Eight months of caloric restriction and resveratrol supplementation failed to prevent functional brain connectivity loss or cognitive decline in TgF344-AD rats, a well-established Alzheimer's disease model. While long-term caloric restriction modestly improved spatial memory in male rats and reduced certain inflammatory markers (IBA-1), it paradoxically decreased resting-state functional connectivity. Resveratrol showed even more limited benefits despite altering regional amyloid burden patterns. This finding challenges the growing enthusiasm for dietary interventions as Alzheimer's prevention strategies. The negative results are particularly significant given caloric restriction's robust protective effects in normal aging and other neurodegenerative contexts. The study's eight-month duration represents genuine long-term intervention in rodent models, making these results more clinically relevant than typical short-term studies. However, the exclusive use of male and female rats limits translational potential, and the TgF344-AD model may not fully capture human Alzheimer's complexity. These results suggest that popular dietary interventions like intermittent fasting or resveratrol supplementation may have more limited therapeutic windows in established neurodegeneration than previously hoped, warranting more realistic expectations for dietary approaches in Alzheimer's prevention.