Alzheimer disease (AD) is a dementing, neurodegenerative disorder that affects approximately 500,000 Canadians and its prevalence is expected to double over the next 30 years. Although several medications may temporarily augment cognitive abilities in AD, there presently exists no proven method to avoid the inevitable clinical deterioration in this devastating condition. The delineation of risk factors for the development of AD offers hope for the advent of effective prevention or interventions that might retard the onset of symptoms. In this article, we provide a comprehensive review of midlife risk factors implicated in the etiopathogenesis of sporadic AD. Although some risk factors are heritable and largely beyond our control, others are determined by lifestyle or environment and are potentially modifiable. In a companion paper, we introduce the concept of an Alzheimer Risk Assessment Clinic for ascertainment and mitigation of these and other putative dementia risk factors in middle-aged adults.