The key to stopping Alzheimer's disease (AD) lies in the pre‐dementia stages, with the goal to stop AD before dementia has started. We present the rationale and design of the ABOARD (A Personalized ...Medicine Approach for Alzheimer's Disease) project, which aims to invest in personalized medicine for AD. ABOARD is a Dutch public–private partnership of 32 partners, connecting stakeholders from a scientific, clinical, and societal perspective. The 5‐year project is structured into five work packages on (1) diagnosis, (2) prediction, (3) prevention, (4) patient‐orchestrated care, and (5) communication and dissemination. ABOARD functions as a network organization in which professionals interact cross‐sectorally. ABOARD has a strong junior training program “Juniors On Board.” Project results are shared with society through multiple communication resources. By including relevant partners and involving citizens at risk, patients, and their care partners, ABOARD builds toward a future with personalized medicine for AD.
Highlights
ABOARD (A Personalized Medicine Approach for Alzheimer's Disease) is a public–private research project executed by 32 partners that functions as a network organization.
Together, the project partners build toward a future with personalized medicine for Alzheimer's disease.
Although ABOARD is a Dutch consortium, it has international relevance.
ABOARD improves diagnosis, prediction, prevention, and patient‐orchestrated care.
Abstract The behavioral characterization of animal models of psychiatric disorders is often based upon independent traits measured at adult age. To model the neurodevelopmental aspects of psychiatric ...pathogenesis, we introduce a novel approach for a developmental behavioral analysis in mice. C57BL/6J (C57) mice were used as a reference strain and compared with 129S1/SvImJ (129Sv), BTBR T+tf/J (BTBR) and A/J (AJ) strains as marker strains for aberrant development. Mice were assessed at pre-adolescence (4 weeks), adolescence (6 weeks), early adulthood (8 weeks) and in adulthood (10–12 weeks) on a series of behavioral tasks measuring general health, neurological reflexes, locomotor activity, anxiety, short- and long-term memory and cognitive flexibility. Developmental delays in short-term object memory were associated with either a hypo-reactive profile in 129Sv mice or a hyper-reactive profile in BTBR mice. Furthermore, BTBR mice showed persistent high levels of repetitive grooming behavior during all developmental stages that was associated with the adult expression of cognitive rigidity. In addition, strain differences in development were observed in puberty onset, touch escape, and body position. These data showed that this longitudinal testing battery provides sufficient behavioral and cognitive resolution during different development stages and offers the opportunity to address the behavioral developmental trajectory in genetic mouse models for neurodevelopmental disorders. Furthermore, the data revealed that the assessment of multiple behavioral and cognitive domains at different developmental stages is critical to determine confounding factors (e.g., impaired motor behavior) that may interfere with the behavioral testing performance in mouse models for brain disorders.
Observational population studies indicate that prevention of dementia and cognitive decline is being accomplished, possibly as an unintended result of better vascular prevention and healthier ...lifestyles. Population aging in the coming decades requires deliberate efforts to further decrease its prevalence and societal burden. Increasing evidence supports the efficacy of preventive interventions on persons with intact cognition and high dementia risk. We report recommendations for the deployment of second-generation memory clinics (Brain Health Services) whose mission is evidence-based and ethical dementia prevention in at-risk individuals. The cornerstone interventions consist of (i) assessment of genetic and potentially modifiable risk factors including brain pathology, and risk stratification, (ii) risk communication with ad-hoc protocols, (iii) risk reduction with multi-domain interventions, and (iv) cognitive enhancement with cognitive and physical training. A roadmap is proposed for concept validation and ensuing clinical deployment.
Computer tools based on artificial intelligence could aid clinicians in memory clinics in several ways, such as by supporting diagnostic decision-making, web-based cognitive testing, and the ...communication of diagnosis and prognosis.
This study aims to identify the preferences as well as the main barriers and facilitators related to using computer tools in memory clinics for all end users, that is, clinicians, patients, and care partners.
Between July and October 2020, we sent out invitations to a web-based survey to clinicians using the European Alzheimer's Disease Centers network and the Dutch Memory Clinic network, and 109 clinicians participated (mean age 45 years, SD 10; 53/109, 48.6% female). A second survey was created for patients and care partners. They were invited via Alzheimer Europe, Alzheimer's Society United Kingdom, Amsterdam Dementia Cohort, and Amsterdam Aging Cohort. A total of 50 patients with subjective cognitive decline, mild cognitive impairment, or dementia (mean age 73 years, SD 8; 17/34, 34% female) and 46 care partners (mean age 65 years, SD 12; 25/54, 54% female) participated in this survey.
Most clinicians reported a willingness to use diagnostic (88/109, 80.7%) and prognostic (83/109, 76.1%) computer tools. User-friendliness (71/109, 65.1%); Likert scale mean 4.5, SD 0.7), and increasing diagnostic accuracy (76/109, 69.7%; mean 4.3, SD 0.7) were reported as the main factors stimulating the adoption of a tool. Tools should also save time and provide clear information on reliability and validity. Inadequate integration with electronic patient records (46/109, 42.2%; mean 3.8, SD 1.0) and fear of losing important clinical information (48/109, 44%; mean 3.7, SD 1.2) were most frequently indicated as barriers. Patients and care partners were equally positive about the use of computer tools by clinicians, both for diagnosis (69/96, 72%) and prognosis (73/96, 76%). In addition, most of them thought favorably regarding the possibility of using the tools themselves.
This study showed that computer tools in memory clinics are positively valued by most end users. For further development and implementation, it is essential to overcome the technical and practical barriers of a tool while paying utmost attention to its reliability and validity.
Background
We studied to what degree and at whose initiative 25 informational topics, formerly identified as important, are discussed in diagnostic consultations.
Methods
Audio recordings of ...clinician–patient consultations of 71 patients and 32 clinicians, collected in eight Dutch memory clinics, were independently content‐coded by two coders. The coding scheme encompassed 25 informational topics.
Results
Approximately half (Mdn = 12) of the 25 topics were discussed per patient during the diagnostic process, with a higher frequency among individuals receiving a dementia diagnosis (Mdn = 14) compared to others (Mdn = 11). Individual topics ranged from being discussed with 2/71 (3%) to 70/71 (99%) of patients. Patients and/or care partners rarely initiated topic discussion (10%). When they did, they often enquired about one of the least frequently addressed topics.
Conclusion
Most patients received information on approximately half of the important informational topics. Providing the topic list to patients and care partners beforehand could allow consultation preparation and stimulate participation.
Background
Patients often perceive a lumbar puncture (LP) as an invasive procedure. We aimed to evaluate the impact of a 3‐minute educational animation‐video explaining the LP procedure, on patients’ ...knowledge, uncertainty, anxiety, and post‐LP complications.
Methods
We included 203 newly referred memory clinic patients, who were randomly assigned to one of three conditions: (1) home viewing of the video, (2) clinic viewing of the video, or (3) control condition (care as usual). Participants completed questionnaires measuring knowledge as information recall, uncertainty, anxiety, and post‐LP complications, the latter when patients underwent an LP procedure (n = 145).
Results
Viewing the video increased information recall for both home (P < .001), and clinic viewers (P < .001) compared to controls. Levels of uncertainty decreased after viewing (Pfor interaction = .044), particularly for clinic viewers. Viewing the video or not did not affect anxiety and post‐LP complications.
Discussion
Preparing individuals for an LP by means of an educational video can help to increase knowledge about the procedure and reduce feelings of uncertainty.
Personalized medicine (PM) and patient-orchestrated care (POC) are frequently used terms in healthcare communication, policy, and research. Clarity of these constructs is important, as ambiguity in ...interpretation may lead to miscommunication and false assumptions both within and across disciplines. We aimed to explore the understanding of PM and POC among interdisciplinary professionals in the field of Alzheimer’s disease (AD).
We conducted semi-structured interviews with 26 senior-level professionals from healthcare, society, industry and academia. Audio-recordings were transcribed and coded inductively and deductively by two researchers independently, using the ‘framework approach’.
Some professionals understood PM from a (bio-)medical perspective (e.g., medication, precision medicine), whereas others additionally employed a social perspective (e.g., personal needs, patient-centeredness). Most professionals distinguished PM from POC, and they mainly understood POC from a social perspective, entailing either full control for the person affected or shared responsibility and decision-making. Professionals agreed that care partners should also be involved in PM and POC.
Professionals appear to understand the construct of PM differently, which could lead to miscommunication. In line with their historically different backgrounds and values, the concepts of PM and POC are perceived distinctively. We plead for a more uniform understanding of PM, which may reduce miscommunication and false assumptions among interdisciplinary professionals, and therewith improve the validity of healthcare policy and research. These results are a first step towards discussions among interdisciplinary professionals in the AD field, allowing for reflection on current standards of good practice and optimization of communication. Moreover, the exact associations and interrelations between the terms PM, POC, person-centeredness, and personalization are currently unclear and this study may pave the way for a preliminary figure.
•How do PM, POC, person-centeredness and personalization interrelate?•How to improve communication among interdisciplinary professionals and translate
Findings: into practice?
► Male rats show a stronger task progression in the r-IGT than female rats. ► Male rats progressively increase their preference for a high over low reward in a T-maze whilst female rats do not. ► ...Male and female rats do not differ in liking, motivation or reward discrimination. ► Sex differences in decision-making are not unique to humans.
The Iowa Gambling Task (IGT) measures decision-making processes by simulating real-life decisions involving reward, punishment, and uncertainty of outcomes. In humans, men show more choices for the advantageous option than women. Here, we investigated sex differences in a rat model of the IGT (r-IGT). In our r-IGT mildly food-deprived rats learn to differentiate a long-term advantageous arm from a long-term disadvantageous arm differing in frequency and amount of sugar pellets as well as unpalatable but not uneatable quinine-treated sugar pellets. We also used a T-maze discrimination procedure in which rats learn to differentiate a high from a low reward arm to further explore sex differences in reward-related decision-making. In line with human data, male rats showed a stronger task progression of choices for the advantageous option than female rats. Furthermore, male rats showed more win-stay and less lose-shift behaviour in the advantageous arm as the task progressed than female rats. Whilst both male and female rats had a stronger preference for the high over the small reward arm in the T-maze, males increased this preference over sessions, whilst females did not. These data are discussed in relation to sex differences in processing rewards and punishments.
This paper introduces automated observations in a modular home cage system as a tool to measure the effects of wheel running on the time distribution and daily organization of cage floor locomotor ...activity in female C57BL/6 mice. Mice (
n
=
16) were placed in the home cage system for 6 consecutive days. Fifty percent of the subjects had free access to a running wheel that was integrated in the home cage. Overall activity levels in terms of duration of movement were increased by wheel running, while time spent inside a sheltering box was decreased. Wheel running affected the hourly pattern of movement during the animals’ active period of the day. Mice without a running wheel, in contrast to mice with a running wheel, showed a clear differentiation between novelty-induced and baseline levels of locomotion as reflected by a decrease after the first day of introduction to the home cage. The results are discussed in the light of the use of running wheels as a tool to measure general activity and as an object for environmental enrichment. Furthermore, the possibilities of using automated home cage observations for e.g. behavioural phenotyping are discussed.
BackgroundPatients treated with immunotherapy are at risk of considerable adverse events, and the ongoing struggle is to accurately identify the subset of patients who will benefit. Tumor mutational ...burden (TMB) has emerged as a promising predictive biomarker but requires tumor tissue which is not always available. Blood-based TMB (bTMB) may provide a minimally invasive assessment of mutational load. However, because of the required sequencing depth, bTMB analysis is costly and prone to false negative results. This study attempted to design a minimally sized bTMB panel, examined a counting-based method for bTMB in patients with stage I to IV non-small cell lung cancer (NSCLC) and evaluated both technical factors such as bTMB and tissue-based TMB (tTMB) cut-off, as well as sample-related factors such as cell-free DNA input mass which influence the correlation between bTMB and tTMB.MethodsTissue, plasma, and whole blood samples collected as part of the LEMA trial (NCT02894853) were used in this study. Samples of 185 treatment naïve patients with stage I to IV NSCLC were sequenced at the Roche Sequencing Solutions with a custom panel designed for TMB, using reagents and workflows derived from the AVENIO Tumor Tissue and circulating tumor DNA Analysis Kits.ResultsA TMB panel of 1.1 Mb demonstrated highly accurate TMB high calls with a positive predictive value of 95% when using a tTMB cut-off of 16 mut/Mb, corresponding with 42 mut/Mb for bTMB. The positive per cent agreement (PPA) of bTMB was relatively low at 32%. In stage IV samples with at least 20 ng of cfDNA input, PPA of bTMB improved to 63% and minimizing the panel to a subset of 577 kb was possible while maintaining 63% PPA.ConclusionPlasma samples with high bTMB values are highly correspondent with tTMB, whereas bTMB low results may also be the result of low tumor burden at earlier stages of disease as well as poorly shedding tumors. For advanced stages of disease, PPA (sensitivity) of bTMB is satisfactory in comparison to tTMB, even when using a panel of less than 600 kb, warranting consideration of bTMB as a predictive biomarker for patients with NSCLC eligible for immunotherapy in the future.
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