Medial temporal lobe hyperactivity during memory processing in older adults is associated with entorhinal tau deposition

Abstract

AbstractBackgroundAging is associated with memory decline and tau accumulation in medial temporal lobe (MTL) structures that support memory. We hypothesized that age‐related differences in functional activation during an fMRI memory task would be related to tau deposition in the entorhinal cortex (EC) and global amyloid‐beta (Aβ). We investigated repetition suppression and subsequent memory as measures of memory processing.Methods46 normal older adults (OA; 78±6 years, 29F) and 21 young adults (YA; 27±5 years, 12F) underwent high‐resolution 3T fMRI while performing a memory task (Figure 1A). Repetition suppression was defined as the contrast of activity between the first presentation compared to the repeated presentation of a stimulus. Subsequent memory was defined as the contrast of activity for stimuli that were later remembered versus forgotten during a post‐scan delayed recognition test. MTL subregions were defined in native space on high‐resolution T2 images using ASHS (Figure 1B). Tau‐PET was performed with 18F‐Flortaucipir (FTP), and mean FTP SUVR was extracted from native space EC ROIs (PVC corrected). Aβ‐PET was performed with 11C‐PiB, and global PiB DVR was extracted. Age‐related differences in activity were compared with independent samples t‐tests, and correlations controlled for age and sex.ResultsCompared to YA, OA showed reduced repetition suppression in MTL ROIs, including the bilateral hippocampus, anterolateral EC (alEC), and posteromedial EC (pmEC; Figure 2A). Post‐hoc analyses determined that this reduction in repetition suppression was driven by hyperactivity to repeated stimuli in OA (Figure 2B/C). For subsequent memory, OA showed reduced activity for remembered versus forgotten stimuli in pmEC‐L (Figure 3A). Post‐hoc analyses revealed hyperactivity in pmEC‐L that was specific to incorrect stimuli, while bilateral hippocampus and alEC‐R demonstrated consistent hyperactivity across both correct and incorrect stimuli (Figure 3B/C). Finally, increased EC FTP, but not global PiB DVR, was related to hyperactivity in bilateral pmEC and hippocampus for subcomponents of both repetition suppression (Figure 4A) and subsequent memory (Figure 4B).ConclusionsAge‐related reductions in activity for repetition suppression and subsequent memory are driven by hyperactivation of MTL structures in hippocampus and EC. These findings are related to EC tau pathology and to failure of stimulus encoding that reflects age‐related memory decline.