Asymptomatic Alzheimer's disease: a prodrome or a state of resilience?

Neuritic plaques and neurofibrillary tangles, the neuropathological hallmarks of AD, are not limited to individuals with dementia. These pathologic changes can also be present in the brains of cognitively normal older adults - a condition we defined as Asymptomatic AD (ASYMAD). Although it remains unclear whether these individuals would remain clinically normal with longer survival, they seem to be able to compensate for or delay the appearance of dementia symptoms. Here, we provide a historical background and highlight the combined clinical, pathologic and morphometric evidence related to ASYMAD. Understanding the nature of changes during this apparently asymptomatic state may shed light on the mechanisms that forestall the progression of the disease and allow for maintenance of cognitive health, an important area of research that has been understudied relative to the identification of risks and pathways to negative health outcomes.