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Nonlinear temporal dynamics of cerebral small vessel disease: The RUN DMC study
Esther M C van Leijsen1, Ingeborg W M van Uden1, Mohsen Ghafoorian1
1From the Donders Institute for Brain, Cognition and Behaviour, Centre for Cognitive Neuroscience, Department of Neurology (E.M.C.v.L., I.W.M.v.U., M.I.B., V.L., E.C.M.K., H.M.v.d.H., A.M.T., E.J.v.D., C.J.M.K., F.-E.d.L.), and Diagnostic Image Analysis Group, Department of Radiology and Nuclear Medicine (M.G., B.P.), Radboud University Medical Centre; Institute for Computing and Information Sciences (M.G.) and Donders Institute for Brain, Cognition and Behaviour, Centre for Cognitive Neuroimaging (D.G.N.), Radboud University, Nijmegen, the Netherlands; Department of Clinical Neurosciences, Neurology Unit (L.C.A.R.-J.), University of Cambridge, UK; and Erwin L. Hahn Institute for Magnetic Resonance Imaging (D.G.N.), University of Duisburg-Essen, Essen, Germany.
Objective:
To investigate the temporal dynamics of cerebral small vessel disease (SVD) by 3 consecutive assessments over a period of 9 years, distinguishing progression from regression.
Methods:
Changes in SVD markers of 276 participants of the Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Imaging Cohort (RUN DMC) cohort were assessed at 3 time points over 9 years. We assessed white matter hyperintensities (WMH) volume by semiautomatic segmentation and rated lacunes and microbleeds manually. We categorized baseline WMH severity as mild, moderate, or severe according to the modified Fazekas scale. We performed mixed-effects regression analysis including a quadratic term for increasing age.
Results:
Mean WMH progression over 9 years was 4.7 mL (0.54 mL/y; interquartile range 0.95-5.5 mL), 20.3% of patients had incident lacunes (2.3%/y), and 18.9% had incident microbleeds (2.2%/y). WMH volume declined in 9.4% of the participants during the first follow-up interval, but only for 1 participant (0.4%) throughout the whole follow-up. Lacunes disappeared in 3.6% and microbleeds in 5.7% of the participants. WMH progression accelerated over time: including a quadratic term for increasing age during follow-up significantly improved the model (p < 0.001). SVD progression was predominantly seen in participants with moderate to severe WMH at baseline compared to those with mild WMH (odds ratio [OR] 35.5, 95% confidence interval [CI] 15.8-80.0, p < 0.001 for WMH progression; OR 5.7, 95% CI 2.8-11.2, p < 0.001 for incident lacunes; and OR 2.9, 95% CI 1.4-5.9, p = 0.003 for incident microbleeds).
Conclusions:
SVD progression is nonlinear, accelerating over time, and a highly dynamic process, with progression interrupted by reduction in some, in a population that on average shows progression.
