Neuromodulation and cognition in late-life depression

Late-life depression (LLD) is associated with cognitive decline and increased risk of dementia. Emerging evidence indicates that impaired cortical synaptic plasticity (due to multiple causes including genetic, developmental, neurodegenerative, vascular conditions, chronic stress, and chronic inflammation) may drive this vulnerability. We focus on how disruptions in prefrontal cortex plasticity related to depression contribute to dementia risk and review plasticity-inducing non-surgical neuromodulations. These neuromodulations include electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS), transcranial electrical stimulation (tES), and focused ultrasound (FUS). These strategies could promote cortical plasticity and, in turn, improve network connectivity and prefrontal function, potentially reducing cognitive decline. Then, we discuss future directions that prioritize personalized, mechanism-based interventions, and use preclinical models to optimize neuromodulation protocols. These approaches aim to address the heterogeneity of LLD and improve outcomes by tailoring treatments based on individual characteristics.