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Pulse Pressure Is Associated With Early Brain Atrophy and Cognitive Decline: Modifying Effects of APOE-ε4

Nation, Daniel A. PhD; Preis, Sarah R. PhD; Beiser, Alexa PhD; Bangen, Katherine J. PhD; Delano-Wood, Lisa PhD; Lamar, Melissa PhD; Libon, David J. PhD; Seshadri, Sudha MD; Wolf, Philip A. MD; Au, Rhoda PhD

Alzheimer Disease & Associated Disorders: July-September 2016 - Volume 30 - Issue 3 - p 210–215
doi: 10.1097/WAD.0000000000000127
Original Articles

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.

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*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, Framingham

Departments 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

Supported by the Framingham Heart Study’s National Heart, Lung, and Blood Institute contract (N01-HC-25195), by Grants (R01-AG16495, R01-AG08122) from the National Institute on Aging, and by Grant (R01-NS17950) from the National Institute of Neurological Disorders and Stroke.

The authors declare no conflicts of interest.

Reprints: Daniel A. Nation, PhD, Department of Psychology, University of Southern California, Building/room: SGM 1016, 3620 South McClintock Ave., Los Angeles, CA 90089-1061 (e-mail:

Received June 23, 2014

Accepted October 21, 2015

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