Type 2 Diabetes Mellitus, Cognitive Performance, and Incident Dementia; Identifying Mediating Pathways and Biomarkers From the Plasma Proteome.

ABSTRACT: Type 2 diabetes mellitus (T2DM) is associated with poorer cognitive performance and increased dementia risk. Pathophysiological mechanisms are not fully understood. In this prospective study of UK Biobank participants, (n = 9943 without T2DM, age = 56.3 ± 8.2 years, 55% female, n = 3752 with T2DM, age = 59.1 ± 7.7 years, 41% female), T2DM was associated with poorer attention (Hedges' g = -0.15[-0.17, -0.10]), processing speed (Hedges' g = -0.14[-0.17, -0.09]), and a higher risk of incident dementia over 15 years (HR = 2.13[1.74, 2.61]). Among 2923 proteins measured by Olink proteomics, 1739 were differentially expressed in T2DM. Four-way decomposition models of proteomic markers, and KEGG pathway analyses, were used to identify potential mediating and moderating effects of biological pathw

SUBMITTER: Perfetto SE 

PROVIDER: S-EPMC12676662 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature