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Lower cerebral vasoreactivity as a predictor of gait speed decline in type 2 diabetes mellitus

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Abstract

Gait speed is an indicator of overall functional health and is correlated with survival in older adults. We prospectively evaluated the long-term association between cerebral vasoreactivity and gait speed during normal walking (NW) and dual-task walking (DTW) in older adults with and without type 2 diabetes mellitus (T2DM). 40 participants (aged 67.3 ± 8.8 years, 20 with T2DM) completed a 2-year prospective study consisting of MRI, blood sampling, and gait assessments. The whole brain vasoreactivity was quantified using continuous arterial spin labeling MRI. Gait speed during DTW was assessed by subtracting serial sevens. Dual-task cost was calculated as the percent change in gait speed from NW to DTW. In the entire cohort, higher glycemic profiles were associated with a slower gait speed. In the diabetic group, lower vasoreactivity was associated with a slower gait speed during NW (\(r_{{{\text{adj}}}}^{2}\) = 0.30, p = 0.019) and DTW (\(r_{{{\text{adj}}}}^{2}\) = 0.35, p = 0.01) and a higher dual-task cost (\(r_{{{\text{adj}}}}^{2}\) = 0.69, p = 0.009) at 2-year follow-up. The participants with T2DM and lower cerebral vasoreactivity had a greater decrease in gait speed during NW and DTW after the 2-year follow-up (\(r_{{{\text{adj}}}}^{2}\) = 0.17, p = 0.04 and \(r_{{{\text{adj}}}}^{2}\) = 0.28, p = 0.03, respectively). Longer diabetes duration was associated with a higher dual-task cost (\(r_{{{\text{adj}}}}^{2}\) = 0.19, p = 0.04) and a greater decrease in gait speed during NW (\(r_{{{\text{adj}}}}^{2}\) = 0.17, p = 0.02). These findings indicate that in older adults with type 2 diabetes, gait performance is highly dependent on the integrity of cerebrovascular regulation.

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Abbreviations

NW:

Normal walking

DTW:

Dual-task walking

T2DM:

Type 2 diabetes mellitus

CASL:

3-D continuous arterial spin labeling

WMH:

White matter hyperintensities

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Acknowledgements

The work was supported by the National Institutes of Health (NIH-NIA 1R01-AG0287601A2, NIH-NIDDK 5R21 DK084463), American Diabetes Association (Clinical 1-03-CR-23 and 1-06-CR-25 to Dr. Vera Novak). The work was also in part supported NIH-NIDDK 1R01DK103902-01A1 to Dr. Novak. The project described was supported by Harvard Clinical and Translational Science Center (Grant Number UL1 RR025758) and National Center for Research Resources (M01-RR-01032). Research reported in this publication was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under Award Number R01DK103902. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Authors and Affiliations

  1. Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, 185 Pilgrim Road, Palmer 127, Boston, MA, 02215, USA

    Chen-Chih Chung, Daniela A. Pimentel Maldonado, Freddy J. Alfaro, Vasileios-Arsenios Lioutas & Vera Novak

  2. Department of Neurology, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan, Republic of China

    Chen-Chih Chung

  3. Department of Gerontology, Beth Israel Deaconess Medical Center, Boston, MA, USA

    Daniela A. Pimentel Maldonado, Azizah J. Jor’dan & Vera Novak

  4. Institute for Aging Research, Hebrew SeniorLife, Harvard Medical School, Boston, USA

    Azizah J. Jor’dan

  5. Biomedical and Clinical Research Center (CINBIOCLI), Santiago, Dominican Republic

    Maria Zunilda Núñez

  6. Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan, Republic of China

    Chen-Chih Chung

  7. Department of Neurology, University of Massachusetts Medical School, Worcester, USA

    Daniela A. Pimentel Maldonado

  8. New England Geriatric Research, Education and Clinical Center, VA Boston Healthcare System, Boston, MA, USA

    Azizah J. Jor’dan

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Contributions

Design and conduct of the study: C-CC, DAPM, VN. Data acquisition and analysis: C-CC, DAPM, AJJ, FAJ, VN. Data interpretation: C-CC, DAPM, AJJ, FAJ, V-AL, MZN, NV. Manuscript preparation: C-CC, DAPM, AJJ, FAJ, V-AL, MZN, NV.

Corresponding author

Correspondence to Vera Novak.

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Ethical standards

All participants that met inclusion/exclusion criteria signed an Informed consent form (ICF) as approved by the Institutional review board (IRB) at Beth Israel Deaconess Medical Center.

Conflicts of interest

Chen-Chih Chung, Daniela A. Pimentel, Freddy J. Alfaro, Vasileios-Arsenios Lioutas, Maria Zunilda Núñez report no disclosures. Vera Novak was funded by the National Institutes of Health (NIH-NIDDK 1R01DK103902 -03, NIH-NIA 1R01- AG0287601A2, NIH-NIDDK 5R21 DK084463), American Diabetes Association (Clinical 1-03-CR-23 and 1-06-CR-25). Azizah J. Jor’dan was funded by NIH T32 Fellowship (5T32AG023480 and HL007374-36), a Diversity Supplement Award (3R01AG041785-02S1) and a Career Development Award (K99AG051766).

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Chung, CC., Pimentel Maldonado, D.A., Jor’dan, A.J. et al. Lower cerebral vasoreactivity as a predictor of gait speed decline in type 2 diabetes mellitus. J Neurol 265, 2267–2276 (2018). https://doi.org/10.1007/s00415-018-8981-x

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