Early Detection and Prevention of Mild Cognitive Impairment Due to Cerebrovascular Disease

This is a randomized, controlled study of intensive medical management and educational
programming (Heart Health Intervention) for controlling stroke and vascular risks that may
impact your thinking and memory (MCI-CVD). This means that if you choose to enroll, it will
be determined by chance ( pulling a number from a hat) whether you will receive the study
intervention or standard-of-care treatment. One-half of all subjects will be enrolled in the
intervention, while the other one half will not. You will have a 50:50 chance of receiving
the intervention, like the flip of a coin. You will be in the study for 36 months if you
enroll.

Even if you do are not in the study group receiving medical management and educational
programs, we will be monitoring your risks for stroke and vascular risks every 6 months and
this information will be provided to your primary doctors, potentially resulting in an
increased level of care as a result of your participation in this study.

You must have an individual (spouse, friend, or relative), called a "study partner", who is
willing to accompany you to all of the study visits or be available by telephone to
communicate changes in your health status over the period of this study.

The study visits include checking vital signs (blood pressure, heart rate weight), regular
blood testing at 6 month intervals to monitor your vascular risks (blood sugar, cholesterol
levels)as well as ensure your safety throughout the study, yearly brain imaging with MRI
scans, and optional spinal fluid collection at enrollment and end of study to help us
understand brain changes that cannot be measured in blood.

Inclusion Criteria:

1. At least 1 of the following vascular risk factors or on treatment for 1 of these
conditions determined by the study physicians to be responsible for the mild memory
and thinking problems you experience:

1. poorly controlled hypertension (systolic blood pressure>130mmHg) or prior history
of hypertension associated with congestive heart failure (CHF)

2. poorly controlled cholesterol (LDL > 70 mg/dL or triglycerides > 150 mg/dL)

3. cardiomyopathy/congestive heart failure with an ejection fraction < 40%

4. diabetes with fasting glucose > 110 mg/dL or glycosylated hemoglobin(HgbA1c) >
7.0%

5. homocysteine > 12umol/L

6. history of stroke or transient ischemic attack (TIA)

7. tobacco use > 30 pk/yr history

8. BMI > 30

2. Age > 55 years

3. Memory complaint

4. Montreal Cognitive Assessment (MoCA)score ≤ 26

5. Either, presence of strategic (caudate, thalamus, subcortical white matter lacunar
infarcts or mild to moderate small vessel ischemic changes (T2-positive) felt to be
sufficient to explain the cognitive decline (in the clinical judgment of the examining
physician)

6. English-speaking

Exclusion Criteria:

1. Functional decline due to cognitive impairment, sufficient to meet clinical criteria
for dementia

2. Other medical, non-CVD causes of cognitive decline including but not limited to
thyroid dysfunction, vitamin B12 deficiency, renal failure with blood urea nitrogen
(BUN) > 30 mg/dL, ammonia > 50 mg/dL, other significant electrolyte abnormalities,
extreme hypo (< 70 mg/dL) or hyper-glycemia (> 300mg/dL)…ect.

3. Evidence for comorbid, non-vascular neurologic disease on clinical exam or on imaging
(i.e. parkinsonism, focal neurologic deficits, amyotrophic lateral sclerosis(ALS),
focal brain lesions other than small lacunar infarcts,…)

4. Focal motor, sensory, visual or auditory deficits that would interfere with cognitive
assessments or are suggestive of other brain pathology

5. Vision and hearing with or without assistive devices sufficient to complete study
protocol including cognitive test procedures