Exploring the links among peripheral immunity, biomarkers, cognition, and neuroimaging in Alzheimer's disease

Abstract INTRODUCTION We analyzed relationships among peripheral immunity markers, cognition, Alzheimer's disease (AD)‐related biomarkers, and neuroimaging to understand peripheral immunity involvement in AD. METHODS Peripheral immunity markers were assessed in AD, non‐AD neurodegenerative disorders, and controls, examining their connections with cognition, AD‐related biomarkers, and neuroimaging using multiple regression models. RESULTS The study included 1579 participants. Higher levels of white blood cell, neutrophil, monocyte, neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), systemic immune‐inflammation index (SII), and lower lymphocyte‐to‐monocyte ratio (LMR) were associated with cognitive decline and more severe anxiety and depression. The impact of lower LMR, lymphocyte count, and higher NLR on cognitive decline is mediated through cerebrospinal fluid amyloid beta (Aβ) levels. Additionally, increased PLR, NLR, and SII were associated with brain atrophy and hippocampal Aβ deposition (amyloid positron emission tomography). DISCUSSION Peripheral immunity markers offer a non‐invasive and cost‐effective means of studying AD‐related pathophysiological changes, providing valuable insights into its pathogenesis and treatment. Highlights Peripheral immunity markers linked to cognitive decline and anxiety/depression. Low LMR, LYM, and high NLR linked to reduced CSF Aβ, impacting cognition. High PLR, NLR, SII associated with brain atrophy and hippocampal Aβ deposition