Alzheimer’s Research & Therapy (Oct 2024)

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

  • Jose Bernal,
  • Inga Menze,
  • Renat Yakupov,
  • Oliver Peters,
  • Julian Hellmann-Regen,
  • Silka Dawn Freiesleben,
  • Josef Priller,
  • Eike Jakob Spruth,
  • Slawek Altenstein,
  • Anja Schneider,
  • Klaus Fliessbach,
  • Jens Wiltfang,
  • Björn H. Schott,
  • Frank Jessen,
  • Ayda Rostamzadeh,
  • Wenzel Glanz,
  • Enise I. Incesoy,
  • Katharina Buerger,
  • Daniel Janowitz,
  • Michael Ewers,
  • Robert Perneczky,
  • Boris-Stephan Rauchmann,
  • Stefan Teipel,
  • Ingo Kilimann,
  • Christoph Laske,
  • Sebastian Sodenkamp,
  • Annika Spottke,
  • Anna Esser,
  • Falk Lüsebrink,
  • Peter Dechent,
  • Stefan Hetzer,
  • Klaus Scheffler,
  • Stefanie Schreiber,
  • Emrah Düzel,
  • Gabriel Ziegler

DOI
https://doi.org/10.1186/s13195-024-01606-5
Journal volume & issue
Vol. 16, no. 1
pp. 1 – 14

Abstract

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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. Trial registration German Clinical Trials Register (DRKS00007966, 04/05/2015).

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