Research Paper Volume 14, Issue 2 pp 596—622

Five years of exercise intervention at different intensities and development of white matter hyperintensities in community dwelling older adults, a Generation 100 sub-study

Anette Arild1, , Torgil Vangberg2,3, , Hanne Nikkels4, , Stian Lydersen5, , Ulrik Wisløff6,7, , Dorthe Stensvold6,7, , Asta K. Håberg1,4, ,

  • 1 Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, NTNU Norwegian University of Science and Technology, Trondheim, Norway
  • 2 Department of Clinical Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway
  • 3 PET Center, University Hospital of North Norway, Tromsø, Norway
  • 4 Department of Radiology and Nuclear Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
  • 5 Department of Mental Health, Faculty of Medicine and Health Sciences, NTNU Norwegian University of Science and Technology, Trondheim, Norway
  • 6 Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, NTNU Norwegian University of Science and Technology, Trondheim, Norway
  • 7 Department of Cardiology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway

Received: November 19, 2021       Accepted: January 4, 2022       Published: January 18, 2022
How to Cite

Copyright: © 2022 Arild et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


We investigated if a five-year supervised exercise intervention with moderate-intensity continuous training (MICT) or high-intensity interval training (HIIT) versus control; physical activity according to national guidelines, attenuated the growth of white matter hyperintensities (WMH). We hypothesized that supervised exercise, in particular HIIT, reduced WMH growth. Older adults from the general population participating in the RCT Generation 100 Study were scanned at 3T MRI at baseline (age 70–77), and after 1-, 3- and 5-years. At each follow-up, cardiorespiratory fitness was measured with ergospirometry, and physical activity plus clinical data collected. Manually delineated total WMH, periventricular (PWMH), deep (DWMH), and automated total white matter hypointensity volumes were obtained. No group by time interactions were present in linear mixed model analyses with the different WMH measurements as outcomes. In the combined exercise (MICT&HIIT) group, a significant group by time interaction was uncovered for PWMH volume, with a larger increase in the MICT&HIIT group. Cardiorespiratory fitness at the follow-ups or change in cardiorespiratory fitness over time were not associated with any WMH measure. Contrary to our hypothesis, taking part in MICT or HIIT over a five-year period did not attenuate WMH growth compared to being in a control group following national physical activity guidelines.


AIC: Akaike’s information criterion; ANOVA: analysis of variance; BDNF: brain-derived neurotrophic factor; BP: blood pressure; CI: confidence interval; DBP: diastolic blood pressure; DWMH: deep white matter hyperintensities; ECG: electrocardiogram; ETL: echo train length; FLAIR: fluid-attenuated inversion recovery; FOV: field-of-view; G100: The Generation 100 Study; HADS: Hospital Anxiety and Depression Scale; HbA1c: glycosylated hemoglobin; HDL: high-density lipoprotein; HIIT: high-intensity interval training; hsCRP: high-sensitive c-reactive protein; ICC: intraclass correlation coefficient; ICV: intracranial volume; IQR: interquartile range; LDL: low-density lipoprotein; MET: metabolic equivalent of task; MICT: moderate-intensity continuous training; MoCA: Montreal Cognitive Assessment; MRI: magnetic resonance imaging; NS: not significant; PWMH: periventricular white matter hyperintensities; RCT: randomized controlled trial; SBP: systolic blood pressure; SD: standard deviation; TE: echo time; TG: triglycerides; TI: inversion time; TR: repetition time; T1W: T1-weighted; T2W: T2-weighted; VO2max: maximal oxygen uptake; VO2peak: peak oxygen uptake; WM: white matter; WMH: white matter hyperintensities.