We have proposed that there are two distinct sets of risk factors for Alzheimer’s disease (AD), those for the pathology of the disease and those for its clinical expression. Although Alzheimer pathology is necessary for the diagnosis, it likely is not sufficient. Autopsy studies have shown that approximately a third of individuals meeting strict criteria for neuropathological AD remain nondemented at the time of their death. Furthermore, people with similar severities of Alzheimer pathology have a very wide distribution of cognitive presentations before death, ranging from intact cognitive function to severe dementia.