OBJECTIVE: The present study examined bidirectional effects between salivary cortisol and cognitive functioning over time. Furthermore, the role of the APOE-ɛ4 allele as a moderator of the associations was investigated. METHODS: Using a prospective population-based study, we analyzed data from 752 older adults followed up over 10 years. A random-intercept Cross-Lagged Panel Model was applied to each combination of one cortisol measure (at waking time, 30 min after waking, 11 am, 8 pm, cortisol awakening response, total daily output, and diurnal slope) and one cognitive measure (primary outcome: Clinical Dementia Rating Scale sum of boxes score, CDR-SB
secondary outcome: Mini-Mental State Examination) resulting in 14 (7 × 2) models. RESULTS: Between-person effects pointed out that a higher cortisol level at 11 am was associated with increased CDR-SB scores, and a higher cortisol awakening response was associated with decreased CDR-SB scores. Within-person effects indicated that cortisol levels at 11 am and 8 pm, and total daily cortisol output were associated with subsequent lower CDR-SB scores. The APOE-ɛ4 allele did not moderate the relationship between cortisol and cognitive functioning. CONCLUSIONS: Our findings revealed within-person associations between higher cortisol levels and better cognitive functioning at the subsequent follow-up, suggesting cortisol protective effects for cognitive decline.