What Is Cerebral Microvascular (Small Vessel) Disease

Cerebral small vessel disease is a pathological process that damages small arterioles, venules, capillaries, and associated structures.

It is the most common cerebrovascular disease.

Cerebral microvascular disease causes 85% of intracerebral hemorrhage, 45% vascular dementia, and 25% ischemic strokes.

It is largely silent in the beginning, so seeing it on imaging is an incidental finding that could surprise the patient.

Who Gets Cerebral Small Vessel Disease

Cerebral microvascular disease is more common in women than men. Women with cerebral microvascular disease are more likely to have cognitive impairment than are men. Women who have not had very much estrogen exposure during their reproductive years, and women who do not take hormone replacement therapy are at increased risk of cerebral microvascular disease.

The incidence of cerebral small vessel disease increases over time. About 5% of people in their 50s have cerebral small vessel disease, while almost 100% of people in their 90s will have it.

What Causes Cerebral Microvessel Disease

Cerebral microvessel disease is caused by

  • Arteriolosclerosis which is most commonly caused by hypertension
  • Cerebral Amyloid Angiopathy caused by vascular deposition of beta-amyloid plaques
  • Blood brain barrier breach
  • Over-activation of microglia

Fundamentally cerebral microvessel disease is caused by some type of inflammation that caused endothelial dysfunction.

What Symptoms and Conditions Are Associated with Cerebral Small Vessel Disease

Cerebral small vessel disease often presents before a patient has any identifiable symptoms. Once it has developed enough to impact brain function, the symptoms will reflect the brain area that is compromised.

Common symptoms and conditions include:

  • Cognitive impairment
  • Stroke
  • Motor impairment
  • Impaired balance/Gait disturbance/Falls
  • Urinary incontinence
  • Depression/Apathy/Personality Change
  • Vascular Parkinson’s PMID: 36575578

What Is the Job of the Cerebral NeuralMicrovascular Unit

  • Regulate cerebral blood flow
  • Regulate nutrient entry into cells
  • Maintain and repair myelin sheath
  • Clear metabolites
  • PMID: 35844225

How Do the Glymphatics Related to Cerebral Microvascular Disease

The glymphatic system cleans the brain of waste products and dumps into the lymphatic system in the neck.

It shares many of the same constituent architecture with the cerebral microvasculature and is impacted by its dysfunction.

When the small vessels in the brain stop working well the glymphatic system will not function well. This leads to cognitive impairment, decreased cerebral waste clearance, and inflammation.

Cerebral Small Vessel Disease is Essentially Endothelial Dysfunction

What is Endothelial Dysfunction?

The endothelium is the inner-most lining of the blood vessels. Its job is to

  • Regulate hemostasis
  • Maintain vascular permeability
  • Mediate acute and chronic immune response
  • Control vascular tone
  • PMID: 32172815

Nitric oxide is a cellular signaling molecule that is produced in healthy endothelium and regulates

  • Vasodilation
  • Insulin secretion
  • Airway tone
  • Peristalsis
  • Angiogenesis
  • Neural development
  • PMID: 25243060

How Is Nitric Oxide Produced in the Endothelium

Nitric oxide is produced in the endothelium of the brain via the primary L-Arginine/Nitric Oxide Synthase (NOS) pathway. The NOS pathway can produce nitric oxide via two anti-inflammatory pathway called endothelial NOS and neural NOS. There is also an inflammatory pathway called inducible NOS.  PMID: 32172815

For nitric oxide to be optimally produced, we need all the ingredients to be in place

  • L-Arginine
  • Oxygen
  • NADPH
  • Calmodulin
  • Heme
  • BH4 PMID: 32172815

If all these components are not in place, we will end up with less nitric oxide and more inflammatory end products.

  • PMID: 25243060

When your body experiences oxidative stress, your body will have increased inflammation, and decreased function.

Oxidative Stress Creates Reactive Oxygen Species that Injure the Endothelium in the Following Ways

  • Increase endothelial apoptosis (programmed cell death)
  • Increase monocyte chemoattractant protein-1 (increase monocytes and macrophages )
  • Increase NF-kB (promote tumor and immune dysregulation)
  • Increase ICAM-1 and VCAM-1 (creates more stickiness inside vasculature and cells)
  • Decrease nitric oxide
  • Decrease endothelial nitric oxide synthase mRNA
  • Decrease angiogenesis
  • Increase contracting factors
    • Endothelin-1
    • Angiotensin II
    • Vascular smooth muscle cells

How To Diagnose Cerebral Small Vessel Disease with Imaging

MRI T2 weighted imaging is preferred for diagnosis. It is more sensitive and specific than CT.

Cerebral small vessel disease is represented by

Biomedical Treatment of Cerebral Microvascular Disease

  • Watchful waiting
  • Treat underlying conditions
    • High blood pressure with ACE inhibitors or ARBs
    • High cholesterol with statins
  • Improve blood flow with isosorbide mononitrate or cilostazol
  • Prevent clots
  • Anti-inflammatory steroidal or non-steroidal drugs
  • Anti-dementia drugs like acetylcholinesterase inhibitors
  • https://www.aginganddisease.org/EN/10.14336/AD.2024.1515

Natural Treatments for Cerebral Microvascular Disease

  • Reduce high blood pressure
    • Individualized care dependent on causative factors
  • Reduce inflammation
    • Delta tocotrienols, magnesium, vitamin C, lipoic acid, Sesame seed oil, resveratrol, omega-3, flavonoids, SOD, silymarin, catalase, L-arginine, L-citrulline
  • Optimize Homocysteine
    • Folate (5-MTFR)
    • Methylcobalamin
    • B6
  • Prevent Blood Clots
    • Omega-3, delta tocotrienols, nattokinase, lumbrokinase
  • Optimize Glucose and Insulin
    • bitter melon, gymnema sylvestre, amla, banaba, alpha-lipoic acid, exercise/build muscle, chromium picolinate, garlic
    • berberine, cinnamon, citrus bergamia, resveratrol, turmeric, fenugreek, panex gingseng
  • Seal Blood Brain Barrier
    • turmeric, resveratrol, baicalin, apigenin, luteolin, rutin, catechins
    • vinpocetin, feverfew, butcher’s broom, ginkgo biloba, cayenne pepper, B2, magnesium
  • Support Brain Nitric Oxide Endothelial Production
    • L-arginine, Iron, 5-MTFR, Vitamin C, NADH, phosphate, Oxygen
    • Huperzine
    • Phosphatidylcholine
    • L-Acetyl-Carnitine
  • Chinese Medicine to Dredge Collaterals, Remove Stasis, Fill/Nourish Kidney/Blood/Yin Chi
    • Buyan Huanwu
  • Decrease Oxidative Stress and Reactive Oxygen Species
    • Avoid: pollution, chemicals, tobacco, alcohol, drugs, heavy metals, infections, high stress, lack of exercise, diet high in sugar/processed foods/transfats, poor sleep quality
    • Bioflavinoids, carotenoids, terpenoids, vitamin C/A/E, NAC, Propionyl-L-carnitine
  • Optimize Estrogen
  • Optimize Minerals
    • Make sure copper and iron aren’t too high
    • Make sure zinc not too low
  • Support Secondary Nitric Oxide Production Pathway
    • Optimize mouth and gut microbiome
    • HCl to optimize stomach function
    • Consume foods high in nitrates like beets, leafy greens,pomegranate, dark chocolate, watermelon, garlic, citrus
  • Manual Hands-On Therapy to Drain Glymphatics