Search

In clinical trials which target pathophysiological mechanisms associated with Alzheimer's disease, research participants who are recruited based on biomarker test results should be informed about their increased risk of developing Alzheimer's dementia. This paper presents the results of a qualitative focus group study of attitudes and concerns toward learning information about biomarker-based risk status among healthy research participants in the United Kingdom and Spain and people with dementia and their supporters/caregivers from countries represented in the European Working Group of People with Dementia of Alzheimer Europe. The study identified expectations related to learning risk status and preferences related to the content, quality, and follow-up of the disclosure process. The latter emphasize distinctions between risk and diagnoses, the importance of clear information about risk, and suggestions for risk reduction, as well as expectations for follow up and support. The implications of these preferences for practice are discussed. Providing details of research participants' experience and views may serve as a guide for the development of processes for the responsible disclosure of Alzheimer's disease biomarkers.

The focus of most of the research on Alzheimer's disease in the last decades has been on senile plaques and neurofibrillary tangles. The vast majority of patients with Alzheimer's disease are over 75 years of age, whereas most of the research focuses on younger subjects. To consider old-age dementia as a homogenous well-defined condition ignores the complexity of this condition and limits the development of new diagnostic methods, preventive strategies, or treatment strategies that could be widely applicable in daily practice in the majority of the older patients. The current research on biomarkers focuses on correlates of plaques and tangles, which are poor markers in older dementia subjects. Acknowledging that dementia in old age is an essentially different condition from dementia at relatively younger age is needed and should lead to new approaches in dementia research.

More and more frequently, clinical trials for Alzheimer disease (AD) are targeting cognitively unimpaired individuals who are at increased risk of developing the disease. It is not always clear whether AD biomarker information should be disclosed to research participants: on the one hand, research participants may be interested in learning this information because of its perceived utility, but on the other hand, learning this information may be harmful, as there are very few effective preventive or therapeutic options available for AD. In this article, we bring together three separate sets of ethical guidance literature: on the return of individual research results, on an individual's right to access personal data, and on transparent enrollment into clinical trials. Based on these literatures, we suggest policies for the disclosure of AD biomarker test results in longitudinal observational cohort studies, clinical trials, and hybrid research projects, such as the European Prevention of Alzheimer's Dementia (EPAD) project, in which we served as an ethics team. We also present and critically discuss recommendations for disclosure of AD biomarkers in practice. We underscore that, as long as the clinical validity of AD biomarkers remains limited, there are good reasons to avoid actively disclosing them to cognitively unimpaired research participants. [ABSTRACT FROM AUTHOR]

Background: Sporadic cerebral amyloid angiopathy (sCAA) research of the past decade has increasingly focused on developing biomarkers that allow for an earlier and more accurate sCAA-diagnosis. Considering that sCAA does not have treatment options available (yet), more fundamental questions concerning the desirability of using such early-sCAA biomarkers in clinical practice need to be addressed.Objective: In this qualitative interview study, we aim to explore the views of vascular neurologists on the purpose and possible consequences of an earlier and more accurate sCAA-diagnosis, using new biomarkers.Methods: Vascular neurologists from around the world were approached via email and interviewed via video call. Topics included views on current sCAA diagnostic practice, considerations on the use of new biomarkers, and expectations and hopes for the future. All interviews were transcribed ad verbatim using a transcription program (Otter.ai). Transcripts were analyzed using inductive content analysis.Results: We interviewed 14 vascular neurologists. Views regarding the desirability of new sCAA-biomarkers differed substantially between interviewees as to when and in whom these biomarkers could be of benefit in clinical practice. These differences were mainly reported with regards to prognosis, risk stratification, and biological precision, between general stroke neurologists and neurologists with specific sCAA-expertise.Conclusion: Views on the use of sCAA-biomarkers in clinical practice differ substantially between vascular neurologists. There is particularly no consensus regarding when, and in whom sCAA biomarkers could be useful in clinical practice. [ABSTRACT FROM AUTHOR]

Background and Objectives The meaning of Alzheimer's disease (AD) is changing in research. It now refers to a pathophysiological process, regardless of whether clinical symptoms are present. In the lay literature, on the other hand, AD is understood as a form of dementia. This raises the question of whether researchers and the lay audience are still talking about the same thing. If not, how will these different understandings of AD shape perspectives on (societal) needs for people with AD? Research Design and Methods We use framing analysis to retrieve the understandings of the term AD that are upheld in the research literature and in national Dutch newspaper articles. We make explicit how the framings of AD steer our normative attitudes toward the disease. Results In the analyzed research articles, AD is framed as a pathological cascade, reflected by biomarkers, starting in cognitively healthy people and ending, inevitably, in dementia. In the lay literature, AD is used as a synonym for dementia, and an AD diagnosis is understood as an incentive to enjoy "the time that is left." Discussion and Implications The two different uses of the term AD in research and in the lay literature may result in misunderstandings, especially those research framings that falsely imply that people with AD biomarkers will inevitably develop dementia. Adoption of the research understanding of AD in clinical practice will have normative implications for our view on priority setting in health care. For example, it legitimizes biomarker testing in people without dementia as improving "diagnostic" certainty. [ABSTRACT FROM AUTHOR]

Background: Hope for future treatments to prevent or slow down dementia motivates researchers to strive for ever-earlier diagnoses of Alzheimer's disease (AD) based on biomarkers, even before symptoms occur. But is a biomarker-based early diagnosis desirable in clinical practice?Objective: This study explores the ethical considerations that shape current clinical practice regarding early AD diagnostics and the use of biomarkers.Methods: In this qualitative study, Dutch physicians were interviewed. Topics included physicians' views concerning early AD diagnosis in persons with no or mild cognitive impairment, physicians' considerations regarding current and expected future practices of early AD diagnosis, the use of biomarkers, and the use of the concepts preclinical and prodromal AD. We analyzed the transcripts using directed content analysis.Results: 15 general practitioners, neurologists, and geriatricians in the Netherlands were interviewed. Most of them interpreted an early AD diagnosis with an early diagnosis of dementia. We identified six clusters of considerations sometimes in favor but most often against pursuing an early AD diagnosis in people with no or mild cognitive impairment that influence physicians' diagnostic decision-making: preferences and characteristics of persons, test characteristics, impact on care, type of setting, disease concepts, and issues on a societal level.Conclusion: The discussion concerning an early AD diagnosis based on biomarkers which is widely held in the scientific field, has not entered clinical practice structurally. A biomarker-based early diagnosis does not fit within Dutch physicians' views on what good care for people with no, subjective, or mild cognitive impairment should entail. [ABSTRACT FROM AUTHOR]

Early 2018 saw the release of new diagnostic guidance on Alzheimer's disease from the National Institute on Ageing and the Alzheimer's Association (NIA-AA). This proposed research framework represents a fundamental change in how we think about Alzheimer's disease, moving from diagnosis based on clinical features to diagnosis based solely on biomarkers. These recommendations are contentious and have important implications for patients, clinicians, policy makers and the pharmaceutical industry. In this commentary, we offer a summary of the NIA-AA research framework. We then focus on five key areas: divorcing neuropathology from the clinical syndrome; the emphasis placed on one dementia subtype; validity of available biomarkers; the changing meaning of the term 'Alzheimer's disease'; and the potential for a research framework to influence clinical practice. [ABSTRACT FROM AUTHOR]

In the hope of future treatments to prevent or slow down the disease, there is a strong movement towards an ever‐earlier detection of Alzheimer's disease (AD). In conjunction with scientific developments, this has prompted a reconceptualization of AD, as a slowly progressive pathological process with a long asymptomatic phase. New concepts such as 'preclinical' and 'prodromal' AD have been introduced, raising a number of conceptual and ethical questions. We evaluate whether these new concepts are theoretically defensible, in light of theories of health and disease, and whether they should be understood as disease or as an at‐risk state. We introduce a pragmatic view on disease concepts and argue that an evaluation of the reconceptualization of AD should also take its aims and effects into account, and assess their ethical acceptability. The reconceptualization of AD is useful to coordinate research into preventive strategies, and may potentially benefit future patients. However, in the short term, early detection and labelling of 'preclinical AD' can potentially harm people. Since there is no treatment available and the predictive value is unclear, it may only create a group of 'patients‐in‐waiting' who may suffer from anxiety, uncertainty and stigmatization, but will never actually develop dementia. We conclude that only if the promise of preventive medication materializes, will the reconceptualization of AD turn out unequivocally to be for the better. Otherwise, the reconceptualization may do more harm than good. [ABSTRACT FROM AUTHOR]

Background: The shift to defining Alzheimer's disease (AD) as a biological continuum, which is characterized by the presence of biomarkers instead of clinical symptoms, has sparked a widespread debate. Insight into the given arguments and their underlying moral values is crucial to ensure well-considered and appropriate AD biomarker testing in the future.Objective: To critically review the arguments in favor of or against AD biomarker testing in people with no or mild cognitive impairment and to explicate their underlying moral values.Methods: Seven databases were systematically searched for publications mentioning arguments of interest. Arguments are identified using qualitative data-analysis and evaluated within an ethical framework.Results: Our search yielded 3,657 articles of which 34 met the inclusion criteria. We discuss the clusters of arguments separate from their evaluation and the assessment of the debate as a whole. The right to know, which derives from the moral value of respect for autonomy, is a central argument in favor of biomarker testing. On the other hand, fear of the disease and lack of a disease-modifying treatment may result in a negative balance of good over inflicted harms, which argues against its use.Conclusion: Critical evaluation and weighing of the given arguments in a specific context, within an ethical framework, demonstrates the necessity to differentiate between what we hope or expect from research and where we currently stand. While AD biomarkers may have an indispensable value for research, the current advantage for clinical practice appears limited. [ABSTRACT FROM AUTHOR]

Post-stroke dementia (PSD) or post-stroke cognitive impairment (PSCI) may affect up to one third of stroke survivors. Various definitions of PSCI and PSD have been described. We propose PSD as a label for any dementia following stroke in temporal relation. Various tools are available to screen and assess cognition, with few PSD-specific instruments. Choice will depend on purpose of assessment, with differing instruments needed for brief screening (e.g., Montreal Cognitive Assessment) or diagnostic formulation (e.g., NINDS VCI battery). A comprehensive evaluation should include assessment of pre-stroke cognition (e.g., using Informant Questionnaire for Cognitive Decline in the Elderly), mood (e.g., using Hospital Anxiety and Depression Scale), and functional consequences of cognitive impairments (e.g., using modified Rankin Scale). A large number of biomarkers for PSD, including indicators for genetic polymorphisms, biomarkers in the cerebrospinal fluid and in the serum, inflammatory mediators, and peripheral microRNA profiles have been proposed. Currently, no specific biomarkers have been proven to robustly discriminate vulnerable patients ('at risk brains') from those with better prognosis or to discriminate Alzheimer's disease dementia from PSD. Further, neuroimaging is an important diagnostic tool in PSD. The role of computerized tomography is limited to demonstrating type and location of the underlying primary lesion and indicating atrophy and severe white matter changes. Magnetic resonance imaging is the key neuroimaging modality and has high sensitivity and specificity for detecting pathological changes, including small vessel disease. Advanced multi-modal imaging includes diffusion tensor imaging for fiber tracking, by which changes in networks can be detected. Quantitative imaging of cerebral blood flow and metabolism by positron emission tomography can differentiate between vascular dementia and degenerative dementia and show the interaction between vascular and metabolic changes. Additionally, inflammatory changes after ischemia in the brain can be detected, which may play a role together with amyloid deposition in the development of PSD. Prevention of PSD can be achieved by prevention of stroke. As treatment strategies to inhibit the development and mitigate the course of PSD, lowering of blood pressure, statins, neuroprotective drugs, and anti-inflammatory agents have all been studied without convincing evidence of efficacy. Lifestyle interventions, physical activity, and cognitive training have been recently tested, but large controlled trials are still missing. [ABSTRACT FROM AUTHOR]

Visit-to-visit blood pressure (BP) variability is a risk factor for cardiovascular disease and cognitive decline. Our aim was to assess the association between visit-to-visit BP variability and progression of white matter hyperintensities (WMH). Post-hoc analysis in the magnetic resonance imaging substudy of the randomized controlled trial prevention of dementia by intensive vascular care. Community-dwelling people age 70–78 years with hypertension. Participants had 3 to 5 twice yearly BP measurements and 2 magnetic resonance imaging scans at 3 and 6 years follow-up. We used linear regression adjusted for age, sex, WMH at scan 1, (change in) total brain volume, and cardiovascular risk factors. Among the 122 participants, there was a modest association between visit-to-visit systolic BP variability and WMH progression [beta = 0.03 mL/y per point increase in variability, 95% confidence interval (CI) 0.00–0.05, P =.058]. Additional adjustment for slope in systolic BP reduced the associated P value to.043. Visit-to-visit diastolic BP variability was not associated with WMH progression (beta = 0.01 mL/y, 95% CI −0.02 to 0.03, P =.68). Visit-to-visit pulse pressure variability was associated with WMH progression (beta 0.03 mL/y, 95% CI 0.01–0.05, P <.01). Higher visit-to-visit systolic BP and pulse pressure variability is associated with more progression of WMH among people age 70–78 years with hypertension. Interventions to reduce visit-to-visit BP variability may be most effective in people with low WMH burden. [ABSTRACT FROM AUTHOR]