Differential Effect of APOE ϵ4 Status and Elevated Pulse Pressure on Functional Decline in Cognitively Normal Older Adults

Abstract

Background/Objective: The APOE ϵ4 allele and increased vascular risk have both been independently linked to cognitive impairment and dementia. Since few studies have characterized how these risk factors affect everyday functioning, we investigated the relationship between APOE ϵ4 genotype and elevated pulse pressure (PP) on functional change in cognitively normal participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Methods: 738 normally aging participants underwent APOE genotyping, and baseline PP was calculated from blood pressure indices. The Functional Activities Questionnaire (FAQ) was completed by participants' informant at baseline and 6, 12, 24, 36, and 48-month follow-up visits. Multiple linear regression and multilevel modeling were used to examine the effects of PP and APOE ϵ4 genotype on cross-sectional and longitudinal FAQ scores, respectively. Results: Adjusting for demographic and clinical covariates, results showed that both APOE ϵ4 status and elevated PP predicted greater functional difficulty trajectories across four years of follow-up. Interestingly, however, elevated PP was associated with greater functional decline over time in ϵ4 non-carriers versus carriers. Conclusion: Results show that, although APOE ϵ4 status is the prominent predictor of functional difficulty for ϵ4 carriers, an effect of arterial stiffening on functional difficulty was observed in non-carriers. Future studies are needed in order to clarify the etiology of the association between PP and different brain aging processes, and further explore its utility as a marker of dementia risk. The present study underscores the importance of targeting modifiable risk factors such as elevated PP to prevent or slow functional decline and pathological brain aging.