Category: Publications

“Memory performance mediates subjective sleep quality associations with cerebrospinal fluid Alzheimer’s disease biomarker levels and hippocampal volume among individuals with mild cognitive symptoms”

Authors: Laura Stankeviciute, Jonathan Blackman, Núria Tort-Colet, Ana Fernández-Arcos, Gonzalo Sánchez-Benavides, Marc Suárez-Calvet, Álex Iranzo, José Luis Molinuevo, Juan Domingo Gispert, Elizabeth Coulthard, Oriol Grau-Rivera

Abstract:

Sleep disturbances are prevalent in Alzheimer’s disease (AD), affecting individuals during its early stages. We investigated associations between subjective sleep measures and cerebrospinal fluid (CSF) biomarkers of AD in adults with mild cognitive symptoms from the European Prevention of Alzheimer’s Dementia Longitudinal Cohort Study, considering the influence of memory performance. A total of 442 participants aged >50 years with a Clinical Dementia Rating (CDR) score of 0.5 completed the Pittsburgh Sleep Quality Index questionnaire and underwent neuropsychological assessment, magnetic resonance imaging acquisition, and CSF sampling. We analysed the relationship of sleep quality with CSF AD biomarkers and cognitive performance in separated multivariate linear regression models, adjusting for covariates. Poorer cross-sectional sleep quality was associated with lower CSF levels of phosphorylated tau and total tau alongside better immediate and delayed memory performance. After adjustment for delayed memory scores, associations between CSF biomarkers and sleep quality became non-significant, and further analysis revealed that memory performance mediated this relationship. In post hoc analyses, poorer subjective sleep quality was associated with lesser hippocampal atrophy, with memory performance also mediating this association. In conclusion, worse subjective sleep quality is associated with less altered AD biomarkers in adults with mild cognitive symptoms (CDR score 0.5). These results could be explained by a systematic recall bias affecting subjective sleep assessment in individuals with incipient memory impairment. Caution should therefore be exercised when interpreting subjective sleep quality measures in memory-impaired populations, emphasising the importance of complementing subjective measures with objective assessments.

DOI: doi.org/10.1111/jsr.14108

Published online: 30 November 2023 in the Journal of Sleep Research

Multi-study validation of data-driven disease
progression models to characterize evolution of
biomarkers in Alzheimer’s disease

On the personal utility of Alzheimer’s disease-related
biomarker testing in the research context

Perspectives on Communicating Biomarker-Based
Assessments of Alzheimer’s Disease to Cognitively
Healthy Individuals

Prediction of Alzheimer’s disease biomarker status
defined by the ‘ATN framework’ among cognitively
healthy individuals: results from the EPAD
longitudinal cohort study

Prescreening for European Prevention of Alzheimer
Dementia (EPAD) trial-ready cohort: impact of AD risk
factors and recruitment settings

Psychological, behavioral and social effects of
disclosing Alzheimer’s disease biomarkers to
research participants: a systematic review

Re-aligning scientific and lay narratives of Alzheimer’s
disease

Recommended cognitive outcomes in preclinical Alzheimer’s
disease – Consensus statement from the European Prevention
of Alzheimer’s Dementia

“Regional associations of white matter hyperintensities and early cortical amyloid pathology”

Authors: Luigi Lorenzini, Loes T Ansems, Isadora Lopes Alves, Silvia Ingala, David Vállez García, Jori Tomassen, Carole Sudre, Gemma Salvadó, Mhnaz Shekari, Gregory Operto, Anna Brugulat-Serrat, Gonzalo Sánchez-Benavides, Mara ten Kate, Betty Tijms, Alle Meije Wink, Henk J M M Mutsaerts, Anouk den Braber, Pieter Jelle Visser, Bart N M van Berckel, Juan Domingo Gispert, Frederik Barkhof, Lyduine E Collij, the AMYPAD consortium, the EPAD consortium, ALFA cohort

Abstract:

White matter hyperintensities (WMHs) have a heterogeneous aetiology, associated with both vascular risk factors and amyloidosis due to Alzheimer’s disease. While spatial distribution of both amyloid and WM lesions carry important information for the underlying pathogenic mechanisms, the regional relationship between these two pathologies and their joint contribution to early cognitive deterioration remains largely unexplored.

We included 662 non-demented participants from three Amyloid Imaging to Prevent Alzheimer’s disease (AMYPAD)-affiliated cohorts: EPAD-LCS (N = 176), ALFA+ (N = 310), and EMIF-AD PreclinAD Twin60++ (N = 176). Using PET imaging, cortical amyloid burden was assessed regionally within early accumulating regions (medial orbitofrontal, precuneus, and cuneus) and globally, using the Centiloid method. Regional WMH volume was computed using Bayesian Model Selection. Global associations between WMH, amyloid, and cardiovascular risk scores (Framingham and CAIDE) were assessed using linear models. Partial least square (PLS) regression was used to identify regional associations. Models were adjusted for age, sex, and APOE-e4 status. Individual PLS scores were then related to cognitive performance in 4 domains (attention, memory, executive functioning, and language).

While no significant global association was found, the PLS model yielded two components of interest. In the first PLS component, a fronto-parietal WMH pattern was associated with medial orbitofrontal–precuneal amyloid, vascular risk, and age. Component 2 showed a posterior WMH pattern associated with precuneus-cuneus amyloid, less related to age or vascular risk. Component 1 was associated with lower performance in all cognitive domains, while component 2 only with worse memory.

In a large pre-dementia population, we observed two distinct patterns of regional associations between WMH and amyloid burden, and demonstrated their joint influence on cognitive processes. These two components could reflect the existence of vascular-dependent and -independent manifestations of WMH-amyloid regional association that might be related to distinct primary pathophysiology.

DOI: 10.1093/braincomms/fcac150

Published online: 15 June 2022 in the journal Brain communications