Role of APOE Genotype in Gait Decline and Disability in Aging

Objectives. Although apolipoprotein E (APOE) genetic variation may influence risk of gait decline and disability in aging through multiple mechanisms, a systematic examination of this relationship has been lacking. Our objective was to quantify the risk of gait decline and disability associated with the APOE epsilon 4 allele in aging. Methods. We evaluated 627 community-dwelling adults aged 70 and older (white 67.8%) with APOE genotype and quantitative gait measurements participating in the Einstein Aging Study over a median follow-up of 3.0 years. Main outcomes were gait speed decline (cm/s/year) and incident disability. Results. APOE epsilon 4 allele frequency was 24.1%. Presence of APOE epsilon 4 was not significantly associated with gait speed decline overall (p = .37) but was associated with faster gait speed decline in older men (estimate: -1.16, 95% CI: -2.31 to -0.01, p = .04). The interaction between the epsilon 4 allele and male sex predicted gait speed decline (estimate: -1.70, 95% CI: -3.33 to -0.07, p = .04). Presence of the APOE epsilon 4 allele was associated with increased risk of disability in older men (HR 3.72, 95% CI: 1.44-9.59, p = .007). Associations of the epsilon 4 allele with study outcomes remained significant even after accounting for several potential confounders including vascular and cognitive status. The strength of the associations was stronger in the white subgroup. Conclusion. This preliminary report suggests that the APOE epsilon 4 allele is associated with increased risk of gait speed decline and disability in older men.