Inflammation is a significant consideration in the aging process, as previous research shows that elevated levels of inflammation may increase the risk for developing Alzheimer’s Disease and other dementias. While inflammation is often associated with age-related changes in cognition (i.e., memory and executive function), some research suggests a relationship between inflammatory proteins and changes in gait speed that is independent of age. Thus, the present study aimed to explore the physiological and neurobiological correlates of cognitive change in a sample of older adults with mild cognitive impairment (MCI), specifically the relationship between inflammatory proteins, cognition, and gait speed.

The sample included 20 older adults (mean 68.15 ± 7.75) with MCI. Most were predominantly White (70%), non-Hispanic (85%), male (90%), and had more than a high school level education (95%). Measures of cognition included the Trail-Making Test (TMT), Stroop Color Word Test (SCWT), and Symbol Digit Modality Test (SDMT). Gait speed was assessed using the 6-Minute Walk Test. Inflammatory proteins were analyzed from whole blood draws using the Olink Target 96 Neurology assay (Uppsala, Sweden). A series of Pearson’s correlations identified significant associations between gait speed, cognition, and inflammatory proteins, while controlling for the effects of age.

Seven inflammatory proteins (i.e., GDNF, uPA, FGF-23, IL-24, CD5, CCL20, CCL28) were significantly correlated (p < 0.05) to both gait speed and at least one measure of cognitive function. Specifically, GDNF (r = -0.76), uPA (r = -0.57), and CCL28 (r = -0.59) were negatively correlated with attention to detail, as measured by TMT-A Errors. CCL20 was positively correlated to SCWT Word Trial (r = 0.57), while CCL28 was positively correlated with SCWT Color Trial (r = 0.52). Performance on the SCWT Color Word Trial was positively associated with CCL28 (r = 0.54) and GDNF (r = 0.54). No biomarkers of inflammation were correlated to SDMT performance.

In a sample of older adults with MCI, markers of inflammation appeared significantly related to both gait speed and cognitive function. Higher concentrations of GDNF, uPA, and CCL28 were associated with better attention to detail, CCL20 and CCL28 with tasks of simple attention, and GDNF and CCL28 with dual task executive functioning. Previous research has shown that GDNF, a glial cell derived neurotrophic factor, prevents apoptosis of dopaminergic and motor neurons commonly associated with Parkinsonian disease. CCL20 and CCL28 are both cytokines that act as chemotactic factors in immunoregulatory and inflammatory processes for a variety of autoimmune conditions. The ligand uPA plays a critical role in neuroprotection and neurogenesis, specifically in those with epilepsy. This study, however, is the first to demonstrate their influence in an older MCI population, suggesting a possible neurobiological correlate associated with changes in gait speed and aspects of cognitive functioning. Future studies should explore how these relationships change over time when incorporating interventions targeting inflammation. Additionally, research should consider assessing a broader range of inflammatory proteins to better understand the scope of these relationships.