UTLight-transcranial Doppler Assessment of Regional Cerebral Autoregulation

Cerebral autoregulation (CA) is a complex mechanism that serves the essential and vital purpose of controlling cerebral blood flow and metabolism. A stable and optimal brain blood flow is imperative for normal brain function; therefore normal function of CA is crucial for brain health. Diabetes mellitus (DM) is associated with microvascular disease and abnormal autoregulation, which increases risk for stroke and death. Failure of CA has serious consequences across the lifespan and, in terms of prevalence adverse outcomes related to failing CA are most prominent in the elderly with diabetes.

Older diabetic adults often suffer from hypotension or fainting upon standing-up and may have abnormal CA. With abnormal CA, cerebral perfusion and tissue oxygenation declines upon standing up. Abnormalities in perfusion regulation in older people, and particularly those with diabetes may accelerate progression of brain atrophy resulting in cognitive decline, vascular dementia or Alzheimer's disease.

UTLight technology (CerOx), provides a new tool for evaluation of regional blood flow and oxygenation in cortical microvasculature, which is lacking in clinical medicine and patient care. UTLight may become a novel tool that would provide an easy and reliable assessment of regional perfusion and CA in specific cortical areas in health and disease that can be widely implemented in outpatient clinics. This is a pilot, observational feasibility study to compare blood flow measurements using UTLight and TCD.

Aim 1: To assess the safety and feasibility of UTLight for evaluation of regional cerebral blood flow regulation in the anterior circulation ((ACA) and/or middle cerebral artery (MCA) territories) in 20 non-diabetic adults >50 yrs old and 40 age-matched adults with type 2 diabetes.

Aim 2: To compare the profiles of UTLight blood flow (UT_BF), regional oximetry (UT_Ox) and TCD-blood flow velocities (TCD_BFV) in response to: 1) blood pressure changes induced by the postural change from supine to head-up tilt, and from sitting to standing-up; and 2) vasodilatation and vasoconstriction responses induced by hypercapnia and hypocapnia.

The investigators hypothesize that:

• UT_BF will accurately track TCD_BFV in responses in the anterior circulation (ACA and/or MCA territory) to blood pressure changes, hypercapnia and hypocapnia challenges in healthy older people.
• UT_BF may be more sensitive to detect abnormalities in regional perfusion in diabetic adults as compared to healthy controls and compared to TCD_BFV.

(UT_Ox) may provide a new indicator to identify older diabetic adults with brain tissue hypoxia during orthostatic challenges that may be at greater risk of brain damage of cognitive decline that will be derived from a change in tissue oxygenation upon standing up that is not routinely evaluated by TCD. Outcomes: Primary outcome is the sensitivity and specificity of UT_BF and TCD_BFV to blood pressure and CO2 challenges, defined as percent change of UT_BF and TCD_BFV in response to hypercapnia and hypocapnia challenges. Secondary outcomes are the differences in cerebral blood flow measured by UT_BF, TCD_BFV between healthy old and diabetic subjects during postural changes. Third outcomes are differences in UT_Ox between healthy old and diabetic subjects.

Inclusion criteria

Diabetes group:

• This group will consist of 40 men and women aged 50-85 years
• diagnosed with type 2 DM and
• treated with oral agents and/or combinations with insulin for at least one year,
• either normotensive [BP <135/85 mm Hg and no medical history of hypertension) or hypertensive [BP >130/85 mm Hg and/or treated for hypertension].

Control group:

• This group will be non-diabetic (normal fasting blood glucose and HbA1c < 6.5%).
• This group will consist of 20 men and women matched with the diabetes group by age ±5 years, and
• subjects will be normotensive [BP <130/85 mm Hg and
• no medical history of hypertension] and
• hypertensive [BP >130/85 mm Hg and/or treated for hypertension].

Exclusion criteria

Persons with any one of the following conditions will be excluded:

• type I diabetes;
• any unstable or acute medical condition;
• myocardial infarction or major surgery within 6 months;
• history of a major stroke;
• dementia (by history) or inability to follow details of the protocol or MMSE < 20;
• carotid stenosis > 80% by medical history, Doppler ultrasound, or MR angiography;
• hemodynamically significant valvular disease;
• clinically significant arrhythmias;
• liver or renal failure or transplant;
• severe hypertension [systolic BP >200 and/or diastolic BP >110 mm Hg or subjects taking ≥3 antihypertensive medications];
• seizure disorders;
• malignant tumors;
• current recreational drug or alcohol abuse;
• active smoking;
• morbid obesity (BMI >40).
• Women in both groups will be required to be postmenopausal.
• TCD exclusion criteria - poor insonation window and TCD signal;
• UT_Light exclusion- poor signal.