Psychedelics such as DMT, LSD, and psilocybin, which act as potent 5-hydroxytryptamine agonists, enhance neural plasticity by activating serotoninergic and glutamatergic systems and modulate signaling pathways in Alzheimer's disease, including brain-derived neurotrophic factor signaling and subsequent activation of mammalian target of rapamycin and autophagy regulators. These compounds show potential for mitigating effects of Alzheimer's disease-related dementia, which lacks a definitive cure. Controlled, dose-dependent administration represents a novel therapeutic intervention, though further studies are needed to establish long-term safety, efficacy, and optimal protocols.
Nearly half of older adults with major depression have treatment-resistant late-life depression (TRLLD). A systematic review of randomized controlled trials up to March 2024 found that aripiprazole (based on two studies), venlafaxine, ketamine, and lithium were associated with reduced depressive symptoms after treatment. Among non-pharmacological approaches, repetitive transcranial magnetic stimulation, sequential bilateral theta burst stimulation, and cognitive remediation also showed significant improvements. However, the quality of evidence ranged from very low to medium, and most studies had small sample sizes. Aripiprazole augmentation appears effective with an acceptable side effect profile, but other treatments lack strong evidence. Large-scale trials are needed for firm conclusions.
Regular practice of mindfulness meditation and loving-kindness and compassion meditation in the aging population may protect against Alzheimer's disease by strengthening attention control, emotion regulation, and prosocial capacities, which could reduce risk factors such as stress and depression while upregulating cognitive reserve. The paper presents this hypothesis and describes the ongoing Medit-Ageing study, which assesses the impact of such non-pharmacological interventions.