Performance on individual Mini-Mental State Examination (MMSE) items can predict incident Alzheimer's disease (AD). The purpose of the current study is to determine whether, in nondemented persons with and without the apolipoprotein E-4 (APOE-4) genetic risk for AD, a subset of MMSE items predict cognitive decline. Fifty-four nondemented subjects, 23 with at least one copy of the APOE-4 allele and 31 without APOE-4, were given the MMSE and cognitive tests at baseline and 2-year follow-up. MMSE total score and a subset of MMSE items including delayed recall, serial 7s, pentagon, and orientation to time and place were used to predict change on cognitive tests. The subset of MMSE items significantly predicted decline in visuo-spatial construction and naming in APOE-4 carriers but not in noncarriers. Performance on a subset of MMSE items, combined with APOE-4 genotype, may aid in identifying high-risk persons for research or follow-up.