Structural variants (SVs) represent a significant source of genetic variation that might provide novel insights into the genetic architecture of Alzheimer disease (AD) beyond what has been captured by single nucleotide polymorphisms (SNPs). We characterized SVs from whole-genome sequences (WGS) from the Midwestern U.S. Amish, a genetically homogenous population, to identify SVs associated with a cognitive preservation phenotype observed in older Amish individuals who remain cognitively intact despite presumed elevated genetic risk.