Improved risk prediction of all‐cause dementia, Alzheimer’s disease, and vascular dementia by inflammation‐related biomarkers

Abstract

AbstractBackgroundDementia risk prediction models, such as the widely used Cardiovascular Risk Factors, Aging and Dementia (CAIDE) model, combining factors from the fields of demographic, cognition, physical and health, have proven themselves. However, it is of interest whether inflammatory biomarkers additionally improve such dementia risk prediction models.MethodsThe Olink Target 96 Inflammation panel was assessed in serum samples of a large German, population‐based cohort study. In a nested case‐cohort design (n=1688), the CAIDE model was used for dementia risk prediction and aimed to improve by adding 72 inflammation‐related biomarkers of the Olink panel. Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression and bootstrapping were utilized to select relevant biomarkers and determine areas under the curve (AUCs) for all‐cause dementia, Alzheimer’s disease (AD) and vascular dementia (VD) in the total cohort, as well as in mid‐life and late‐life sub‐samples.ResultsOver 17 years of follow‐up, 440 participants developed dementia. Of those, 147 were diagnosed with AD and 195 with VD. The prediction model including APOE ε4 carrier status (CAIDE model 2) had a better discriminative ability for all‐cause dementia, AD, and VD than the model without APOE ε4 (CAIDE model 1) with AUCs of 0.751, 0.767, and 0.725, respectively. Adding 16 inflammation‐related biomarkers selected by LASSO regression to the CAIDE model significantly increased the AUC for all‐cause dementia risk prediction by 0.025 (95%CI: 0.001–0.045). The AUC increases for AD (0.024) and VD (0.019) were of similar magnitude but not statistically significant due to lower case numbers. Moreover, the CAIDE model generally performed better in mid‐life (50‐64 years) than in late‐life (65‐75 years) sub‐samples, and all increases in the AUC caused by inflammation‐related biomarkers were larger in the mid‐life sub‐sample.ConclusionInflammation‐related biomarkers significantly improved the CAIDE model for all‐cause dementia prediction. Especially the predictive abilities of these blood‐based biomarkers in mid‐life are of clinical relevance to guide early preventive measures.