Associations between physical activity, brain health, cognitive function, and circulating GPLD1 in healthy older (65–85 years) individuals

Declines in physical and cognitive function are common in older adults. The circulating enzyme glycosylphosphatidylinositol (GPI)-specific phospholipase D1 (GPLD1) is elevated after exercise and has been associated with improved cognitive function when administered to aged mice. The purpose of this study was to investigate the relationship between GPLD1 and both cognitive function and brain structure/function in older adults with either high or low levels of physical activity. Healthy men and women aged 65 to 85 years with a body mass index between 20 and 35 kg/m² and a rapid assessment of physical activity score of 1–3 (inactive) or 6–7 (highly active) were recruited. Participants wore an accelerometer to assess objectively physical activity. At a single clinical visit, fasting blood was collected for assessment of circulating GPLD1 while cognitive function via the Mini-Mental State Exam and NIH Toolbox® Cognition Battery, and brain magnetic resonance imaging (MRI and fMRI) were completed. As expected, highly active participants had a higher number of steps and total minutes of moderate-to-vigorous physical activity over 7 days (both p = 0.003). However, no difference in GPLD1 was observed between highly active and inactive participants (p = 0.751). Cognitive function was also similar between groups. Higher circulating GPLD1 was associated with poorer processing speed (r = 0.461, p = 0.027) but tended to be associated with greater functional MRI activation of Attention Network Task alerting regions of interest (r = 0.391, p = 0.120). Unlike hypothesized, physical activity status did not determine circulating GPLD1. No clear relationship was found between GPLD1 and cognitive function or brain structure and function. ClinicalTrials.gov Identifier: NCT04645134 (Physical Activity and Cognitive Function in Older Adults: A Novel Role for GPLD1).