The effect of aerobic exercise on cerebral perfusion in patients with vascular cognitive impairment, the Excersion-VCI randomised controlled clinical trial

Liz R van Hout; Justine Moonen; Annebet E Leeuwis; Juliette van Alphen; Mathijs Dijsselhof; Raquel P Amier; Frederik Barkhof; Esther E Bron; Doeschka A Ferro; Alexander G J Harms; Rosalie J Huijsmans; Joost P A Kuijer; Sanne Kuipers; Matthias J P van Osch; Niels D Prins; Marc B Rietberg; Charlotte E Teunissen; Henk Jan Mutsaerts; Geert Jan Biessels; Wiesje M van der Flier; Heart-Brain Connection Consortium

doi:10.1016/j.cccb.2025.100386

The effect of aerobic exercise on cerebral perfusion in patients with vascular cognitive impairment, the Excersion-VCI randomised controlled clinical trial

Cereb Circ Cogn Behav. 2025 May 24:8:100386. doi: 10.1016/j.cccb.2025.100386. eCollection 2025.

Authors

Liz R van Hout^{1

2

3}, Justine Moonen^{1

2}, Annebet E Leeuwis^{1

2}, Juliette van Alphen^{1

2}, Mathijs Dijsselhof^{2

4

5}, Raquel P Amier⁶, Frederik Barkhof^{2

4

7}, Esther E Bron⁵, Doeschka A Ferro⁸, Alexander G J Harms⁵, Rosalie J Huijsmans⁹, Joost P A Kuijer⁴, Sanne Kuipers⁸, Matthias J P van Osch¹⁰, Niels D Prins^{1

11}, Marc B Rietberg⁹, Charlotte E Teunissen^{1

2

12}, Henk Jan Mutsaerts^{2

4}, Geert Jan Biessels⁸, Wiesje M van der Flier^{1

2}; Heart-Brain Connection Consortium

Affiliations

¹ Alzheimer Centre Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, Amsterdam, The Netherlands.
² Amsterdam Neuroscience, Neurodegeneration, Amsterdam, The Netherlands.
³ Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, The Netherlands.
⁴ Department of Radiology and Nuclear Medicine, Amsterdam UMC, VU University Medical Centre, Amsterdam, The Netherlands.
⁵ Biomedical Imaging Group Rotterdam, Department of Radiology & Nuclear Medicine, Erasmus MC University Medical Centre Rotterdam, The Netherlands.
⁶ Department of Cardiology, VU University Medical Centre, Amsterdam, The Netherlands.
⁷ Institute of Healthcare Engineering, University College London, London, UK; Institute of Neurology, University College London, London, UK.
⁸ Department of Neurology, University Medical Centre Utrecht, Utrecht, The Netherlands.
⁹ Department of Rehabilitation, Amsterdam UMC, location VUmc, Amsterdam, The Netherlands.
¹⁰ C.J. Gorter MRI Centre, Department of Radiology, Leiden University Medical Centre, Leiden, The Netherlands.
¹¹ Brain Research Centre, Amsterdam, The Netherlands.
¹² Neurochemistry Laboratory, Department of Clinical Chemistry.

Abstract

Aerobic exercise may improve cerebral perfusion and may thereby attenuate, or delay, cognitive decline. Excersion-VCI aimed to evaluate the effect of aerobic exercise on cerebral perfusion in patients with vascular cognitive impairment (VCI). This Randomized Controlled Trial included non-demented adults ≥50 years diagnosed with VCI. Patients were randomly assigned either home-based aerobic interval training (exercise group) or information sessions (control group). Primary outcome was change in Arterial Spin Labelling MRI grey matter cerebral perfusion from baseline to 14-week follow-up. Per-protocol analysis was performed in patients who completed the follow-up. Secondary outcomes were VO_2max and cognitive function. Exploratory outcomes were depression and apathy, White Matter Hyperintensities, cerebral volumes, and blood biomarkers. Fifty-eight VCI patients (mean age 67.0 ± 6.7 years) were allocated to the exercise (n = 28) or control group (n = 30). Intention-to-treat analyses showed that change in grey matter cerebral perfusion in the exercise group did not differ from the control group (p = 0.38), nor were there group differences in change in VO2max (p = 0.17). The exercise group showed an increase in triglycerides compared to the control group (p = 0.04). No group differences were found for other outcomes. Per protocol analyses showed improvement in VO_2max in the exercise group compared to the control group (p = 0.04). An aerobic exercise program in VCI patients improved cardiorespiratory fitness in those who adhered to the protocol, but did not show significant effects on grey matter cerebral perfusion or other outcomes. The intervention duration of 14-weeks may have been too short to measure changes in perfusion or improvements in cognitive function.

Keywords: Arterial spin labelling; Cerebral blood flow; Exercise; Randomised clinical trial; Vascular cognitive impairment; cognition.