Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Jan 6;21(1):19.
doi: 10.1186/s13063-019-3798-1.

Blood biomarkers as surrogate endpoints of treatment responses to aerobic exercise and cognitive training (ACT) in amnestic mild cognitive impairment: the blood biomarkers study protocol of a randomized controlled trial (the ACT Trial)

Danni Li  1 , Michelle M Mielke  2 , W Robert Bell  3 , Cavan Reilly  4 , Lin Zhang  4 , Feng Vankee Lin  5 , Fang Yu  6
Affiliations

Blood biomarkers as surrogate endpoints of treatment responses to aerobic exercise and cognitive training (ACT) in amnestic mild cognitive impairment: the blood biomarkers study protocol of a randomized controlled trial (the ACT Trial)

Danni Li et al. Trials. .

Abstract

Background: Alzheimer's disease (AD) is an epidemic with tremendous public health impacts because there are currently no disease-modifying therapeutics. Randomized controlled trials (RCTs) for prevention of AD dementia often use clinical endpoints that take years to manifest (e.g., cognition) or surrogate endpoints that are costly or invasive (e.g., magnetic resonance imaging [MRI]). Blood biomarkers represent a clinically applicable alternative surrogate endpoint for RCTs that would be both cost-effective and minimally invasive, but little is known about their value as surrogate endpoints for treatment responses in the prevention of AD dementia.

Methods: The objective of this study is to investigate blood neuropathological, neurodegenerative, and neurotrophic biomarkers as surrogate endpoints for treatment responses to three interventions in older adults with amnestic mild cognitive impairment (aMCI, a prodromal stage of AD): aerobic exercise, cognitive training, and combined aerobic exercise and cognitive training (ACT). We chose these three sets of biomarkers for their unique mechanistic associations with AD pathology, neurodegeneration and neurogenesis. This study is built on the ACT Trial (1R01AG055469), a single-blinded, multi-site, 2 × 2 factorial phase II RCT that examines the synergistic effects of a 6-month ACT intervention on cognition and MRI biomarkers (AD-signature cortical thickness and hippocampal volume) (n = 128). In this ACT Trial blood biomarkers study, we will enroll 120 ACT Trial participants with aMCI and measure blood biomarkers at baseline and at 3, 6, 12, and 18 months. The goals are to (1) determine the effect of interventions on blood biomarkers over 6 months, (2) evaluate blood biomarkers as surrogate endpoints for predicting cognitive responses to interventions over 18 months, and (3, exploratory) examine blood biomarkers as surrogate endpoints for predicting brain MRI biomarker responses to interventions over 18 months.

Discussion: This study aims to identify new blood biomarkers that can track cognitive decline or AD-related brain atrophy among patients with aMCI subjected to a regimen of aerobic exercise and cognitive training. Findings from this study will drive the further use of blood biomarkers in developing effective prevention and treatment strategies for AD dementia.

Trial registration: ClinicalTrials.gov, NCT03313895. Registered on 18 October 2017.

Keywords: Aerobic exercise; Alzheimer’s disease; Blood biomarkers; Cognitive training; Neurodegenerative biomarkers; Neuropathological biomarkers; Neurotrophic biomarkers; Surrogate endpoints; Treatment responses and amnestic mild cognitive impairment.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Schedule of enrollment, interventions, and blood collections
Fig. 2
Fig. 2
Schedule of enrollment, interventions, and blood collections
See this image and copyright information in PMC

References

    1. Alzheimer’s Association 2018 Alzheimer’s disease facts and figures. Alzheimers Dement. 2018;14(3):367–429.
    1. Hebert LE, Weuve J, Scherr PA, Evans DA. Alzheimer disease in the United States (2010-2050) estimated using the 2010 census. Neurology. 2013;80(19):1778–1783. - PMC - PubMed
    1. Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, Braun LT, de Ferranti S, Faiella-Tommasino J, Forman DE, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the management of blood cholesterol: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019;73(24):3168–3209. - PubMed
    1. Ovod V, Ramsey KN, Mawuenyega KG, Bollinger JG, Hicks T, Schneider T, Sullivan M, Paumier K, Holtzman DM, Morris JC, et al. Amyloid beta concentrations and stable isotope labeling kinetics of human plasma specific to central nervous system amyloidosis. Alzheimers Dement. 2017;13(8):841–849. - PMC - PubMed
    1. Nakamura A, Kaneko N, Villemagne VL, Kato T, Doecke J, Dore V, Fowler C, Li QX, Martins R, Rowe C, et al. High performance plasma amyloid-beta biomarkers for Alzheimer’s disease. Nature. 2018;554(7691):249–254. - PubMed

Publication types

MeSH terms

Associated data