Cerebral Vasoregulation In Elderly with Stroke

Summary

Principal Investigator: Vera Novak
Abstract: Stroke is the third leading cause of death and the leading cause of disability in older people. Our long-term goal is to determine the effects of stroke on cerebral vasoregulation. Our hypotheses are as follows: Hypothesis 1: The older adults with ischemic stroke have impaired cerebral vasoregulation, rendering cerebral blood flow dependent on blood pressure (BP). Therefore, we will evaluate cerebral vasoregulation in response to CO2 and BP challenges to determine whether cerebral blood flow is higher with increased perfusion pressure in stroke-hypertensive than stroke-normotensive subjects. Hypothesis 2: Autonomic BP control is altered after stroke. Therefore, activities of daily living may induce orthostatic hypotension (OH), posing a risk of cerebral hypoperfusion. We will evaluate cerebral blood flow and BP responses during orthostatic stress to identify subjects with OH, who may develop cerebral hypoperfusion. Hypothesis 3: The distribution of impaired vasoreactivity extends beyond the infarct site into surrounding areas of gray and white matter affecting different vascular territories. We will quantify cerebral blood flow in gray and white matter using arterial spin labeling at 3 Tesla MRI and evaluate the distribution of vasoreactivity during hypo-and hypercapnia. We will use T2-weighted FLAIR MRI to measure the distribution of infarcts and white matter changes and compare it to the cerebral blood flow maps. We will study 60 subjects (>60 years old, normotensive and hypertensive with the first hemispheric large vessel infarct affecting <1/3 of middle cerebral artery territory [MCA], >6 months post-stroke) and compare them to 60 normotensive and hypertensive subjects without stroke. To evaluate vasoreactivity to CO2 stimulus we will measure blood flow velocity (BFV) in both MCAs during hypo- and hypercapnia using transcranial Doppler ultrasound. Cerebral vasoreactivity to BP stimulus will be evaluated from BFV responses to Valsalva maneuver, sit-to-stand test and head-up tilt. We expect to find that with impaired vasoregulation cerebral blood flow becomes dependent on perfusion pressure. Therefore, in older adults with stroke, OH may trigger cerebral hypoperfusion and cause further damage to an already compromised cerebrovascular bed. The results of this study may improve our understanding of optimal BP targets for the maintenance of cerebral perfusion in elderly people with stroke.
Funding Period: 2004-07-01 - 2010-03-31
more information: NIH RePORT

Top Publications

  1. pmc Infarct hemisphere and noninfarcted brain volumes affect locomotor performance following stroke
    I Hsuan Chen
    From the Division of Gerontology I H C, V N, B M, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA Institute for Aging Research B M, Hebrew SeniorLife, Boston Department of Physical Therapy and Assistive Technology I H C, National Yang Ming University, Taipei and the Center for Dynamical Biomarkers and Translational Medicine I H C, V N, B M, National Central University, Jhongli, Taiwan
    Neurology 82:828-34. 2014
  2. pmc Nonlinear assessment of cerebral autoregulation from spontaneous blood pressure and cerebral blood flow fluctuations
    Kun Hu
    Division of Gerontology, Beth Israel Deaconess Medical Center, Harvard Medical School, 812 Stoneman Bldg, 330 Brookline Avenue, Boston, MA 02115, USA
    Cardiovasc Eng 8:60-71. 2008
  3. pmc The relationship between brain volume and walking outcomes in older adults with and without diabetic peripheral neuropathy
    Brad Manor
    Beth Israel Deaconess Medical Center, Boston, MA, USA
    Diabetes Care 35:1907-12. 2012
  4. pmc A nonlinear dynamic approach reveals a long-term stroke effect on cerebral blood flow regulation at multiple time scales
    Kun Hu
    Division of Sleep Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS Comput Biol 8:e1002601. 2012
  5. pmc Impaired cerebral autoregulation is associated with brain atrophy and worse functional status in chronic ischemic stroke
    Mikio C Aoi
    Biomathematics Program, Department of Mathematics, North Carolina State University, Raleigh, NC, USA
    PLoS ONE 7:e46794. 2012
  6. pmc Posturo-respiratory synchronization: effects of aging and stroke
    Brad D Manor
    Division of Gerontology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    Gait Posture 36:254-9. 2012
  7. pmc Association of blood pressure elevation and nocturnal dipping with brain atrophy, perfusion and functional measures in stroke and nonstroke individuals
    Ihab Hajjar
    Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
    Am J Hypertens 23:17-23. 2010
  8. pmc Hypertension and cerebral vasoreactivity: a continuous arterial spin labeling magnetic resonance imaging study
    Ihab Hajjar
    Harvard Medical School, Institute for Aging Research Hebrew SeniorLife, Division of Gerontology, Beth Israel Deaconess Medical Center, Boston, MA 02131, USA
    Hypertension 56:859-64. 2010
  9. pmc White matter hyperintensities and dynamics of postural control
    Vera Novak
    Division of Gerontology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
    Magn Reson Imaging 27:752-9. 2009
  10. pmc Nonlinear phase interaction between nonstationary signals: a comparison study of methods based on Hilbert-Huang and Fourier transforms
    Men Tzung Lo
    Division of Gerontology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    Phys Rev E Stat Nonlin Soft Matter Phys 79:061924. 2009

Scientific Experts

  • Mette S Olufsen
  • Ihab M Hajjar
  • Vera Novak
  • Brad Manor
  • Kun Hu
  • Magdy H Selim
  • Men Tzung Lo
  • C K Peng
  • I Hsuan Chen
  • Mikio C Aoi
  • Min Lou
  • P Zhao
  • David Last
  • Zhi Chen
  • Richard P Goddeau
  • Adel Al-Hazzani
  • D C Alsop
  • P Novak
  • Yanhui Liu
  • L Caplan
  • A Abduljalil
  • L Lipsitz
  • David C Alsop
  • Jerry Cavallerano
  • Albert C C Yang
  • Amir M Abduljalil
  • Cedric De Bazelaire
  • Robert P Marquis
  • Ary L Goldberger
  • Plamen Ch Ivanov
  • H Eugene Stanley

Detail Information

Publications29

  1. pmc Infarct hemisphere and noninfarcted brain volumes affect locomotor performance following stroke
    I Hsuan Chen
    From the Division of Gerontology I H C, V N, B M, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA Institute for Aging Research B M, Hebrew SeniorLife, Boston Department of Physical Therapy and Assistive Technology I H C, National Yang Ming University, Taipei and the Center for Dynamical Biomarkers and Translational Medicine I H C, V N, B M, National Central University, Jhongli, Taiwan
    Neurology 82:828-34. 2014
    ....
  2. pmc Nonlinear assessment of cerebral autoregulation from spontaneous blood pressure and cerebral blood flow fluctuations
    Kun Hu
    Division of Gerontology, Beth Israel Deaconess Medical Center, Harvard Medical School, 812 Stoneman Bldg, 330 Brookline Avenue, Boston, MA 02115, USA
    Cardiovasc Eng 8:60-71. 2008
    ....
  3. pmc The relationship between brain volume and walking outcomes in older adults with and without diabetic peripheral neuropathy
    Brad Manor
    Beth Israel Deaconess Medical Center, Boston, MA, USA
    Diabetes Care 35:1907-12. 2012
    ..We hypothesized that walking outcomes would be more closely related to regional gray matter volumes in older adults with DPN as compared with nonneuropathic diabetic patients and nondiabetic control subjects...
  4. pmc A nonlinear dynamic approach reveals a long-term stroke effect on cerebral blood flow regulation at multiple time scales
    Kun Hu
    Division of Sleep Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS Comput Biol 8:e1002601. 2012
    ....
  5. pmc Impaired cerebral autoregulation is associated with brain atrophy and worse functional status in chronic ischemic stroke
    Mikio C Aoi
    Biomathematics Program, Department of Mathematics, North Carolina State University, Raleigh, NC, USA
    PLoS ONE 7:e46794. 2012
    ..002). Our results indicate that better dynamic cerebral perfusion regulation is associated with less atrophy and better long-term functional status in older adults with chronic ischemic infarctions...
  6. pmc Posturo-respiratory synchronization: effects of aging and stroke
    Brad D Manor
    Division of Gerontology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    Gait Posture 36:254-9. 2012
    ..As evidenced by increased posturo-respiratory synchronization with advanced age and central lesion, this novel metric may be used as a clinical marker of altered postural control...
  7. pmc Association of blood pressure elevation and nocturnal dipping with brain atrophy, perfusion and functional measures in stroke and nonstroke individuals
    Ihab Hajjar
    Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
    Am J Hypertens 23:17-23. 2010
    ..Although both blood pressure elevation and lower nocturnal dipping increase vascular risk, it is not known whether either or both are also associated with brain atrophy, cerebral perfusion, and functional status...
  8. pmc Hypertension and cerebral vasoreactivity: a continuous arterial spin labeling magnetic resonance imaging study
    Ihab Hajjar
    Harvard Medical School, Institute for Aging Research Hebrew SeniorLife, Division of Gerontology, Beth Israel Deaconess Medical Center, Boston, MA 02131, USA
    Hypertension 56:859-64. 2010
    ..Because lower vasoreactivity is associated with poor outcomes, studies of the impact of antihypertensive on vasoreactivity are important...
  9. pmc White matter hyperintensities and dynamics of postural control
    Vera Novak
    Division of Gerontology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
    Magn Reson Imaging 27:752-9. 2009
    ..This study evaluated the relationship between WMHs and dynamics of postural control in older adults without history of falls...
  10. pmc Nonlinear phase interaction between nonstationary signals: a comparison study of methods based on Hilbert-Huang and Fourier transforms
    Men Tzung Lo
    Division of Gerontology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    Phys Rev E Stat Nonlin Soft Matter Phys 79:061924. 2009
    ..Furthermore, we propose certain strategies that can be implemented in the TFA and the MMPF methods to reduce the effects of nonstationarities, thus improving the performances of the two methods...
  11. ncbi Relationship between white-matter hyperintensities and hematoma volume and growth in patients with intracerebral hemorrhage
    Min Lou
    Second Affiliated Hospital of Zhejiang University, Hangzhou, China
    Stroke 41:34-40. 2010
    ..The presence of white-matter hyperintensities (WMHs) has been linked to intracerebral hemorrhage (ICH). We sought to determine whether the severity of WMHs influences hematoma growth and ICH volume...
  12. pmc Cerebral flow velocities during daily activities depend on blood pressure in patients with chronic ischemic infarctions
    Vera Novak
    Division of Gerontology, Beth Israel Deaconess Medical Center, 110 Francis Street, Boston, MA 02215, USA
    Stroke 41:61-6. 2010
    ..Target blood pressure (BP) values for optimal cerebral perfusion after an ischemic stroke are still debated. We sought to examine the relationship between BP and cerebral blood flow velocities (BFVs) during daily activities...
  13. pmc Altered control of postural sway following cerebral infarction: a cross-sectional analysis
    B Manor
    Division of Gerontology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
    Neurology 74:458-64. 2010
    ..We examined dependence upon vision and noninfarcted regional brain tissue volumes for postural control in individuals with right and left hemisphere middle cerebral artery (MCA) infarcts...
  14. pmc Vasoreactivity and peri-infarct hyperintensities in stroke
    P Zhao
    Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    Neurology 72:643-9. 2009
    ..We investigated the regional differences in CO2 vasoreactivity (CO2 VR) and their relationships to peri-infarct T2 hyperintensities (PIHs), chronic infarct volumes, and clinical outcomes...
  15. pmc Nonlinear pressure-flow relationship is able to detect asymmetry of brain blood circulation associated with midline shift
    Kun Hu
    Division of Gerontology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
    J Neurotrauma 26:227-33. 2009
    ..Moreover, mean pressure-flow phase shift is sensitive to the displacement of midline of the brain, and may potentially serve as a marker of asymmetry of cerebral autoregulation...
  16. pmc High-resolution ultrahigh-field MRI of stroke
    Vera Novak
    Department of Medicine Gerontology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
    Magn Reson Imaging 23:539-48. 2005
    ..Ultrahigh-field MRI at 8 T offers unprecedented resolution for imaging brain structures and microvasculature...
  17. pmc Cross-correlation of instantaneous phase increments in pressure-flow fluctuations: applications to cerebral autoregulation
    Zhi Chen
    Center for Polymer Studies and Department of Physics, Boston University, Boston, Massachusetts 02215, USA
    Phys Rev E Stat Nonlin Soft Matter Phys 73:031915. 2006
    ....
  18. ncbi Modeling baroreflex regulation of heart rate during orthostatic stress
    Mette S Olufsen
    Dept of Mathematics, North Carolina State Univ, Campus Box 8205, Raleigh, NC 27695, USA
    Am J Physiol Regul Integr Comp Physiol 291:R1355-68. 2006
    ....
  19. pmc Cerebral blood flow velocity and periventricular white matter hyperintensities in type 2 diabetes
    Vera Novak
    Division of Gerontology, Beth Israel Deaconess Medical Center, 110 Francis St, Boston, MA 02215, USA
    Diabetes Care 29:1529-34. 2006
    ....
  20. pmc Global and regional effects of type 2 diabetes on brain tissue volumes and cerebral vasoreactivity
    David Last
    Division of Gerontology, Beth Israel Deaconess Medical Center, Harvard Medical School, 110 Francis St, Boston, MA 02215, USA
    Diabetes Care 30:1193-9. 2007
    ..The aim of this study was to evaluate the regional effects of type 2 diabetes and associated conditions on cerebral tissue volumes and cerebral blood flow (CBF) regulation...
  21. ncbi Statistical physics approach to categorize biologic signals: from heart rate dynamics to DNA sequences
    C K Peng
    Margret and H A Rey Institute for Nonlinear Dynamics in Medicine, Division of Interdisciplinary Medicine and Biotechnology, Beth Israel Deaconess Medical Center Harvard Medical School, Boston, Massachusetts 02215, USA
    Chaos 17:015115. 2007
    ..We use human cardiac interbeat interval time series and DNA sequences as examples to illustrate the applicability of this generic approach to real-world problems...
  22. ncbi The relationship between nighttime dipping in blood pressure and cerebral hemodynamics in nonstroke patients
    Ihab Hajjar
    Beth Israel Deaconess Medical Center, Institute for Aging Research at Hebrew SeniorLife, Boston, MA 02131, USA
    J Clin Hypertens (Greenwich) 9:929-36. 2007
    ..03) were associated with higher daytime BFV and lower CVR (P=.01 for systolic BP; P=.02 for diastolic BP). Inadequate nocturnal BP dipping is associated with lower daytime cerebral blood flow, especially during head-up tilt...
  23. pmc Modeling heart rate regulation--part I: sit-to-stand versus head-up tilt
    Mette S Olufsen
    Department of Mathematics, North Carolina State University, Campus Box 8205, Raleigh, NC 27695, USA
    Cardiovasc Eng 8:73-87. 2008
    ....
  24. pmc The effects of body mass index on cerebral blood flow velocity
    Magdy Selim
    Dept of Neurology, Stroke Division, Beth Israel Deaconess Medical Center, Boston, MA, USA
    Clin Auton Res 18:331-8. 2008
    ..Obesity is a risk factor for cerebrovascular disease. We aimed to determine the effects of high body mass index (BMI) on cerebral blood flow regulation in patients with type-2 diabetes mellitus, hypertension, and stroke...
  25. pmc Blood pressure and blood flow variation during postural change from sitting to standing: model development and validation
    Mette S Olufsen
    Department of Mathematics, North Carolina State University, Raleigh, 27695, USA
    J Appl Physiol (1985) 99:1523-37. 2005
    ..Finally, we formulate an inverse least-squares problem to estimate parameters and demonstrate that our mathematical model is in agreement with physiological data from a young subject during postural change from sitting to standing...