Cerebral vasoregulation in elderly with stroke (1R01-NS045745-01A2)
This study is focused on cerebral blood flow and systemic pressure regulation in elderly persons with stroke. TCD is used to evaluate cerebral vasoregulation in normotensive and hypertensive subjects with and without stroke. The hypotheses are as follows: 1) Cerebral vasoregulation is impaired in elderly adults with a clinical history of ischemic stroke, rendering cerebral blood flow dependent on blood pressure. 2) Activities of daily living may lead to cerebral hypoperfusion when blood pressure falls below an autoregulated range. 3) The distribution of impaired vasoreactivity extends beyond the infarct site into brain regions affected by white matter changes (WMC) and silent infarcts, affecting larger areas of gray and white matter. High-resolution T2-weighted FLAIR and arterial spin labeling MRI at 3 Tesla was implemented to evaluate the impact of WMHs and silent infarcts on cerebral perfusion. This project will provide a link between cerebral vasoregulation and blood pressure post-stroke and will yield new insights into age-related decline in cerebrovascular regulations.
Cerebral vasoregulation in diabetes (1-03-CR-23 American Diabetes Association)
We assessed the effects of type 2 diabetes mellitus (DM) on blood flow velocities (BFV) in the middle cerebral arteries in order to determine the effects of white matter hyperintensities (WMHs) on MRI on BFV. We measured BFV in 28 type 2 DM and 22 control subjects (age 62.3 ± 7.2 years) using transcranial Doppler ultrasound during baseline, hyperventilation, and CO 2 rebreathing. WMH were graded and their volume was quantified from fluid-attenuated inversion recovery (FLAIR) images at 3 Tesla MRI. The DM group demonstrated decreased mean BFV and increased cerebrovascular resistance during baseline, hypocapnia, and hypercapnia and impaired CO 2 reactivity. WMH volume was negatively correlated with baseline BFV. A regression model revealed that baseline BFV were negatively associated with periventricular WMH, hemoglobin A1c, and inflammatory markers and positively associated with systolic pressure (R 2 = 0.86, p<0.0001). Microvascular disease in type 2 DM that manifests as white matter abnormalities on MRI is associated with reduced cerebral blood flow velocities and increased resistance in middle cerebral arteries and inflammation. Improvement of DM control may lead to enhancement of cerebral blood flow in older adults with type 2 DM. Completed: December 2005. Novak et al. Diabetes Care 2006.
Cerebral perfusion and cognitive decline in type 2 diabetes (1-06-CR-25 American Diabetes Association)(2006-2009)
Type 2 diabetes mellitus is associated with cerebral microvascular disease, presenting as impairments in vasoregulation and blood flow distribution, white matter abnormalities on MRI, and declined cognitive and motor performance. We plan to determine correlates of microcirculatory disturbance in type 2 DM using the measures of cerebral vasoregulation with transcranial Doppler ultrasound, regional blood flow distribution using continuous arterial spin labeling (CASL) at 3 Tesla MRI, volume and distribution of white matter changes on T2-weighted MRI and clinical cognitive, and balance tasks in older adults with type 2 DM, compared to the healthy controls.We hypothesize that poor glycemic control increases the severity of microvascular disease in elderly people with type 2 DM. Higher hemoglobin A1c levels are associated with reduced cerebral blood flow and more WMHs and executive dysfunction. Disturbance of blood flow regulation in the fronto-temporal cortex and periventricular white matter changes contribute to executive dysfunction in type 2 DM. We plan to evaluate the effects of glycemic control on severity of microvascular disease, we will determine the relationship between HbA1c and cerebral perfusion and WMHs volume in fronto-temporal cortex, diabetic retinopathy, and executive function scores. Start date January 1, 2006.
Multimodal pressure-flow analysis: a Doppler-based method to measure cerebral autoregulation dynamics (CIMIT- New Concept Grant -W81XWH, STTR -NINDS -1R41NS053128-01A2)
Regulation of cerebral blood flow in response to fluctuations in systemic blood pressure (BP) is impaired post-stroke. The autoregulatory dynamics,
however, are difficult to assess because of the nonstationarity and nonlinearity of the component signals. A new technique, multimodal pressure-flow
analysis (MMPF), was implemented to analyze these short, nonstationary signals. MMPF analysis decomposes complex BP and BFV signals into
multiple empirical modes, representing their instantaneous frequency-amplitude modulation. The empirical mode corresponding to the VM BP
profile was used to construct the continuous phase diagram. The MMPF method enables evaluation of autoregulatory dynamics based on
instantaneous BP-BFV phase analysis. The regulation of BP-BFV dynamics is altered after minor stroke, rendering blood flow dependent
on blood pressure (Novak V. et al., BMC Eng 2004). The commercial software will be developed by DynaDx Technologies to license
this method to transcranial Doppler companies as a module for evaluation of cerebral autoregulation (NodeCrest, LLC and Terumo,Inc).
(Novak V. et al. Technology Disclosure, BIDMC January 5, 2004)
Older American Pepper Center Research Resource Core B
The noninvasive 8-channel gait monitoring wearable computer system (Gait Logger) was developed to monitor stride interval and to provide vibratory feedback for each step. Preliminary results have shown that step-synchronized vibration stimulation reduced stride variability. (Novak V. et al., Technology Disclosure, BIDMC, March 21, 2003)
Gait effects on cardiovascular dynamics in healthy young and elderly
Complex physiological mechanisms are required to control locomotor and cardiovascular systems during normal walking. We evaluated effects of aging on foot pressure distribution (FPD) during normal walking. In elderly subjects, weight bearing on the lateral side of the foot during heel touch and toe-off phases may affect stability during walking. (Hessert M. et al. BMC Geriatrics 2005). The effects of aging on cardiac-locomotor coupling was studied using treadmill walking at incremental speeds from 0.8 mph to normal walking speed (NWS) in healthy young and elderly subjects. Step intervals and heartbeat intervals were significantly correlated, and maximum foot pressure was correlated with systolic blood pressure in the old, but not in the young subjects. Cardiac-locomotor coupling during walking becomes manifest with aging. In elderly people, forces generated during the gait cycle may be transmitted to arterial pressure and thus synchronize the central cardiovascular network with the stepping rhythm. Novak V et al. in Press: Journal of Gerontology, 2007
Step synchronized vibration stimulation in Parkinson's disease
In collaboration with Dr. P. Novak, Dept. of Neurology, Boston University, we evaluated the effects of real-time vibration stimulation in patients with Parkinson's disease (PD) during normal walking. We found that step-synchronized stimulation increased walking speed and reduced stride variability in PD subjects. (Novak P, Novak V. J. NeuroEng and Rehabilitation, 2006)
Mathematical modeling of cerebrovascular and autonomic control
Complex cardiovascular and cerebrovascular mechanisms control physiological adaptation to orthostatic stress. In collaboration with Dr. M. Olufsen, we have developed a multicompartmental model that can distinguish contributions of multiple regulatory mechanisms to the orthostatic response. This multidisciplinary project is in collaboration among the Departments of Mathematics at the NC State Univ. (Dr. Olufsen, Dr. Tran), Roskilde Univ., Denmark (Dr. Ottesen), Graz Univ., Austria (Dr. Kappel, Dr. Batzel), and the SAFE laboratory at the BIDMC . My role, as a physiologist, is to provide a theoretical basis for physiological processes that regulate cerebral blood flow, cardiovascular and respiratory adaptation to orthostatic stress in the cardiovascular and cerebrovascular models that are developed by this group and to provide physiological training predoctoral students in applied mathematics (Olufsen etal, JAP 2005; Olufsen et al AJP 2006- the most read article in Oct issues of AJP.
Identifying and overcoming barriers to diabetes management in the elderly: An intervention study
In collaboration with Dr. Medha Munshi - Director of Gerontology diabetes clinic this project evaluates whether a short term focused intervention by a geriatric multidisciplinary diabetes team (GDT) specifically directed at overcoming potential barriers to diabetes management can cost-effectively improve diabetes control, functional status and quality of life in elderly. We hypothesize that the intervention by GDT will empower elderly patients in their self-management, so that there would be a longer lasting effect on outcome measures. We will evaluate whether an improvement in glycemic control through short-term focused intervention by multidisciplinary geriatric team may improve cerebral blood flow and vasoreactivity in elderly people.