐modality regression model.ResultPCA on each PET ligand consistently identified one component in anterior temporal regions, and another in posterior temporo‐parietal regions, while for MRI, a single component was identified across all regions. Worse annual rate of cognitive decline correlated with higher [11C]PK11195 in the anterior temporal component (r = −0.47, p = 0.002), and in posterior temporo‐parietal regions (r = −0.39, p = 0.012). An optimal multi‐modality model was identified by stepwise regression and Bayesian selection, that included the anterior [11C]PK11195 component and both [18F]AV‐1451 components as predictors of cognitive decline (R2 = 0.418; p = 0.001), but not their interaction and not the baseline MRI.ConclusionThese results suggest that in addition to tau pathology, microglial activation in the anterior temporal lobe plays a key role in predicting future cognitive decline in patients with AD. The results support therapeutic strategies targeting tau and microglial activation as disease‐modifying therapy against AD.
The impact of a nutritional intervention in prodromal Alzheimer’s disease: The LipiDiDiet clinical trial
Authors: Hartmann Tobias , Solomon Alina , Visser Pieter Jelle , Hendrix Suzanne B , Blennow Kaj , Kivipelto Miia , Soininen Hilkka ,   LipiDiDiet Clinical Study Group
Published: December 2020

AbstractBackgroundDiet and nutrition are important modifiable risk factors for Alzheimer’s disease (AD). For the last two decades, the LipiDiDiet consortium has been investigating the role of nutrients and their synergistic action on key AD pathological features. Based on preclinical results, 11 nutrients were selected which, when applied in this specific combination, gave the best results in rodent AD models: i.e. the omega‐3 fatty acids DHA and EPA, phospholipids, vitamins B6, B12, folic acid, C and E, choline, selenium, and UMP. The LipiDiDiet trial1 is a 6‐year, double‐blind, parallel‐group, multi‐centre, randomised controlled clinical trial, designed to investigate effects of the specific multinutrient combination Fortasyn Connect on cognition and related measures in prodromal AD. Initial 24 month results showed significant benefit on clinical dementia rating‐sum of boxes (CDR‐SB) and hippocampal and ventricular volumes in the modified intention‐to‐treat population. Here we report previously specified primary and secondary outcomes over 36 months of intervention.MethodProdromal AD participants (n=311) were randomised to receive either active product (125 mL drink containing Fortasyn Connect) or a calorie‐matched placebo control once daily.Result162 participants completed the 36‐month period. With increasing treatment duration, the benefit of the active group over the control group exceeded what had been observed for the first 24 months (Soininen et al., Lancet Neurology 2017). For the 5‐item neuropsychological test battery (NTB) on cognition, a significant between‐group difference was observed in estimated mean change from baseline over 36 months favouring active intervention (0.212 [95% CI 0.044 to 0.380]; p=0.014; 60% reduction in decline). In addition, significant benefits were found on CDR‐SB, NTB memory, and hippocampal, ventricular, and whole brain volumes on MRI. Self‐reported compliance to the study product was high and there was no indication of safety concern.ConclusionWe observed significantly slower decline in cognition including memory, CDR‐SB measuring cognition and function, and brain structural measures. Importantly, prolonged intervention with this specific combination of nutrients resulted in a broader range of endpoints showing statistically significant differences. Sustainable benefits lasting for 3 or more years have not been reported before in prodromal AD. Dutch Trial Register: NTR1705. 1EUFP7 N°211696 LipiDiDiet.
Change in retinal layer thickness and vascular parameters in preclinical Alzheimer’s disease: A 2‐year longitudinal study
Authors: Bruinenberg Annelies E. , van de Kreeke Aleid , Verbraak Frank , Bouwman Femke H. , Yaqub Maqsood , Van Berckel Bart N.M. , Tomassen Jori , den Braber Anouk , Visser Pieter Jelle 
Published: December 2020

AbstractBackgroundThe past year, the retina has received increasing attention as a possible biomarker for (preclinical) Alzheimer’s disease (AD). Though cross‐sectional differences where inconsistently replicated in literature, longitudinal change over time of retinal layer thickness and/or retinal vascular parameters (RVPs) may differ between preclinical AD and controls.Method149 cognitively healthy monozygotic twins aged ≥60 were included from the EMIF‐AD PreclinAD study.1 Participants were classified as preclinical AD (Aβ+) based on a positive [18F]flutemetamol PET image and as controls (Aβ‐) on a negative flutemetamol PET image. As a continuous measure of Aβ aggregation we used the [18F]flutemetamol PET binding potential (BP
ND). At baseline and follow‐up, after a mean of 22 months (range 15 – 32 months), the total and individual inner retinal layer thickness in the macular region (ETDRS ring), the peripapillary retinal nerve fiber layer thickness and 7 RVPs were measured on optical coherence tomography (OCT) and fundus images. OCT measurements could be analyzed in 145 participants and fundus images in 114 participants. Ocular measurements were compared between Aβ+ and Aβ‐ participants and related to the BP
ND.ResultThere were no differences in change over time in any of the measured retinal layer thicknesses between pre‐clinical AD patients (n=16) and controls (n=129) (see figure 1). We did, however, find a positive association between BP
ND values and an increase in the inner plexiform layer (IPL) thickness in the inner perifoveal ETDRS ring (CI: 0.575 – 2.841, p=0.003). Although arteriolar caliber, venular caliber and tortuosity of arteries all showed a significant decrease over time in the total group, no differences were found between Aβ+ (n=13) en Aβ‐ participants (n=111, table 1), nor did these RVP changes show a relation to BP
ND value at baseline.ConclusionThe use of OCT measurements and RVPs as a longitudinal screening method for preclinical AD seems limited, but IPL changes may serve as a starting point for future research. Reference: (1) Konijnenberg E, Carter SF, Ten Kate M, den Braber A, Tomassen J, Amadi C, et al. The EMIF‐AD PreclinAD study: study design and baseline cohort overview. Alzheimers Res Ther. 2018;10(1):75.
Delirium READI:(Researching Efficient Approaches for Delirium Identification): Clinician experiences and perspectives when screening for delirium in persons with dementia
Authors: Fick Donna Marie , Boltz Marie , Husser Erica , Ngo Long H , Shrestha Priyanka , Inouye Sharon K , Marcantonio Edward R 
Published: December 2020

AbstractBackgroundLess than half of all delirium in persons with dementia is identified. By 2050, 14 million older persons in the United States will have dementia. These individuals are more likely to be hospitalized than those without dementia, and more than 50% will experience delirium during hospitalization. Previous work suggests that delirium may accelerate the clinical course and trajectory of cognitive decline, and is associated with worse outcomes and suffering. Despite this evidence, we know little about clinician experience with screening and management of delirium superimposed on dementia (DSD). Therefore, we interviewed hospital‐based clinicians to inform implementation of hospital‐wide systematic delirium identification, including clinician knowledge and experience with DSD.MethodWe conducted in‐depth qualitative interviews in person and over the phone as part of a larger mixed methods study of N=934 (535 older adults and 399 clinicians) that tested a two‐step process for delirium identification using the Ultra‐brief two item delirium screen (UB‐2) and 3D‐CAM. We report on the qualitative analysis of 14 interviews with 6 physicians, 4 registered nurses and 4 nursing assistants who had screened for DSD in the larger study at two hospital study sites. Data were analyzed using coding and thematic analysis (Creswell, 2016). Interviews ranged in length from 14 to 47 minutes.ResultAlthough clinicians valued the quick tools to detect delirium, they described skepticism and challenges in evaluating DSD. One physician noted, "Many times I think healthcare providers, whether it's a doctor, a nurse, whatever, we just chalk up behavior in the hospital, "Oh, they're demented. They have dementia. You expect this [confusion]... People who are confused, they get up and they fall. Preliminary themes identified were: skepticism, bias and low expectations, stage of dementia as important, fluctuation and repeated screening, role of family in screening, nonverbal communication and cues, and knowing the person.ConclusionOur study suggests that clinicians lack knowledge and confidence in assessing for and managing DSD. Clinicians may still consider DSD to be “normal” in hospitalized patients with dementia. Future implementation studies should also address attitudes and knowledge regarding delirium assessment, management and prevention in DSD.