Effect of Ibuprofen on BrainAGE: A Randomized, Placebo-Controlled, Dose-Response Exploratory Study

Abstract

Background: The age of a person's brain can be estimated from structural brain images using an aggregate measure of variation in morphology across the whole brain. The brain age gap estimation (BrainAGE) score is computed as the difference between kernel-estimated brain age and chronological age. In this exploratory study, we investigated the application of the BrainAGE measure to identify potential novel effects of pharmacological agents on brain morphology.

Methods: Twenty healthy participants (23-47 years of age) completed three structural magnetic resonance imaging scans 45 minutes after administration of placebo or 200 or 600 mg of ibuprofen in a double-blind, crossover study. An externally derived BrainAGE model from a sample of 480 healthy participants was used to examine the acute effect of ibuprofen on temporary neuroanatomical changes in healthy individuals.

Results: The BrainAGE model produced age prediction for each participant with a mean absolute error of 6.7 years between the estimated and chronological age. The intraclass correlation coefficient for BrainAGE was 0.96. Relative to placebo, 200 and 600 mg of ibuprofen significantly decreased BrainAGE by 1.18 and 1.15 years, respectively (p < .05). The trained BrainAGE model identified the medial prefrontal cortex to be the strongest age predictor.

Conclusions: BrainAGE is a potentially useful construct to examine neurological effects of therapeutic drugs. Ibuprofen temporarily reduces BrainAGE by approximately 1 year, which is likely due to its acute anti-inflammatory effects.

Trial registration: ClinicalTrials.gov NCT02507219.

Keywords: BrainAGE; Ibuprofen; Pharmacological manipulation; Prefrontal cortex; Structural imaging; Support vector.

Conflict of interest statement

The authors report no biomedical financial interests or potential conflicts of interest.

Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1.

Plot of the 510 most important attributes (support vector regression importance score >0.1) in the derived brain age gap estimation model: (A) axial view, (B) sagittal view, (C) coronal view. Red and blue indicate the most and least important voxels, respectively.

Figure 2.

Brain-predicted age vs. chronological age of participants in the ibuprofen study. The dots are connected if they belong to the same participant. Participants tended to have older brain-predicted age when given placebo (circles).

Figure 3.

Effect of ibuprofen dosage on brain age gap estimation (BrainAGE). Participants who were given 200 or 600 mg of ibuprofen show a 1.1-year-younger BrainAGE.