The concept of reserve applies to many human physiologic systems (e.g., pulmonary, renal, hepatic, cardiac [14–20]). These functional systems are highly redundant and considerable tissue destruction must take place before systems are compromised and signs of disease become evident. Although the nervous system is more complex, it has long been recognized that some type of reserve can protect the nervous system from expressing pathology or injury as functional impairment. For example, a number of studies in the early 1990s found that education and occupation were associated with a reduction in AD risk [21,22], and investigators concluded that these lifestyle factors might alter brain reserve. Data on the relation of head circumference to AD provided further support for the reserve concept [23,24]. Finally, neuroimaging studies provided evidence of neurobiologic correlates of reserve [25–28].
