Inflammation biomarkers for future development of all‐cause dementia, Alzheimer's disease, and vascular dementia

Background Inflammation is one of the key mechanisms involved in the development and progression of dementia. However, not all details on the association between inflammation and dementia have been explored yet. Inflammatory biomarkers can be measured at an early stage of dementia and thus can contribute to an early diagnosis. Besides, these biomarkers could contribute to drug development or therapeutic strategies. Method Biomarkers from the Olink Proseek® Inflammation panel were analyzed in blood samples of a longitudinal German, population‐based cohort including 1782 older adults. Logistic regression models were used to identify associations of these biomarkers with all‐cause dementia, Alzheimer's disease (AD), and vascular dementia (VD) incidence. Strongly associated biomarkers were further analyzed in subgroup and sensitivity analyses for dementia risk factors like age, diabetes, and APOE ε4 polymorphism. Moreover, clusters including highly correlated biomarkers (r > 0.5) were built based on these biomarkers. Result During 17 years of follow‐up, 504 participants were diagnosed with dementia, including 163 AD and 195 VD cases. A total number of 56 biomarkers showed a significant association with all‐cause dementia, 22 biomarkers were significantly associated with AD, and 33 with VD incidence, even after correction for multiple testing. The strongest, independent associations were found for the biomarkers CX3CL1 (OR [95% CI] per 1 standard deviation (SD): 1.41 [1.24‐1.60]) and EN‐RAGE (1.41 [1.25‐1.60]) with all‐cause dementia incidence, EN‐RAGE (1.51 [1.25‐1.83]) and LAP TGF‐beta‐1 (1.46 [1.21‐1.76]) with AD incidence, and VEGF‐A (1.43 [1.20‐1.70]) with VD incidence. Conclusion This study was the first to assess the associations of blood‐based biomarkers from the Olink Proseek® Inflammation panel with all‐cause dementia, AD, and VD incidence in a large, prospective, population‐based cohort study. The biomarkers CX3CL1, EN‐RAGE, LAP TGF‐beta‐1, and VEGF‐A, were independently associated with different forms of dementia and have great potential as predictive biomarkers.