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BackgroundCognitive reserve may protect against cognitive decline. However, its effect on physiological measures of cognitive workload in adults with cognitive impairments is unclear.ObjectiveThe aim was to determine the association between cognitive reserve and physiological measures of cognitive workload in older adults with and without cognitive impairments.Methods29 older adults with cognitive impairment (age: 75±6, 11 (38%) women, MOCA scores 20±7) and 19 with normal cognition (age: 74±6; 11 (58%) women; MOCA 28±2) completed a working memory test of increasing task demand (0-, 1-, 2-back). Cognitive workload was indexed using amplitude and latency of the P3 event-related potential (ERP) at electrode sites Fz, Cz, and Pz, and changes in pupillary size, converted to an index of cognitive activity (ICA). The Cognitive Reserve Index questionnaire (CRIq) evaluated Education, Work Activity, and Leisure Time as a proxy of cognitive reserve.ResultsHigher CRIq total scores were associated with larger P3 ERP amplitude (p=0.048), independent of cognitive status (p=0.80), task demand (p=0.003), and electrode site (pConclusionCognitive reserve affects cognitive workload and neural efficiency, regardless of cognitive status. Future longitudinal studies should investigate the causal relationship between cognitive reserve and physiological processes of neural efficiency across cognitive aging.