Dementia risk is complex: aging plus genetic, environmental, and cardiovascular factors are involved. Multiple pathologic proteins with or without cerebral small vessel disease contribute to dementia presentation. No potential disease-modifying drugs have passed the rigor of clinical trials. One likely reason for their failure is that in symptomatic dementia, the proteinopathy has taken hold, so it is too late for a drug to work. Thus, the development of novel methods to identify individuals at risk for dementia using neuroimaging biomarkers is a critical line of investigation.