It all began in 1983…  A group in Sweden noticed that there were differenced in blood glucose and insulin levels in patients with AD.  Bucht 1983 Changes in Blood Glucose and Insulin Secretion in Patients with Senile Dementia of Alzheimer Type 2

Alzheimer’s and Diabetes  LSUHSCS Library’s OVID database searched  Alzheimer’s cross-referenced with Diabetes:  Found 486 articles  Over 300 evaluated  231 reports retrieved and reviewed 3

And Every Year We Learn More… 4

Why Would Anyone Want to Treat Alzheimer’s With Insulin??  Because Alzheimer’s disease (AD) and Diabetes have the same underlying cause.  AD is now being called “Type 3 Diabetes” 5

Alzheimer’s   Diabetes  Hoyer 1998  Is Sporadic Alzheimer Disease the Brain Type of Non- Insulin Dependent Diabetes Mellitus? (yes)  Steen 2005  Impaired Insulin…Expression and Signaling Mechanisms in Alzheimer’s Disease – is this Type 3 Diabetes? (yes)  De La Monte 2006  Therapeutic Rescue of Neurodegeneration in Experimental Type 3 Diabetes: Relevance to Alzheimer’s disease  Kroner 2009  The Relationship Between Alzheimer’s Disease and Diabetes: Type 3 Diabetes? (yes) 6

OK, So Why Isn’t Insulin Already Being Used to Treat AD?  It is!  Diabetic medicines, subcutaneous insulin, intravenous (IV) insulin, and even intranasal insulin – have all been used. 7

IV Insulin Therapy (non-pulsatile) (Suzanne Craft’s Laboratory - U. Washington, Seattle) 1993 Effects of Hyperglycemia on Memory in AD 1996 Memory Improvement Following Induced Hyperinsulinemia in AD 1999 Enhancement of Memory in AD With Insulin 2000 Insulin Effects on Glucose Metabolism, Memory, and Plasma Amyloid Precursor Protein in AD 2003 Insulin dose–response effects on memory and plasma amyloid precursor protein in AD 2004 Modulation of memory by insulin and glucose in AD 2006 Modulation of plasma β-amyloid by Insulin in Patients With AD 8

Intranasal Insulin Therapy (Suzanne Craft’s Laboratory - U. Washington, Seattle) 2004 (Germany) Intranasal insulin improves memory in humans 2006 Effects of intranasal insulin on cognition in memory-impaired older adults: Modulation by APOE genotype 2008 Intranasal insulin improves cognition and modulates β-amyloid in early AD 2008 Intranasal Insulin Modulates Verbal Memory and Plasma Amyloid-β in Memory-Impaired Older Adults 2010 Clinical Trial of Intranasal Insulin Shows Some Benefits in Alzheimer's and MCI 9

So Why Do Pulsatile IV Insulin for AD?  Because non-pulsatile IV and intranasal insulin therapy:  Are disease modifying agents, yes  Slow progression of AD, yes  Even improve AD in some cases, yes  BUT: DO NOT address the underlying metabolic dysfunction. 10

Pulsatile IV Insulin Therapy is Distinctly Different  This is an absolutely critical distinction to make:  Pulsatile IV insulin is a different “drug” than insulin delivered any other way, even non- pulsatile IV insulin!  It addresses the underlying metabolic dysfunction  decision made to call it Cellular Activation Therapy 11

Pulses of insulin were discovered to be the normal mode of pancreatic insulin delivery to the liver  Insulin is secreted from beta cells in the pancreas almost exclusively in pulses.  The results of the study show that very large pulses of insulin go into the portal vein and then directly into the liver  Prior to this study, no one had shown this effect in human beings  “Insulin release in the human portal vein occurs at a mean periodicity of 4.4 ± 0.2 min with a high signal- to-noise ratio (pulse amplitude 660% of basal).”  Peter Butler and Soon Song received the Endocrine Society's first prize for best clinical paper published in The Journal of Clinical Endocrinology and Metabolism in the year  Butler, et al: “Direct Measurement of Pulsatile Insulin Secretion from the Portal Vein in Human Subjects”, Am J Physiol Endocrinol Metab 2002 Mar;282(3):E695-E702

1. When given glucose, normal people metabolize it 2. And lipid use goes down 3. Abnormal Metabolism 4. Elevated Lipids 6. And thus lower lipids 5.Now activated, they burn carbohydrates Diabetic’s Metabolism Returns to Normal CAT changes diabetics from unable to metabolize glucose, to able to burn, store and release glucose, thereby reducing the high levels of lipid oxidation.

Cellular Activation Therapy (CAT) Bionica MicroDose Pump Mimics the Pancreas  Provides what a healthy person’s pancreas provides to a non-diabetic liver, pulses of insulin in the presence of glucose.  Proven safe and effective way to reawaken the liver to provide the enzymes for proper metabolism  The Bionica MicroDose FDA approved delivery system is unique and has been in continuous use for almost 20 years  In over 100,000 treatments there has never been an adverse reaction, and never been a pump failure or injury  This is because the treatment provides the stimulation that a normal body needs and receives.

 The Bionica pump delivers extremely precise pulses of insulin at pressure.  This special delivery is required to stimulate the liver and reawaken dormant metabolism.  The unique Bionica pump is the only FDA & CE pump labeled (authorized) for IV Pulsed Insulin. 15

One 6 hour treatment per week starting in the early morning. The Bionica Pump delivers the pulses tailored to mimic a normal pancreas. Special software ensures proper treatment and tracks results. Patients see their metabolism restored to normal healthy levels. “I would have been dead 3 years ago without CAT. My doctor gave me six months.” (E. Iaconis) What to Expect During Treatment

Now We Know:  Alzheimer’s (AD) and Diabetes Mellitus (DM) are essentially the same disease, in different organs  Standard Insulin therapy helps with DM, but there are still problems  Pulsatile IV Insulin  Cellular Activation Therapy  greatly improves DM  IV or inhaled insulin helps AD, but there are still problems  Cellular Activation Therapy for AD…is what we need to do next! 17