Common and distinct plasma proteomic signature of aerobic and motor physical activity interventions and their link to episodic memory.

Aging is accompanied by chronic low-grade inflammation which has been associated with cognitive decline. Physical activity might regulate plasma levels of inflammatory-related proteins and may contribute to cognitive benefits, although the underlying mechanisms remain poorly understood. This exploratory secondary analysis aimed to evaluate whether different physical activity modalities were associated with distinct inflammatory-related plasma proteomic signatures in healthy older adults and to explore whether these proteomic changes were associated with changes in cognitive performance. An inflammation-centered proteomic analysis was performed on plasma samples from 34 healthy older adults before and after a 12-week intervention program. Participants were randomly assigned to aerobic exercise (AE), gross motor abilities (GMA), or cognitive training (COG) group. Proteomic data were used to explore associations between changes in protein levels and changes in cognitive functions. Differential protein expression, pathway enrichment analyses, and exploratory association analyses were conducted to investigate relationships between proteomic changes and cognitive outcomes. Comparative analyses identified a common signature of 24 differentially abundant proteins shared by AE and GMA, together with an additional signature of 33 proteins specifically associated with AE. Pathway enrichment analyses suggested that these signatures were related to biological processes involved in immune regulation and vascular adaptation. Episodic memory improved following AE, and exploratory analyses identified a 51-protein signature associated with changes in Delayed Recall performance. In this exploratory secondary analysis, different exercise modalities were associated with both shared and distinct inflammatory-related plasma proteomic signatures in healthy physically inactive older adults. These proteomic signatures were also associated with improvements in episodic memory, generating hypotheses regarding biological processes that may contribute to exercise-related cognitive benefits.