Neuroinflammation in mild cognitive impairment and Alzheimer's disease: A meta-analysis

Background: Increasingly, evidence from brain imaging supports the role of neuroinflammation in dementia progression. Yet, it is not clear if there are patterns of spatial and temporal susceptibility to neuroinflammatory processes in the brain that may correspond to dementia staging or symptom expression. Methods: We searched literature databases for case-control studies examining levels of translocator protein (TSPO) levels using positron emission tomography, representing neuroinflammation, in regional analyses between healthy controls and mild cognitive impairment (MCI) or Alzheimer's disease (AD) subjects. Standardised mean differences (SMDs) were calculated and results meta-analysed using random-effects models. Quality assessments, sensitivity analysis, subgroup analysis and meta-regressions were also performed. Results: Twenty-eight studies comprising 755 (HC = 318, MCI = 168, AD = 269) participants and 37 brain regions were included. Compared to HCs, AD participants had increased TSPO levels throughout the brain (SMD range: 0.43-1.76), especially within fronto-temporal regions. MCI subjects also had increased TSPO levels, mainly within the neocortex, with more modest effects (SMD range: 0.46 - 0.90). Meta-regression analysis identified an inverse association between TSPO levels in the parietal region and Mini-Mental State Examination scores, a proxy for disease severity, in AD subjects (estimate: -0.11, 95% confidence interval: 0.21 to 0.02; P = 0.024). Conclusions: Our findings support the association of increased neuroinflammation during the progression of MCI and AD, relative to HCs.