AbstractBackgroundGlucose levels, together with hemoglobin A1c (HA1c), have been associated with reduced cognitive performance, particularly on executive functioning and memory measures. Numerous studies using the Loewenstein‐Acevedo Scales for Semantic Interference and Learning (LASSI‐L) have demonstrated that proactive semantic interference (PSI) and failure to recover from PSI (frPSI) are sensitive to early cognitive changes present in the preclinical stages of Alzheimer's disease (AD).MethodThe aim of the present study was to examine the association between PSI, frPSI, blood glucose levels, and hemoglobin A1c (HA1c) among cognitively normal middle‐aged adults. Seventy‐five adults (Age: 50.8 ± 6.67; Education: 16.23 ± 2.93; Sex: 68% female) without psychological disorders, substance use disorders, or previous cognitive diagnoses were recruited as part of a memory and aging study. Sixty‐seven participants identified as White (89%) and eight as African American (11%). They were fluent in English and/or Spanish and were tested in their dominant and preferred language (65% English, 35% Spanish), as assessed by the Language Experience and Proficiency Questionnaire. All participants underwent a neuropsychological evaluation and administration of the Clinical Dementia Rating Scale (CDR); all were diagnosed as cognitively normal by trained neuropsychologists. Participants fasted six to eight hours prior to providing a blood sample. Comparisons were made between participants using t‐tests and Chi‐square tests. An additional Spearman correlation was used to determine the relationship between the variables. Blood glucose and HA1c levels were compared to LASSI‐L scores, including the number of words correctly recalled and the number of intrusion errors (IE) on the PSI (List B Cued Recall 1) and frPSI (List B Cued Recall 2) trials.ResultThere was no significant association between glucose and the LASSI‐L Scales. However, higher HA1c levels were correlated with lower intrusion errors sensitive to proactive semantic interference.ConclusionOur findings are inconsistent with previous research, as an increase of blood glucose and HA1c levels have been formerly found to lead to reduced cognitive performance. Based on these findings, further investigations are warranted to better understand the associations between HA1C levels, proactive semantic interference, and varying cognitive domains.