Category: Publications

Detecting cognitive changes in preclinical Alzheimer’s disease:
A review of its feasibility

Development of interventions for the secondaryprevention of Alzheimer’s dementia: the EuropeanPrevention of Alzheimer’s Dementia (EPAD) project

Disease modelling of cognitive outcomes and biomarkers in
the European Prevention of Alzheimer’s Dementia
Longitudinal Cohort

“Eigenvector centrality dynamics are related to Alzheimer’s disease pathological changes in non-demented individuals”

Authors: Luigi Lorenzini, Silvia Ingala, Lyduine E Collij, Viktor Wottschel, Sven Haller, Kaj Blennow, Giovanni Frisoni, Gaël Chételat, Pierre Payoux, Pablo Lage-Martinez, Michael Ewers, Adam Waldman, Joanna Wardlaw, Craig Ritchie, Juan Domingo Gispert, Henk J M M Mutsaerts, Pieter Jelle Visser, Philip Scheltens, Betty Tijms, Frederik Barkhof, Alle Meije Wink

Abstract:

Amyloid-β accumulation starts in highly connected brain regions and is associated with functional connectivity alterations in the early stages of Alzheimer’s disease. This regional vulnerability is related to the high neuronal activity and strong fluctuations typical of these regions. Recently, dynamic functional connectivity was introduced to investigate changes in functional network organization over time. High dynamic functional connectivity variations indicate increased regional flexibility to participate in multiple subnetworks, promoting functional integration. Currently, only a limited number of studies have explored the temporal dynamics of functional connectivity in the pre-dementia stages of Alzheimer’s disease. We study the associations between abnormal cerebrospinal fluid amyloid and both static and dynamic properties of functional hubs, using eigenvector centrality, and their relationship with cognitive performance, in 701 non-demented participants from the European Prevention of Alzheimer’s Dementia cohort. Voxel-wise eigenvector centrality was computed for the whole functional magnetic resonance imaging time series (static), and within a sliding window (dynamic). Differences in static eigenvector centrality between amyloid positive (A+) and negative (A-) participants and amyloid-tau groups were found in a general linear model. Dynamic eigenvector centrality standard deviation and range were compared between groups within clusters of significant static eigenvector centrality differences, and within 10 canonical resting-state networks. The effect of the interaction between amyloid status and cognitive performance on dynamic eigenvector centrality variability was also evaluated with linear models. Models were corrected for age, sex, and education level. Lower static centrality was found in A+ participants in posterior brain areas including a parietal and an occipital cluster; higher static centrality was found in a medio-frontal cluster. Lower eigenvector centrality variability (standard deviation) occurred in A+ participants in the frontal cluster. The default mode network and the dorsal visual networks of A+ participants had lower dynamic eigenvector centrality variability. Centrality variability in the default mode network and dorsal visual networks were associated with cognitive performance in the A- and A+ groups, with lower variability being observed in A+ participants with good cognitive scores. Our results support the role and timing of eigenvector centrality alterations in very early stages of Alzheimer’s disease and show that centrality variability over time adds relevant information on the dynamic patterns that cause static eigenvector centrality alterations. We propose that dynamic eigenvector centrality is an early biomarker of the interplay between early Alzheimer’s disease pathology and cognitive decline.

DOI: https://doi.org/10.1093/braincomms/fcad088

Published online: 28 March 2023 in the Journal Brain Communications

Ethical Arguments Concerning the Use of Alzheimer’s Disease
Biomarkers in Individuals with No or Mild Cognitive
Impairment: A Systematic Review and Framework for
Discussion

Ethical challenges in preclinical Alzheimer’s disease
observational studies and trials: Results of the
Barcelona summit

“Ethical Frameworks for Disclosure of Alzheimer Disease Biomarkers to Research Participants: Conflicting Norms and a Nuanced Policy”

Authors: Eline M. Bunnik, Marthe Smedinga, Richard Milne, Jean Georges, Edo Richard, Maartje H. N. Schermer

Abstract: 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.

DOI: 10.1002/eahr.500146

Published online: 31 October 2022 in the Journal Ethics & Human Research

Ethical issues in the development of readiness
cohorts in Alzheimer’s disease research

European Prevention of Alzheimer’s Dementia Registry:
Recruitment and prescreening approach for a longitudinal
cohort and prevention trials

European Prevention of Alzheimer’s Dementia
Longitudinal Cohort Study (EPAD LCS): study
protocol