Neutrophil activation and related disrupted frontolimbic circuit may contribute to cognitive progression of minimal depressive symptoms in non-dementia elderly

As a more common but easily neglected disorder, minimal depressive symptoms (MDS), it is unclear whether and why it increases the risk of cognitive progression in non-dementia elderly. The Alzheimer's disease Neuroimaging Initiative (ADNI) database was used to assign 1065 non-dementia elderly into normal control (n = 380) and MDS (n = 685) groups via the Geriatric Depression Scale (GDS). Blood neutrophils, transcriptomics and metabolomics, cerebrospinal fluid (CSF) proteomics, and magnetic resonance imaging (MRI) data were analyzed. MDS was found to increase the risk of cognitive progression independently of multiple psychological symptoms. Increased levels of blood neutrophils were associated with cognitive progression in MDS, as supported by neutrophil-related pathways by transcriptomic enrichment analysis and multi-omics joint analysis. A disrupted frontolimbic circuit was associated with neutrophil activation in MDS. The heterogeneity of the sample limited the generalizability of results, and the lack of follow-up data limited the research on the mechanism of neutrophil activation influencing cognitive function in MDS. Cognitive progression occurs as early as the MDS stage. And this phenomenon may attribute to the neutrophil activation and the related disrupted frontolimbic circuit. •Minimal depressive symptoms (MDS) increase the risk of cognitive progression in non-dementia elderly.•MDS increases the risk of cognitive progression independently of multiple psychological symptoms.•The neutrophil activation process was associated with cognitive progression in MDS.•A disrupted frontolimbic circuit was associated with neutrophil activation in MDS.