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!
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
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
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
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.