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Life Extension Magazine

Outwitting Our Aging Brain

January 2014

By William Faloon

William Faloon
William Faloon

We are zeroing in on a prime culprit behind Alzheimer’s, stroke, and age-related cognitive impairment.

The term for this reversible disorder is “hypoperfusion.” It means an inadequate supply of blood to a body part.

Hypoperfusion of the brain occurs in response to reduced blood flow. The result of hypoperfusion is a series of harmful changes that severely diminish neurological function.

We have long known about structural changes that adversely impact the aging brain. Preceding this structural deterioration, however, is a decline in microvascular blood flow.

What researchers are increasingly recognizing is that most aging humans suffer from obstructions to cerebral blood flow that result in chronic hypoperfusion.1 This sets in motion a cascade of neuronal injuries that can manifest as memory loss,2 depression,3-6 and cognitive dysfunction.7-9 The long-term impact of hypoperfusion is a higher risk of stroke,10,11 vascular dementia,12,13 and Alzheimer’s disease.14-16

Life Extension® members will find comfort that their healthy lifestyle choices have been proven to help protect against hypoperfusion. We must never underestimate, however, the fragile nature of our aging circulatory systems.

This article represents a compilation of new findings that will profoundly change how neurodegenerative disease is viewed. It provides a rational basis to prevent and reverse the circulatory deficits that cripple and destroy our aging brains.

Don’t Let Your Brain Shrink!

Don’t Let Your Brain Shrink!  

Normal aging is associated with diminished blood flow to the brain. This pathology is known as hypoperfusion and causes cell injury and death.17

Hypertension (high blood pressure) accelerates brain atrophy in humans.18 It does this by damaging the cerebral circulatory system to the point that it cannot adequately transport blood.19,20

Blood vessels damaged by hypertension (and other factors) lose their ability to nourish cells, which can result in chronic hypoperfusion and loss of brain function.20

The combination of hypertension and hypoperfusion is associated with smaller brain volume.18

Once the cerebral vasculature is damaged, lowering blood pressure will not reverse brain shrinkage, and shrinkage may continue despite successful blood pressure control.20 The reason is that deformed and dysfunctional cerebral arteries may require higher blood pressure to avoid hypoperfusion.19 In other words, in some people with cerebrovascular damage, higher blood pressure may be needed to “squeeze” blood into their brain. This “squeezing” process results in additional blood vessel damage and increased stroke risk.19

While hypertension is a significant cause of arterial damage and hypoperfusion, aging humans have to do more than lower their blood pressure to reverse hypoperfusion.

Role Of Hypoperfusion In Alzheimer’s Disease

Role Of Hypoperfusion In Alzheimer’s Disease  

Hypoperfusion is no longer a controversial aspect of Alzheimer’s disease.15,21

Disrupted blood flow (hypoperfusion) is evident when Alzheimer’s manifests in its initial stage as mild cognitive impairment all the way to full-blown dementia.7,14-16,21

Hypoperfusion is also evident in cognitively healthy persons at high-risk for developing Alzheimer’s due to family history or genetic factors.21

Through the advent of advanced imaging technologies, it is now known that Alzheimer’s disease is associated with both global and regional cerebral hypoperfusion.21,22 Scientists have discovered that perfusion deficits in regions of the brain observed in Alzheimer’s disease patients are also present in people at increased risk for Alzheimer’s.21

While there is still debate as to whether decreased blood flow in Alzheimer’s is a cause or consequence of the disease, hypoperfusion is definitively associated with both structural and functional changes in the Alzheimer’s brain.21

Aging humans now have documented opportunities to aggressively explore treatments to prevent, or at least slow the progression of diseases like Alzheimer’s and stroke by guarding against hypoperfusion,also known as cerebrovascular insufficiency.

Hypoperfusion Associated With Reduced Memory Function

Metabolic syndrome is a cluster of cardiovascular risk factors that is also associated with cognitive decline and dementia.2

Common characteristics of metabolic syndrome include elevated glucose,23 high triglycerides,23 insulin resistance,24 abdominal obesity,23,24 low testosterone (in men),25,26 and hypertension.24

A study of late middle-aged adults showed that mean cerebral blood flow was 15% lower in those with metabolic syndrome compared to age-matched controls. The metabolic syndrome group also had lower immediate memory function. In this study,abdominal obesity and elevated triglycerides were most strongly associated with lower cerebral blood flow (hypoperfusion).2

Our “Tiny” Capillaries
Our 'Tiny' Capillaries

With each heartbeat, blood is thrust into arteries that branch into smaller arterioles that branch further into capillaries where they deliver oxygen and nutrients to cells.27 Even medically-educated individuals forget just how tiny capillaries that oxygenate our neurons really are.

A typical red blood cell is 6-10 micrometers, but capillary diameter is only 8-10 micrometers on average.27,28 Capillaries are so narrow that red blood cells often have to bend their shape to squeeze through them.29

Platelets are usually 2-4 micrometers,30 but anything that causes abnormal platelet clumping (thrombosis) creates a mass that cannot fit through thread-like capillaries.31 This helps explain how precarious our aging cerebral vascular system is and how readily hypoperfusion develops via disrupted capillary beds.

Not only are capillaries tiny, but they are also extremely delicate. Instead of the tough layers that make up arteries, capillaries consist only of a single layer of endothelial cells lying on a basement membrane.29,32 Hypertension destroys fragile capillaries leaving in its wake hypoperfused regions of the brain, often described as cerebral perfusion deficits .33

Capillaries surround neurons and diffuse oxygen and nutrients into them.33 Any interruption to capillary blood flow has the potential to injure or kill neurons.33 This is why hypoperfusion must be prevented or reversed if we are to preserve our cognitive integrity.

Abnormal platelet aggregation increases as humans age, which explains why thrombosis is an increasing threat with aging.34,35 Any blood particle larger than 5-10 micrometers can clog capillaries, and if enough capillaries become occluded in the brain, an ischemic stroke can occur.33

Risk factors in the blood that cause brain vasculature to become blocked include excess homocysteine,36 fibrinogen,37 C-reactive protein,38 and triglycerides.39 Homocysteine creates more havoc at the capillary level than it does in large blood vessels.40 Fibrinogen promotes occlusive thrombosis.41 Inflammation42 damages the delicate endothelium, and triglycerides clog capillary beds.43

Maintaining capillary integrity is essential to prevent hypoperfusion and the neurodegeneration that invariably accompanies it. Most Life Extension members already take steps to guard their overall health, which confers tremendous benefits in sustaining capillary blood flow, thus protecting against hypoperfusion.

Hypoperfusion Associated With Weakened Heart Function

A group of 211 men aged 68 went through a battery of tests to assess cognitive and cardiac function. These same men were tested 14 years later.44 Those with weakened hearts as measured on an echocardiogram and abnormal EKG patterns at baseline scored lower on verbal and speed-performance neurological tests. The doctors who conducted this study concluded that heart deficiencies in the study subjects were “associated with lower cognitive test results and may predict cognitive decline and silent cerebral perfusion abnormalities 14 years later.44

Another study found reduced cerebral perfusion in elderly men with abnormal EKGs and nighttime blood pressure dipping. The doctors who conducted this study concluded:

Silent myocardial ischemia may contribute to cerebrovascular disease in non-demented elderly men. Cerebral perfusion seems to be most vulnerable to myocardial ischemia in elderly with nocturnal blood pressure dipping.”45

These and other studies show that circulatory interruptions caused by even relatively mild cardiac disturbances deprive the brain of blood flow and result in cognitive impairments. So taking supplements like coenzyme Q10,46 lipoic acid,47 carnitine48,49 and PQQ50-53 not only help boost cardiac output to the brain, but also protect the brain and enhance mitochondrial energy production within brain cells (neurons).

Visualizing The Aging Brain

Don’t Let Your Brain Shrink!  

Advanced neuroimaging methods are enabling doctors to observe structural, functional, and biochemical changes in the brain, thus allowing earlier diagnosis of neurodegenerative diseases.54

A review of studies using enhanced neuroimaging techniques showed significant individual differences in the rate of cerebral aging (such as a decay of brain volume and reduction of blood flow) that accompanies loss of cognitive function.54

One neuroimaging study looked at degeneration in regions of the brain (frontal and temporal lobes) and their relationship with hypoperfusion. The researchers found worsening of frontal-temporal degeneration in response to lower cerebral blood flow. More severe hypoperfusion related to greater functional deficit.55

Preventing Progression To Senility

Mild cognitive impairment is considered an early stage of dementia. A group of researchers conducted a 3-year test and found the conversion rate from mild cognitive impairment to dementia was 11.65% each year.56

They found that cognitive decline and hypoperfusion were related to diabetes, carotid stenosis, and changes in the white matter area of the brain. The researchers conducting this study concluded:

“… our findings could imply that controlling blood glucose, removing carotid stenosis, and improving cerebral perfusion could be effective measures to delay cognitive decline in patients with mild cognitive impairment and prevent conversion from mild cognitive impairment to dementia.”56

Another study looked at structural alterations (such as amyloid beta deposition) and vascular organization in brains of aged monkeys and human Alzheimer’s brain tissue. The findings suggest that amyloid plaque brain formation relates to multiple underlying pathologies that occur in partnership with vascular or metabolic deficit.57 This data provides a mechanistic explanation for why senile plaques (as seen in Alzheimer’s) are present preferentially near the cerebral vasculature, and the importance of guarding against hypoperfusion.

Reversing Brain Damage In Former NFL Players

Brain injuries are common in professional football players and severe cases sometimes make headline news stories.59-62

A clinical trial was conducted on 30 retired NFL players who demonstrated brain damage and cognitive impairment. They underwent baseline testing of cognitive function and brain perfusion as measured by SPECT imaging.63

Participants were encouraged to lose weight (if appropriate) and take the following supplements for six months:

Reversing Brain Damage In Former NFL Players

Fish oil 64-66

1,720 mg EPA
1,160 mg DHA

Vinpocetine 67-72

15 mg

Ginkgo extract 73-78

120 mg

Alpha Lipoic Acid 79-82

300 mg

Acetyl L-Carnitine 80,83-85

1,000 mg

Huperzine A 86-88

150 mcg

N-acetyl-cysteine 89-93

600 mg

High-potency multivitamin 94,95

The rationale behind using these nutrients was that they were individually shown to enhance blood flow, protect against free radicals, enhance brain cell membrane structure, boost acetylcholine, enhance neuronal metabolic activity, and reduce chronic inflammatory markers.

After six months, the tests were repeated. There were statistically significant increases in scores of attention, memory, reasoning, information processing speed, and accuracy in these retired NFL players. The SPECT scan showed increased perfusion in areas throughout much of the brain. The researchers who conducted this trial concluded:

“This study demonstrates that cognitive and cerebral blood flow improvements are possible in this group with multiple interventions.”63

Neurological trauma during football events accelerates brain aging. Life Extension members should be gratified to know that they have been taking most, if not all of the nutrients shown in this study to reverse brain damage in retired NFL players. This brain damage clearly linked hypoperfusion with cognitive impairment.