120 Chapter 6 6.4 RESULTS The total sample included 3056 community-dwelling older adults. The average time to follow-up for dementia outcome (yes/ no) was 9.9 ± 2.6 years (min–max range 0.6–13.4 years). The baseline characteristics of the total sample are presented in Table 6.1. A hierarchical clustering model was applied on brain MRI markers (WMH volumes, brain volumes, WMH shape markers, infarcts, enlarged perivascular spaces, microbleeds). The optimal cut-off of the hierarchical clustering model was determined to be at 15 subgroups (Figure 6.2), based on the Dunn index (supplementary figure S.6.8.2., links.lww.com/WNL/D459) and the heatmap (Figure 6.2). The sizes of the subgroups ranged from 42 to 425 participants. As a sensitivity analysis to test the robustness of the clustering method, we reran the model on 2 random subsets (subset 1: n = 2,311 and subset 2: n = 2,250). On average, 68% of participants remained in the same cluster compared with the main analysis. Baseline characteristics of the study sample per subgroup are shown in Table 2. The subgroups differed significantly in age (min–max range of mean age 71.6–78.8 years), sex (min–max range of mean sex distribution 37%–81% females), cognitive status at baseline (min–max range of mean prevalence 3%–15%), hypertension (min–max range of mean prevalence 64%–90%), type 2 diabetes mellitus (min–max range of mean prevalence 4%–15%), cholesterol levels (min–max range of mean 5.20–5.97 mmol/L), coronary artery disease (min– max range of mean prevalence 7%–30%), and time to follow-up (min–max range of mean time to follow-up 8.2–10.9 years; Table 6.2). Brain MRI markers per subgroup are presented in Table 6.3. All brain MRI markers differed significantly between subgroups, as could be expected as the subgroups were based on the hierarchical clustering result. The main MRI markers per subgroup are illustrated in a simplified and summarized manner in Figure 6.3. The brain MRI phenotypes of the subgroups ranged from limited burden (subgroup 10), mostly irregular WMH shape and cerebral atrophy (subgroup 12), mostly irregularly shaped WMH and microbleeds (subgroup 9), mostly cortical infarcts and atrophy (subgroup 15), mostly irregularly shaped WMH and cerebral atrophy (subgroup 3) to multiburden subgroups (subgroup 2, subgroup 14). A complete and detailed description of the main MRI markers of each subgroup can be found in S.6.8.1 supplementary results (links.lww.com/WNL/D459). Subgroup 10 was determined to have the least amount of brain abnormalities and was used as the reference subgroup in the survival analysis (Figure 6.4). Dementia cases at follow-up ranged from 6% to 46% per subgroup. Compared with the reference subgroup, most other subgroups (except subgroup 4, subgroup 7, and subgroup 8) showed a higher long-term risk for dementia. The range of statistically
RkJQdWJsaXNoZXIy MTk4NDMw