N-lactoyl-phenylalanine as a possible biomarker of cognition? Association between neuroproteins, cytokines, body composition, physical fitness and cognitive function in older adults

Cognitive decline during aging may be influenced by peripheral factors, including neuroproteins and pro-inflammatory cytokine levels, body composition, and physical fitness. However, the specific associations between these factors and cognitive performance remain underexplored. A comprehensive assessment, including peripheral cytokine and neuroprotein levels, body composition, physical performance (aerobic fitness and muscle strength), and cognitive function was performed in a cohort of 87 older adults (mean age: 69.3 ± 3.4 years; 66 females, 21 males) with a range of Body Mass Index (BMI): 19.7 – 41.9. Elevated blood levels of N-lactoyl-phenylalanine (Lac-Phe) were associated with better psychomotor speed (r = −0.223, p = 0.034) as measured by the Trial Making Test-A (TMT-A). Elevated pro-inflammatory cytokines (IL-6, IL-8, IL-12) and peripheral clusterin concentrations were also associated with poorer cognitive performance. No significant associations were found between cortisol, brain-derived neurotrophic factor and cognitive function. BMI and fat mass (kg) were positively associated with performance on the Stroop Test, suggesting a negative effect of increased adipose tissue on inhibitory control. In contrast, greater skeletal muscle mass was positively associated with better memory. Physical fitness parameters, including VO2peak, handgrip strength, and maximal aerobic power, showed positive associations primarily with short-term visuospatial memory. Findings from our study suggest that higher levels of adiposity and inflammation are detrimental to cognitive health. Cardiorespiratory fitness, skeletal muscle mass and strength show a protective role, particularly for memory performance in older adults. Future studies assessing the impact of aging and associated cognitive decline should include Lac-Phe and clusterin as biomarkers associated with specific cognitive domains.