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

Abstract

IntroductionExercise 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 analysisThis 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 disseminationWe 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 numberNCT01954550.

Effects of physical activities on dementia‐related biomarkers: A systematic review of randomized controlled trials

“…Several RCT protocols were published recently aiming to investigate the PA effects on cognition and incorporating different dementia‐related biomarkers of participants with MCI, AD, or dementia 66–71 . Completion of these studies should significantly expand the knowledge base about PA and biomarkers.…”

An integrative review of exercise interventions among community‐dwelling adults with Alzheimer's disease

“…Hence, objective measurements (e.g. MRI, vascular biomarkers) should be added to assess cognitive function in intervention studies, which could avoid the interference (Li et al, ; Yu et al, ). However, only van der Kleij et al () used brain MRI in the involved studies, and the results showed that moderate‐to‐high intensity exercise was not sufficient to produce a consistent increase in whole or regional cerebral blood flow in patients with AD, especially when the intervention did not last enough time.…”

Plasma Neurofilament Light and Future Declines in Cognition and Function in Alzheimer’s Disease in the FIT-AD Trial

“…After collections, blood specimens were stored immediately on wet ice. A laboratory technician processed and aliquoted these specimens according to an established protocol [ 18 ]. Briefly, plasma EDTA tubes were mixed and centrifuged in 4°C using a temperature-controlled centrifuge with a Swing out Rotor at 1,439 g for 15 min.…”

“…The tubes were removed from the centrifuge immediately after completion. Plasma samples were aliquoted and stored in a –80°C freezer [ 18 ]. Plasma NfL was measured using the Simoa ® NF-light Advantage kit on a HD-1 analyzer (Quanterix, Billerica, MA).…”