Increased Aerobic Fitness Is Associated with Cortical Thickness in Older Adults with Mild Vascular Cognitive Impairment
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Vascular cognitive impairment (VCI) results from cerebrovascular disease and is the second most common type of cognitive dysfunction. Sub-cortical ischemic vascular cognitive impairment (SIVCI) is the most common form of VCI. Current evidence suggests that increased or maintained cortical thickness might be one mechanism by which aerobic exercise preserves cognitive function in older adults. Whether this is also a potential pathway among older adults with SIVCI is unknown. Therefore, the aim of this secondary analysis of a 6-month proof-of-concept single-blinded randomized controlled trial of aerobic exercise was to investigate the associations between (1) aerobic-induced improvements in aerobic fitness capacity and change in cortical thickness in older adults with mild SIVCI; and (2) change in cortical thickness and changes in executive functions. This is a secondary analysis of neuroimaging data from a randomized controlled trial with 71 older adults with SIVCI who were randomly assigned to either a 6-month thrice-weekly aerobic training program or a 6-month nutrition program (i.e., control). Outcome measures were assessed at baseline and trial completion (i.e., 6 months). Aerobic fitness capacity was assessed with the 6-min walk test (6MWT). Magnetic resonance imaging data were acquired at both measurement points from 28 participants to look at changes in cortical thickness. Executive functions were assessed using (1) the Stroop test, (2) the trail making test (part A&B), and (3) the digit symbol substitution test (DSST). At trial completion, compared with the control group, participants in the aerobic training group showed significantly improved 6MWT performance (p = .037). Improved 6MWT performance was independently and significantly associated with increased change in cortical thickness, after controlling for baseline cortical thickness, baseline age, and baseline MoCA (p = .045). Specifically, change in 6MWT performance was significantly positively associated with change in the right superior temporal gyrus thickness (r = .557, p = .002). Maintenance of cortical thickness was independently and significantly associated with improved processing speed performance on the DSST over the 6-month trial, after controlling for baseline DSST performance, baseline age, and baseline MoCA (p = .014). Specifically, change in DSST performance was significantly positively associated with change in the right superior frontal thickness (r = .595, p = .002). Thus, a 6-month aerobic training program may promote cognitive outcomes in older adults with mild SIVCI by improving aerobic fitness capacity and maintaining cortical thickness.
KeywordsRandomized controlled trial Aerobic exercise Vascular cognitive impairment Cortical thickness Processing speed
TLA was involved in study concept, design, and acquisition of data. TLA AND LTB were involved in preparation of the manuscript. LTB, TLA, CLH, JRB, and CKB were involved in writing and critically reviewing the manuscript. We thank Dr. Philip Lee for screening potential participants.
LTB is a Mitacs Accelerate Doctoral Trainee. CLH is an Alzheimer Society Research Program Doctoral Trainee. JRB is a Canadian Institutes of Health Research and Michael Smith Foundation of Health Research Postdoctoral Fellow. CKB is a Michael Smith Foundation for Health Research/Pacific Alzheimer Research Foundation Postdoctoral Fellow. TLA is a Canada Research Chair (Tier II) in Physical Activity, Mobility and Cognitive Neuroscience. This work was supported by Canadian Stroke Network and the Heart and Stroke Foundation of Canada to TLA and the Jack Brown and Family Alzheimer Research Foundation Society to TLA.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
Ethics approval was provided by the University of British Columbia’s Clinical Research Ethics Board (H07-01160).
- Barha, C. K., Davis, J. C., Falck, R. S., Nagamatsu, L. S., & Liu-Ambrose, T. (2017). Sex differences in exercise efficacy to improve cognition: a systematic review and meta-analysis of randomized controlled trials in older humans. Frontiers in Neuroendocrinology, 46, 71–85. https://doi.org/10.1016/j.yfrne.2017.04.002.CrossRefPubMedGoogle Scholar
- Burzynska, A. Z., Nagel, I. E., Preuschhof, C., Gluth, S., Backman, L., Li, S. C., … Heekeren, H. R. (2012). Cortical thickness is linked to executive functioning in adulthood and aging. Human Brain Mapping, 33(7), 1607–1620. https://doi.org/10.1002/hbm.21311.
- Chee, M. W., Chen, K. H., Zheng, H., Chan, K. P., Isaac, V., Sim, S. K., … Ng, T. P. (2009). Cognitive function and brain structure correlations in healthy elderly east Asians. NeuroImage, 46(1), 257–269. https://doi.org/10.1016/j.neuroimage.2009.01.036.
- Desikan, R. S., Segonne, F., Fischl, B., Quinn, B. T., Dickerson, B. C., Blacker, D., … Killiany, R. J. (2006). An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. NeuroImage, 31(3), 968–980. https://doi.org/10.1016/j.neuroimage.2006.01.021.
- Drexel, H., Saely, C. H., Langer, P., Loruenser, G., Marte, T., Risch, L., … Aczel, S. (2008). Metabolic and anti-inflammatory benefits of eccentric endurance exercise—a pilot study. European Journal of Clinical Investigation, 38(4), 218–226.Google Scholar
- Enright, P. L., McBurnie, M. A., Bittner, V., Tracy, R. P., McNamara, R., Arnold, A., … Cardiovascular Health, S. (2003). The 6-min walk test: a quick measure of functional status in elderly adults. Chest, 123(2), 387–398.Google Scholar
- Erickson, K., & Kramer, A. F. (2008). Exercise effects on cognitive and neural plasticity in older adults. British Journal of Sports Medicine.Google Scholar
- Erkinjuntti, T., Inzitari, D., Pantoni, L., Wallin, A., Scheltens, P., Rockwood, K., … Desmond, D. W. (2000). Research criteria for subcortical vascular dementia in clinical trials. Journal of Neural Transmission. Supplementum, 59, 23–30.Google Scholar
- Fischl, B., Salat, D. H., Busa, E., Albert, M., Dieterich, M., Haselgrove, C., … Dale, A. M. (2002). Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain. Neuron, 33(3), 341–355.Google Scholar
- Fischl, B., van der Kouwe, A., Destrieux, C., Halgren, E., Segonne, F., Salat, D. H., … Dale, A. M. (2004b). Automatically parcellating the human cerebral cortex. Cerebral Cortex, 14(1), 11–22.Google Scholar
- Gorelick, P. B., Scuteri, A., Black, S. E., Decarli, C., Greenberg, S. M., Iadecola, C., … Anesthesia. (2011). Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke, 42(9), 2672–2713. https://doi.org/10.1161/STR.0b013e3182299496.
- Hsu, C. L., Best, J. R., Davis, J. C., Nagamatsu, L. S., Wang, S., Boyd, L. A., … Liu-Ambrose, T. (2017). Aerobic exercise promotes executive functions and impacts functional neural activity among older adults with vascular cognitive impairment. British Journal of Sports Medicine. https://doi.org/10.1136/bjsports-2016-096846.
- ICH Expert Working Group. (1999). ICH harmonised tripartite guideline. Statistical principles for clinical trials. International Conference on Harmonisation E9 expert working group. Stat Med, 18(15), 1905–1942.Google Scholar
- Johnson, J. L., Slentz, C. A., Houmard, J. A., Samsa, G. P., Duscha, B. D., Aiken, L. B., … Kraus, W. E. (2007). Exercise training amount and intensity effects on metabolic syndrome (from studies of a targeted risk reduction intervention through defined exercise). The American Journal of Cardiology, 100(12), 1759–1766.Google Scholar
- Jonasson, L. S., Nyberg, L., Kramer, A. F., Lundquist, A., Riklund, K., & Boraxbekk, C. J. (2016). Aerobic exercise intervention, cognitive performance, and brain structure: results from the physical influences on brain in aging (PHIBRA) study. Frontiers in Aging Neuroscience, 8, 336. https://doi.org/10.3389/fnagi.2016.00336.PubMedGoogle Scholar
- Jouvent, E., Mangin, J. F., Porcher, R., Viswanathan, A., O'Sullivan, M., Guichard, J. P., … Chabriat, H. (2008). Cortical changes in cerebral small vessel diseases: a 3D MRI study of cortical morphology in CADASIL. Brain, 131(Pt 8), 2201–2208. https://doi.org/10.1093/brain/awn129.
- Lezak, M. D. (1995). Neuropsychological assessment (3rd ed.). New York: Oxford University Press.Google Scholar
- Liu-Ambrose, T., Best, J. R., Davis, J. C., Eng, J. J., Lee, P. E., Jacova, C., … Hsiung, G. R. (2016a). Aerobic exercise and vascular cognitive impairment: a randomized controlled trial. Neurology, 87(20), 2082–2090. doi: https://doi.org/10.1212/WNL.0000000000003332.
- Liu-Ambrose, T., Best, J. R., Davis, J. C., Eng, J. J., Lee, P. E., Jacova, C., … Hsiung, G. R. (2016b). Aerobic exercise and vascular cognitive impairment: a randomized controlled trial. Neurology. https://doi.org/10.1212/WNL.0000000000003332.
- Liu-Ambrose, T., Eng, J. J., Boyd, L. A., Jacova, C., Davis, J. C., Bryan, S., … Hsiung, G. Y. (2010). Promotion of the mind through exercise (PROMoTE): a proof-of-concept randomized controlled trial of aerobic exercise training in older adults with vascular cognitive impairment. BMC Neurology, 10, 14. https://doi.org/10.1186/1471-2377-10-14.
- Nasreddine, Z. S., Phillips, N. A., Bedirian, V., Charbonneau, S., Whitehead, V., Collin, I., … Chertkow, H. (2005). The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. Journal of the American Geriatrics Society, 53(4), 695–699.Google Scholar
- O'Brien, J. T., Erkinjuntti, T., Reisberg, B., Roman, G., Sawada, T., Pantoni, L., … Gorelick, P. B. (2003). Vascular cognitive impairment. The Lancet Neurology, 2(2), 89–98.Google Scholar
- Prakash, R. S., Voss, M. W., Erickson, K. I., & Kramer, A. F. (2015). Physical activity and cognitive vitality. Annual Review of Psychology, 66, 769–797. https://doi.org/10.1146/annurev-psych-010814-015249.CrossRefPubMedGoogle Scholar
- Reiter, K., Nielson, K. A., Smith, T. J., Weiss, L. R., Alfini, A. J., & Smith, J. C. (2015). Improved cardiorespiratory fitness is associated with increased cortical thickness in mild cognitive impairment. Journal of the International Neuropsychological Society, 21(10), 757–767. https://doi.org/10.1017/S135561771500079X.CrossRefPubMedPubMedCentralGoogle Scholar
- Righart, R., Duering, M., Gonik, M., Jouvent, E., Reyes, S., Herve, D., … Dichgans, M. (2013). Impact of regional cortical and subcortical changes on processing speed in cerebral small vessel disease. Neuroimage Clin, 2, 854–861. https://doi.org/10.1016/j.nicl.2013.06.006.
- Smith, P. J., Blumenthal, J. A., Hoffman, B. M., Cooper, H., Strauman, T. A., Welsh-Bohmer, K., … Sherwood, A. (2010). Aerobic exercise and neurocognitive performance: a meta-analytic review of randomized controlled trials. Psychosomatic Medicine, 72(3), 239–252. https://doi.org/10.1097/PSY.0b013e3181d14633.
- Spreen, O., & Strauss, E. (1998). A compendium of neurological tests (2nd ed.). New York: Oxford University Press, Inc..Google Scholar
- Stewart, K. J., Bacher, A. C., Turner, K., Lim, J. G., Hees, P. S., Shapiro, E. P., … Ouyang, P. (2005). Exercise and risk factors associated with metabolic syndrome in older adults. American Journal of Preventive Medicine, 28(1), 9–18.Google Scholar
- Thong, J. Y., Du, J., Ratnarajah, N., Dong, Y., Soon, H. W., Saini, M., … Qiu, A. (2014). Abnormalities of cortical thickness, subcortical shapes, and white matter integrity in subcortical vascular cognitive impairment. Human Brain Mapping, 35(5), 2320–2332. https://doi.org/10.1002/hbm.22330.
- Verdelho, A., Madureira, S., Ferro, J. M., Baezner, H., Blahak, C., Poggesi, A., et al. (2012). Physical activity prevents progression for cognitive impairment and vascular dementia: results from the LADIS (leukoaraiosis and disability) study. Stroke, 43(12), 3331–3335. https://doi.org/10.1161/STROKEAHA.112.661793.CrossRefPubMedGoogle Scholar