Differential Effect of APOE ɛ4 Status and Elevated Pulse Pressure on Functional Decline in Cognitively Normal Older Adults

Article type: Research Article

Authors: Werhane, Madeleine L.^{a; b; c} | Thomas, Kelsey R.^{a; c} | Edmonds, Emily C.^{a; c} | Bangen, Katherine J.^{a; c} | Tran, My^d | Clark, Alexandra L.^{a; b; c} | Nation, Daniel A.^e | Gilbert, Paul E.^b | Bondi, Mark W.^{a; c} | Delano-Wood, Lisa^{a; c; *} | and for the Alzheimer’s Disease Neuroimaging Initiative¹

Affiliations: [a] Veterans Affairs San Diego Healthcare System, San Diego, CA, USA | [b] San Diego State University/University of California, San Diego (SDSU/UCSD) Joint Doctoral Program in Clinical Psychology, San Diego, CA, USA | [c] Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA | [d] Department of Psychology, San Diego State University, San Diego, CA, USA | [e] Department of Psychology, University of Southern California, Los Angeles, CA, USA

Correspondence: [*] Correspondence to: Lisa Delano-Wood, PhD, 3350 La Jolla Village Drive, San Diego, CA 92161 USA. Tel.: +1 858 552 8585/Ext.2667; ldelano@ucsd.edu.

Note: [1] Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of the ADNI and/or provided data but did not participate in analysis or writing of this article. A complete listing of ADNI investigators can be found at http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.

Abstract: Background/Objective:The APOE ɛ4 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 ɛ4 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 ɛ4 genotype on cross-sectional and longitudinal FAQ scores, respectively. Results:Adjusting for demographic and clinical covariates, results showed that both APOE ɛ4 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 ɛ4 non-carriers versus carriers. Conclusion:Results show that, although APOE ɛ4 status is the prominent predictor of functional difficulty for ɛ4 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.

Keywords: Activities of daily living, aging, apolipoprotein E4, arterial stiffness, genetic susceptibility

DOI: 10.3233/JAD-170918

Journal: Journal of Alzheimer's Disease, vol. 62, no. 4, pp. 1567-1578, 2018