Smaller Doses of Alcohol May Be Protective Against Alzheimer’s

Alcohol consumption has been a two-edged sword in the scientific research.  Study has shown that it can substantially contribute to the development of chronic disease in a number of body systems such as the cardiovascular system and in the liver.  Other study has shown the opposite with alcohol consumption actually being preventative of chronic disease such as that in the cardiovascular system.

This apparent conflict in data is explained by the “dose response curve”.  This is a measure of the outcomes associated with different daily doses of intake.  The graphic shows the dose response curve looking at total mortality.  The risk of non-drinkers is assigned a relative risk of 1.0.  Notice the risk is 0.8 at 20 grams which is approximately 1 ½ -2 glasses of wine consumption, or 20% risk reduction.  With heavy consumption,  risk increased compared to non-drinkers.  The truth is in the dosage.

This relationship between alcohol consumption and brain health has been less clear.  Chronic, excessive use is a risk factor for the development of all forms of dementia.  What has been less understood has been if alcohol and the brain follows a typical dose response curve seen for its intake and other diseases.  Some new research is suggesting it may.

The study examined the impact of 3 different daily doses of alcohol on brain “glymphatic flow” and inflammation in mice.  Brain glymphatic flow is the equivalent to lymphatic flow in the rest of the body.  The lymphatic system is used as a “highway” that the immune system uses to remove different toxic waste generated by infections or other exposures.

It was thought until recently that no lympathic flow occurred in the brain which created a mystery about how it detoxifies efficiently.  Recently some innovative research injected mice with a tracer that glows when exposed to a specific type of light into the lymphatic system to better see all of its pathways.  Surprisingly, the brain lit up as did the rest of the body confirming that there is lymphatic flow in this area.  The term for it was coined as glymphatic flow.

In the recent alcohol study, low alcohol intake increased glymphatic flow 39.8% compared to the control group consuming none. Higher consumption did just the opposite decreasing this flow.  The response in inflammatory markers followed the same pattern, improving with low dose consumption and increasing with high dose.

While this was an animal model study, dose impact studies on the relationship between alcohol and other health risks such as cardiovascular disease have supported the “dose response” relationship with 1-2 drinks daily decreasing the risk compared to non-drinkers and high dose use increasing the risk.  The relationship appears to be similar in the brain.

Lundgaard et al.  Beneficial effects of low alcohol exposure, but adverse effects of high alcohol intake on glymphatic function.  Scientific Reports, 2018;8:2246.

More New Research on Chronic Inflammation and the Development of Alzheimer’s

Inflammation is a critical process for the protection against short-termed stressors, such as infection.  While it is crucial for survival, it becomes a primary mechanism driving chronic disease when it is sustained and unsuppressed.

This dual role of inflammation is perhaps best explained by Dr. Russel Tracy, Associate Director of Research, University of Vermont School of Medicine; “Aging is not simply the passage of time, it is actually something that our bodies create, a side effect of the essential inflammatory system that protects us from infectious disease.  As we fight off invaders, we inflict massive collateral damage on ourselves… We are our own worst enemy.”

At the epicenter of this understanding is the relationship between ongoing inflammation and Alzheimer’s disease.  Extensive research has supported this relationship while a new study supports the strength of it.(1)  The study measured one of the more accurate inflammatory markers, high sensitivity C-reactive protein (hsCRP), and looked at its predictive power for the subsequent development of Alzheimer’s in subjects 60 and up.  

Elevated hsCRP increased the risk of Alzheimer’s by a striking 137% in the 8 years of follow-up.  This study added considerable strength to the association between chronic inflammation and Alzheimer’s risk.  It also was important as it confirmed a measurable marker that can be used to monitor disease risk.  hsCRP also is a valuable marker that can be used to monitor the effectiveness of a comprehensive lifestyle treatment program once the disease is present.  It is a fundamental biomarker used in the Bredesen Protocol™. 

The useful translation of how this biomarker is helpful in managing the disease relates to the diverse group of factors that cause chronic inflammation including diet, toxicity such as heavy metals, chronic infections and others.  The correction of these factors is successful in dampening chronic inflammation positively mitigating the disease process, and the effect can be monitored over time with repeat measurements of hsCRP.

The best time to be monitoring inflammation and correct it is before the disease develops.  However, it remains equally important in those with the disease as comprehensive lifestyle management reducing inflammation is proving successful in reversing the disease.

          1. Gabin et al.  The association of high sensitivity C-reactive protein and incident Alzheimer disease in patients 60 years and older: The HUNT study, Norway.  Immun Ageing. 2018 Jan 22;15:4.

Genetic Predisposition to Alzheimer’s Does Not Prevent Lifestyle Intervention from Helping

A large, ongoing study of a multipart lifestyle intervention (Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability) has been investigating the ability of this type of treatment to prevent cognitive decline in older subjects.  One of the latest analyses in this study sought to determine if the most common genetic variant that increases Alzheimer’s risk, the apoE4 gene variation, would prevent these individuals from benefiting from this intervention as persons without the gene variant.

Subjects between the ages of 60 and 77 were blindly randomized to the intensive management group which included diet, exercise, cognitive training, and vascular risk management, while the control subjects received only general health advice.  Equal numbers of participants in each group carried the high risk (3-10 times) apoE4 gene or the normal risk apoE3 gene.

Cognitive function was measured before the study with a comprehensive neuropsychological test battery and after 6 years.  Those participating in the intensive management group had significantly better cognitive scores at the end of the 6 years, and the benefit was the same in both the normal or high genetic risk subjects.  The two important conclusions are that a comprehensive lifestyle management program does prevent cognitive decline and that this prevention occurs both in those with and without the apoE mediated risk. 

These results are reassuring as approximately 1 in 6 adults have the higher risk apoE4 gene.  While this genetic variant increases their risk to the development of the disease, it does not prevent the benefits of a comprehensive lifestyle management program from helping.  The increased risk associated with the apoE4 gene appears to require those with it to be more meticulous about their lifestyle both to prevent the disease onset as well as to manage it once cognitive decline appears.

The above statement does not give a free ride about being less concerned about lifestyle management to those with the “normal risk” apoE3 gene.  The normal risk for Alzheimer’s is still 1 out of 6 by age 65-70, and 1 out of 3 by age 80.  Dale Bredesen, MD the innovator of the successful lifestyle program called ReCODE, explains the relationship between lifestyle and Alzheimer’s risk best based on extensive research.  He comments that Alzheimer’s appears to not be just a brain disease but rather a brain manifestation of systemic metabolic disease.  An example of this relationship is the 2-3 times greater risk of Alzheimer’s in those who develop type two diabetes which is highly related to lifestyle.

ApoE4 remains a risk factor for the development of Alzheimer’s disease.  While it increases this risk, it fortunately does not compromise the ability of a comprehensive lifestyle management program to help the disease once signs of it are present.  Importantly, the apoE4 genotype serves as a warning of the disease risk and the important preventative role of a comprehensive lifestyle program before the disease manifests.  The best treatment is not to develop the disease in the first place.