Madeleine L Werhane1,2,3, Kelsey R Thomas1,3, Emily C Edmonds1,3, Katherine J Bangen1,3, My Tran4, Alexandra L Clark1,2,3, Daniel A Nation5, Paul E Gilbert2, Mark W Bondi1,3, Lisa Delano-Wood1,3. 1. Veterans Affairs San Diego Healthcare System, San Diego, CA, USA. 2. San Diego State University/University of California, San Diego (SDSU/UCSD) Joint Doctoral Program in Clinical Psychology, San Diego, CA, USA. 3. Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA. 4. Department of Psychology, San Diego State University, San Diego, CA, USA. 5. Department of Psychology, University of Southern California, Los Angeles, CA, USA.
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.
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.
Authors: Madeleine L Werhane; Kelsey R Thomas; Katherine J Bangen; Alexandra J Weigand; Emily C Edmonds; Daniel A Nation; Erin E Sundermann; Mark W Bondi; Lisa Delano-Wood Journal: Front Aging Neurosci Date: 2021-10-25 Impact factor: 5.702
Authors: Katherine J Bangen; Madeleine L Werhane; Alexandra J Weigand; Emily C Edmonds; Lisa Delano-Wood; Kelsey R Thomas; Daniel A Nation; Nicole D Evangelista; Alexandra L Clark; Thomas T Liu; Mark W Bondi Journal: Front Aging Neurosci Date: 2018-09-10 Impact factor: 5.750
Authors: Juliet Fockler; Winnie Kwang; Miriam T Ashford; Derek Flenniken; Joshua Hwang; Diana Truran; R Scott Mackin; Chengshi Jin; Ruth O'Hara; Joachim F Hallmayer; Jerome A Yesavage; Michael W Weiner; Rachel L Nosheny Journal: Alzheimers Dement (N Y) Date: 2021-02-14