Objective: To determine whether HPAA dysfunction is prospectively associated with global cognitive impairment in later life Methods: This cross-cohort study integrates two large longitudinal datasets: Whitehall II and the National Survey for Health and Development (NSHD), on data collected in the Whitehall II study in 2002/2004, 2007/2009 and 2012/2013; and for NSHD in 2006/2010 and 2015. Serial salivary cortisol samples were collected multiple times within a 24-hour period at mean ages 61.2 and 65.9 years in Whitehall II and at age 60-64 from NSHD participants. Cortisol profile is defined using cortisol awakening response (CAR) and am:pm ratio. Cognitive function was measured using the MMSE in Whitehall II and ACE-III in NSHD, harmonised into a thirty-point score. Models were adjusted for age, sex, diagnoses of hypertension, diabetes, BMI, educational attainment and interval between HPAA and cognitive assessments. Results: In fully adjusted models, increased am:pm cortisol ratio was prospectively associated with better later-life cognitive function years later (0.02 fewer errors per SD increase in am:pm cortisol ratio, p<0.01) and verbal fluency (0.03 SD increase in verbal fluency per SD increase in am:pm ratio, p<0.01). Increasing age, lower educational attainment, diagnosis of hypertension, diagnosis of diabetes and increased BMI were associated with worse cognitive function and poorer verbal fluency. There were no associations between depression and later-life cognition or reverse associations between cognition and later-life cortisol profiles. Conclusions: Loss of diurnal HPAA variation is evident in individuals subsequently experiencing more cognitive impairment. It may serve as an early pre-clinical marker of cognitive decline.