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A longitudinal study of motor performance and striatal [18F]fluorodopa uptake in Parkinson’s disease

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Abstract

Although [18F]fluoro-l-dopa [FDOPA] positron emission tomography (PET) has been used as a surrogate outcome measure in Parkinson’s disease therapeutic trials, this biomarker has not been proven to reflect clinical status longitudinally. We completed a retrospective analysis of relationships between computerized sampling of motor performance, FDOPA PET, and clinical outcome scales, repeated over 4 years, in 26 Parkinson’s disease (PD) patients and 11 healthy controls. Mixed effects analyses showed that movement time and tongue strength best differentiated PD from control subjects. In the treated PD cohort, motor performance measures changed gradually in contrast to a steady decline in striatal FDOPA uptake. Prolonged reaction and movement time were related to lower caudate nucleus FDOPA uptake, and abnormalities in hand fine force control were related to mean striatal FDOPA uptake. These findings provide evidence that regional loss of nigrostriatal inputs to frontostriatal networks affects specific aspects of motor function.

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Abbreviations

D:

Dominant side

FDOPA:

[18F]fluoro-l-dopa

MRI:

Magnetic resonance imaging

ND:

Non-dominant side

PD:

Parkinson’s disease

PET:

Positron emission tomography

UPDRS:

Unified Parkinson’s Disease Rating Scale

VOI:

Volume of interest

References

  • Aarsland, D., & Kurz, M. W. (2009). The epidemiology of dementia associated with Parkinson disease. J Neurol Sci.

  • Alexander, G. E., DeLong, M. R., & Strick, P. L. (1986). Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annual Review of Neuroscience, 9, 357–381.

    Article  PubMed  CAS  Google Scholar 

  • Barlow, S. M., & Abbs, J. H. (1984). Orofacial fine motor control impairments in congenital spasticity: evidence against hypertonus-related performance deficits. Neurology, 34(2), 145–150.

    PubMed  CAS  Google Scholar 

  • Bernheimer, H., Birkmayer, W., Hornykiewicz, O., Jellinger, K., & Seitelberger, F. (1973). Brain dopamine and the syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations. Journal of the Neurological Sciences, 20(4), 415–455.

    Article  PubMed  CAS  Google Scholar 

  • Braak, H., Del Tredici, K., Rub, U., de Vos, R. A., Jansen Steur, E. N., & Braak, E. (2003). Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiology of Aging, 24(2), 197–211.

    Article  PubMed  Google Scholar 

  • Brown, W. D., Taylor, M. D., Roberts, A. D., Oakes, T. R., Schueller, M. J., Holden, J. E., et al. (1999). FluoroDOPA PET shows the nondopaminergic as well as dopaminergic destinations of levodopa. Neurology, 53(6), 1212–1218.

    PubMed  CAS  Google Scholar 

  • Bruck, A., Aalto, S., Nurmi, E., Vahlberg, T., Bergman, J., & Rinne, J. O. (2006). Striatal subregional 6-[18F]fluoro-L-dopa uptake in early Parkinson’s disease: a two-year follow-up study. Movement Disorders, 21(7), 958–963.

    Article  PubMed  Google Scholar 

  • Carbon, M., Felice Ghilardi, M., Dhawan, V., & Eidelberg, D. (2007). Correlates of movement initiation and velocity in Parkinson’s disease: a longitudinal PET study. Neuroimage, 34(1), 361–370.

    Article  PubMed  Google Scholar 

  • Connor, N. P., Russell, J. A., Wang, H., Jackson, M. A., Mann, L., & Kluender, K. (2009). Effect of tongue exercise on protrusive force and muscle fiber area in aging rats. Journal of Speech, Language, and Hearing Research, 52(3), 732–744.

    Article  PubMed  Google Scholar 

  • Crow, H. C., & Ship, J. A. (1996). Tongue strength and endurance in different aged individuals. The Journals of Gerontology. Series A: Biological Sciences and Medical Sciences, 51(5), M247–250.

    Article  CAS  Google Scholar 

  • de la Fuente-Fernandez, R., Kishore, A., Calne, D. B., Ruth, T. J., & Stoessl, A. J. (2000). Nigrostriatal dopamine system and motor lateralization. Behavioural Brain Research, 112(1–2), 63–68.

    Article  PubMed  Google Scholar 

  • Desmurget, M., Grafton, S. T., Vindras, P., Grea, H., & Turner, R. S. (2003). Basal ganglia network mediates the control of movement amplitude. Experimental Brain Research, 153(2), 197–209.

    Article  CAS  Google Scholar 

  • Diederich, N. J., Moore, C. G., Leurgans, S. E., Chmura, T. A., & Goetz, C. G. (2003). Parkinson disease with old-age onset: a comparative study with subjects with middle-age onset. Archives of Neurology, 60(4), 529–533.

    Article  PubMed  Google Scholar 

  • Draper, I. T., & Johns, R. J. (1964). The disordered movement in Parkinsonism and the effect of drug treatment. Bulletin of the Johns Hopkins Hospital, 115, 465–480.

    PubMed  CAS  Google Scholar 

  • El Sharkawi, A., Ramig, L., Logemann, J. A., Pauloski, B. R., Rademaker, A. W., Smith, C. H., et al. (2002). Swallowing and voice effects of Lee Silverman Voice Treatment (LSVT): a pilot study. Journal of Neurology, Neurosurgery and Psychiatry, 72(1), 31–36.

    Article  CAS  Google Scholar 

  • Elbaz, A., Bower, J. H., Maraganore, D. M., McDonnell, S. K., Peterson, B. J., Ahlskog, J. E., et al. (2002). Risk tables for Parkinsonism and Parkinson’s disease. Journal of Clinical Epidemiology, 55(1), 25–31.

    Article  PubMed  Google Scholar 

  • Evarts, E. V., Teravainen, H., & Calne, D. B. (1981). Reaction time in Parkinson’s disease. Brain, 104(Pt 1), 167–186.

    Article  PubMed  CAS  Google Scholar 

  • Fahn, S., Elton, R. L., & Members, U. P. (1987). Unified Parkinson’s Disease Rating Scale. In S. Fahn, C. D. Marsden, M. Goldstein, & D. B. Calne (Eds.), Recent developments in Parkinsons disease (Vol. 2, p. 153–163, 293–304). Florham Park: McMillan Healthcare Information.

    Google Scholar 

  • Flowers, K. (1975). Ballistic and corrective movements on an aiming task. Intention tremor and parkinsonian movement disorders compared. Neurology, 25(5), 413–421.

    PubMed  CAS  Google Scholar 

  • Gentil, M., Tournier, C. L., Pollak, P., & Benabid, A. L. (1999). Effect of bilateral subthalamic nucleus stimulation and dopatherapy on oral control in Parkinson’s disease. European Neurology, 42(3), 136–140.

    Article  PubMed  CAS  Google Scholar 

  • Gibb, W. R., & Lees, A. J. (1988). The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson’s disease. Journal of Neurology, Neurosurgery and Psychiatry, 51(6), 745–752.

    Article  CAS  Google Scholar 

  • Hallett, M., & Khoshbin, S. (1980). A physiological mechanism of bradykinesia. Brain, 103(2), 301–314.

    Article  PubMed  CAS  Google Scholar 

  • Hauber, W., & Schmidt, W. J. (1994). Differential effects of lesions of the dorsomedial and dorsolateral caudate-putamen on reaction time performance in rats. Behavioural Brain Research, 60(2), 211–215.

    Article  PubMed  CAS  Google Scholar 

  • Hoehn, M. M., & Yahr, M. D. (1967). Parkinsonism: onset, progression and mortality. Neurology, 17(5), 427–442.

    PubMed  CAS  Google Scholar 

  • Lasker, A. G., & Zee, D. S. (1997). Ocular motor abnormalities in Huntington’s disease. Vision Research, 37(24), 3639–3645.

    Article  PubMed  CAS  Google Scholar 

  • Levy, G., Louis, E. D., Cote, L., Perez, M., Mejia-Santana, H., Andrews, H., et al. (2005). Contribution of aging to the severity of different motor signs in Parkinson disease. Archives of Neurology, 62(3), 467–472.

    Article  PubMed  Google Scholar 

  • Marek, K., Innis, R., van Dyck, C., Fussell, B., Early, M., Eberly, S., et al. (2001). [123I]beta-CIT SPECT imaging assessment of the rate of Parkinson’s disease progression. Neurology, 57(11), 2089–2094.

    PubMed  CAS  Google Scholar 

  • Montgomery, E. B., Jr., Nuessen, J., & Gorman, D. S. (1991). Reaction time and movement velocity abnormalities in Parkinson’s disease under different task conditions. Neurology, 41(9), 1476–1481.

    PubMed  Google Scholar 

  • Morrish, P. K., Sawle, G. V., & Brooks, D. J. (1996a). An [18F]dopa-PET and clinical study of the rate of progression in Parkinson’s disease. Brain, 119(Pt 2), 585–591.

    Article  PubMed  Google Scholar 

  • Morrish, P. K., Sawle, G. V., & Brooks, D. J. (1996b). Regional changes in [18F]dopa metabolism in the striatum in Parkinson’s disease. Brain, 119(Pt 6), 2097–2103.

    Article  PubMed  Google Scholar 

  • Nagasawa, H., Saito, H., Kogure, K., Hatazawa, J., Itoh, M., Fujiwara, T., et al. (1993). 6-[18F]fluorodopa metabolism in patients with hemiparkinsonism studied by positron emission tomography. Journal of the Neurological Sciences, 115(2), 136–143.

    Article  PubMed  CAS  Google Scholar 

  • Nocera, J., Horvat, M., & Ray, C. T. (2009). Effects of home-based exercise on postural control and sensory organization in individuals with Parkinson disease. Parkinsonism Relat Disord.

  • O’Day, C., Frank, E., Montgomery, A., Nichols, M., & McDade, H. (2005). Repeated tongue and hand strength measurements in normal adults and individuals with Parkinson’s disease. Intenational Journal of Orofacial Myology, 31, 15–25.

    Google Scholar 

  • Patlak, C. S., & Blasberg, R. G. (1985). Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data. Generalizations. Journal of Cerebral Blood Flow Metabolism, 5(4), 584–590.

    Article  PubMed  CAS  Google Scholar 

  • Pirker, W. (2003). Correlation of dopamine transporter imaging with parkinsonian motor handicap: how close is it? Movement Disorders, 18(Suppl 7), S43–51.

    Article  PubMed  Google Scholar 

  • Rinne, J. O., Portin, R., Ruottinen, H., Nurmi, E., Bergman, J., Haaparanta, M., et al. (2000). Cognitive impairment and the brain dopaminergic system in Parkinson disease: [18F]fluorodopa positron emission tomographic study. Archives of Neurology, 57(4), 470–475.

    Article  PubMed  CAS  Google Scholar 

  • Russmann, H., Ghika, J., Villemure, J. G., Robert, B., Bogousslavsky, J., Burkhard, P. R., et al. (2004). Subthalamic nucleus deep brain stimulation in Parkinson disease patients over age 70 years. Neurology, 63(10), 1952–1954.

    PubMed  CAS  Google Scholar 

  • Seibyl, J. P., Marek, K. L., Quinlan, D., Sheff, K., Zoghbi, S., Zea-Ponce, Y., et al. (1995). Decreased single-photon emission computed tomographic [123I]beta-CIT striatal uptake correlates with symptom severity in Parkinson’s disease. Annals of Neurology, 38(4), 589–598.

    Article  PubMed  CAS  Google Scholar 

  • Solomon, N., Lorell, D., Robin, D., Rodnitzky, R., & Luscheni, E. (1995). Tongue strength and endurance in mild to moderate Parkinson’s disease. Journal of medical Speech-Language Pathology, 3, 15–26.

    Google Scholar 

  • Stelmach, G. E., Teasdale, N., Phillips, J., & Worringham, C. J. (1989). Force production characteristics in Parkinson’s disease. Experimental Brain Research, 76(1), 165–172.

    Article  CAS  Google Scholar 

  • Tunik, E., Houk, J. C., & Grafton, S. T. (2009). Basal ganglia contribution to the initiation of corrective submovements. Neuroimage, 47(4), 1757–1766.

    Article  PubMed  Google Scholar 

  • Van Dyck, C. H., Avery, R. A., MacAvoy, M. G., Marek, K. L., Quinlan, D. M., Baldwin, R. M., et al. (2008). Striatal dopamine transporters correlate with simple reaction time in elderly subjects. Neurobiology of Aging, 29, 1237–1246.

    Article  PubMed  Google Scholar 

  • Vingerhoets, F. J., Schulzer, M., Calne, D. B., & Snow, B. J. (1997). Which clinical sign of Parkinson’s disease best reflects the nigrostriatal lesion? Annals of Neurology, 41(1), 58–64.

    Article  PubMed  CAS  Google Scholar 

  • Whone, A. L., Watts, R. L., Stoessl, A. J., Davis, M., Reske, S., Nahmias, C., et al. (2003). Slower progression of Parkinson’s disease with ropinirole versus levodopa: The REAL-PET study. Annals of Neurology, 54(1), 93–101.

    Article  PubMed  CAS  Google Scholar 

  • Wing, A. M. (1988). A comparison of the rate of pinch grip force increases and decreases in Parkinsonian bradykinesia. Neuropsychologica, 26(3), 479–482.

    Article  CAS  Google Scholar 

  • Yousefi, B., Tadibi, V., Khoei, A. F., & Montazeri, A. (2009). Exercise therapy, quality of life, and activities of daily living in patients with Parkinson disease: a small scale quasi-randomised trial. Trials, 10, 67.

    Article  PubMed  Google Scholar 

  • Yust-Katz, S., Tesler, D., Treves, T. A., Melamed, E., & Djaldetti, R. (2008). Handedness as a predictor of side of onset of Parkinson’s disease. Parkinsonism & Related Disorders, 14(8), 633–635.

    Article  Google Scholar 

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Acknowledgements

This work was supported with use of facilities at the William S. Middleton Memorial Veterans Hospital Geriatric Research Education and Clinical Center and the Waisman Laboratory for Brain Imaging and Behavior, Madison, WI, USA. The manuscript was edited by Gundega Korsts, Science Editor, Madison, WI.

Funding

This work was supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Clinical Science Research and Development Service [grant to C.G]; National Institutes of Health [grant number 1R29NS31612 to D.B] and University of Wisconsin Institute for Clinical and Translational Research, funded through a National Institutes of Health Clinical and Translational Science Award, [grant number 1UL1RR025011 to C.G.].

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Authors and Affiliations

  1. William S. Middleton Memorial Veterans Hospital, 6112B, 2500 Overlook Terrace Dr., Madison, WI, 53792, USA

    Catherine L. Gallagher

  2. Department of Neurology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

    Catherine L. Gallagher & James H. Abbs

  3. Department of Medicine, University of Wisconsin, Madison, WI, USA

    Sterling C. Johnson, Barbara B. Bendlin & Guofan Xu

  4. Geriatric Research Education and Clinical Center, William S. Middleton Memorial Veterans Hospital, Madison, WI, USA

    Sterling C. Johnson, Barbara B. Bendlin & Guofan Xu

  5. Department of Biostatistics and Medical Informatics, University of Wisconsin, Madison, WI, USA

    Moo K. Chung & Richard A. Konopacki

  6. Waisman Center for Brain Imaging and Behavior, Madison, WI, USA

    Moo K. Chung & Terrence R. Oakes

  7. Department of Medical Physics, University of Wisconsin, Madison, WI, USA

    James E. Holden, Robert J. Nickles & Onofre T. DeJesus

  8. Carolinas Neuromuscular/ALS-MDA Center, Charlotte, NC, USA

    Benjamin R. Brooks

  9. Aurora Sinai Medical Center, Milwaukee, WI, USA

    Selami Dogan

  10. Department of Radiology, University of Wisconsin, Madison, WI, USA

    Robert W. Pyzalski

  11. Department of Radiology, Medical College of Wisconsin, Milwaukee, WI, USA

    W. Douglas Brown

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  1. Catherine L. Gallagher
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  2. Sterling C. Johnson
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  3. Barbara B. Bendlin
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  9. Selami Dogan
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  12. Robert J. Nickles
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  14. Onofre T. DeJesus
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  15. W. Douglas Brown
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Correspondence to Catherine L. Gallagher.

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Gallagher, C.L., Johnson, S.C., Bendlin, B.B. et al. A longitudinal study of motor performance and striatal [18F]fluorodopa uptake in Parkinson’s disease. Brain Imaging and Behavior 5, 203–211 (2011). https://doi.org/10.1007/s11682-011-9124-5

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