Research
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.
