Category: Publications

Secondary prevention of Alzheimer’s dementia:
neuroimaging contributions

“Self-reported diabetes is associated with allocentric spatial processing in the European Prevention of Alzheimer’s Dementia Longitudinal Cohort Study”

Authors: Sarah Gregory, Kaj Blennow, Natalie Z. M. Homer, Craig W. Ritchie, Graciela Muniz-Terrera

Abstract:

Type 2 diabetes is a robust predictor of cognitive impairment. Impairment in allocentric processing may help identify those at increased risk for Alzheimer’s disease dementia. The objective of this study was to investigate the performance of participants with and without diabetes on a task of allocentric spatial processing. This was a cross-sectional secondary data analysis study using baseline data from the European Prevention of Alzheimer’s Dementia Longitudinal Cohort Study (EPAD LCS). Participants were aged 50 years and above and were free of dementia at baseline. Participants with no missing data on the variables of interest were included in this study. Our exposure variable was diabetes reported in the medical history. Our primary outcome was the Four Mountains Test (4MT), a novel task of allocentric processing. Covariates included demographics (age, sex, family history of dementia and years of education), APOEε4 carrier status, cognitive status (Clinical Dementia Rating scale), cerebrospinal fluid phosphorylated tau and amyloid-beta 1-42. Of 1324 participants (mean age = 65.95 (±7.45)), 90 had diabetes. Participants with diabetes scored 8.32 (±2.32) on the 4MT compared with 9.24 (±2.60) for participants without diabetes. In a univariate model, diabetes was significantly associated with worse 4MT total scores (β = -.92, p = .001), remaining significant in a fully adjusted model (β = -.64, p = .01). Cerebrospinal fluid phosphorylated tau was significantly higher in participants with diabetes compared with those without. Novel cognitive tests, such as the 4MT, may be appropriate to identify early cognitive changes in this high-risk group. Identifying those at greatest risk for future neurodegeneration is key to prevention efforts.

DOI: doi.org/10.1111/ejn.15821

Published online: 14 September 2022 in the European Journal of Neuroscience

The European Prevention of Alzheimer’s Dementia
(EPAD) Longitudinal Cohort Study: Baseline Data
Release V500.0

The influence of diversity on the measurement of functional
impairment: An international validation of the Amsterdam
IADL Questionnaire in eight countries

“The Open-Access European Prevention of Alzheimer’s Dementia (EPAD) MRI dataset and processing workflow”

Authors: Luigi Lorenzini,Silvia Ingala, Alle Meije Wink, Joost P.A. Kuijer, Viktor Wottschel, Mathijs Dijsselhof, Carole H. Sudre, Sven Haller, Jose Luis Molinuevo, Juan Domingo Gispert, David M. Cash, David L. Thomas, Sjoerd B. Vos, Ferran Prados, Jan Petr, Robin Wolz, Alessandro Palombit, Adam J. Schwarz Gael Chetelat, Pierre Payoux, Carol Di Perri, Joanna M. Wardlaw, Giovanni B. Frisoni, Christopher Foley, Nick C. Fox, Craig Ritchie, Cyril Pernet, Adam Waldman, Frederik Barkhof, Henk J.M.M. Mutsaerts

Abstract:

The European Prevention of Alzheimer Dementia (EPAD) is a multi-center study that aims to characterize the preclinical and prodromal stages of Alzheimer’s Disease. The EPAD imaging dataset includes core (3D T1w, 3D FLAIR) and advanced (ASL, diffusion MRI, and resting-state fMRI) MRI sequences. Here, we give an overview of the semi-automatic multimodal and multisite pipeline that we developed to curate, preprocess, quality control (QC), and compute image-derived phenotypes (IDPs) from the EPAD MRI dataset. This pipeline harmonizes DICOM data structure across sites and performs standardized MRI preprocessing steps. A semi-automated MRI QC procedure was implemented to visualize and flag MRI images next to site-specific distributions of QC features – i.e. metrics that represent image quality. The value of each of these QC features was evaluated through comparison with visual assessment and step-wise parameter selection based on logistic regression. IDPs were computed from 5 different MRI modalities and their sanity and potential clinical relevance were ascertained by assessing their relationship with biological markers of aging and dementia. The EPAD v1500.0 data release encompassed core structural scans from 1356 participants 842 fMRI, 831 dMRI, and 858 ASL scans. From 1356 3D T1w images, we identified 17 images with poor quality and 61 with moderate quality. Five QC features – Signal to Noise Ratio (SNR), Contrast to Noise Ratio (CNR), Coefficient of Joint Variation (CJV), Foreground-Background energy Ratio (FBER), and Image Quality Rate (IQR) – were selected as the most informative on image quality by comparison with visual assessment. The multimodal IDPs showed greater impairment in associations with age and dementia biomarkers, demonstrating the potential of the dataset for future clinical analyses.

DOI: 10.1016/j.nicl.2022.103106

Published online: 7 July 2022 in the Journal NeuroImage: Clinical

The Rationale Behind the New Alzheimer’s Disease
Conceptualization: Lessons Learned During the Last
Decades

The relation between APOE genotype and cerebral
microbleeds in cognitively unimpaired middle- and old-aged
individuals

“Using LC-MS/MS to Determine Salivary Steroid Reference Intervals in a European Older Adult Population”

Authors: Sarah Gregory, Scott G Denham, Patricia Lee, Joanna P Simpson, Natalie Z M Homer

Abstract:

A number of steroids, including glucocorticoids and sex hormones, have been associated with neurodegenerative and cardiovascular conditions common in aging populations. The application of liquid chromatography tandem mass spectrometry (LC-MS/MS) steroid analysis offers an opportunity to conduct simultaneous multiplex steroid analysis within a given sample. In this paper, we describe the application of an LC-MS/MS steroid analysis method for the assessment of reference ranges of steroids in human saliva samples (200 µL) collected from older adults (age 50 years and above) enrolled in a European cohort investigating the risk for Alzheimer’s dementia. Saliva samples were prepared using supported liquid extraction (SLE) along with a calibration curve and analysed using a Waters I-Class UPLC (Ultra Performance Liquid Chromatography) and a Sciex QTrap 6500+ mass spectrometer. Mass spectrometry parameters of steroids were optimised for each steroid and a method for the chromatographic separation of 19 steroids was developed. Lower limits of quantitation (LLOQs), linearity and other method criteria were assessed. In total, data from 125 participants (500 samples) were analysed and assessed for reference ranges (64 male, 61 female). A total of 19 steroids were detected in saliva within the range of the method. There were clear diurnal patterns in most of the steroid hormones detected. Sex differences were observed for androstenedione (A4), testosterone (T), cortisone (E) and aldosterone (Aldo). In the first sample of the day, dehydroepiandrosterone (DHEA) was significantly higher in healthy volunteers compared to those with Alzheimer’s disease biomarkers. This LC-MS/MS method is suitable for the analysis of 19 steroids in saliva in adults.

DOI: https://doi.org/10.3390/metabo13020265

Published online: 13 February 2023 in the Journal Metabolites

“Ready for What” Timing and Speculation in Alzheimer’sDisease Drug Development