AbstractBackgroundAlcohol Use Disorder (AUD) has previously been identified as a risk factor for Alzheimer’s disease and cognitive impairment. However, the mechanisms underlying the connection between AUD and Alzheimer’s disease remain unclear. Episodic memory is impaired in both AUD and mild cognitive impairment (MCI), and is associated with the transition from MCI to Alzheimer’s disease. This study used functional magnetic resonance imaging (fMRI) to compare activation during encoding of an episodic memory task in mid‐life AUD subjects to subjects with mild cognitive impairment (MCI), a prodromal stage of Alzheimer’s disease.MethodParticipants included 14 AUD subjects age 45 to 65 (M = 56 years), and 14 MCI subjects age 45 to 85 (M = 67 years). Healthy control subjects were matched to AUD and MCI groups by age and sex. Images were acquired on a 3T Siemens Prisma (3 mm3 voxels, TR = 1.1s, TE = 30 ms). During the fMRI task, participants viewed pictures of faces and objects and were instructed to remember these pictures for later. Activation maps were produced through general linear model analysis using cluster correction thresholding (Z>3.3, p = .05) in FSL (version 6.0).ResultsAUD and MCI groups showed reduced extent of BOLD activation during encoding versus baseline (Figure 1). Compared to matched controls, AUD and MCI subjects showed less medial temporal lobe (amygdala), brainstem, and thalamus activation. Additionally, AUD subjects did not exhibit the frontal activation that was present in MCI and matched controls.ConclusionsGiven the small sample sizes, caution should be taken in interpreting these results. Nonetheless, these preliminary findings suggest that mid‐life AUD subjects show similar patterns of reduced activation during episodic encoding to those with MCI. Reduced medial temporal lobe activation may represent vulnerability to Alzheimer’s disease, which is present in both MCI and AUD. Explanations for the differences in frontal activation might include compensatory mechanisms in MCI or executive dysfunction in AUD. Future analyses will aim to disentangle these effects by examining the relationship between BOLD signal activation and behavioral outcomes.