Long-term dietary interventions fail to mitigate functional connectivity loss and cognitive decline in the TgF344-AD rat model of Alzheimer's disease

Short-term caloric restriction (CR) and resveratrol (Rsv) supplementation have shown potential in preserving brain function in aging and neurodegenerative diseases such as AD. However, there is a lack of knowledge regarding the potential benefits of long-term CR or Rsv on brain health in context of AD. Therefore, we aimed to assess the effects of short-term (1 month) CR and Rsv administration on resting-state functional connectivity (rs-FC), as well as the effect of long-term (8 months) CR or Rsv supplementation on rs-FC, spatial memory, amyloid burden, and neuroinflammation in male and female TgF344-AD (Tg) and wild-type (WT) rats. In Tg rats, short-term CR decreased rs-FC in female rats, while long-term CR decreased rs-FC and modestly improved spatial memory in male rats. Long-term CR and Rsv altered regional amyloid burden, and CR decreased IBA-1 in males without affecting GFAP. Overall, long-term CR and Rsv failed to mitigate FC loss and cognition, underscoring the potentially limited impact of these dietary interventions in AD.