Correlation of Microglial Activation with White Matter Changes in Dementia with Lewy Bodies

ABSTRACTDementia with Lewy bodies (DLB) is the second-leading degenerative dementia after Alzheimer’s disase. Neuropathologically, it is characterized by alpha-synuclein protein deposition with variable degree of concurrent Alzheimer pathology. Neuroinflammation is increasingly recognized as a significant contributor of degeneration.Objectiveto examine the relationship between microglial activation as measured with [11C]-PK11195 brain PET and MR diffusion tensor imaging (DTI) in DLB.Methodsnineteen clinically probable DLB and 20 similarly aged controls underwent structural MRI with T1-weighted and 3T DTI sequences. Eighteen DLB subjects also underwent [11C]-PK11195 PET imaging. Tract-Based Spatial Statistics (TBSS) were performed to compare DTI parameters in DLB relative to controls and identify associations of [11C]-PK11195 binding with white matter integrity.ResultsTBSS showed widespread changes in all DTI parameters in the DLB group compared to controls (Threshold Free Cluster Enhancement (TFCE) p < 0.05). [11C]-PK11195 binding in parietal cortices also correlated with widespread lower mean and radial diffusivity (TFCE p < 0.05).ConclusionOur study demonstrates that higher PK11195 binding is associated with a relative preservation of white matter, positioning neuroinflammation as a potential early marker in the DLB pathogenic cascade.