TNF and Alzheimer disease: It has been shown in a clinical population of AD patients that Systemic Inflammatory Events (SIEs) were associated with more rapid cognitive decline over 6 months (approximately 2-fold) and when those patients with SIE also had elevated plasma TNF-α levels, this was associated with a 10-fold greater rate of cognitive decline over the 6 month observation period (Holmes et al., 2009).