Skip to main content
SpringerLink
Log in

Basal ganglia cerebral blood flow associates with psychomotor speed in adults with type 1 diabetes

  • Original Research
  • Published:
Brain Imaging and Behavior Aims and scope Submit manuscript

Abstract

Type 1 diabetes is associated with slower psychomotor speed, but the neural basis of this relationship is not yet understood. The basal ganglia are a set of structures that are vulnerable to small vessel disease, particularly in individuals with type 1 diabetes. Thus, we examined the relationship between psychomotor speed and resting state resting cerebral blood flow in a sample of adults with diabetes onset during childhood (≤ 17 years of age). The sample included 77 patients (39 M, 38 F) with a mean age of 47.43 ± 5.72 years, age of onset at 8.50 ± 4.26 years, and duration of disease of 38.92 ± 4.18 years. Resting cerebral blood flow was quantified using arterial spin labeling. After covarying for sex, years of education and normalized gray matter volume, slower psychomotor speed was associated with lower cerebral blood flow in bilateral caudate nucleus-thalamus and a region in the superior frontal gyrus. These results suggest that the basal ganglia and frontal cortex may underlie slower psychomotor speed in individuals with type 1 diabetes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Alsop, D. C., Detre, J. A., Golay, X., Günther, M., Hendrikse, J., Hernandez-Garcia, L., … Zaharchuk, G. (2015). Recommended implementation of arterial spin-labeled perfusion MRI for clinical applications: a consensus of the ISMRM perfusion study group and the European consortium for ASL in dementia. Magnetic Resonance in Medicine, 73(1), spcone. https://doi.org/10.1002/mrm.25607.

  • Batista, S., Zivadinov, R., Hoogs, M., Bergsland, N., Heininen-Brown, M., Dwyer, M. G., … Benedict, R. H. B. (2012). Basal ganglia, thalamus and neocortical atrophy predicting slowed cognitive processing in multiple sclerosis. Journal of Neurology, 259(1), 139–146. https://doi.org/10.1007/s00415-011-6147-1.

  • Bernbaum, M., Menon, B. K., Fick, G., Smith, E. E., Goyal, M., Frayne, R., & Coutts, S. B. (2015). Reduced blood flow in normal white matter predicts development of leukoaraiosis. Journal of Cerebral Blood Flow and Metabolism: Official Journal of the International Society of Cerebral Blood Flow and Metabolism, 35(10), 1610–1615. https://doi.org/10.1038/jcbfm.2015.92.

    Article  CAS  Google Scholar 

  • Bolo, N. R., Musen, G., Simonson, D. C., Nickerson, L. D., Flores, V. L., Siracusa, T., … Jacobson, A. M. (2015a). Functional connectivity of insula, basal ganglia, and prefrontal executive control networks during hypoglycemia in type 1 diabetes. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 35(31), 11012–11023. https://doi.org/10.1523/JNEUROSCI.0319-15.2015.

  • Bolo, N. R., Musen, G., Simonson, D. C., Nickerson, L. D., Flores, V. L., Siracusa, T., … Jacobson, A. M. (2015b). Functional connectivity of insula, basal ganglia, and prefrontal executive control networks during hypoglycemia in type 1 diabetes. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 35(31), 11012–11023. https://doi.org/10.1523/JNEUROSCI.0319-15.2015.

  • Cranston, I., Reed, L. J., Marsden, P. K., & Amiel, S. A. (2001). Changes in regional brain (18)F-fluorodeoxyglucose uptake at hypoglycemia in type 1 diabetic men associated with hypoglycemia unawareness and counter-regulatory failure. Diabetes, 50(10), 2329–2336.

    Article  CAS  Google Scholar 

  • Detre, J. A., Rao, H., Wang, D. J. J., Chen, Y. F., & Wang, Z. (2012). Applications of arterial spin labeled MRI in the brain. Journal of Magnetic Resonance Imaging: JMRI, 35(5), 1026–1037. https://doi.org/10.1002/jmri.23581.

    Article  PubMed  Google Scholar 

  • Detre J. A., & Wang, J. (2002). Technical aspects and utility of fMRI using BOLD and ASL. Clinical Neurophysiology, 113, 621–634. https://doi.org/10.1016/S1388-2457(02)00038-X.

    Article  PubMed  Google Scholar 

  • Duckrow, R. B. (1995). Decreased cerebral blood flow during acute hyperglycemia. Brain Research, 703(1–2), 145–150.

    Article  CAS  Google Scholar 

  • Feil, D. G., Zhu, C. W., & Sultzer, D. L. (2012). The relationship between cognitive impairment and diabetes self-management in a population-based community sample of older adults with Type 2 diabetes. Journal of Behavioral Medicine, 35(2), 190–199. https://doi.org/10.1007/s10865-011-9344-6.

    Article  PubMed  Google Scholar 

  • Gallardo-Moreno, G. B., González-Garrido, A. A., Gudayol-Ferré, E., & Guàrdia-Olmos, J. (2015). Type 1 diabetes modifies brain activation in young patients while performing visuospatial working memory tasks. Journal of Diabetes Research, 2015, 703512. https://doi.org/10.1155/2015/703512.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Graybiel, A. M., Aosaki, T., Flaherty, A. W., & Kimura, M. (1994). The basal ganglia and adaptive motor control. Science (New York), 265(5180), pp. 1826–1831.

    Article  CAS  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. https://doi.org/10.1007/s10571-015-0261-z.

    Article  PubMed  PubMed Central  Google Scholar 

  • Heikkilä, O., Lundbom, N., Timonen, M., Groop, P.-H., Heikkinen, S., & Mäkimattila, S. (2010). Evidence for abnormal glucose uptake or metabolism in thalamus during acute hyperglycaemia in type 1 diabetes—a 1H MRS study. Metabolic Brain Disease, 25(2), 227–234. https://doi.org/10.1007/s11011-010-9199-5.

    Article  CAS  PubMed  Google Scholar 

  • Hughes, T. M., Ryan, C. M., Aizenstein, H. J., Nunley, K., Gianaros, P. J., Miller, R., … Rosano, C. (2013). Frontal gray matter atrophy in middle aged adults with type 1 diabetes is independent of cardiovascular risk factors and diabetes complications. Journal of Diabetes and Its Complications, 27(6), 558–564. https://doi.org/10.1016/j.jdiacomp.2013.07.001.

  • Hwang, M., Tudorascu, D. L., Nunley, K., Karim, H., Aizenstein, H. J., Orchard, T. J., & Rosano, C. (2016). Brain activation and psychomotor speed in middle-aged patients with type 1 diabetes: relationships with hyperglycemia and brain small vessel disease. Journal of Diabetes Research, 2016, 9571464. https://doi.org/10.1155/2016/9571464.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jacobs, H. I. L., Leritz, E. C., Williams, V. J., Van Boxtel, M. P. J., van der Elst, W., Jolles, J., … Salat, D. H. (2013). Association between white matter microstructure, executive functions, and processing speed in older adults: the impact of vascular health. Human Brain Mapping, 34(1), 77–95. https://doi.org/10.1002/hbm.21412.

  • Jiménez-Bonilla, J. F., Quirce, R., Hernández, A., Vallina, N. K., Guede, C., Banzo, I., … Carril, J. M. (2001). Assessment of cerebral perfusion and cerebrovascular reserve in insulin-dependent diabetic patients without central neurological symptoms by means of 99mTc-HMPAO SPET with acetazolamide. European Journal of Nuclear Medicine, 28(11), 1647–1655. https://doi.org/10.1007/s002590100595.

  • Jokinen, P., Karrasch, M., Brück, A., Johansson, J., Bergman, J., & Rinne, J. O. (2013). Cognitive slowing in Parkinson’s disease is related to frontostriatal dopaminergic dysfunction. Journal of the Neurological Sciences, 329(1–2), 23–28. https://doi.org/10.1016/j.jns.2013.03.006.

    Article  CAS  PubMed  Google Scholar 

  • Kikano, G. E., LaManna, J. C., & Harik, S. I. (1989). Brain perfusion in acute and chronic hyperglycemia in rats. Stroke; a Journal of Cerebral Circulation, 20(8), 1027–1031.

    Article  CAS  Google Scholar 

  • Miller, R. G., Secrest, A. M., Sharma, R. K., Songer, T. J., & Orchard, T. J. (2012). Improvements in the life expectancy of type 1 diabetes: the Pittsburgh Epidemiology of Diabetes Complications study cohort. Diabetes, 61(11), 2987–2992. https://doi.org/10.2337/db11-1625.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mogenson, G. J., Jones, D. L., & Yim, C. Y. (1980). From motivation to action: functional interface between the limbic system and the motor system. Progress in Neurobiology, 14(2–3), 69–97.

    Article  CAS  Google Scholar 

  • Moulton, C. D., Costafreda, S. G., Horton, P., Ismail, K., & Fu, C. H. Y. (2015). Meta-analyses of structural regional cerebral effects in type 1 and type 2 diabetes. Brain Imaging and Behavior, 9(4), 651–662. https://doi.org/10.1007/s11682-014-9348-2.

    Article  PubMed  Google Scholar 

  • Naismith, S., Hickie, I., Ward, P. B., Turner, K., Scott, E., Little, C., … Parker, G. (2002). Caudate nucleus volumes and genetic determinants of homocysteine metabolism in the prediction of psychomotor speed in older persons with depression. The American Journal of Psychiatry, 159(12), 2096–2098. https://doi.org/10.1176/appi.ajp.159.12.2096.

  • Northam, E. A., Rankins, D., Lin, A., Wellard, R. M., Pell, G. S., Finch, S. J., … Cameron, F. J. (2009). Central nervous system function in youth with type 1 diabetes 12 years after disease onset. Diabetes Care, 32(3), 445–450. https://doi.org/10.2337/dc08-1657.

  • Nunley, K. A., Rosano, C., Ryan, C. M., Jennings, J. R., Aizenstein, H. J., Zgibor, J. C., … Saxton, J. A. (2015). Clinically relevant cognitive impairment in middle-aged adults with childhood-onset type 1 diabetes. Diabetes Care, 38(9), 1768–1776. https://doi.org/10.2337/dc15-0041.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nunley, K. A., Ryan, C. M., Aizenstein, H. J., MacCloud, R. L., Orchard, T. J., & Rosano, C. (2017). Regional gray matter volumes as related to psychomotor slowing in adults with type 1 diabetes. Psychosomatic Medicine. https://doi.org/10.1097/PSY.0000000000000449.

  • Nunley, K. A., Ryan, C. M., Orchard, T. J., Aizenstein, H. J., Jennings, J. R., Ryan, J., … Rosano, C. (2015). White matter hyperintensities in middle-aged adults with childhood-onset type 1 diabetes. Neurology, 84(20), 2062–2069. https://doi.org/10.1212/WNL.0000000000001582.

  • O’Brien, L. M., Ziegler, D. A., Deutsch, C. K., Frazier, J. A., Herbert, M. R., & Locascio, J. J. (2011). Statistical adjustments for brain size in volumetric neuroimaging studies: some practical implications in methods. Psychiatry Research, 193(2), 113–122. https://doi.org/10.1016/j.pscychresns.2011.01.007.

    Article  PubMed  PubMed Central  Google Scholar 

  • Pambianco, G., Costacou, T., Ellis, D., Becker, D. J., Klein, R., & Orchard, T. J. (2006). The 30-year natural history of type 1 diabetes complications. Diabetes, 55(5), 1463–1469. https://doi.org/10.2337/db05-1423.

    Article  CAS  PubMed  Google Scholar 

  • Pantoni, L. (2010). Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. The Lancet Neurology, 9(7), 689–701. https://doi.org/10.1016/S1474-4422(10)70104-6.

    Article  PubMed  Google Scholar 

  • Pell, G. S., Lin, A., Wellard, R. M., Werther, G. A., Cameron, F. J., Finch, S. J., … Northam, E. A. (2012). Age-related loss of brain volume and T2 relaxation time in youth with type 1 diabetes. Diabetes Care, 35(3), 513–519. https://doi.org/10.2337/dc11-1290.

  • Quirce, R., Carril, J. M., Jiménez-Bonilla, J. F., Amado, J. A., Gutiérrez-Mendiguchía, C., Banzo, I., … Montero, A. (1997). Semi-quantitative assessment of cerebral blood flow with 99mTc-HMPAO SPET in type I diabetic patients with no clinical history of cerebrovascular disease. European Journal of Nuclear Medicine, 24(12), 1507–1513.

  • Rooijackers, H. M. M., Wiegers, E. C., Tack, C. J., van der Graaf, M., & de Galan, B. E. (2016). Brain glucose metabolism during hypoglycemia in type 1 diabetes: insights from functional and metabolic neuroimaging studies. Cellular and Molecular Life Sciences: CMLS, 73(4), 705–722. https://doi.org/10.1007/s00018-015-2079-8.

    Article  CAS  PubMed  Google Scholar 

  • Ryan, C. M., Geckle, M. O., & Orchard, T. J. (2003). Cognitive efficiency declines over time in adults with Type 1 diabetes: effects of micro- and macrovascular complications. Diabetologia, 46(7), 940–948. https://doi.org/10.1007/s00125-003-1128-2.

    Article  CAS  PubMed  Google Scholar 

  • Seaquist, E. R. (2015). The impact of diabetes on cerebral structure and function. Psychosomatic Medicine, 77(6), 616–621. https://doi.org/10.1097/PSY.0000000000000207.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Selvarajah, D., Wilkinson, I. D., Gandhi, R., Griffiths, P. D., & Tesfaye, S. (2011). Microvascular perfusion abnormalities of the Thalamus in painful but not painless diabetic polyneuropathy: a clue to the pathogenesis of pain in type 1 diabetes. Diabetes Care, 34(3), 718–720. https://doi.org/10.2337/dc10-1550.

    Article  PubMed  PubMed Central  Google Scholar 

  • Tagougui, S., Fontaine, P., Leclair, E., Aucouturier, J., Matran, R., Oussaidene, K., … Heyman, E. (2015). Regional cerebral hemodynamic response to incremental exercise is blunted in poorly controlled patients with uncomplicated type 1 diabetes. Diabetes Care, 38(5), 858–867. https://doi.org/10.2337/dc14-1792.

  • Terada, S., Sato, S., Nagao, S., Ikeda, C., Shindo, A., Hayashi, S., … Uchitomi, Y. (2013). Trail making test B and brain perfusion imaging in mild cognitive impairment and mild Alzheimer’s disease. Psychiatry Research, 213(3), 249–255. https://doi.org/10.1016/j.pscychresns.2013.03.006.

  • van Golen, L. W., Kuijer, J. P. A., Huisman, M. C., Ijzerman, R. G., Barkhof, F., Diamant, M., & Lammertsma, A. A. (2013). Quantification of cerebral blood flow in healthy volunteers and type 1 diabetic patients: Comparison of MRI arterial spin labeling and [(15) O]H2 O positron emission tomography (PET). Journal of Magnetic Resonance Imaging: JMRI. https://doi.org/10.1002/jmri.24484.

    Article  PubMed  Google Scholar 

  • Wagener, D. K., Sacks, J. M., LaPorte, R. E., & MaCgregor, J. M. (1982). The Pittsburgh study of insulin-dependent diabetes mellitus: risk for diabetes among relatives of IDDM. Diabetes, 31(2), 136–144. https://doi.org/10.2337/diab.31.2.136.

    Article  CAS  PubMed  Google Scholar 

  • Wang, J., Aguirre, G. K., Kimberg, D. Y., Roc, A. C., Li, L., & Detre, J. A. (2003). Arterial spin labeling perfusion fMRI with very low task frequency. Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine, 49(5), 796–802. https://doi.org/10.1002/mrm.10437.

    Article  Google Scholar 

  • Wolk, D. A., & Detre, J. A. (2012). Arterial spin labeling MRI: an emerging biomarker for Alzheimer’s disease and other neurodegenerative conditions. Current Opinion in Neurology, 25(4), 421–428. https://doi.org/10.1097/WCO.0b013e328354ff0a.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wong, R. H. X., Scholey, A., & Howe, P. R. C. (2014). Assessing premorbid cognitive ability in adults with type 2 diabetes mellitus–a review with implications for future intervention studies. Current Diabetes Reports, 14(11), 547. https://doi.org/10.1007/s11892-014-0547-4.

    Article  PubMed  Google Scholar 

  • Wright, S. N., Hong, L. E., Winkler, A. M., Chiappelli, J., Nugent, K., Muellerklein, F., … Kochunov, P. (2015). Perfusion shift from white to gray matter may account for processing speed deficits in schizophrenia. Human Brain Mapping, 36(10), 3793–3804. https://doi.org/10.1002/hbm.22878.

  • Wu, M., Rosano, C., Butters, M., Whyte, E., Nable, M., Crooks, R., … Aizenstein, H. J. (2006). A fully automated method for quantifying and localizing white matter hyperintensities on MR images. Psychiatry Research, 148(2–3), 133–142. https://doi.org/10.1016/j.pscychresns.2006.09.003.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors wish to acknowledge Dr. Christopher Ryan and Dr. Judith Saxton for their assistance in the development and administration of the neuropsychology protocol.

Funding

This study was funded by National Institutes of Health grants DK095759 (Ryan), AG037451 (Rosano), DK089028 (Rosano), AG024827 (Rosano), DK034818 (Orchard) and the Rossi Memorial Fund (Orchard).

Author information

Authors and Affiliations

  1. Department of Psychiatry, University of Pittsburgh School of Medicine, 3811 O’Hara St., Pittsburgh, PA, 15213, USA

    John P. Ryan & Howard J. Aizenstein

  2. Department of Epidemiology, Diabetes and Lipid Research Building, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA

    Trevor J. Orchard

  3. Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA

    Karen A. Nunley & Caterina Rosano

  4. Department of Bioengineering, University of Pittsburgh Swanson School of Engineering, Pittsburgh, PA, USA

    Helmet Karim

Authors
  1. John P. Ryan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Howard J. Aizenstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Trevor J. Orchard
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Karen A. Nunley
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Helmet Karim
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Caterina Rosano
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

JPR analyzed the data and wrote the manuscript; HJA oversaw data analysis and processing; TJO is responsible for recruitment and maintenance of the cohort; KAN oversaw data collection, management and assisted in manuscript preparation; HK performed data analyses and assisted in manuscript preparation; CR designed the study, oversaw data collection/management, and assisted in manuscript preparation.

Corresponding author

Correspondence to John P. Ryan.

Ethics declarations

All participants provided written informed consent prior to study participation. The University of Pittsburgh Institutional Review Board approved the study.

Sources of support

DK095759 (Ryan), AG037451 (Rosano), DK089028 (Rosano), AG024827 (Rosano), DK034818 (Orchard), and the Rossi Memorial Fund (Orchard).

Conflict of interest

The authors have no conflicts of interest to disclose.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 23 KB)

Supplementary material 2 (DOCX 4349 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ryan, J.P., Aizenstein, H.J., Orchard, T.J. et al. Basal ganglia cerebral blood flow associates with psychomotor speed in adults with type 1 diabetes. Brain Imaging and Behavior 12, 1271–1278 (2018). https://doi.org/10.1007/s11682-017-9783-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11682-017-9783-y

Keywords

Search

Navigation