A peripheral neutrophil-related inflammatory factor predicts a decline in executive function in mild Alzheimer's disease

Background Studies suggest a role of the innate immune system, including the activity of neutrophils, in neurodegeneration related to Alzheimer's disease (AD), but prospective cognitive data remain lacking in humans. We aimed to investigate the predictive relationship between neutrophil-associated inflammatory proteins in peripheral blood and changes in memory and executive function over 1 year in patients with AD. Methods Participants with AD were identified from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Neutrophil gelatinase-associated lipocalin (NGAL), myeloperoxidase (MPO), interleukin-8 (IL-8), macrophage inflammatory protein-1 beta (MIP-1 beta), and tumor necrosis factor (TNF) were assayed by luminex immunofluorescence multiplex assay at baseline. Confirmatory factor analysis was used to test an underlying neutrophil associated plasma inflammatory factor. Composite z-scores for memory and executive function were generated from multiple tests at baseline and at 1 year. A multiple linear regression model was used to investigate the association of the baseline inflammatory factor with changes in memory and executive function over 1 year. Results Among AD patients (n = 109, age = 74.8 +/- 8.1, 42% women, Mini Mental State Examination [MMSE] = 23.6 +/- 1.9), the neutrophil-related inflammatory proteins NGAL (lambda = 0.595, p < .001), MPO (lambda = 0.575, p < .001), IL-8 (lambda = 0.525, p < .001), MIP-1 beta (lambda = 0.411, p = .008), and TNF (lambda = 0.475, p < .001) were found to inform an underlying factor. Over 1 year, this inflammatory factor predicted a decline in executive function (beta = - 0.152, p = 0.015) but not memory (beta = 0.030, p = 0.577) in models controlling for demographics, brain atrophy, white matter hyperintensities, the ApoE epsilon 4 allele, concomitant medications, and baseline cognitive performance. Conclusions An inflammatory factor constructed from five neutrophil-related markers in peripheral blood predicted a decline in executive function over 1 year in people with mild AD.