Background and ObjectivesObservational research has shown that a substantial proportion of all dementia cases worldwide are attributable to modifiable risk factors. Dementia risk scores might be useful to identify high-risk individuals and monitor treatment adherence. The objective of this study was to investigate whether a dementia risk score, the Lifestyle for Brain Health (LIBRA) index, is associated with MRI markers and cognitive functioning/impairment in the general population.MethodsCross-sectional data were used from the observational population-based cohort of The Maastricht Study. The weighted compound score of LIBRA (including 12 dementia risk and protective factors, e.g., hypertension, physical inactivity) was calculated, with higher scores indicating higher dementia risk. Standardized volumes of white matter, gray matter, and CSF (as proxy for general brain atrophy), white matter hyperintensities, and presence of cerebral small vessel disease were derived from 3T MRI. Cognitive functioning was tested in 3 domains: memory, information processing speed, and executive function and attention. Values ≤1.5 SDs below the average were defined as cognitive impairment. Multiple regression analyses and structural equation modeling were used, adjusted for age, sex, education, intracranial volume, and type 2 diabetes.ResultsParticipants (n = 4,164; mean age 59 years; 49.7% men) with higher LIBRA scores (mean 1.19, range −2.7 to 9.2), denoting higher dementia risk, had higher volumes of white matter hyperintensities (β = 0.051, p = 0.002) and lower scores on information processing speed (β = −0.067, p = 0.001) and executive function and attention (β = −0.065, p = 0.004). Only in men, associations between LIBRA score and volumes of gray matter (β = −0.093, p < 0.001) and CSF (β = 0.104, p < 0.001) and memory (β = −0.054, p = 0.026) were found. White matter hyperintensities and CSF volume partly mediated the association between LIBRA score and cognition.DiscussionHigher health- and lifestyle-based dementia risk is associated with markers of general brain atrophy, cerebrovascular pathology, and worse cognition, suggesting that LIBRA meaningfully summarizes individual lifestyle-related brain health. Improving LIBRA factors on an individual level might improve population brain health. Sex differences in lifestyle-related pathology and cognition need to be further explored.Classification of EvidenceThis study provides Class II evidence that higher LIBRA scores are significantly associated with lower scores in some cognitive domains and a higher risk of cognitive impairment.