Vascular biomarkers to predict response to exercise in Alzheimer's disease: the study protocol

Danni Li, Robin Thomas, Michael Y Tsai, Ling Li, David M Vock, Susan Greimel, Fang Yu, Danni Li, Robin Thomas, Michael Y Tsai, Ling Li, David M Vock, Susan Greimel, Fang Yu

Abstract

Introduction: Exercise interventions are a promising treatment for improving cognition in persons with Alzheimer's disease. This is similar to Alzheimer's disease pharmacotherapies in which only 18-48% of treated patients demonstrate improvement in cognition. Aerobic exercise interventions positively affect brain structure and function through biologically sound pathways. However, an under-studied mechanism of aerobic exercise's effects is n-3 fatty acids in plasma. The objective of this pilot study is to inform a future large-scale study to develop n-3 fatty acids-based prediction of cognitive responses to aerobic exercise treatment in Alzheimer's disease.

Methods and analysis: This study will recruit and follow a cohort of 25 subjects enrolled in the FIT-AD Trial, an ongoing randomised controlled trial that investigates the effects of a 6-month moderate-intensity cycling intervention on cognition and hippocampal volume in older adults with mild to moderate Alzheimer's disease over a year. This study will collect blood from subjects at baseline and at 3 and 6 months to assay vascular biomarkers (ie, plasma fatty acids). Global cognition as measured by the Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog) at baseline, 3, 6, 9 and 12 months will be used as the main outcome. A multiple linear-regression model will be used with 12-month change in cognition as the outcome and baseline measure of n-3 fatty acids or changes in the ratio of n-3 to n-6 fatty-acid levels in plasma at 3 and/or 6 months, randomised treatment group, and their interaction as predictors.

Ethics and dissemination: We have obtained Institutional Review Board approval for our study. We obtain consent or assent/surrogate consent from all subjects depending on their consenting capacity assessment. Data of this study are/will be stored in the Research Electronic Data Capture (REDCap). We plan to present and publish our study findings through presentations and manuscripts.

Trial registration number: NCT01954550.

Keywords: Alzheimer’s disease; Exercise; Fatty Acids; Phospholipids; Vascular biomarkers.

Conflict of interest statement

Conflicts of Interest: None declared.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

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