The purpose of this article is to examine how psychosocial distress and HSV-1 might interact to foster early cognitive vulnerability in otherwise healthy middle-aged adults. Several environmental risk factors, including mental stress and chronic viral infections, can increase cognitive vulnerability and lead to cognitive decline. Considering the anticipated dramatic increase in the number of older adults with dementia in the next 40 years and the current lack of dementia cures, it is imperative that we explore any modifiable risk factors for brain vulnerability that may facilitate the development of interventions to prevent or delay the onset of severe cognitive impairment.