Longitudinal evidence for a mutually reinforcing relationship between white matter hyperintensities and cortical thickness in cognitively unimpaired older adults

Bernal, Jose; Menze, Inga; Yakupov, Renat; Peters, Oliver; Hellmann-Regen, Julian; Freiesleben, Silka Dawn; Priller, Josef; Spruth, Eike Jakob; Altenstein, Slawek; Schneider, Anja; Fliessbach, Klaus; Wiltfang, Jens; Schott, Björn H.; Jessen, Frank; Rostamzadeh, Ayda; Glanz, Wenzel; Incesoy, Enise I.; Buerger, Katharina ; Janowitz, Daniel ; Ewers, Michael ; Perneczky, Robert ; Rauchmann, Boris-Stephan ; Teipel, Stefan; Kilimann, Ingo; Laske, Christoph; Sodenkamp, Sebastian; Spottke, Annika; Esser, Anna; Lüsebrink, Falk; Dechent, Peter; Hetzer, Stefan; Scheffler, Klaus; Schreiber, Stefanie; Düzel, Emrah und Ziegler, Gabriel (2024): Longitudinal evidence for a mutually reinforcing relationship between white matter hyperintensities and cortical thickness in cognitively unimpaired older adults. In: Alzheimer's Research & Therapy 16:240

Abstract

Background : For over three decades, the concomitance of cortical neurodegeneration and white matter hyperintensities (WMH) has sparked discussions about their coupled temporal dynamics. Longitudinal studies supporting this hypothesis nonetheless remain scarce. Methods : We applied global and regional bivariate latent growth curve modelling to determine the extent to which WMH and cortical thickness were interrelated over a four-year period. For this purpose, we leveraged longitudinal MRI data from 451 cognitively unimpaired participants (DELCODE; median age 69.71 [IQR 65.51, 75.50] years; 52.32% female). Participants underwent MRI sessions annually over a four-year period (1815 sessions in total, with roughly four MRI sessions per participant). We adjusted all models for demographics and cardiovascular risk. Results : Our findings were three-fold. First, larger WMH volumes were linked to lower cortical thickness (σ = -0.165, SE = 0.047, Z = -3.515, P < 0.001). Second, individuals with higher WMH volumes experienced more rapid cortical thinning (σ = -0.226, SE = 0.093, Z = -2.443, P = 0.007), particularly in temporal, cingulate, and insular regions. Similarly, those with lower initial cortical thickness had faster WMH progression (σ = -0.141, SE = 0.060, Z = -2.336, P = 0.009), with this effect being most pronounced in temporal, cingulate, and insular cortices. Third, faster WMH progression was associated with accelerated cortical thinning (σ = -0.239, SE = 0.139, Z = -1.710, P = 0.044), particularly in frontal, occipital, and insular cortical regions. Conclusions : Our study suggests that cortical thinning and WMH progression could be mutually reinforcing rather than parallel, unrelated processes, which become entangled before cognitive deficits are detectable.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Munich Cluster for Systems Neurology (SyNergy) ; Medizin > Institut für Schlaganfall- und Demenzforschung (ISD) ; Medizin > Klinikum der LMU München > Klinik und Poliklink für Psychiatrie und Psychotherapie ; Medizin > Klinikum der LMU München > Klinik und Poliklinik für Radiologie
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1758-9193
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198