Is amnestic mild cognitive impairment a neuro-immune condition?

Background The pathophysiology of amnestic Mild Cognitive Impairment (aMCI) is largely unknown, although some papers found signs of immune activation. Aims To assess the cytokine network in aMCI after excluding patients with major depression (MDD) and to examine the immune profiles of quantitative aMCI (qMCI) and distress symptoms of old age (DSOA) scores. Methods A cross-sectional study was conducted on 61 Thai aMCI participants and 60 healthy old adults (both without MDD). The Bio-Plex Pro human cytokine 27-plex test kit and LUMINEX 200 were used to assay cytokines/chemokines/growth factors in fasting plasma samples. Results aMCI is characterized by significant general immnosuppression, and reductions in T helper 1 (Th)1 and T cell growth profiles, the immune-inflammatory responses system, interleukin (IL)1β, IL6, IL7, IL12p70, IL13, GM-CSF, and MCP-1 as compared with controls. These 7 cytokines/chemokines exhibit neuroprotective effects at physiologic concentrations. In multivariate analyses, three neurotoxic chemokines, CCL11, CCL5, and CXCL8, emerged as significant predictors of aMCI. Logistic regression showed that aMCI was best predicted by combining IL7, IL1β, MCP-1, years of education (all inversely associated) and CCL5 (positively associated). We found that 38.2% of the variance in the qMCI score was explained by IL7, IL1β, MCP-1, IL13, years of education (inversely associated) and CCL5 (positively associated). The DSOA were not associated with any immune data. Discussion A dysbalance between lowered levels of neuroprotective cytokines and chemokines, and relative increases in neurotoxic chemokines are key factors in aMCI. Future MCI research should always control for the confounding effects of affective symptoms. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This research is supported by the Ratchadapisek Sompoch Fund, Faculty of Medicine, Chulalongkorn University (Grant no. GA66/037); and the 90th Anniversary of Chulalongkorn University Scholarship under the Ratchadapisek Somphot Endowment Fund (Grant no. GCUGR1125661006D), Thailand. MM received funding from the Thailand Science Research and Innovation Fund, Chulalongkorn University (HEA663000016), and a Sompoch Endowment Fund (Faculty of Medicine), MDCU (RA66/016). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The present study received approval from the Institutional Review Board (IRB) of the Faculty of Medicine at Chulalongkorn University in Bangkok, Thailand (No. 0372/65). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The dataset generated during and/or analysed during the current study will be available from MM upon reasonable request and once the authors have fully exploited the dataset.