Feasibility and preliminary effects of exercise interventions on plasma biomarkers of Alzheimer's disease in the FIT-AD trial: a randomized pilot study in older adults with Alzheimer's dementia

Fang Yu, Seung Yong Han, Dereck Salisbury, Jeremy J Pruzin, Yonas Geda, Richard J Caselli, Danni Li, Fang Yu, Seung Yong Han, Dereck Salisbury, Jeremy J Pruzin, Yonas Geda, Richard J Caselli, Danni Li

Abstract

Background: Alzheimer's disease (AD) biomarkers have provided a unique opportunity to understand AD pathogenesis and monitor treatment responses. However, exercise trials show mixed effects on imagining and cerebrospinal fluid biomarkers of AD. The feasibility and effects of exercise on plasma biomarkers remain unknown. The primary objective of this study was to examine the feasibility of recruitment, retention, and blood sample collection in community-dwelling older adults with mild-to-moderate AD dementia. Secondarily, it estimated the preliminary effects of 6-month aerobic and stretching exercise on plasma amyloid-β42 and Aβ40 (Aβ42/40) ratio, phosphorylated tau (p-tau) 181, and total tau (t-tau).

Methods: This pilot study was implemented in year 2 of the 2-parallel group FIT-AD trial that randomized 96 participants on a 2:1 allocation ratio to moderate-intensity cycling or low-intensity stretching for 20-50 min, 3 times/week for 6 months with 6-month follow-up. Investigators (except for the statistician) and data collectors were blinded to group assignment. Fasting blood samples were collected from 26 participants at baseline and 3 and 6 months. Plasma Aβ42, Aβ40, p-tau181, and t-tau were measured using Simoa™ assays. Data were analyzed using intention-to-treat, Cohen's d, and linear mixed models.

Resultss: The sample averaged 77.6±6.99 years old and 15.4±3.00 years of education with 65% being male and 96.2% being apolipoprotein epsilon 4 gene carriers. The recruitment rate was 76.5%. The retention rate was 100% at 3 months and 96.2% at 6 months. The rate of blood collection was 88.5% at 3 months and 96.2% at 6 months. Means (standard deviation) of within-group 6-month difference in the stretching and cycling group were 0.001 (0.012) and -0.001 (0.010) for Aβ42/40 ratio, 0.609 (1.417) pg/mL and 0.101(1.579) pg/mL for p-tau181, and -0.020 (0.279) pg/mL and -0.075 (0.215) pg/mL for t-tau. Effect sizes for within-group 6-month difference were observed for p-tau181 in stretching (d=0.43 [-0.33, 1.19]) and t-tau in cycling (-0.35 [-0.87, 0.17]).

Conclusions: Blood collections with fasting were well received by participants and feasible with high recruitment and retention rates. Plasma biomarkers of AD may be modifiable by exercise intervention. Important design considerations are provided for future Phase III trials.

Trials registration: ClinicalTrials.gov Identifier: NCT01954550 and posted on October 1, 2013.

Keywords: Alzheimer’s disease; Biomarkers; Exercise; Feasibility; Pilot.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
CONSORT diagram for blood collections
Fig. 2
Fig. 2
Observed levels of plasma ratio at baseline, 3 months, and 6 months by groups. Note: The sample sizes for the stretching and the cycling groups are 8 and 18, 8 and 15, and 8 and 17 at baseline, 3 months, and 6 months, respectively
Fig. 3
Fig. 3
Observed levels of p-tau181 at baseline, 3 months, and 6 months by groups. Note: The sample sizes for the stretching and the cycling groups are 7 and 15, 8 and 15, and 8 and 16 at baseline, 3 months, and 6 months, respectively
Fig. 4
Fig. 4
Observed levels of t-tau at baseline, 3 months, and 6 months by groups

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