The Link Between Cardiovascular Disease and Alzheimer’s Disease

The brain on the right is shrunken and the spaces are larger because of Alzheimer’s Disease...

Alzheimer’s disease is the condition that I most fear. For me, my mind is that most critical part of me. It is what makes me who I am. When that is lost, all is lost. The great good news is that we are understanding enough about this dreaded disease that we can prevent it in many people and we can slow it down. Doctor Sanjay Gupta just performed in a documentary on Alzheimer’s disease named The Last Alzheimer’s Patient and it is very enlightening. He even visited with some patients that improved over 5 years!

 Many studies show that atherosclerotic vascular disease and dementia occur frequently together. Nearly 4 million Americans over 65 years old had Alzheimer’s disease in 2017 and this condition is predicted to more than double to 9.3 million cases by 2060. There are no really effective treatments for this condition now. At best, the current widely available treatments improve mental function for a short time.  Development of disease‐modifying treatments are challenging because Alzheimer’s disease develops over decades with no symptoms or minimal symptoms. Studies link Alzheimer’s with cardiovascular risk factors such as hypertension, inflammation, high cholesterol, and especially diabetes. Both Alzheimer’s and cardiovascular disease are progressive conditions with decades‐long development periods.  Cardiovascular disease may show up years earlier than Alzheimer’s, making vascular disease and its risk factors a potential predictor of future Alzheimer’s.

This association makes sense and is one more fact that supports a unifying hypothesis of chronic disease and aging. Cardiovascular disease is not merely associated with heart failure and Alzheimer’s disease. It is also associated with chronic kidney disease, fatty liver, and fat-induced hepatitis of the liver with cirrhosis. The common denominator for all of these conditions is increased oxidant production and inflammation that kills the functional cells of the organ and so multi-organ failure is common in patients with cardiovascular disease. Alzheimer’s disease, congestive heart failure, and kidney failure can exist in the same patient and they often do.

The answer to all of this is to identify patients with excess oxidant production and inflammation and coach them in the diet, intermittent fasting, and exercise that have antioxidant and anti-inflammatory properties. Lisinopril, losartan, amlodipine, and eplerenone for hypertension, atorvastatin for cholesterol, and metformin and Jardiance for type 2 diabetes are all antioxidant and anti-inflammatory and they protect every organ and every cell in the body.

The links between cardiovascular disease and Alzheimer’s disease have been confirmed in studies and experimental data. The major component of the characteristic plaques in the brain with Alzheimer disease is amyloid β protein (Aβ). Secreted, soluble Aβ is a product of normal cell metabolism and found in various body fluids, including the blood.  The presence of heart artery disease is independently associated with increased circulating amyloid beta (Aβ1‐40) levels among adults with normal brain function. Individuals with more favorable levels of cardiovascular health have a significantly lower risk for several of the leading causes of death, including heart artery disease and Alzheimer’s disease.  The American Heart Association and American Stroke Association are working in areas of brain health  to reduce the leading causes of death and disability including Alzheimer’s disease that directly influence years of life lost and years of disability

Traditional risk factors for cardiovascular disease and related conditions including high blood pressure, high bad cholesterol, low good cholesterol, obesity, and cigarette smoking, may predispose individuals to Alzheimer’s disease by promoting amyloid deposit development in the brain. In addition, atherosclerosis without symptoms in heart, neck, and leg arteries has been linked with dementia and Alzheimer’s disease.  Genetic mutations like APOε4 may add to the risk. At a molecular level, increased inflammation, and excess oxidant production decrease Aβ protein clearance and breakdown. Decreased Aβ protein clearance has been demonstrated in adults with cardiovascular risk factors and heart attack but no memory impairment. Possible mechanisms by which smoking increases both Alzheimer’s disease and  risk cardiovascular disease risk include an increase of oxidative stress, impairments of the housekeeping function of the cell , and increased inflammation.

Diabetes, smoking, air pollution, depression, social isolation, and education levels have also been identified as potentially modifiable late‐life dementia and cardiovascular disease risk factors. Diabetes and physical inactivity are correlated with increased cardiovascular risk as well as increased inflammation and oxidative stress in the brain. Inflammatory responses and thus, worsening cardiovascular  and Alzheimer’s disease risk, have also been associated with smoking and air pollution, which enhance oxidant production and inflammatory responses. Depression and social isolation are also associated with accelerated brain and cardiovascular aging and poor health behaviors.

There is enough evidence to show that cardiovascular disease and Alzheimer’s start decades before the clinical events (including heart attack, memory loss,  or death). Thus, there is a prolonged window of opportunity during which preventive interventions can reduce disease burden.

It is not just that we know that cardiovascular risk factors and Alzheimer’s disease risk factors are the same. The epigenetic changes and resulting molecular biology of both diseases have much in common. If your western diet leads to an accumulation of extra abdominal fat, an accelerated progression to Alzheimer's disease has already begun. Extra abdominal fat is the largest gland in the body. Abdominal fat leads to activating the renin-angiotensin system which in turn causes increased production of the hormones angiotensin II and aldosterone. These hormones have been studied in the genesis of high blood pressure, chronic kidney disease and cardiovascular disease almost exclusively, but now we are learning that they affect every organ and cell in the body when they are overactivated.

Alzheimer’s disease (AD) is a well-known neurodegenerative disease characterized by the presence of changes in Tau proteins and Aβ proteins. Drugs targeting the Renin Angiotensin System  commonly used for the treatment of hypertension, are showing a high potential to delay Alzheimer’s disease development due to their precise blocking of the effects of angiotensin II and aldosterone in the brain. Indeed, the renin-angiotensin system is believed to be upregulated in Alzheimer’s disease and to be responsible for deleterious effects such as increased oxidative stress and neuroinflammation.  Scientific studies demonstrate a reduced risk of developing Alzheimer’s disease among people taking  medication that blocks the effects of angiotensin II or aldosterone. Losartan, lisinopril, spironolactone, or eplerenone don’t merely lower your blood pressure and protect your heart and kidney. It is highly likely that they protect your brain as well.

The mTOR and AMPK axis also has an important role in Alzheimer’s development.  Increased mTOR activity interferes with the housekeeping function of the cell and the removal of β-amyloid (Aβ) proteins. When mTOR is activated, AMPK is deactivated. AMPK enhances the house keeping function of the cell and it is a survival switch that protects all organs and cells, including the brain. Activating mTOR and deactivating AMPK increases the likelihood of Alzheimer’s disease. Diet, exercise and intermittent fasting switch off mTOR and activate AMPK. Losartan, lisinopril, spironolactone and eplerenone for hypertension, atorvastatin for bad cholesterol, and metformin or Jardiance for type 2 diabetes do the same thing. That is how these precise interventions will protect your brain and delay Alzheimer’s disease. I doubt there will be a cure for Alzheimer’s disease once established, but it seems very likely that we can prevent it for many people, slow down the progression, and even see improvement over years in some. When you treat your vascular disease more effectively, you are also protecting your brain.