Skip to main content Accessibility help

Improved Cardiorespiratory Fitness Is Associated with Increased Cortical Thickness in Mild Cognitive Impairment

  • Katherine Reiter (a1), Kristy A. Nielson (a1) (a2), Theresa J. Smith (a3), Lauren R. Weiss (a3), Alfonso J. Alfini (a3) and J. Carson Smith (a3)...

Cortical atrophy is a biomarker of Alzheimer’s disease (AD) that correlates with clinical symptoms. This study examined changes in cortical thickness from before to after an exercise intervention in mild cognitive impairment (MCI) and healthy elders. Thirty physically inactive older adults (14 MCI, 16 healthy controls) underwent MRI before and after participating in a 12-week moderate intensity walking intervention. Participants were between the ages of 61 and 88. Change in cardiorespiratory fitness was assessed using residualized scores of the peak rate of oxygen consumption (V̇O2peak) from pre- to post-intervention. Structural magnetic resonance images were processed using FreeSurfer v5.1.0. V̇O2peak increased an average of 8.49%, which was comparable between MCI and healthy elders. Overall, cortical thickness was stable except for a significant decrease in the right fusiform gyrus in both groups. However, improvement in cardiorespiratory fitness due to the intervention (V̇O2peak) was positively correlated with cortical thickness change in the bilateral insula, precentral gyri, precuneus, posterior cingulate, and inferior and superior frontal cortices. Moreover, MCI participants exhibited stronger positive correlations compared to healthy elders in the left insula and superior temporal gyrus. A 12-week moderate intensity walking intervention led to significantly improved fitness in both MCI and healthy elders. Improved V̇O2peak was associated with widespread increased cortical thickness, which was similar between MCI and healthy elders. Thus, regular exercise may be an especially beneficial intervention to counteract cortical atrophy in all risk groups, and may provide protection against future cognitive decline in both healthy elders and MCI. (JINS, 2015, 21, 757–767)

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Improved Cardiorespiratory Fitness Is Associated with Increased Cortical Thickness in Mild Cognitive Impairment
      Available formats
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Improved Cardiorespiratory Fitness Is Associated with Increased Cortical Thickness in Mild Cognitive Impairment
      Available formats
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Improved Cardiorespiratory Fitness Is Associated with Increased Cortical Thickness in Mild Cognitive Impairment
      Available formats
Corresponding author
Correspondence and reprint requests to: J. Carson Smith, Department of Kinesiology, 2351 SPH Bldg. #255, College Park, MD 20742. E-mail:
Hide All
Albert, M.S., DeKosky, S.T., Dickson, D., Dubois, B., Feldman, H.H., Fox, N.C., & Phelps, C.H. (2011). The diagnosis of mild cognitive impairment due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s & Dementia, 7(3), 270279. doi:10.1016/j.jalz.2011.03.008
Alzheimer’s Association. (2013). 2013 Alzheimer’s disease facts and figures. Alzheimer’s & Dementia, 9(2), 208245. doi:10.1016/j.jalz.2013.02.003
American College of Sports Medicine. (2010). ACSM’s guidelines for exercise testing and prescription (8th ed.). Philadelphia: Lippincott Williams & Wilkins.
American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Washington, D.C.: Author.
Apostolova, L.G., Green, A.E., Babakchanian, S., Hwang, K.S., Chou, Y.Y., Toga, A.W., & Thompson, P.M. (2012). Hippocampal atrophy and ventricular enlargement in normal aging, mild cognitive impairment (MCI), and Alzheimer Disease. Alzheimer Disease and Associated Disorders, 26(1), 1727. doi:10.1097/WAD.0b013e3182163b62
Baker, L.D., Frank, L.L., Foster-Schubert, K., Green, P.S., Wilkinson, C.W., McTiernan, A., & Craft, S. (2010). Effects of aerobic exercise on mild cognitive impairment: A controlled trial. Archives of Neurology, 67(1), 7179.
Benton, A., & Hamsher, K.d.S. (1978). Multilingual aphasia exam manual. Iowa City, IA: University of Iowa.
Borg, G. (1998). Borg’s perceived exertion and pain scales. Champaign, IL: Human Kinetics.
Buckner, R.L., Snyder, A.Z., Shannon, B.J., LaRossa, G., Sachs, R., Fotenos, A.F., & Mintun, M.A. (2005). Molecular, structural, and functional characterization of Alzheimer’s disease: Evidence for a relationship between default activity, amyloid, and memory. The Journal of Neuroscience, 25(34), 77097717.
Colcombe, S.J., Erickson, K.I., Scalf, P.E., Kim, J.S., Prakash, R., McAuley, E., & Kramer, A.F. (2006). Aerobic exercise training increases brain volume in aging humans. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 61(11), 11661170.
Cook, D.B., O’Connor, P.J., Eubanks, S.A., Smith, J.C., & Lee, M. (1997). Naturally occurring muscle pain during exercise: Assessment and experimental evidence. Medicine and Science in Sports and Exercise, 29(8), 9991012.
Cosentino, S., Jefferson, A., Chute, D.L., Kaplan, E., & Libon, D.J. (2004). Clock drawing errors in dementia: Neuropsychological and neuroanatomical considerations. Cognitive and Behavioral Neurology, 17(2), 7484.
Cotman, C.W., & Berchtold, N.C. (2002). Exercise: A behavioral intervention to enhance brain health and plasticity. Trends in Neuroscience, 25(6), 295301.
Daviglus, M.L., Bell, C.C., Berrettini, W., Bowen, P.E., Connolly, E.S., Cox, N.J., & Trevisan, M. (2010). NIH State-of-the-Science Conference Statement: Preventing Alzheimer’s disease and cognitive decline. NIH Consensus and State-of-the-Science Statements, 27(4), 130. doi:2010-00034-STMT [pii].
DeKosky, S.T., & Marek, K. (2003). Looking backward to move forward: Early detection of neurodegenerative disorders. Science, 302(5646), 830834.
Desikan, R.S., Cabral, H.J., Hess, C.P., Dillon, W.P., Glastonbury, C.M., Weiner, M.W., Alzheimer’s Disease Neuroimaging Initiative. (2009). Automated MRI measures identify individuals with mild cognitive impairment and Alzheimer’s disease. Brain, 132(Pt 8), 20482057. doi:10.1093/brain/awp123
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), 968980. doi:10.1016/j.neuroimage.2006.01.021
Devanand, D.P., Pradhaban, G., Liu, X., Khandji, A., De Santi, S., Segal, S., & de Leon, M.J. (2007). Hippocampal and entorhinal atrophy in mild cognitive impairment: Prediction of Alzheimer disease. Neurology, 68, 828836.
Eadie, B.D., Redila, V.A., & Christie, B.R. (2005). Voluntary exercise alters the cytoarchitecture of the adult dentate gyrus by increasing cellular proliferation, dendritic complexity, and spine density. The Journal of Comparative Neurology, 486(1), 3947. doi:10.1002/cne.20493
Erickson, K.I., Leckie, R.L., & Weinstein, A.M. (2014). Physical activity, fitness, and gray matter volume. Neurobiology of Aging, 35(Suppl. 2), S20S28. doi:10.1016/j.neurobiolaging.2014.03.034
Erickson, K.I., Voss, M.W., Prakash, R.S., Basak, C., Szabo, A., Chaddock, L., & White, S.M. (2011). Exercise training increases size of hippocampus and improves memory. Proceedings of the National Academy of Sciences of the United States of America, 108, 30173022.
Eriksson, P.S., Perfilieva, E., Bjork-Eriksson, T., Alborn, A.M., Nordborg, C., Peterson, D.A., & Gage, F.H. (1998). Neurogenesis in the adult human hippocampus. Nature Medicine, 4(11), 13131317.
Fjell, A.M., Westlye, L.T., Grydeland, H., Amlien, I., Espeseth, T., Reinvang, I., … Alzheimer Disease Neuroimaging Initiative. (2014). Accelerating cortical thinning: Unique to dementia or universal in aging? Cerebral Cortex, 24(4), 919934. doi:10.1093/cercor/bhs379
Folstein, M.F., Folstein, S.E., & McHugh, P.R. (1975). “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12(3), 189198.
Gauthier, S., Reisberg, B., Zaudig, M., Petersen, R.C., Ritchie, K., Broich, K., & Winblad, B. (2006). Mild cognitive impairment. The Lancet, 367(9518), 12621270. doi:10.1016/s0140-6736(06)68542-5
Gomar, J.J., Bobes-Bascaran, M.T., Conejero-Goldberg, C., Davies, P., Goldberg, T.E., & Alzheimer’s Disease Neuroimaging Initiative. (2011). Utility of combinations of biomarkers, cognitive markers, and risk factors to predict conversion from mild cognitive impairment to Alzheimer disease in patients in the Alzheimer’s disease neuroimaging initiative. Archives of General Psychiatry, 68(9), 961969.
Goodglass, H., & Kaplan, E. (1983). The assessment of aphasia and related disorders. Philadelphia: Lea & Febiger.
Hogstrom, L.J., Westlye, L.T., Walhovd, K.B., & Fjell, A.M. (2012). The structure of the cerebral cortex across adult life: Age-related patterns of surface area, thickness, and gyrification. Cerebral Cortex, 23(11), 25212530. doi:10.1093/cercor/bhs231
Honjo, K., Black, S.E., & Verhoeff, N.P. (2012). Alzheimer’s disease, cerebrovascular disease, and the beta-amyloid cascade. The Canadian Journal of Neurological Sciences, 39(6), 712728.
Intlekofer, K.A., & Cotman, C.W. (2013). Exercise counteracts declining hippocampal function in aging and Alzheimer’s disease. Neurobiology of Disease, 57, 4755.
Jack, C.R. Jr., Vemuri, P., Wiste, H.J., Weigand, S.D., Aisen, P.S., Trojanowski, J.Q., … Alzheimer’s Disease Neuroimaging Initiative. (2011). Evidence for ordering of Alzheimer disease biomarkers. Archives of Neurology, 68(12), 15261535. doi:10.1001/archneurol.2011.183
Jurica, P.J., Leitten, C.L., & Mattis, S. (2004). DRS-2 dementia rating scale-2: Professional manual. Los Angeles, CA: Psychological Assessment Resources.
Karas, G.B., Scheltens, P., Rombouts, S.A., Visser, P.J., van Schijndel, R.A., Fox, N.C., & Barkhof, F. (2004). Global and local gray matter loss in mild cognitive impairment and Alzheimer’s disease. Neuroimage, 23(2), 708716. doi:10.1016/j.neuroimage.2004.07.006
Kramer, A.F., Erickson, K.I., & Colcombe, S.J. (2006). Exercise, cognition, and the aging brain. Journal of Applied Physiology (1985), 101(4), 12371242. doi:10.1152/japplphysiol.00500.2006
Lautenschlager, N.T., Cox, K.L., Flicker, L., Foster, J.K., van Bockxmeer, F.M., Xiao, J., & Almeida, O.P. (2008). Effect of physical activity on cognitive function in older adults at risk for Alzheimer disease: A randomized trial. Journal of the American Medical Association, 300(9), 10271037.
Lawton, M.P., & Brody, E.M. (1970). Assessment of older people: Self-maintaining and instrumental activities of daily living. Nursing Research, 19(3), 278.
Llabre, M.M., Spitzer, S.B., Saab, P.G., Ironson, G.H., & Schneiderman, N. (1991). The reliability and specificity of delta versus residualized change as measures of cardiovascular reactivity to behavioral challenges. Psychophysiology, 28(6), 701711.
Martins, I.J., Hone, E., Foster, J.K., Sunram-Lea, S.I., Gnjec, A., Fuller, S.J., & Martins, R.N. (2006). Apolipoprotein E, cholesterol metabolism, diabetes, and the convergence of risk factors for Alzheimer’s disease and cardiovascular disease. Molecular Psychiatry, 11(8), 721736. doi:10.1038/
Mazzeo, R.S., & Tanaka, H. (2001). Exercise prescription for the elderly: Current recommendations. Sports Medicine, 31(11), 809818.
McDonald, C., McEvoy, L., Gharapetian, L., Fennema-Notestine, C., Hagler, D., Holland, D., & Dale, A. (2009). Regional rates of neocortical atrophy from normal aging to early Alzheimer disease. Neurology, 73(6), 457465.
McDonald, C.R., Gharapetian, L., McEvoy, L.K., Fennema-Notestine, C., Hagler, D.J. Jr., Holland, D., … Alzheimer’s Disease Neuroimaging Initiative. (2012). Relationship between regional atrophy rates and cognitive decline in mild cognitive impairment. Neurobiology of Aging, 33(2), 242253. doi:10.1016/j.neurobiolaging.2010.03.015
McEvoy, L.K., Fennema-Notestine, C., Roddey, J.C., Hagler, D.J. Jr., Holland, D., Karow, D.S., … Alzheimer’s Disease Neuroimaging Initiative. (2009). Alzheimer disease: Quantitative structural neuroimaging for detection and prediction of clinical and structural changes in mild cognitive impairment. Radiology, 251(1), 195205. doi:10.1148/radiol.2511080924
McSweeny, J.A., Naughle, R.I., Chelune, G.J., & Lüders, H. (1993). “T scores for change”: An illustration of a regression approach to depicting change in clinical neuropsychology. The Clinical Neuropsychologist, 7(3), 300312.
Middleton, L.E., Corbett, D., Brooks, D., Sage, M.D., Macintosh, B.J., McIlroy, W.E., &Black, S.E. (2013). Physical activity in the prevention of ischemic stroke and improvement of outcomes: A narrative review. Neuroscience and Biobehavioral Reviews, 37(2), 133137. doi:10.1016/j.neubiorev.2012.11.011
Misra, C., Fan, Y., & Davatzikos, C. (2009). Baseline and longitudinal patterns of brain atrophy in MCI patients, and their use in prediction of short-term conversion to AD: Results from ADNI. Neuroimage, 44(4), 14151422. doi:10.1016/j.neuroimage.2008.10.031
Pereira, A.C., Huddleston, D.E., Brickman, A.M., Sosunov, A.A., Hen, R., McKhann, G.M., & Small, S.A. (2007). An in vivo correlate of exercise-induced neurogenesis in the adult dentate gyrus. Proceedings of the National Academy of Science of the United States of America, 104(13), 56385643.
Petersen, R.C. (2000). Mild cognitive impairment: Transition between aging and Alzheimer’s disease. Neurologia, 15(3), 93101.
Petersen, R.C., Stevens, J.C., Ganguli, M., Tangalos, E.G., Cummings, J.L., & DeKosky, S.T. (2001). Practice parameter: Early detection of dementia: Mild cognitive impairment (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology, 56(9), 11331142.
Reuter, M., Rosas, H.D., & Fischl, B. (2010). Highly accurate inverse consistent registration: A robust approach. Neuroimage, 53(4), 11811196. doi:10.1016/j.neuroimage.2010.07.020
Reuter, M., Schmansky, N.J., Rosas, H.D., & Fischl, B. (2012). Within-subject template estimation for unbiased longitudinal image analysis. Neuroimage, 61(4), 14021418. doi:10.1016/j.neuroimage.2012.02.084
Rey, A. (1964). L’examen clinique en psychologie [Clinical psychological examination]. Paris: Presses Universitaires de France.
Ruscheweyh, R., Willemer, C., Kruger, K., Duning, T., Warnecke, T., Sommer, J., & Floel, A. (2011). Physical activity and memory functions: An interventional study. Neurobiology of Aging, 32(7), 13041319. doi:10.1016/j.neurobiolaging.2009.08.001
Smith, A. (1991). Symbol Digit Modality Test (SDMT). Los Angeles, CA: Western Psychological Services.
Smith, J.C., Nielson, K.A., Antuono, P., Lyons, J.A., Hanson, R.J., Butts, A.M., & Verber, M.D. (2013). Semantic memory functional MRI and cognitive function after exercise intervention in mild cognitive impairment. Journal of Alzheimers Disease, 37(1), 197215. doi:Doi 10.3233/Jad-130467
Smith, J.C., Nielson, K.A., Woodard, J.L., Seidenberg, M., Durgerian, S., Hazlett, K.E., & Matthews, M.A. (2014). Physical activity reduces hippocampal atrophy in elders at genetic risk for Alzheimer’s disease. Frontiers in Aging Neuroscience, 6, 61.
Sperling, R.A., Laviolette, P.S., O’Keefe, K., O’Brien, J., Rentz, D.M., Pihlajamaki, M., & Johnson, K.A. (2009). Amyloid deposition is associated with impaired default network function in older persons without dementia. Neuron, 63(2), 178188.
Swain, R.A., Harris, A.B., Wiener, E.C., Dutka, M.V., Morris, H.D., Theien, B.E., & Greenough, W.T. (2003). Prolonged exercise induces angiogenesis and increases cerebral blood volume in primary motor cortex of the rat. Neuroscience, 117(4), 10371046.
Temkin, N.R., Heaton, R.K., Grant, I., & Dikmen, S.S. (1999). Detecting significant change in neuropsychological test performance: A comparison of four models. Journal of International Neuropsychological Society, 5, 357369.
ten Brinke, L.F., Bolandzadeh, N., Nagamatsu, L.S., Hsu, C.L., Davis, J.C., Miran-Khan, K., & Liu-Ambrose, T. (2015). Aerobic exercise increases hippocampal volume in older women with probable mild cognitive impairment: A 6-month randomised controlled trial. British Journal of Sports Medicine, 49(4), 248254. doi:10.1136/bjsports-2013-093184
van Praag, H., Kempermann, G., & Gage, F.H. (1999). Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nature Neuroscience, 2(3), 266270. doi:10.1038/6368
Voloboueva, L.A., & Giffard, R.G. (2011). Inflammation, mitochondria, and the inhibition of adult neurogenesis. Journal of Neuroscience Research, 89(12), 19891996. doi:10.1002/jnr.22768
Voss, M.W., Erickson, K.I., Prakash, R.S., Chaddock, L., Kim, J.S., Alves, H., & Kramer, A.F. (2013). Neurobiological markers of exercise-related brain plasticity in older adults. Brain, Behavior, and Immunity, 28, 9099. doi:10.1016/j.bbi.2012.10.021
Wechsler, D. (1997). Wechsler Adult Intelligence Scale (WAIS-IIIuk): Wechsler Memory Scale (WMS-IIIuk). Los Angeles, CA: Psychological Corporation.
Whitwell, J.L., Przybelski, S.A., Weigand, S.D., Knopman, D.S., Boeve, B.F., Petersen, R.C., & Jack, C.R. Jr. (2007). 3D maps from multiple MRI illustrate changing atrophy patterns as subjects progress from mild cognitive impairment to Alzheimer’s disease. Brain, 130(Pt 7), 17771786. doi:10.1093/brain/awm112
Xie, C., Bai, F., Yu, H., Shi, Y., Yuan, Y., Chen, G., & Li, S.J. (2012). Abnormal insula functional network is associated with episodic memory decline in amnestic mild cognitive impairment. Neuroimage, 63(1), 320327. doi:10.1016/j.neuroimage.2012.06.062
Yao, Z., Hu, B., Liang, C., Zhao, L., Jackson, M., & Alzheimer’s Disease Neuroimaging Initiative (2012). A longitudinal study of atrophy in amnestic mild cognitive impairment and normal aging revealed by cortical thickness. PLoS One, 7(11), e48973. doi:10.1371/journal.pone.0048973
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Journal of the International Neuropsychological Society
  • ISSN: 1355-6177
  • EISSN: 1469-7661
  • URL: /core/journals/journal-of-the-international-neuropsychological-society
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed