Dementia: Paradigm shifting into high gear.

Redressing the rising threat of dementia demands not only an increase, but a diversification of efforts. We need new approaches, trials, and partners. We cannot afford to continue to only round up the usual suspects, β amyloid, and tau and try to stop them with a single drug "silver bullet". Dementia of late onset is not a disease, but an amalgam of interactive pathologies on the shifting background of aging, requiring multimodal targeting. Cerebrovascular diseases coexist and coact with all major neurodegenerative pathologies, increasing two-fold the likelihood that they will manifest clinically. Cerebrovascular diseases need to be controlled, to give antidegenerative drugs a chance to succeed. This calls for new types of trials and designs. Stroke doubles the chances of developing dementia and decreases in stroke incidence correlate with decreases in dementia. Ninety percent of strokes are potentially preventable and so are a proportion of dementias. The stroke and dementia communities need to partner and complement the search for silver bullets with the golden opportunity of doing something now.