Brainstem and midbrain structures involved in memory encoding in healthy aging and mild cognitive impairment, a 3T task‐fMRI study

Abstract Background Memory decline, which is especially prevalent in Alzheimer’s disease (AD), has been studied via fMRI, primarily focusing on the prefrontal cortex and hippocampus. However, emerging evidence suggests that the brainstem, alongside various midbrain regions, is an initial target for pathological processes like hyperphosphorylated TAU protein accumulation. Among these, the locus coeruleus, a noradrenergic nucleus in the pons, projects to critical midbrain areas supporting memory encoding. Hence, our study aimed to investigate BOLD task activations in AD relevant to memory, while focusing on differences in responses to emotional versus neutral stimuli in the brainstem and midbrain. Method Using event‐related fMRI, 53 subjects (28 healthy older adults, 25 with mild cognitive impairment (MCI)) (see table 1) underwent an incidental recognition memory task involving emotional and neutral images. Memory tests followed immediately, and 4 hours after encoding. Group differences in brain activations for remembered versus not remembered images using the study template were examined. Result Results revealed a trend for greater activation in the left caudate nucleus in older adults, compared to those with MCI, when subsequently remembered items were compared with not remembered ones (small volume correction (SVC), cluster level p FWE‐corr = 0.08). Similarly, a significant increased activation was observed in the locus coeruleus (SVC, cluster level p FWE‐corr = 0.018). However, after adjusting for group and individual differences in LC integrity and global grey matter volume (GMV), no significant differences persisted, suggesting that structural changes contribute significantly to differences in LC activation between healthy controls and MCI participants (see Figures 1 and 2). Conclusion In conclusion, our findings underscore the caudate nucleus’s role in memory encoding for healthy older adults versus those with MCI. A decline in LC function in MCI appears related to a decline in LC integrity. These insights contribute to understanding memory mechanisms in healthy aging versus MCI. Future studies are needed to explore potential neural memory compensatory processes in MCI.