Downregulation of hippocampal activity improves memory performance in individuals at risk of Alzheimer's disease

INTRODUCTIONIn people at risk of Alzheimers disease (AD), hippocampal hyperactivity relates to worse hippocampus-dependent task performance and promotes AD pathology. Reducing hippocampal hyperactivity promises to improve hippocampus-dependent memory performance. METHODS78 participants (69.29{+/-}5.87 years old, 60% female) used real-time fMRI neurofeedback twice to downregulate the hippocampus or a control region. We assessed hippocampal activity and memory performance before and after neurofeedback. We classified AD pathology risk using a blood-based biomarker, an established risk-score, or clinical characterisation. RESULTSDuring hippocampus, but not during control-region neurofeedback, individuals significantly downregulated hippocampal activity with the effect still detectable one week later. In those at high risk of AD pathology, with all three classifications, stronger hippocampal downregulation resulted in stronger memory improvement, independent of baseline hippocampal hyperactivity. DISCUSSIONDownregulating hippocampal activity using fMRI neurofeedback may be a complementary treatment for people at risk for AD, well before there is hippocampal hyperactivity.