Alzheimer's disease (AD), the most common cause of dementia, is posing serious threat to public health and health care system in both developed and developing nations due to a rapid increase in the aging population. Identification of etiological factors for AD and active implementation of interventions targeting those modifiable factors that may prevent or postpone clinical onset of the dementing disorder will provide an opportunity to cope with this challenge. Multidisciplinary research involving epidemiology, neuropathology, and neuroimaging has provided moderately strong evidence supporting the role of vascular factors and related disorders (e.g., midlife high blood pressure and obesity, diabetes, cerebral microvascular lesions, and smoking) as risk factors and the possible role of psychosocial factors (e.g., high educational achievements, mentally-stimulating activity, social engagement, and physical exercise) as protective factors in the development and clinical manifestation of the dementia syndrome, including AD. The implementation of long-term, multidomain interventions designed for the modification of multiple vascular risk factors and the maintenance of socially-integrated lifestyles and mentally-stimulating activities is expected to postpone the clinical onset of AD and dementia, and thus, substantially reduce the burden of the disease at both the individual and societal levels.