Aging is associated with a gradual decline in cognitive function, and more dramatic cognitive impairments occur in patients affected by Alzheimer’s disease (AD). Studies performed in the last two decades in aged animals and in animal models of AD have revealed that deterioration of cognitive performances is associated with significant changes in synaptic plasticity. In particular, electrophysiological studies have well documented that alterations in long-term declarative memory, extremely vulnerable to age and neurodegenerative diseases, are linked with deficits in induction and maintenance of long-term potentiation of synaptic transmission (LTP) in the hippocampus and in other temporal lobe regions involved in this form of memory. Interestingly, we have found that long-term depression of synaptic transmission (LTD) in the perirhinal cortex, a cellular correlate of visual recognition memory formation, is impaired very early (at three months of age) in a mouse transgenic model of AD. Moreover, recent morphological studies performed in aged animals have revealed a clear-cut correlation between the quality of memory performance and the extent of morphologic changes (remodeling) in synaptic contacts occurring during memory consolidation. Nutritional studies performed in aged animals have documented the effect of different diets on synaptic plasticity or morphology; interestingly, some diet supplements were found to reverse age-induced deficits in LTP or alterations in synaptic morphology.