Neuroinflammation in medial temporal regions predicts cognitive decline in dementia with Lewy bodies

Abstract

AbstractBackgroundNeuroinflammation is implicated in the pathogenesis of neurodegenerative disorders including dementia with Lewy bodies (DLB), but its relationship with disease progression, including cognitive decline, is less well understood. We investigated the predictive value of microglial activation, assessed in vivo using positron emission tomography (PET) imaging with [11C]PK11195, on the rate of annual cognitive decline in patients with DLB. We hypothesised a detrimental effect of inflammation on cognition over time.MethodNineteen patients with DLB underwent baseline assessment, including [11C]PK11195 PET and cognitive tests from the Neuroimaging of Inflammation in Memory and Related Other Disorders (NIMROD) study. Cognitive performance was then assessed at an average of 1.1‐year intervals (standard deviation (SD) ± 0.03 years) up to 3.4 years (average ± SD = 3.20 ± 0.16) using the revised Addenbrooke's Cognitive Examination (ACE‐R) and Cambridge Neuropsychological Test Automated Battery (CANTAB). Regional [11C]PK11195 binding potential values were included in a principal component analysis (PCA). Linear mixed effects models were applied to the longitudinal ACE‐R scores. Individual component scores were included in analysis of interaction with time to test for associations between [11C]PK11195 uptake at baseline and longitudinal cognitive performance scores. Age and sex were included as covariates in the models.ResultPatients showed a mean 8.8‐point loss per year on the ACE‐R total score (p<0.001) (Figure 1, left panel). The PCA identified five components, explaining >80% of variance. Annual rate of change in the ACE‐R total score (estimate=‐2.90, p=0.0226) (Figure 1, right panel), memory (estimate=‐1.14, p=0.004) and attention/executive function (estimate=‐0.80, p=0.022) sub‐scores was negatively associated with increased microglial activation in component #4, which was mainly loaded onto the hippocampus, amygdala and pallidum but also parahippocampal cortex and the pre‐subgenual frontal area.ConclusionHigher levels of neuroinflammation in medial temporal regions and pallidum predict faster cognitive decline in patients with DLB, particularly in the domains of memory and attention/executive function. Our results encourage the application of [11C]PK11195 PET in DLB to inform prognosis, and to improve patient stratification for clinical trials.