title: Pulse Pressure Is Associated With Early Brain Atrophy and Cognitive Decline: Modifying Effects of APOE-ε4.
abstract: We investigated whether midlife pulse pressure is associated with brain atrophy and cognitive decline, and whether the association was modified by apolipoprotein-E ε4 (APOE-ε4) and hypertension. Participants (549 stroke-free and dementia-free Framingham Offspring Cohort Study participants, age range=55.0 to 64.9 y) underwent baseline neuropsychological and magnetic resonance imaging (subset, n=454) evaluations with 5- to 7-year follow-up. Regression analyses investigated associations between baseline pulse pressure (systolic-diastolic pressure) and cognition, total cerebral volume and temporal horn ventricular volume (as an index of smaller hippocampal volume) at follow-up, and longitudinal change in these measures. Interactions with APOE-ε4 and hypertension were assessed. Covariates included age, sex, education, assessment interval, and interim stroke. In the total sample, baseline pulse pressure was associated with worse executive ability, lower total cerebral volume, and greater temporal horn ventricular volume 5 to 7 years later, and longitudinal decline in executive ability and increase in temporal horn ventricular volume. Among APOE-ε4 carriers only, baseline pulse pressure was associated with longitudinal decline in visuospatial organization. Findings indicate arterial stiffening, indexed by pulse pressure, may play a role in early cognitive decline and brain atrophy in mid to late life, particularly among APOE-ε4 carriers.
authors.affiliation: *Department of Psychology, University of Southern California, Los Angeles∥Veterans Affairs San Diego Healthcare System¶Department of Psychiatry, University of California, San Diego, La Jolla, CA†The Framingham Heart Study, FraminghamDepartments of ‡Biostatistics§Department of Neurology, Boston University School of Medicine, Boston, MA#Department of Psychiatry, University of Illinois at Chicago, Chicago, IL**Drexel Neuroscience Institute, College of Medicine, Drexel University, Philadelphia, PA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Nation
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Preis
authors.forename: Alexa
authors.initials: A
authors.lastname: Beiser
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Bangen
authors.forename: Lisa
authors.initials: L
authors.lastname: Delano-Wood
authors.forename: Melissa
authors.initials: M
authors.lastname: Lamar
authors.forename: David J
authors.initials: DJ
authors.lastname: Libon
authors.forename: Sudha
authors.initials: S
authors.lastname: Seshadri
authors.forename: Philip A
authors.initials: PA
authors.lastname: Wolf
authors.forename: Rhoda
authors.initials: R
authors.lastname: Au
mesh_terms: D000483:Alleles; D053327:Apolipoprotein E4 / Q000235:genetics*; D001284:Atrophy / Q000473:pathology*; D001794:Blood Pressure / Q000502:physiology*; D001921:Brain / Q000473:pathology*; D060825:Cognitive Dysfunction / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D012307:Risk Factors
chemical_list: D053327:Apolipoprotein E4