Effects of age and APOE ϵ4 genotype on the relationship between pulse pressure and executive function in older adults...

Pulse pressure (PP) calculated as systolic minus diastolic blood pressure is a surrogate measure of arterial stiffness that may affect executive function; however, this relationship could be moderated by age and genetic risk for Alzheimer's disease (AD). We therefore examined relationships among PP, age, AD risk (i.e., APOE genotype) and executive function measured by the NIH Toolbox Cognition Battery (NIHTB-CB) in older adults.

PP was determined in 216 older adults without dementia (mean age: 77.5 ± 7.9 years, education: 16.8 ± 2.4 years, 55% women, 34.8% APOE ϵ4+) who were tested with the NIHTB-CB as part of the Advancing Reliable Measurement of Alzheimer's Disease and Cognitive Aging (ARMADA) study.

Multiple linear regression revealed PP × Age × APOE genotype interaction effects for List Sorting Working Memory (β = 0.04; p = .007) and Picture Sequence Memory (β = 0.04; p = .006); higher PP was associated with worse scores in younger APOE ϵ4+ older adults (same pattern for fluid and total cognition composite scores). Higher PP was associated with lower Picture Vocabulary scores in ApoE ϵ4+ (PP X APOE interaction: β = -0.19; p = .022). Higher PP was associated with lower Flanker Inhibitory Control scores (β = -0.13; p = .005) across all participants.

Arterial stiffness measured by PP in older adults is associated with worse performance on NIHTB-CB tests of executive function, working memory, and episodic sequence memory, particularly in younger APOE ϵ4 carriers. Arterial stiffness and AD risk may work synergistically in an age dependent manner to adversely affect cognition.