<p>This study investigated the associations of modifiable lifestyle factors with incident dementia, dementia subtypes, and structural brain changes, examined whether these associations differed across KDIGO-defined kidney function risk categories. We analyzed 304,369 participants from the UK Biobank. Kidney function was classified using the KDIGO risk framework, with participants grouped into low- and increased-risk categories. A composite lifestyle score, derived from the American Heart Association Life’s Essential 8 framework, was constructed based on eight modifiable components: diet quality, physical activity, smoking status, sleep duration, body mass index, blood lipid, blood glucose, and blood pressure. Outcomes included incident dementia and total and regional brain volumes. Among participants at increased KDIGO-defined risk, those in the intermediate and highest tertiles of the lifestyle score had a lower risk of dementia compared with those in the lowest tertile (hazard ratios, 0.826 [95% CI, 0.689–0.990] and 0.749 [95% CI, 0.585–0.958], respectively). Associations differed by dementia subtype: higher lifestyle scores were consistently associated with a lower risk of vascular dementia, whereas no overall association was observed with Alzheimer’s disease. Higher lifestyle scores were also associated with larger total grey matter volume and greater volumes of subcortical structures, including caudate, pallidum, putamen, and thalamus, as well as lower volumes of total, deep, and periventricular white matter hyperintensities. Similar associations were observed in the low-risk group. A healthier lifestyle was associated with a lower risk of dementia, particularly vascular dementia, and with more favorable structural brain characteristics, with similar associations across KDIGO risk groups.</p>