105 White matter hyperintensity shape is associated with long-term dementia risk 5 S.5.8.5. Sensitivity analyses in which the primary analyses were performed with volume-weighted WMH shape marker estimation. No dementia at follow-up (mean ± SD) Dementia at follow-up (mean ± SD) Model 1 HR (95% CI) Model 2 HR (95% CI) Model 3 HR (95% CI) Periventricular/confluent WMH shape Solidity 0.23 ± 0.13 0.18 ± 0.08 1.44 (1.26–1.63)*** 1.42 (1.25–1.62)*** 1.43 (1.25–1.62)*** Convexity 1.02 ± 0.18 0.92 ± 0.20 1.38 (1.28–1.49)*** 1.39 (1.29–1.50)*** 1.38 (1.28–1.50)*** Concavity Index 1.26 ± 0.16 1.37 ± 0.17 1.44 (1.34–1.56)*** 1.45 (1.34–1.57)*** 1.45 (1.34–1.57)*** Fractal Dimension 1.67 ± 0.12 1.74 ± 0.12 1.34 (1.24–1.45)*** 1.34 (1.24–1.45)*** 1.33 (1.23–1.44)*** Deep WMH shape Eccentricity 0.35 ± 0.10 0.36 ± 0.08 0.95 (0.88–1.03) 0.96 (0.88–1.03) 0.96 (0.89–1.04) Fractal dimension 1.76 ± 0.13 1.76 ± 0.12 1.02 (0.94–1.10) 1.01 (0.94–1.10) 1.01 (0.93–1.09) WMH Volume Total WMH Volume 16.95 ± 15.31 28.89 ± 21.80 1.68 (1.53–1.85)*** 1.70 (1.54–1.87)*** 1.70 (1.54–1.87)*** Periventricular/confluent WMH Volume 15.47 ± 14.92 27.13 ± 21.55 1.71 (1.55–1.89)*** 1.73 (1.56–1.91)*** 1.72 (1.56–1.91)*** Deep WMH Volume 1.48 ± 1.36 1.75 ± 1.36 1.16 (1.07–1.26)*** 1.17 (1.07–1.27)*** 1.16 (1.07–1.27)*** To control for (small) lesion volume, the WMH shape markers were weighted based on their individual volumes. Shape parameters were calculated for each individual lesion and then multiplied with their volume percentage of the total lesion volume per type. The sum of the volume-weighted shape parameters was used in the cox regression models. A hazard ratio below 1 means that higher values decrease the risk of developing dementia. A hazard ratio above 1 means that higher values increase the risk of developing dementia. Model 1: controlled for age, sex, cognitive status at baseline. Model 2: controlled for age, sex, cognitive status at baseline, BMI, diabetes, hypertension, cholesterol level, smoking status. Model 3: controlled for age, sex, cognitive status at baseline, BMI, diabetes, hypertension, cholesterol level, smoking status, infarcts, coronary artery disease. WMH volumes are additionally controlled for intracranial volume. HR: hazard ratio; CI: confidence interval; WMH: white matter hyperintensities; BMI: body mass index. ***p<0.001
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