Objective: To determine if subjects with dementia with Lewy bodies(DLB) have increased microglial activation in vivo compared to matched healthy controls as assessed using PET imaging of the radioligand [11C]PK11195, which preferentially binds to activated microglia, and to assess whether there are correlations with clinical features.

Background: Evidence of neuroinflammation in the pathogenesis of Lewy body dementia continues to accumulate, with recent PET studies showing microglial activation in vivo in Parkinson’s disease dementia that negatively correlates with cognitive ability[1]. It is unclear whether similar changes occur in DLB, though alpha-synuclein is known to activate microglia and pathology studies suggest neuroinflammation in the pathogenesis of DLB[2].

Methods: Using dynamic PET imaging of [11C]PK11195, we compared [11C]PK11195 binding overall and within 10 regions of interest, between 11 subjects with probable DLB and 13 age and education matched healthy controls. Binding was quantified using non-displaceable binding potential (BPND) determined with the simplified reference tissue model. We also assessed correlations between regional BPND and key clinical variables including cognition (ACE-R score) and disease duration.  

Results: There was significantly increased BPND in the basal ganglia (putamen) and the occipital lobe (cuneus) in DLB compared to the control group (p<0.005, Mann-Whitney U).  The BPND within the cuneus correlated positively with ACE-R scores (p<0.005, Spearman R), but there was no significant correlation with disease duration.

Conclusions: Our results show increased [11C]PK11195 binding consistent with microglial activation in brain regions known to be affected in DLB, suggesting that neuroinflammation can be demonstrated in vivo. Although its significance remains unclear, the positive correlation with ACE-R scores suggests that microglial activation is elevated in mild disease and diminishes in later stages. This suggests that either inflammation is protective in DLB, or that the potential immunotherapeutic window is narrow and early in disease.

References: 1         Fan Z, Aman Y, Ahmed I, et al. Influence of microglial activation on neuronal function in Alzheimer’s and Parkinson’s disease dementia. Alzheimers Dement 2014;:1–14. doi:10.1016/j.jalz.2014.06.016

2         Mackenzie IR. Activated microglia in dementia with Lewy bodies. Neurology 2000;55:132–4.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/11cpk11195-pet-imaging-reveals-neuroinflammation-in-dementia-with-lewy-bodies-nimrod-study/