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Fitness, independent of physical activity is associated with cerebral blood flow in adults at risk for Alzheimer’s disease

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Abstract

Patterns of decreased resting cerebral blood flow (CBF) within the inferior temporal gyri, angular gyri, and posterior cingulate are a feature of aging and Alzheimer’s disease (AD) and have shown to be predictive of cognitive decline among older adults. Fitness and physical activity are both associated with many indices of brain health and may positively influence CBF, however, the majority of research to date has examined these measures in isolation, leaving the potential independent associations unknown. The purpose of this study was to determine the unique contributions of fitness and physical activity when predicting CBF in cognitively healthy adults at risk for AD. One hundred participants (63% female) from the Wisconsin Registry for Alzheimer’s Prevention underwent a maximal exercise test, physical activity monitoring, and a 3-D arterial spin labeling magnetic resonance imaging scan. For the entire sample, fitness was significantly associated with CBF while accounting for physical activity, age, gender, APOE ε4, family history of AD, education, and handedness (p = .026). Further, fitness explained significantly more variance than the combined effect of the covariates on CBF (R2 change = .059; p = .047). These results appear to be gender dependent, our data suggest fitness level, independent of physical activity, is associated with greater CBF in regions that are known to decline with age and AD for female (p = .011), but not male participants.

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References

  • Alfini, A. J., Weiss, L. R., Leitner, B. P., Smith, T. J., Hagberg, J. M., & Smith, J. C. (2016). Hippocampal and cerebral blood flow after exercise cessation in master athletes. Frontiers in Aging Neuroscience, 8.

  • Alsop, D. C., Dai, W., Grossman, M., & Detre, J. A. (2010). Arterial spin labeling blood flow MRI: Its role in the early characterization of Alzheimer's disease. Journal of Alzheimer's Disease, 20(3), 871–880.

    PubMed  Google Scholar 

  • American College of Sports Medicine, ed. (2013). ACSM's health-related physical fitness assessment manual. Lippincott Williams & Wilkins.

  • Angevaren, M., Aufdemkampe, G., Verhaar, H. J., Aleman, A., & Vanhees, L. (2008). Physical activity and enhanced fitness to improve cognitive function in older people without known cognitive impairment. Cochrane Database of Systematic Reviews, 3(3).

  • Austin, B. P., Nair, V. A., Meier, T. B., Xu, G., Rowley, H. A., Carlsson, C. M., Johnson, S. C., & Prabhakaran, V. (2011). Effects of hypoperfusion in Alzheimer's disease. Journal of Alzheimer's Disease, 26(s3), 123–133.

    PubMed  PubMed Central  Google Scholar 

  • Baker, L. D., Frank, L. L., Foster-Schubert, K., Green, P. S., Wilkinson, C. W., McTiernan, A., ... & Duncan, G. E. (2010). Effects of aerobic exercise on mild cognitive impairment: a controlled trial. Archives of neurology, 67(1), 71-79.

  • Balke, B., & Ware, R. W. (1959). An experimental study of physical fitness of air force personnel. United States Armed Forces Medical Journal, 10(6), 675–688.

    CAS  PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • Barnes, J. N. (2017). Sex-specific factors regulating pressure and flow. Experimental Physiology, 102(11), 1385–1392.

    PubMed  PubMed Central  Google Scholar 

  • Barnes, J. N., & Corkery, A. T. (2018). Exercise improves vascular function, but does this Translate to the Brain?. Brain Plasticity, (Preprint), 1–15.

  • Benedictus, M. R., Leeuwis, A. E., Binnewijzend, M. A., Kuijer, J. P., Scheltens, P., Barkhof, F., ... & Prins, N. D. (2017). Lower cerebral blood flow is associated with faster cognitive decline in Alzheimer’s disease. European Radiology, 27(3), 1169–1175.

  • Billinger, S. A., Vidoni, E. D., Morris, J. K., Thyfault, J. P., & Burns, J. M. (2017). Exercise test performance reveals evidence of the cardiorespiratory fitness hypothesis. Journal of Aging and Physical Activity, 25(2), 240–246.

    PubMed  Google Scholar 

  • Borg, G. A. (1982). Psychophysical bases of perceived exertion. Medicine and Science in Sports and Exercise, 14, 377–381.

    CAS  PubMed  Google Scholar 

  • Bouchard, C., & Rankinen, T. (2001). Individual differences in response to regular physical activity. Medicine and Science in Sports and Exercise, 33.6(Suppl), S446–S451.

    Google Scholar 

  • Bouchard, C., An, P., Rice, T., Skinner, J. S., Wilmore, J. H., Gagnon, J., Pérusse, L., Leon, A. S., & Rao, D. C. (1999). Familial aggregation of Vo 2 max response to exercise training: Results from the HERITAGE family study. Journal of Applied Physiology, 87(3), 1003–1008.

    CAS  PubMed  Google Scholar 

  • Bouchard, C., Sarzynski, M. A., Rice, T. K., Kraus, W. E., Church, T. S., Sung, Y. J., Rao, D. C., & Rankinen, T. (2011). Genomic predictors of the maximal O 2 uptake response to standardized exercise training programs. Journal of Applied Physiology, 110(5), 1160–1170.

    CAS  PubMed  Google Scholar 

  • Brown, A. D., McMorris, C. A., Longman, R. S., Leigh, R., Hill, M. D., Friedenreich, C. M., & Poulin, M. J. (2010). Effects of cardiorespiratory fitness and cerebral blood flow on cognitive outcomes in older women. Neurobiology of Aging, 31(12), 2047–2057.

    PubMed  Google Scholar 

  • Burzynska, A. Z., Chaddock-Heyman, L., Voss, M. W., Wong, C. N., Gothe, N. P., Olson, E. A., et al. (2014). Physical activity and cardiorespiratory fitness are beneficial for white matter in low-fit older adults. PLoS One, 9(9), e107413.

    PubMed  PubMed Central  Google Scholar 

  • Carrick-Ranson, G., Hastings, J. L., Bhella, P. S., Fujimoto, N., Shibata, S., Palmer, M. D., Boyd, K., Livingston, S., Dijk, E., & Levine, B. D. (2014). The effect of lifelong exercise dose on cardiovascular function during exercise. Journal of Applied Physiology, 116(7), 736–745.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Caspersen, C. J., Powell, K. E., & Christenson, G. M. (1985). Physical activity, exercise, and physical fitness: Definitions and distinctions for health-related research. Public Health Reports, 100(2), 126–131.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chao, L. L., Buckley, S. T., Kornak, J., Schuff, N., Madison, C., Yaffe, K., Miller, B. L., Kramer, J. H., & Weiner, M. W. (2010). ASL perfusion MRI predicts cognitive decline and conversion from MCI to dementia. Alzheimer Disease and Associated Disorders, 24(1), 19–27.

    PubMed  PubMed Central  Google Scholar 

  • Chapman, S. B., Aslan, S., Spence, J. S., DeFina, L. F., Keebler, M. W., Didehbani, N., & Lu, H. (2013). Shorter term aerobic exercise improves brain, cognition, and cardiovascular fitness in aging. Frontiers in Aging Neuroscience, 5, 75.

    PubMed  PubMed Central  Google Scholar 

  • Chen, Y., Wolk, D. A., Reddin, J. S., Korczykowski, M., Martinez, P. M., Musiek, E. S., ... & Detre, J. A. (2011). Voxel-level comparison of arterial spin-labeled perfusion MRI and FDG-PET in Alzheimer disease. Neurology, WNL-0b013e31823a0ef7.

  • Colcombe, S., & Kramer, A. F. (2003). Fitness effects on the cognitive function of older adults: A meta-analytic study. Psychological Science, 14(2), 125–130.

    PubMed  Google Scholar 

  • Dai, W., Garcia, D., De Bazelaire, C., & Alsop, D. C. (2008). Continuous flow-driven inversion for arterial spin labeling using pulsed radio frequency and gradient fields. Magnetic Resonance in Medicine: An Official Journal of the International Society for Magnetic Resonance in Medicine, 60(6), 1488–1497.

    Google Scholar 

  • Davenport, M. H., Hogan, D. B., Eskes, G. A., Longman, R. S., & Poulin, M. J. (2012). Cerebrovascular reserve: The link between fitness and cognitive function? Exercise and Sport Sciences Reviews, 40(3), 153–158.

    PubMed  Google Scholar 

  • DeFina, L. F., Haskell, W. L., Willis, B. L., Barlow, C. E., Finley, C. E., Levine, B. D., & Cooper, K. H. (2015). Physical activity versus cardiorespiratory fitness: Two (partly) distinct components of cardiovascular health? Progress in Cardiovascular Diseases, 57(4), 324–329.

    PubMed  Google Scholar 

  • Dougherty, R. J., Ellingson, L. D., Schultz, S. A., Boots, E. A., Meyer, J. D., Lindheimer, J. B., et al. (2016). Meeting physical activity recommendations may be protective against temporal lobe atrophy in older adults at risk for Alzheimer's disease. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, 4, 14–17.

    Google Scholar 

  • Dougherty, R. J., Schultz, S. A., Boots, E. A., Ellingson, L. D., Meyer, J. D., Van Riper, S., ... & Korcarz, C. E. (2017a). Relationships between cardiorespiratory fitness, hippocampal volume, and episodic memory in a population at risk for Alzheimer's disease. Brain and Behavior, 7(3).

  • Dougherty, R. J., Schultz, S. A., Kirby, T. K., Boots, E. A., Oh, J. M., Edwards, D., Gallagher, C. L., Carlsson, C. M., Bendlin, B. B., Asthana, S., Sager, M. A., Hermann, B. P., Christian, B. T., Johnson, S. C., Cook, D. B., & Okonkwo, O. C. (2017b). Moderate physical activity is associated with cerebral glucose metabolism in adults at risk for Alzheimer’s disease. Journal of Alzheimer’s Disease : JAD, 58(4), 1089–1097.

    CAS  PubMed  Google Scholar 

  • Dougherty, R. J., Lindheimer, J. B., Stegner, A. J., Van Riper, S., Okonkwo, O. C., & Cook, D. B. (2018). An objective method to accurately measure cardiorespiratory fitness in older adults who cannot satisfy widely used oxygen consumption criteria. Journal of Alzheimer’s Disease, 61(2), 601–611.

    PubMed  Google Scholar 

  • Dyrstad, S. M., Hansen, B. H., Holme, I. M., & Anderssen, S. A. (2014). Comparison of self-reported versus accelerometer-measured physical activity. Medicine & Science in Sports & Exercise, 46(1), 99–106.

    Google Scholar 

  • Eaton, C. B., Lapane, K. L., Garber, C. E., Assaf, A. R., Lasater, T. M., & Carleton, R. A. (1995). Physical activity, physical fitness, and coronary heart disease risk factors. Medicine and Science in Sports and Exercise, 27(3), 340–346.

    CAS  PubMed  Google Scholar 

  • Erickson, K. I., Leckie, R. L., & Weinstein, A. M. (2014). Physical activity, fitness, and gray matter volume. Neurobiology of Aging, 35, S20–S28.

    PubMed  Google Scholar 

  • Etnier, J. L., Nowell, P. M., Landers, D. M., & Sibley, B. A. (2006). A meta-regression to examine the relationship between aerobic fitness and cognitive performance. Brain Research Reviews, 52(1), 119–130.

    PubMed  Google Scholar 

  • Garcia, D. M., Duhamel, G., & Alsop, D. C. (2005). Efficiency of inversion pulses for background suppressed arterial spin labeling. Magnetic Resonance in Medicine, 54(2), 366–372.

    PubMed  Google Scholar 

  • Haskell, W. L., Lee, I. M., Pate, R. R., Powell, K. E., Blair, S. N., Franklin, B. A., ... & Bauman, A. (2007). Physical activity and public health: Updated recommendation for adults from the American College of Sports Medicine and the American Heart Association. Circulation, 116(9), 1081, 1093.

  • Hayes, S. M., Alosco, M. L., Hayes, J. P., Cadden, C., Peterson, K. M., Allsup, K., Forman, D. E., Sperling, R. A., & Verfaellie, M. (2015). Physical activity is positively associated with episodic memory in aging. Journal of the International Neuropsychological Society, 21, 780–790.

    PubMed  PubMed Central  Google Scholar 

  • Hays, C. C., Zlatar, Z. Z., & Wierenga, C. E. (2016). The utility of cerebral blood flow as a biomarker of preclinical Alzheimer’s disease. Cellular and Molecular Neurobiology, 36(2), 167–179.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Iturria-Medina, Y., Sotero, R. C., Toussaint, P. J., Mateos-Perez, J. M., Evans, A. C., & Alzheimer’s Disease Neuroimaging Initiative. (2016). Early role of vascular dysregulation on late-onset Alzheimer/'s disease based on multifactorial data-driven analysis. Nature communications, 7.

  • Jack, C. R., Knopman, D. S., Jagust, W. J., Shaw, L. M., Aisen, P. S., Weiner, M. W., ... & Trojanowski, J. Q. (2010). Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade. The Lancet Neurology, 9(1), 119–128.

  • Johnson, N. A., Jahng, G. H., Weiner, M. W., Miller, B. L., Chui, H. C., Jagust, W. J., ... & Schuff, N. (2006, June). Pattern of cerebral hypoperfusion in Alzheimer's disease and mild cognitive impairment measured with arterial spin-labeling MR imaging: Initial experience. In International Congress Series (Vol. 1290, pp. 108–122). Elsevier.

  • Joyner, M. J., Barnes, J. N., Hart, E. C., Wallin, B. G., & Charkoudian, N. (2015). Neural control of the circulation: How sex and age differences interact in humans. Comprehensive Physiology, 5(1), 193–215.

    PubMed  PubMed Central  Google Scholar 

  • Kaminsky, L. A., Arena, R., & Myers, J. (2015, November ). Reference standards for cardiorespiratory fitness measured with cardiopulmonary exercise testing: Data from the fitness registry and the importance of exercise national database. In Mayo Clinic Proceedings (Vol. 90, no. 11, pp. 1515-1523). Elsevier.

  • Kampert, J. B., Blair, S. N., Barlow, C. E., & Kohl, H. W., III. (1996). Physical activity, physical fitness, and all-cause and cancer mortality: A prospective study of men and women. Annals of Epidemiology, 6(5), 452–457.

    CAS  PubMed  Google Scholar 

  • Kohrt, W. M., Malley, M. T., Coggan, A. R., Spina, R. J., Ogawa, T. A. K. E. S. H. I., Ehsani, A. A., ... & Holloszy, J. O. (1991). Effects of gender, age, and fitness level on response of VO2max to training in 60-71 yr olds. Journal of Applied Physiology, 71(5), 2004–2011.

  • Kramer, A. F., Hahn, S., Cohen, N. J., Banich, M. T., McAuley, E., Harrison, C. R., Chason, J., Vakil, E., Bardell, L., Boileau, R. A., & Colcombe, A. (1999). Ageing, fitness and neurocognitive function. Nature, 400(6743), 418–419.

    CAS  PubMed  Google Scholar 

  • Landau, S. M., Harvey, D., Madison, C. M., Koeppe, R. A., Reiman, E. M., Foster, N. L., et al. (2011). Associations between cognitive, functional, and FDG-PET measures of decline in AD and MCI. Neurobiology of Aging, 32(7), 1207–1218.

    PubMed  Google Scholar 

  • Lee, D. C., Sui, X., Ortega, F. B., Kim, Y. S., Church, T. S., Winett, R. A., ... & Blair, S. N. (2010). Comparisons of leisure-time physical activity and cardiorespiratory fitness as predictors of all-cause mortality in men and women. British journal of sports medicine, bjsports66209.

  • Lyden, K., Keadle, S. K., Staudenmayer, J., & Freedson, P. S. (2014). A method to estimate free-living active and sedentary behavior from an accelerometer. Medicine and Science in Sports and Exercise, 46(2), 386–397.

    PubMed  PubMed Central  Google Scholar 

  • Lu, H., Xu, F., Rodrigue, K. M., Kennedy, K. M., Cheng, Y., Flicker, B., ... & Park, D. C. (2010). Alterations in cerebral metabolic rate and blood supply across the adult lifespan. Cerebral cortex, 21(6), 1426–1434.

  • Makizako, H., Liu-Ambrose, T., Shimada, H., Doi, T., Park, H., Tsutsumimoto, K., & Suzuki, T. (2015). Moderate-intensity physical activity, hippocampal volume, and memory in older adults with mild cognitive impairment. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 70, 480–486.

    CAS  Google Scholar 

  • Middleton, L., Kirkland, S., & Rockwood, K. (2008). Prevention of CIND by physical activity: different impact on VCI-ND compared with MCI. Journal of the neurological sciences, 269(1–2), 80–84.

  • Miller, V. M., Garovic, V. D., Kantarci, K., Barnes, J. N., Jayachandran, M., Mielke, M. M., Joyner, M. J., Shuster, L. T., & Rocca, W. A. (2013). Sex-specific risk of cardiovascular disease and cognitive decline: Pregnancy and menopause. Biology of Sex Differences, 4(1), 6.

    PubMed  PubMed Central  Google Scholar 

  • Myers, J., Kaykha, A., George, S., Abella, J., Zaheer, N., Lear, S., Yamazaki, T., & Froelicher, V. (2004). Fitness versus physical activity patterns in predicting mortality in men. The American Journal of Medicine, 117(12), 912–918.

    PubMed  Google Scholar 

  • Nebel, R. A., Aggarwal, N. T., Barnes, L. L., Gallagher, A., Goldstein, J. M., Kantarci, K., et al. (2018). Understanding the impact of sex and gender in Alzheimer's disease: A call to action. Alzheimer's & Dementia., 14, 1171–1183.

    Google Scholar 

  • Okonkwo, O. C., Xu, G., Oh, J. M., Dowling, N. M., Carlsson, C. M., Gallagher, C. L., ... & LaRue, A. (2014a). Cerebral blood flow is diminished in asymptomatic middle-aged adults with maternal history of Alzheimer's disease. Cerebral Cortex, 24(4), 978–988.

  • Okonkwo, O. C., Schultz, S. A., Oh, J. M., Larson, J., Edwards, D., Cook, D., ... & Bendlin, B. B. (2014b). Physical activity attenuates age-related biomarker alterations in preclinical AD. Neurology, 83(19), 1753–1760.

  • Park, M. S., Chung, S. Y., Chang, Y., & Kim, K. (2009). Physical activity and physical fitness as predictors of all-cause mortality in Korean men. Journal of Korean Medical Science, 24(1), 13–19.

    PubMed  PubMed Central  Google Scholar 

  • Pereira, A. C., Huddleston, D. E., Brickman, A. M., Sosunov, A. A., Hen, R., McKhann, G. M., Sloan, R., Gage, F. H., Brown, T. R., & Small, S. A. (2007). An in vivo correlate of exercise-induced neurogenesis in the adult dentate gyrus. Proceedings of the National Academy of Sciences, 104(13), 5638–5643.

    CAS  Google Scholar 

  • Physical Activity Guidelines Advisory Committee. (2018). Physical activity guidelines advisory committee scientific report. Washington, DC: U.S. Department of Health and Human Services.

    Google Scholar 

  • Piercy K. L., Troiano R. P., Ballard R. M., Carlson, S. A., Fulton, J. E., Galuska, D. A., George, S. M., Olson, R. D. (2018). The physical activity guidelines for Americans. JAMA. Published online November 12, 2018. https://doi.org/10.1001/jama.2018.14854

  • Prince, S. A., Adamo, K. B., Hamel, M. E., Hardt, J., Gorber, S. C., & Tremblay, M. (2008). A comparison of direct versus self-report measures for assessing physical activity in adults: A systematic review. International Journal of Behavioral Nutrition and Physical Activity, 5(1), 56.

    PubMed  Google Scholar 

  • Sager, M. A., Hermann, B., & La Rue, A. (2005). Middle-aged children of persons with Alzheimer’s disease: APOE genotypes and cognitive function in the Wisconsin registry for Alzheimer’s prevention. Journal of Geriatric Psychiatry and Neurology, 18(4), 245–249.

    PubMed  Google Scholar 

  • Saltin, B., Blomqvist, G., Mitchell, J. H., et al. (1968). Response to exercise after bed rest and after training: a longitudinal study of adaptive changes in oxygen transport and body composition. Circulation, 37/38(suppl VII), VII-1–VII-78.

    Google Scholar 

  • Seals, D. R., Hagberg, J. M., Hurley, B. F., Ehsani, A. A., & Holloszy, J. O. (1984). Endurance training in older men and women. I. Cardiovascular responses to exercise. Journal of applied physiology, 57(4), 1024–1029.

    CAS  PubMed  Google Scholar 

  • Seals, D. R., DeSouza, C. A., Donato, A. J., & Tanaka, H. (2008). Habitual exercise and arterial aging. Journal of Applied Physiology, 105(4), 1323–1332.

    PubMed  PubMed Central  Google Scholar 

  • Skinner, J. S., Wilmore, K. M., Krasnoff, J. B., JaskÓlski, A., JaskÓlska, A., Gagnon, J., ... & Bouchard, C. (2000). Adaptation to a standardized training program and changes in fitness in a large, heterogeneous population: The HERITAGE family study. Medicine and Science in Sports and Exercise, 32(1), 157–161.

  • Stern, Y. (2012). Cognitive reserve in ageing and Alzheimer's disease. The Lancet Neurology, 11(11), 1006–1012.

  • Tager, I. B., Hollenberg, M., & Satariano, W. A. (1998). Association between self-reported leisure-time physical activity and measures of cardiorespiratory fitness in an elderly population. American Journal of Epidemiology, 147(10), 921–931.

    CAS  PubMed  Google Scholar 

  • Tarumi, T., & Zhang, R. (2017). Cerebral blood flow in normal aging adults: Cardiovascular determinants, clinical implications, and aerobic fitness. Journal of Neurochemistry.

  • Thambisetty, M., Beason-Held, L., An, Y., Kraut, M. A., & Resnick, S. M. (2010). APOE ε4 genotype and longitudinal changes in cerebral blood flow in normal aging. Archives of Neurology, 67(1), 93–98.

    PubMed  PubMed Central  Google Scholar 

  • Thomas, B. P., Yezhuvath, U. S., Tseng, B. Y., Liu, P., Levine, B. D., Zhang, R., & Lu, H. (2013). Life-long aerobic exercise preserved baseline cerebral blood flow but reduced vascular reactivity to CO2. Journal of Magnetic Resonance Imaging, 38(5), 1177–1183.

    PubMed  Google Scholar 

  • Troiano, R. P., Berrigan, D., Dodd, K. W., Masse, L. C., Tilert, T., & McDowell, M. (2008). Physical activity in the United States measured by accelerometer. Medicine and Science in Sports and Exercise, 40(1), 181–188.

    PubMed  Google Scholar 

  • Voss, M. W., Weng, T. B., Burzynska, A. Z., Wong, C. N., Cooke, G. E., Clark, R., ... & McAuley, E. (2016). Fitness, but not physical activity, is related to functional integrity of brain networks associated with aging. Neuroimage, 131, 113–125.

  • Wang, Z., Das, S. R., Xie, S. X., Arnold, S. E., Detre, J. A., Wolk, D. A., & Alzheimer's Disease Neuroimaging Initiative. (2013). Arterial spin labeled MRI in prodromal Alzheimer's disease: A multi-site study. NeuroImage: Clinical, 2, 630–636.

    Google Scholar 

  • Wei, M., Gibbons, L. W., Kampert, J. B., Nichaman, M. Z., & Blair, S. N. (2000). Low cardiorespiratory fitness and physical inactivity as predictors of mortality in men with type 2 diabetes. Annals of Internal Medicine, 132(8), 605–611.

    CAS  PubMed  Google Scholar 

  • Wierenga, C. E., Clark, L. R., Dev, S. I., Shin, D. D., Jurick, S. M., Rissman, R. A., Liu, T. T., & Bondi, M. W. (2013). Interaction of age and APOE genotype on cerebral blood flow at rest. Journal of Alzheimer's Disease, 34(4), 921–935.

    CAS  PubMed  Google Scholar 

  • Wierenga, C. E., Hays, C. C., & Zlatar, Z. Z. (2014). Cerebral blood flow measured by arterial spin labeling MRI as a preclinical marker of Alzheimer's disease. Journal of Alzheimer's Disease, 42(s4), S411–S419.

    PubMed  Google Scholar 

  • Xu, G., Rowley, H. A., Wu, G., Alsop, D. C., Shankaranarayanan, A., Dowling, M., Christian, B. T., Oakes, T. R., & Johnson, S. C. (2010). Reliability and precision of pseudo-continuous arterial spin labeling perfusion MRI on 3.0 T and comparison with 15O-water PET in elderly subjects at risk for Alzheimer's disease. NMR in Biomedicine, 23(3), 286–293.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ye, F. Q., Frank, J. A., Weinberger, D. R., McLaughlin, A. C. (2000). Noise reduction in 3D perfusion imaging by attenuating the static signal in arterial spin tagging (ASSIST). Magn Reson Med. 44, 92–100.

  • Zimmerman, B., Sutton, B. P., Low, K. A., Fletcher, M. A., Tan, C. H., Schneider-Garces, N., ... & Fabiani, M. (2014). Cardiorespiratory fitness mediates the effects of aging on cerebral blood flow. Frontiers in Aging Neuroscience, 6: 59.

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Acknowledgements

The authors gratefully acknowledge Jennifer Oh for her assistance in the data analysis and the support of researchers and staff at the University of Wisconsin-Madison for their assistance in recruitment and data collection. Above all, the authors thank their dedicated volunteers for their participation in this research.

This work was supported by National Institute on Aging grants K23 AG045957 (OCO), R21 AG051858 (OCO), R01 AG027161 (SCJ), R01 AG021155 (SCJ), P50 AG033514 (SA); and by a Clinical and Translational Science Award (UL1RR025011) to the University of Wisconsin, Madison. Portions of this research were supported by the Extendicare Foundation, the Alzheimer’s Association, Wisconsin Alumni Research Foundation, the Helen Bader Foundation, Northwestern Mutual Foundation, and the Veterans Administration including facilities and resources at the Geriatric Research Education and Clinical Center of the William S. Middleton Memorial Veterans Hospital, Madison, WI. Ryan J. Dougherty was supported by a National Research Service Award from the National Institute on Aging of the National Institutes of Health under Award Number F31AG062009. Jacob B. Lindheimer was supported by Career Development Award Number IK2 CX001679 from the United States (U.S.) Department of Veterans Affairs Clinical Sciences R&D (CSR&D) Service. The contents do not represent the views of the National Institutes of Health, Department of Veterans Affairs or the United States Government.

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Ryan J. Dougherty, Elizabeth A. Boots, Jacob B. Lindheimer, Aaron J. Stegner, Stephanie Van Riper, Dorothy F. Edwards, Catherine L. Gallagher, Cynthia M. Carlsson, Howard A. Rowley, Barbara B. Bendlin, Sanjay Asthana, Bruce P. Hermann, Mark A. Sager, Sterling C. Johnson, Ozioma C. Okonkwo, and Dane B. Cook declare no conflicts of interest.

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All procedures followed were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

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Dougherty, R.J., Boots, E.A., Lindheimer, J.B. et al. Fitness, independent of physical activity is associated with cerebral blood flow in adults at risk for Alzheimer’s disease. Brain Imaging and Behavior 14, 1154–1163 (2020). https://doi.org/10.1007/s11682-019-00068-w

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