Dose-Response of Aerobic Exercise on Cognition: A Community-Based, Pilot Randomized Controlled Trial

Abstract

Epidemiological studies suggest a dose-response relationship exists between physical activity and cognitive outcomes. However, no direct data from randomized trials exists to support these indirect observations. The purpose of this study was to explore the possible relationship of aerobic exercise dose on cognition. Underactive or sedentary participants without cognitive impairment were randomized to one of four groups: no-change control, 75, 150, and 225 minutes per week of moderate-intensity semi-supervised aerobic exercise for 26-weeks in a community setting. Cognitive outcomes were latent residual scores derived from a battery of 16 cognitive tests: Verbal Memory, Visuospatial Processing, Simple Attention, Set Maintenance and Shifting, and Reasoning. Other outcome measures were cardiorespiratory fitness (peak oxygen consumption) and measures of function functional health. In intent-to-treat (ITT) analyses (n = 101), cardiorespiratory fitness increased and perceived disability decreased in a dose-dependent manner across the 4 groups. No other exercise-related effects were observed in ITT analyses. Analyses restricted to individuals who exercised per-protocol (n = 77) demonstrated that Simple Attention improved equivalently across all exercise groups compared to controls and a dose-response relationship was present for Visuospatial Processing. A clear dose-response relationship exists between exercise and cardiorespiratory fitness. Cognitive benefits were apparent at low doses with possible increased benefits in visuospatial function at higher doses but only in those who adhered to the exercise protocol. An individual’s cardiorespiratory fitness response was a better predictor of cognitive gains than exercise dose (i.e., duration) and thus maximizing an individual’s cardiorespiratory fitness may be an important therapeutic target for achieving cognitive benefits.

Trial registration: ClinicalTrials.gov NCT01129115.

Fig 1. Study enrollment flow.

Baseline measures of enrolled participants are provided in Table 1. Of the intent-to-treat (ITT) cohort (n = 101), 8 individuals withdrew due to time or travel concerns, 8 withdrew due to medical issues, 1 was dissatisfied with his group allocation, and 1 was lost to follow-up. Another 6 individuals were non-adherent to the exercise prescription. Those who did not adhere had slightly more education (17.8yrs [3.2] vs 16.1yrs [2.4]) otherwise there were no significant differences. The remaining 77 individuals were included in per-protocol (PP) analyses: control (n = 23), 75min/wk (n = 18), 150min/wk (n = 21), and 225min/wk (n = 15).

Fig 2. Visuospatial processing but not attention increases with increasing aerobic exercise dose.

Percent change in VO₂ peak (blue bars) increases in a dose-response fashion across the PP exercise groups. The best fitting model of Visuospatial Processing (red bars) follows a similar dose-response pattern. The best fitting model of Simple Attention (green bars) shows that any exercise results in improvement.

Fig 3. Cardiorespiratory fitness change mediates exercise duration effects on visuospatial performance.

In the basic model without cardiorespiratory fitness change (%change in VO2 peak over 26 weeks) as a mediator, total number of minutes exercised (Exercise Duration) was associated with change in Visuospatial Processing. When change in cardiorespiratory fitness was added to the model as a potential mediator, it fully mediated the relationship of Exercise Duration and Visuospatial Processing improvement. Betas (Standard Error) are reported as the product of simultaneous regression with bootstrap replacement.