126 Chapter 6 Figure 6.4. Hazard ratios per subgroup based on the Cox regression analysis. Controlled for age, sex, and cognitive status at baseline. Subgroup 10 was used as the reference subgroup in the model, as it was the subgroup with the lowest amount of brain abnormalities. S: subgroup; HR: hazard ratio; CI: confidence interval. 6.5 DISCUSSION We showed that distinct brain MRI phenotypes can be identified in communitydwelling older adults. Some of the 15 distinct subgroups that were identified showed a different long-term dementia risk, with an increased risk, especially in individuals in the multi-burden brain pathology subgroups, and in the subgroup with relatively severe WMH and atrophy. Most subgroups showed a significantly increased risk for dementia compared with the reference subgroup that showed the least abnormalities on brain MRI. The exact underlying structural correlates of the early predisposition to dementia remain largely unknown. Many validated and commonly used brain MRI markers are nonspecific to pathology and disease and commonly occur with ageing.19 Nevertheless, previous studies frequently focused on single or small groups of MRI markers and their relationship with neurovascular or neurodegenerative diseases.20-23 A combined analysis of brain MRI markers could improve our understanding of the pathophysiology of and early predisposition for dementia, as different brain diseases usually lead to patterns of different brain abnormalities.24 In other fields of research, combined analysis to identify phenotypes has previously been performed. Examples are the identification of asthma phenotypes25,26 and subphenotypes of chronic
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