• Katharina Brueggen, Martin Dyrba, Arturo Cardenas-Blanco, Anja Schneider, Klaus Fliessbach, Katharina Buerger, Daniel Janowitz, Oliver Peters, Felix Menne, Josef Priller, Eike Spruth, Jens Wiltfang, Ruth Vukovich, Christoph Laske, Martina Buchmann, Michael Wagner, Sandra Röske, Annika Spottke, Janna Rudolph, Coraline D Metzger, Ingo Kilimann, Laura Dobisch, Emrah Düzel, Frank Jessen, Stefan J Teipel, and DELCODE Study Group.
• German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany. katharina.brueggen@dzne.de.
• J. Neurol. 2019 Oct 1; 266 (10): 2465-2474.

IntroductionSubjective cognitive decline (SCD) can represent a preclinical stage of Alzheimer's disease. Diffusion tensor imaging (DTI) could aid an early diagnosis, yet only few monocentric DTI studies in SCD have been conducted, reporting heterogeneous results. We investigated microstructural changes in SCD in a larger, multicentric cohort.Methods271 participants with SCD, mild cognitive impairment (MCI) or Alzheimer's dementia (AD) and healthy controls (CON) were included, recruited prospectively at nine centers of the observational DELCODE study. DTI was acquired using identical protocols. Using voxel-based analyses, we investigated fractional anisotropy (FA), mean diffusivity (MD) and mode (MO) in the white matter (WM). Discrimination accuracy was determined by cross-validated elastic-net penalized regression. Center effects were explored using variance analyses.ResultsMO and FA were lower in SCD compared to CON in several anterior and posterior WM regions, including the anterior corona radiata, superior and inferior longitudinal fasciculus, cingulum and splenium of the corpus callosum (p < 0.01, uncorrected). MD was higher in the superior and inferior longitudinal fasciculus, cingulum and superior corona radiata (p < 0.01, uncorrected). The cross-validated accuracy for discriminating SCD from CON was 67% (p < 0.01). As expected, the AD and MCI groups had higher MD and lower FA and MO in extensive regions, including the corpus callosum and temporal brain regions. Within these regions, center accounted for 3-15% of the variance.ConclusionsDTI revealed subtle WM alterations in SCD that were intermediate between those in MCI and CON and may be useful to detect individuals with an increased risk for AD in clinical studies.

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