Brain MRI will be used to test the hypotheses that 6 months of aerobic training, but not stretching-toning training, is associated with the following: (1) increases in brain volume, specifically cortical grey and white matter volume, including the frontal lobes and cortical areas implicated in attention control and memory processes [27] and hippocampal volume [78]; (2) increases in MRI measured resting CBF [79]; (3) reduced progression of white matter hyperintensities of presumed vascular origin; and (4) increases in functional connectivity of the default mode network [80].

Neuroimaging data will be collected on the 3-T scanner (General Electric Discovery 750, GE Healthcare, USA). Our 37-min MRI protocol is built on the multi-site Alzheimer Disease Neuroimaging Initiative protocol [81]. Our protocol (see Table Table5)5) includes a high-resolution whole-brain 3D T1-weighted structural image, a T2-weighted fluid-attenuated inversion recovery (FLAIR) image to evaluate white matter hyperintensities, resting perfusion measured with arterial spin labelling (ASL), high angular resolution diffusion imaging to calculate mean diffusivity and fractional anisotropy and for tractography analysis, and resting-state blood oxygen level-dependent (BOLD) functional MRI for functional connectivity analyses. Further, we will generate cerebrovascular reactivity maps from BOLD and ASL time series acquired during hypercapnia [8287]. It is expected that 60–70% of participants will consent to the MRI component of the study; however, participants with contraindication for an MRI exam will not be included in this part of the study. Therefore, an additional 10–20% non-completion rate is expected for participants who do consent to an MRI.

MRI acquisition parameters

Abbreviations: FLAIR, weighted fluid attenuated inversion recovery; BOLD, resting-state blood oxygen level dependent; CVR, cerebrovascular reactivity; pCASL, pseudo-continuous arterial spin labelling

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