91 White matter hyperintensity shape is associated with long-term dementia risk 5 our cohort (n = 1338). Lastly, to test the influence of neurodegenerative brain changes on the found associations, we repeated the models while adding hippocampal volume as an atrophy-sensitive variable. All analyses were performed in SPSS version 25. A p value of <0.05 was considered statistically significant. 5.4 RESULTS Baseline characteristics and cardiovascular risk factors of the study population are shown in Table 1. Of the 3077 participants, at follow-up 705 participants developed dementia (23%) and 2372 (77%) did not. The average age at baseline of participants who developed dementia at follow-up was significantly higher (p <0.001) compared to the age of participants who did not develop dementia at follow-up. Sixty-two percent of female participants were included in the total study population, with no differences between the two study groups. The average time to follow-up was significantly shorter for the dementia group (7.2 ± 2.5, p <0.001) compared to the follow-up time of participants without dementia (10.7 ± 1.9). The average BMI was significantly lower (p <0.001) compared to the BMI of participants without dementia. The percentage of participants who had hypertension or brain infarcts at baseline was significantly higher for the study group who developed dementia. No significant differences were found for diabetes mellitus, smoking status, cholesterol level, or occurrence of coronary artery disease (p >0.05). 5.4.1 WMH shape and long-term occurrence of dementia Examples of WMHs and values of their respective shape markers are shown in Figure 5.2. Mean values (± standard deviation (SD)) for WMH shape markers are shown in Figure 5.3A and Table 5.2. Results of the Cox proportional hazard models for WMH shape markers at baseline are shown in Table 5.2 (see Table S.5.8.2 for area under the curve characteristics). The Cox proportional hazard Model 1 was adjusted for age, sex, and cognitive status at baseline. A more irregular shape of periventricular/confluent WMHs was associated with an increased long-term dementia risk (lower values for solidity (HR 1.34, 95% CI 1.17 to 1.52; p <0.001) and convexity (HR 1.38, 95% CI 1.28 to 1.49; p <0.001) and higher values for concavity index (HR 1.43, 95% CI 1.32 to 1.54; p <0.001) and fractal dimension (HR 1.45, 95% CI 1.32 to 1.58; p <0.001)). Additional adjustments for cardiovascular risk factors, infarcts, and coronary artery disease (Models 2 and 3) did not affect the association of periventricular/confluent WMH shape markers and longterm dementia risk. Therefore, the associations were independent of cardiovascular risk factors, the occurrence of coronary artery disease, or having brain infarcts at baseline.
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