The impact of exercise on blood-based biomarkers of Alzheimer's disease in cognitively unimpaired older adults

Abstract

Physical activity is a promising preventative strategy for Alzheimer's disease: it is associated with lower dementia risk, better cognition, greater brain volume and lower brain beta-amyloid. Blood-based biomarkers have emerged as a low-cost, non-invasive strategy for detecting preclinical Alzheimer's disease, however, there is limited literature examining the effect of exercise (a structured form of physical activity) on blood-based biomarkers. The current study investigated the influence of a 6-month exercise intervention on levels of plasma beta-amyloid (Aβ42_, Aβ40, Aβ42/40), phosphorylated tau (p-tau181), glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) chain in cognitively unimpaired older adults, and as a secondary aim, whether blood-based biomarkers related to cognition. Ninety-nine community-dwelling older adults (69.1 ± 5.2) were allocated to an inactive control, or to moderate or high intensity exercise groups where they cycled twice weekly for six months. At baseline and six months (post-intervention), fasted blood was collected and analysed using single molecule array (SIMOA) assays, and cognition was assessed. Results demonstrated no change in levels of any plasma biomarker from pre- to post-intervention. At baseline, higher NfL was associated with poorer cognition (β = -0.33, SE = 0.13, adjusted p = .042). Exploratory analyses indicated higher cardiorespiratory fitness was associated with higher NfL and GFAP levels in apolipoprotein E (APOE) ε4 non-carriers compared to ε4 carriers (NfL, β = -0.43, SE = 0.19, p = .029; GFAP, β = -0.41, SE = 0.20, p = .044), though this association was mediated by body mass index (BMI). These results highlight the importance of considering BMI in analysis of blood-based biomarkers, especially when investigating differences between APOE ε4 carriers and non-carriers. Our results also indicate that longer follow-up periods may be required to observe exercise-induced change in blood-based biomarkers.

Keywords: Alzheimer’s disease; Blood biomarkers; Cognition; Exercise.

Fig. 1

Flow diagram indicating number of participants with data available for inclusion for each analysis. The complete Consolidated Standards Of Reporting Trials diagram is detailed in Brown et al. [26]. Abbreviations: IPAC, Intense Physical Activity and Cognition study; BMI, body mass index; ITT, intention-to-treat

Fig. 2

Interaction between cardiorespiratory fitness (measured by VO_2peak mL/kg/min) and APOE ε4 carrier status on plasma NfL levels at baseline, adjusted for age and sex (β = -0.43, SE = 0.19, p = .029). The slope of fitness on NfL is significant within APOE ε4 non-carriers (p = .02), but not carriers (p = .53). Abbreviations: APOE, apolipoprotein E gene; NfL, Neurofilament Light chain; VO_2peak, volume of oxygen uptake during peak exercise

Fig. 3

Interaction between cardiorespiratory fitness (measured by VO_2peak mL/kg/min) and APOE ε4 carrier status on plasma GFAP levels at baseline, adjusted for age and sex (β = -0.41, SE = 0.20, p = .044). The slope of fitness on GFAP is non-significant within APOE ε4 carriers (p = .15) and non-carriers (p = .36). Abbreviations: APOE, apolipoprotein E gene; GFAP, Glial Fibrillary Acidic Protein; VO_2peak, volume of oxygen uptake during peak exercise