The relationship between annual predicted future population growth rates and elderly suicide rates.

(p= 0.03, r2 = 0.49) and higher NPI total scores (p= 0.01, r2 = 0.63) (see Figures S1A and S1B, respectively; available as supplementary material attached to the electronic version of this letter at www.journals.cambridge.org/jid_IPG). Similarly, there were trend level correlations of IL-6 release with worse ratings on the CDR (p= 0.08, r2 = 0.33) and MMSE (p= 0.05, r2 = 0.39). In this pilot project, we sought to replicate prior findings suggesting that IL-6 release from LPS-stimulated PBMCs is higher in AD than cognitively normal controls. We found increased IL6 release ratios in AD, with trend level significance at the higher LPS concentration only. This is not surprising given the small sample; since the results are in the predicted direction they offer support for hypothesis 1. We sought to extend prior results by adding an AD-specific stimulus (A-β1-42), in an attempt to more closely model the neuroinflammatory processes of AD. Modest support was seen for hypothesis 2 with A-β1-42 increasing the IL-6 release ratio by a factor of 2 in AD patients but not controls, although this was not statistically significant; these results are in the direction predicted by hypothesis 2. Additionally we found a significant trend correlation between IL-6 release ratio and several clinical variables, including verbal category fluency (animals), NPI, CDR and MMSE. A higher IL-6 release ratio was associated with worse illness severity (higher NPI total and CDR, lower MMSE and category fluency). This suggests that the IL-6 release ratio may have value as a marker of AD disease severity, especially severity of neuropsychiatric symptoms (NPS). The latter appears to be a unique finding, and may reflect the involvement of inflammatory mechanisms (peripheral and central) in the development of NPS. This study is limited by small sample size, assessment of only one candidate cytokine, and limited capacity to assess multiple reaction conditions. The strengths of the study include a well-characterized cohort of AD and control participants and the extension of prior results to neuropsychiatric and functional as well as cognitive findings. These preliminary results suggest that IL-6 release from PBMCs may be a useful marker of disease severity and NPS severity in AD, thus meriting further study.