Mortality in amnestic mild cognitive impairment: A prospective community study

OBJECTIVE: To assess the hazard of death in persons with and without amnestic mild cognitive impairment (aMCI). METHODS: From 1987 through 2003, persons with aMCI (n = 243) and an age- and gender-matched reference group of cognitively normal persons in Olmsted County, MN, were recruited through the Mayo Clinic Alzheimer's Disease Patient Registry and followed prospectively through 2004. Survival was estimated using Kaplan-Meier survival curves, and the hazard of death for the aMCI cohort vs the reference cohort was estimated using Cox proportional hazards models. RESULTS: Over a median follow-up of 5.7 years, persons with aMCI had increased mortality (hazard ratio [HR] = 1.7; 95% CI: 1.3 to 2.3) vs reference subjects. The hazard of death by aMCI subtype was 1.5 in persons with single-domain aMCI (95% CI: 1.1 to 2.1) and 2.9 in persons with multiple-domain aMCI (95% CI: 1.9 to 4.6) vs reference subjects. Analyses restricted to aMCI cases showed an interaction between aMCI subtype and APOE-ϵ4 allele status (p = 0.003). Among aMCI cases with an APOE-ϵ4 allele, there was no difference in mortality between single- and multiple-domain aMCI (HR = 1.2; 95% CI: 0.6 to 2.3). However, among aMCI cases with no APOE-ϵ4 allele, the hazard of death in multiple-domain aMCI was 4.6 (95% CI: 2.3 to 9.1) vs single-domain aMCI. CONCLUSIONS: Amnestic mild cognitive impairment is associated with increased mortality, which is greater in multiple-domain aMCI than in single-domain aMCI. Mortality in aMCI subtypes may vary by APOE-ϵ4 allele status.