Longitudinal changes in brain activity during mnemonic discrimination over the course of Alzheimer’s disease

BACKGROUND: Mnemonic discrimination tasks (MDTs) hold potential for early detection of memory changes in Alzheimer’s disease (AD). Object and scene processing tasks differently tap into memory networks vulnerable to early tau and amyloid pathology, respectively. We used an object and scene MDT to assess longitudinal effects of AD on distinct functional memory networks and investigate their potential as markers for different disease stages. METHOD: 202 participants from the DELCODE study completed an object and scene MDT of highly similar objects and scenes during fMRI scanning each year from baseline to 36‐month follow‐up. Participants were classified as cognitively unimpaired (CU; Table 1) or having subjective cognitive decline (SCD), mild cognitive impairment (MCI), or dementia of the Alzheimer’s type (DAT). RESULT: The combined MCI/DAT group showed object and scene mnemonic discrimination impairment. SCDs only differed from CUs on scenes, but trended towards object discrimination decline over follow‐up. Cross‐sectionally, amygdala, BA35/36, anterior hippocampus, and parahippocampal cortex showed increased activity during successful discrimination of both scenes and objects. Entorhinal cortex, posterior hippocampus, and precuneus did so only for scenes, dovetailing with the framework of partially dissociable memory networks. Longitudinally, CUs showed increasing brain activity during object but not scene memory throughout the medial temporal lobe. SCDs showed a pattern of longitudinally increasing activity during scene memory coupled with decreasing activity during object memory in BA35, BA36, and hippocampus. Strikingly, the opposite was true for BA35 and entorhinal cortex in the MCI/DAT group. CONCLUSION: These results provide a first glimpse at longitudinal changes in brain activity during mnemonic discrimination throughout the AD continuum. Both neural and behavioural indices of the MDT may be sensitive to longitudinal disease effects. Future analyses will assess the complex relationship between disease effects on neurodegeneration, neural activity, and memory to better understand how early AD erodes memory and brain systems.