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December 8, 2025Journal of Neurochemistry

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

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Authors

SPSofia E. PerfettoSRSi Won RyooHCHugo Cogo‐Moreira

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Overview

Prospective study links cognitive performance to inflammatory and metabolic pathways in Type 2 Diabetes, suggesting targets for dementia prevention.

Key Points

  • This study aims to identify biological pathways and biomarkers linking Type 2 Diabetes Mellitus to cognitive performance and dementia risk.
  • Prospective analysis of UK Biobank participants with and without Type 2 Diabetes.
  • Measurement of 2923 plasma proteins via Olink proteomics.
  • Utilization of four‐way decomposition models and KEGG pathway analyses to explore mediating effects.
  • Subgroup analyses based on sex, apolipoprotein E ε4 status, and age.
  • Type 2 Diabetes is associated with reduced attention and processing speed.
  • Increased risk of incident dementia was noted (HR = 2.13).
  • 1739 proteins were differentially expressed in T2DM; highlights of inflammatory pathways and cholesterol metabolism.
  • Models improved dementia prediction accuracy with proteomic markers compared to clinical factors alone.

Cite This Study

Perfetto et al. (2025) studied this question.

synapsesocial.com/papers/693624ad4fa91c937236c7aahttps://doi.org/10.1111/jnc.70306
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