AbstractBackgroundPrevious studies have shown that resting state brain function begins to change in the years leading up to the development of cognitive impairment. This study examines temporal lobe function during memory encoding approximately 2.5 years before the onset of cognitive impairment in Baltimore Longitudinal Study of Aging (BLSA) participants.MethodBLSA participants with subsequent memory impairment (Subsequently Impaired (SI), n = 22, mean age = 83.6, time to impairment = 2.5 ± 1.1 SD years post‐scan) and age, sex, and education matched cognitively normal participants (Cognitively Normal (CN), n = 64, mean age = 84.9) performed a face‐scene encoding task during fMRI scanning. Group differences in task performance and brain activation patterns were examined during encoding trials they later remembered, and trials they later forgot during the recognition phase of the task.ResultThe SI group performed more poorly than the CN group during the recognition phase of the task. Both CN and SI activated the occipitotemporal visual pathway during memory encoding. Yet relative to CN participants, the SI group showed decreased activation of the hippocampus, entorhinal cortex, parahippocampal gyrus, and fusiform gyrus during encoding of face‐scene pairs. This decreased activation was seen during both encoding of pairs they later remembered and pairs they forgot during recognition.ConclusionBoth memory dysfunction and decreased temporal lobe activity during encoding begin before the onset of clinically evident cognitive impairment. In the SI group, the decreased temporal lobe activation was seen regardless of whether they later remembered or forgot the face‐scene pairs during the recognition task. This suggests that those who go on to develop impairment have an overall weaker functional response in temporal lobe regions during memory encoding. Further examination of the functional connectivity of these regions may help to determine if differences in brain network characteristics are related to subsequently remembered or forgotten visual stimuli during encoding. This work was supported by the Intramural Research Program of the NIH, National Institute on Aging.