Functional and Blood-Based Biomarkers of Brain Aging in Senior Airline Pilots Approaching Mandatory Retirement: A Case-Control Comparison With Age-Matched Office Workers

Background While mandatory retirement ages for commercial air transport (CAT) pilots are based on assumptions about age-related cognitive decline, empirical evidence examining brain aging in senior professionals in this field remains scarce. The aim of this study was to compare functional and blood-based biomarkers of brain aging between senior CAT pilots approaching retirement and age-matched office workers. Methods We conducted a case-control study involving 31 male CAT pilots aged 60-64 years and 31 age- and sex-matched office workers. Following the Aging Biomarker Consortium framework, we assessed functional biomarkers of brain aging, including processing speed (Trail Making Test Part A), episodic memory (Cued Recall Test and Auditory Verbal Learning Test [AVLT]), and fine motor control (Nine-Hole Pegboard Test). In addition, plasma concentrations of phosphorylated tau-181 (p-tau181) and neurofilament light chain (NfL) were measured as blood-based biomarkers of brain aging. Results Senior CAT pilots demonstrated significantly superior processing speed (Trail Making Test Part A: 26.8 ± 4.1 <i>versus</i> 31.5 ± 5.0 seconds; <i>p</i> < 0.001) and episodic memory performance (cued recall: 13.2 ± 1.9 <i>versus</i> 11.8 ± 2.3; p = 0.007; AVLT: 56.7 ± 7.8 <i>versus</i> 51.4 ± 8.1; p = 0.002) compared to office workers. However, no differences were observed in fine motor control. Regarding biochemical markers, CAT pilots showed significantly lower plasma NfL concentrations compared to office workers (7.5 ± 2.4 <i>versus</i> 9.9 ± 3.5 pg/mL; p = 0.012), whereas p-tau181 levels did not differ between groups. Across the entire cohort, higher plasma NfL concentrations were associated with slower processing speed (r = -0.30, p = 0.001), an association that remained significant after multivariable adjustment (standardized β = -0.27, p = 0.003). Conclusions Our findings suggest that experienced CAT pilots exhibit cognitive performances and a biochemical marker profile associated with healthier brain aging, raising questions about assumptions underlying mandatory retirement policies based solely on age, though the mechanisms underlying these differences warrant further investigation.