A double‐blind, placebo‐controlled study of the effect of a TNFα inhibitor, Etanercept, on microglial activation in amyloid PET‐positive patients with mild cognitive impairment due to AD‐intermediate likelihood:...

Background: Previous studies have shown that systemic TNFα is associated with increased disease progression in AD and that this may be modulated by the anti‐TNFα agent Etanercept. The effect of Etanercept on microglial activation in patients with MCI due to AD is unknown. Method: A total of 13 patients (from a planned 46 patients) with a clinical diagnosis of MCI due to AD were randomised to receive either placebo or 50 mg of Etanercept (weekly s.c injection) over one year. Aß deposition was established by AmyvidTM ([18F]Florbetapir‐PET) scan. Clinical assessments, [11C]‐(R)‐PK‐11195 PET (a marker of microglial activation) and [18F]Florbetapir‐PET were performed at baseline and after 1 year. Result: 10 out 13 enrolled participants completed the whole study. 6 on Etanercept and 4 on placebo. The region of interest analysis of the [11C]‐(R)‐PK‐11195 binding potential (BP) at baseline showed a widespread increase in MCI patients as compared to age‐matched controls with the cingulate gyrus being targeted. When comparing the change of regional and global PK11195 BP for these 10 patients between baseline and follow‐up after one year, there were no significant differences in the placebo or in the active drug group. Likewise, we found no major changes in measurement of memory function or other cognitive tasks in those subjects taking Etanercept compared with placebo. However, study power was severely compromised. Conclusion: MCI patients show increased microglial activation as compared to healthy controls. In our relatively small treatment group Etanercept does not seem to modify microglial activation as measured with [11C]‐(R)‐PK‐11195 PET. [ABSTRACT FROM AUTHOR]