Alzheimer’s Disease is a progressively devastating, fatal disease that affects 5.2 million Americans and over 44 million people throughout the world.   This disease is often more difficult on the families and caregivers, then on the patient’s themselves.  With my office located near three of the country’s largest retirement communities, it is a disease that I see and treat every single day.

A paper published in the Journal of Alzheimer’s Disease this week, confirmed suspicions and patterns that I have been seeing for over 15 years.  A  significant number of my patients with Alzheimer’s dementia (AD) also have insulin resistance, impaired fasting glucose or diabetes mellitus – type II.  I have long wondered if there was a tie to these diseases because of the patterns seen in my office.  However, much of the research examining the association between type II diabetes and AD have come to differing conclusions about the cause.  Some have concluded that insulin resistance is to blame and others have concluded that insulin deficiency may play a role.  Other studies have found that a hormone called amylin secreted with insulin is to blame.  And, other articles have found that both amylin and amyloid-beta protein form the plaques within the brain common to AD.  Lastly, more recent data complied appears to point to the opposite conclusion – that amylin provides neruro-protective effects and may actually reduce the symptoms of AD. So, what are we to make of all of this?  How is the doctor in the trenches to interpret and then advise those with or at risk for Alzheimer’s Disease?

The paper referenced above, by Dr. Schilling, takes all of this data into account and with careful attention to research methods and compiling immense amounts of data from all of these studies, it identifies the integration points with insulin and insulin-degrading enzyme (IDE) that have begun to disentangle the research. What it reveals is fascinating information.

First, under normal circumstances, we now know that insulin stimulates the expression of IDE, which subsequently breaks insulin down after it is used.  IDE, however, also plays  a roll in breaking down amyloid-beta protein and other amyloidogenic peptides.  Alzheimer’s disease is caused by a build up of these amyloid based proteins forming plaques within the human brain.

Second, the body’s system for breaking down and removing these plaques can fail or become inefficient in four different ways.  What has been confusion for many years to researchers is now much more clear with our clarified understanding of insulin resistance moving through five different stages (see my article on Diabetes Mellitus type II – really the fourth stage of insulin resistance).

What are these four possible points of breakdown?

1. In the fifth or last stage of insulin resistance (where insulin deficiency occurs due to pancreatic failure and lack of adequate insulin production) or in a type 1 diabetes patient who makes no insulin at all, inadequate IDE can result in accumulation of amyloid-beta in the brain. Poor IDE production may cause amylin and amyloid-beta plaques in the brain.
2. Diminished IDE production due to any other cause may lead to amylin and amyloid-beta plaque formation leading to AD
3. Excessive production of insulin, occurring in stages I-IV of insulin resistance, stimulates increased amylin production which competitively inhibit breakdown of amyloid-beta resulting in AD.
4. Production of more than the typical level of amyloidogenic peptide that outpaces the formation of IDE is the fourth mechanism occurring with insulin resistance and stimulates the formation of amyloid plaque in the brain consistent with AD.

Further study is essential to tease out what the nuts and bolts of the mechanism may be, but with our understanding of stages of insulin resistance, the puzzle pieces are falling into place. This conglomeration of data provides further confirmation that insulin resistance is likely the key player in the progression of Alzheimer’s Disease years before type II diabetes or type I insulin dependence are ever diagnosed in the individual.

What is the take home message today?  Impaired fasting glucose, diabetes mellitus and Alzheimer’s disease are later expressions of the underlying problem: insulin resistance.  This is where a low carbohydrate and/or ketogenic diet begins to play a huge role in both prevention and treatment of Alzheimer’s Disease.

More to come . . . In the mean time, pass the butter and the Keto//OS.