Vascular and neurodegenerative disease commonly cooccur in older persons. We review findings from the Rush Religious Orders Study and Memory and Aging Project. Both studies enroll subjects without diagnosed dementia, perform annual evaluations, and obtain autopsies proximate to death. We found that macroscopic infarcts are common, lower the threshold for cognitive impairment, and often coexist with Alzheimer's disease pathology. We also found that vascular pathology may be associated with memory impairment and may be difficult to distinguish from clinical Alzheimer's disease. Finally, because dementia in older persons often results from mixed pathology and the clinical phenotypes overlap, some risk factors may increase risk for clinical Alzheimer's disease through an increase in vascular pathology.