Patients with comparable degree of neuropathology could show different cognitive impairments. This could be explained with the concept of cognitive reserve (CR), which includes a passive and an active component. In particular, CR is used to explain the gap between tissue damage and clinical symptoms that has been observed in dementia and, in particular, in patients affected by Alzheimer disease (AD). Different studies confirm brain neuroplasticity. Our preliminary study demonstrated that AD patients with high education showed a CR inversely associated with glucose uptake measured in fluorodeoxyglucose positron emission tomography (FDG-PET), whereas the inverse correlation was observed in AD patients with low education. In other words, our findings suggest that CR compensates the neurodegeneration and allows the maintenance of patients’ cognitive performance. Best understanding of the concept of CR could lead to interventions to slow cognitive aging or reduce the risk of dementia.