Cortical neurodegeneration influences annual posterior white matter hyperintensity progression
Year: 2024
Type: article
Abstract: Background For over three decades, the concomitance of cortical neurodegeneration and white matter hyperintensities (WMH) has sparked discussion about their coupled temporal dynamics (Garnier‐Crussard et al. 2023). Longitudinal evidence supporting this hypothesis remains nonetheless scarce (Ter Telgte et al. 2018). We integrated surface‐based morphometry and bivariate latent change score modelling (BLCSM) to examine interrelationships between individual WMH and cortical thickness changes over a one‐year period in cognitively unimpaired participants. Method We analysed baseline and 12‐month follow‐up data from cognitively unimpaired DELCODE participants (n=393; median age 70.31 [IQR 66.06‐74.87] years; 52% females). We used T2w FLAIR and T1w MPRAGE data to segment WMH (LST; Schmidt and Wink 2019) and estimate cortical thicknesses (CAT12; Gaser et al., n.d.). Using BLCSM in a vertex‐wise fashion, we tested whether baseline WMH volumes predicted cortical thinning rates and whether baseline cortical thickness predicted WMH volumes increases (Figure 1). Due to the posterior dominance of WMH in AD (Bernal et al. 2023), we focussed on parietal and occipital WMH. All models included age, sex, years of education, and total cardiovascular risk factors as covariates on baseline and change scores. We log‐10 transformed WMH volumes and corrected WMH volumes and thicknesses measurements for TICV via residualisation. We finally tested for moderation effects of CSF‐derived Aβ42/40 and pTau181 on cross‐domain coupling. Result BLCSM generally provided good data fits (RMSEA≤0.05, CFI≥0.095, SRMR≤0.05) across all analyses. The mean thickness across precuneal and superiorparietal cortices at baseline predicted the progression of WMH better than any other cortical region (Figure 2B; βThick→ΔWMH=‐0.051, SE=0.011, Z=‐4.535, p‐value<0.001). This was especially evident with lower CSF‐derived Aβ42/40 (βThick*Aβ42/40→ΔWMH=0.176, SE=0.053, Z=3.309, p‐value=0.001). WMH volume at baseline explained, in part, the level of thinning of parts of the fusiform cortex (Figure 2D; βWMH→ΔThick=‐0.139, SE=0.028, Z=‐5.030, p‐value<0.001). This interrelationship was moderated by CSF‐derived pTau181 (βWMH*pTau181→ΔThick=‐0.144, SE=0.053, Z=‐2.711, p‐value=0.007). Conclusion Cortical thinning and WMH progression may be mutually reinforcing processes that become reciprocally coupled prior to any detectable cognitive deficits. Hallmark AD proteins appear to moderate their interrelationships.
Source: Alzheimer s & Dementia
DOI: 10.1002/alz.086414
Authors: Jose Bernal Moyano, Inga Menze, Renat Yakupov, Oliver Peters, Josef Priller, Anja Schneider, Klaus Fliessbach, Jens Wiltfang, Frank Jessen, Katharina Buerger, Robert Perneczky, Stefan Teipel, Christoph Laske, Annika Spottke, Michael T. Heneka, Stefanie Schreiber, Emrah Düzel, Gabriel Ziegler
Institutions: German Center for Neurodegenerative Diseases, Otto-von-Guericke-Universität Magdeburg, Humboldt-Universität zu Berlin, Freie Universität Berlin, Charité - Universitätsmedizin Berlin, UK Dementia Research Institute, Stiftung Charité, Technical University of Munich, University of Edinburgh, University of Bonn, Universitätsmedizin Göttingen, University of Aveiro, University of Göttingen, University of Cologne, Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases, Institut für Schlaganfall- und Demenzforschung, Ludwig-Maximilians-Universität München, LMU Klinikum, Munich Cluster for Systems Neurology, University of Rostock, Hertie Institute for Clinical Brain Research, University of Tübingen, University of Luxembourg, Luxembourg Centre for Systems Biomedicine
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,000
OpenAlex ID: W4406201549