Category: Publications

Associations Between Multimorbidity and Cerebrospinal Fluid
Amyloid: A Cross-Sectional Analysis of the European
Prevention of Alzheimer’s Dementia (EPAD) V500.0 Cohort

At, with and beyond risk: expectations of living with
the possibility of future dementia

Brain Amyloid Pathology and Cognitive Function
Alzheimer Disease Without Dementia?

Cognitive Dispersion is not Associated with Cerebrospinal Fluid
Biomarkers of Alzheimer’s Disease: Results from the European
Prevention of Alzheimer’s Dementia (EPAD) v500.0 Cohort

Cognitive Functions as Predictors of Alzheimer’s Disease
Biomarker Status in the European Prevention of Alzheimer’s
Dementia Cohort

“Cross-sectional and longitudinal association of sleep and Alzheimer biomarkers in cognitively unimpaired adults”

Authors: Jonathan Blackman, Laura Stankeviciute, Eider M Arenaza-Urquijo, Marc Suárez-Calvet, Gonzalo Sánchez-Benavides, Natalia Vilor-Tejedor, Alejandro Iranzo, José Luis Molinuevo, Juan Domingo Gispert, Elizabeth Coulthard, Oriol Grau-Rivera, for the European Prevention of Alzheimer’s Disease (EPAD) Consortium

Abstract:

Sleep abnormalities are prevalent in Alzheimer’s disease, with sleep quality already impaired at its preclinical stage. Epidemiological and experimental data point to sleep abnormalities contributing to the risk of Alzheimer’s disease. However, previous studies are limited by either a lack of Alzheimer’s disease biomarkers, reduced sample size or cross-sectional design. Understanding if, when, and how poor sleep contributes to Alzheimer’s disease progression is important so that therapies can be targeted to the right phase of the disease. Using the largest cohort to date, the European Prevention of Alzheimer’s Dementia Longitudinal Cohort Study, we test the hypotheses that poor sleep is associated with core Alzheimer’s disease CSF biomarkers cross-sectionally and predicts future increments of Alzheimer’s disease pathology in people without identifiable symptoms of Alzheimer’s disease at baseline. This study included 1168 adults aged over 50 years with CSF core Alzheimer’s disease biomarkers (total tau, phosphorylated tau and amyloid-beta), cognitive performance, and sleep quality (Pittsburgh sleep quality index questionnaire) data. We used multivariate linear regressions to analyse associations between core Alzheimer’s disease biomarkers and the following Pittsburgh sleep quality index measures: total score of sleep quality, binarized score (poor sleep categorized as Pittsburgh sleep quality index > 5), sleep latency, duration, efficiency and disturbance. On a subsample of 332 participants with CSF taken at baseline and after an average period of 1.5 years, we assessed the effect of baseline sleep quality on change in Alzheimer’s disease biomarkers over time. Cross-sectional analyses revealed that poor sleep quality (Pittsburgh sleep quality index total > 5) was significantly associated with higher CSF t-tau; shorter sleep duration (<7 h) was associated with higher CSF p-tau and t-tau; and a higher degree of sleep disturbance (1-9 versus 0 and >9 versus 0) was associated with lower CSF amyloid-beta. Longitudinal analyses showed that greater sleep disturbances (1-9 versus 0 and >9 versus 0) were associated with a decrease in CSF Aβ42 over time. This study demonstrates that self-reported poor sleep quality is associated with greater Alzheimer’s disease-related pathology in cognitively unimpaired individuals, with longitudinal results further strengthening the hypothesis that disrupted sleep may represent a risk factor for Alzheimer’s disease. This highlights the need for future work to test the efficacy of preventive practices, designed to improve sleep at pre-symptomatic stages of disease, on reducing Alzheimer’s disease pathology.

DOI: 10.1093/braincomms/fcac257

Published online: 3 November 2022 in the Journal Brain communications

“Data-Driven Thresholding Statistically Biases ATN Profiling across Cohort Datasets”

Authors: Y. Salimi, D. Domingo-Fernández, M. Hofmann-Apitius, C. Birkenbihl, the Alzheimer’s Disease Neuroimaging Initiative, the Japanese Alzheimer’s Disease Neuroimaging Initiative, the Alzheimer’s Disease Repository Without Borders Investigators & the European Prevention of Alzheimer’s Disease (EPAD) Consortium

Abstract:

Background: While the amyloid/tau/neurodegeneration (ATN) framework has found wide application in Alzheimer’s disease research, it is unclear if thresholds obtained using distinct thresholding methods are concordant within the same dataset and interchangeable across cohorts.

Objectives: To investigate the robustness of data-driven thresholding methods and ATN profiling across cohort datasets.

Design and Setting: We evaluated the impact of thresholding methods on ATN profiles by applying five commonly-used methodologies across cohort datasets. We assessed the generalizability of disease patterns discovered within ATN profiles by clustering individuals from different cohorts who were assigned to the same ATN profile.

Participants and Measurements: Participants with available CSF amyloid-β 1–42, phosphorylated tau, and total tau measurements were included from eleven AD cohort studies.

Results: We observed high variability among obtained ATN thresholds, both across methods and datasets that impacted the resulting profile assignments of participants significantly. Clustering participants from different cohorts within the same ATN category indicated that identified disease patterns were comparable across most cohorts and biases introduced through distinct thresholding and data representations remained insignificant in most ATN profiles.

Conclusion: Thresholding method selection is a decision of statistical relevance that will inevitably bias the resulting profiling and affect its sensitivity and specificity. Thresholds are likely not directly interchangeable between independent cohorts. To apply the ATN framework as an actionable and robust profiling scheme, a comprehensive understanding of the impact of used thresholding methods, their statistical implications, and a validation of results is crucial.

DOI: https://doi.org/10.14283/jpad.2023.100

Published online: 6 September 2023 in the Journal of Prevention of Alzheimer’s Disease

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