Association of peripheral immunity with cognition, neuroimaging, and Alzheimer’s pathology

Abstract

Background: Neuroinflammation has been considered to be a driving force of Alzheimer’s disease. However, the association between peripheral immunity and AD has been rarely investigated. Methods: Separate regression analyses were conducted to explore the associations among peripheral immune markers and cognition, neuroimaging, and AD pathology. Causal mediation analyses were used to investigate whether the associations with cognition were mediated by AD pathology. Results: A total of 1107 participants (43.9% female, mean age of 73.2 years) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) were included. Regression analyses indicated that elevated neutrophils (NEU) count and neutrophil-lymphocyte ratio (NLR) were associated with lower levels of global cognition, memory function (MEM), and executive function (EF), and reduced brain metabolism by 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) as well as greater ventricular volume. An elevated NLR was associated with a lower level of β-amyloid (Aβ) and a higher level of total tau (T-tau) in cerebrospinal fluid (CSF), smaller hippocampal volume (HV), and lesser entorhinal cortex (EC) thickness. On the contrary, an elevated level of lymphocytes (LYM) was associated with a higher level of Aβ and a lower level of T-tau in CSF, better cognition, and less atrophy of brain regions (ventricular volume, HV, and EC thickness). The associations of LYM and NLR with cognition were mediated by Aβ and T-tau pathology (proportion: 18%~64%; p < 0.05). Conclusions: We revealed that two types of peripheral immune cells (NEU and LYM) and the ratio of these two cell types (NLR) had associations with cognition, neuroimaging, and AD pathology. The associations might be mediated by Aβ and tau pathology.