Fig. 1: Overview of methods and derived summary inflammation and brain measures.

A A panel of 16 immune-related markers was measured in CSF at baseline in the DELCODE sample. FLAIR and T1-weighted MR images at baseline were acquired in a subsample of participants. White matter hyperintensity (WMH) lesion maps were derived by segmentation of FLAIR images (LST toolbox). Gray matter (GM) and white matter (WM) volume probability maps were derived by segmentation of T1 images (CAT/SPM toolbox). As global summary measures we derived global WMH volume as well as GM and WM volume. GM rate of change maps were derived for subjects with 3 longitudinal T1-images using Jacobian integration (SPM). A PCA on the GM rate of volume change maps was performed within an AD vulnerable atrophy mask (see methods) to create subject-level summary measure (first eigenvariate) of atrophy over follow-ups. B A PCA on the immune markers resulted in 4 principal components (PCs). For each PC, the individual markers with highest loadings are depicted, which were all positive. See Supplementary Fig. 2 for the loadings.