Systematic review finds inflammatory markers elevated in Alzheimer's disease compared to healthy controls across 41 studies

BACKGROUND: Dementia has been linked to several modifiable risk factors, including mental illness. The inflammatory-mediated neurodegeneration hypothesis posits a causal relationship between the two whereby mental illness triggers an inflammatory response, which in turn acts as a catalyst for the neurodegenerative changes that lead to dementia. Existing meta-analyses have yet to investigate inflammatory markers in Alzheimer's disease (AD), vascular dementia (VaD), dementia with Lewy bodies (DLB), or fronto-temporal dementia (FTD) in the context of the inflammatory-mediated neurodegeneration hypothesis. This meta-analysis therefore explored whether a) AD, VaD, DLB, and FTD are each associated with greater inflammation than healthy controls, independent of comorbid mental or physical health problems with a known inflammatory response, and b) there are any similarities in the inflammatory profiles associated with these dementia subtypes. METHODS: PubMed, EMBASE, PsycINFO and CINAHL searches identified 41 eligible studies. RESULTS: AD is associated with an inflammatory response, with tentative evidence to indicate that VaD, DLB, and FTD are also associated with inflammation. However, the inflammatory response appears to differ across these conditions. LIMITATIONS: The data for VaD, DLB, FTD and a number of inflammatory markers were limited. CONCLUSIONS: Although tentative, AD, VaD, DLB, and FTD appear to be associated with discrete inflammatory processes that are not attributable to other common comorbid mental or physical health problems that cause inflammation. Whether this inflammatory response plays a causal role in the development of dementia and/or is triggered by prior mental illness remains to be determined.