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Previous research suggests that glucoregulation and nutrient interventions, which alter circulating glucose, impact cognitive function. To examine the effect of modulating glycemic response using isomaltulose on cognitive function 24 healthy male adult participants consumed energy and macronutrient-matched milk-based drinks containing 50 g isomaltulose, 50 g sucrose or a water control in a counterbalanced within-subject design. Interstitial glucose was measured continuously in 12 subjects and all provided 9 capillary measures on each test day. A 30-min cognitive test battery was administered before and twice (+35 and +115 min) after drink ingestion. Immediate, delayed, recognition, verbal and working memory, and psychomotor performance were assessed. Glycemic profiles induced by the drinks differed significantly during the first but not the second post-drink test battery. Neither administration of the sucrose nor isomaltulose drinks produced consistent effects on verbal or working memory, or psychomotor performance. This study used isomaltulose as an investigative tool to lower glycemic response. Importantly, it demonstrates a lack of effect of modulating glucose on cognitive performance based on reliable, continuously measured glycemia. It refutes the hypothesis that glycemia is associated with cognitive performance and questions the suggestion that isomaltulose has an effect on cognitive performance.