Evolving Past Alzheimer's

This week's guest is Dr Ross Grant, a clinical professor of medicine at Sydney Adventist in Sydney, Australia. He is considered one of the world's foremost authorities on NAD+ science and therapeutics.

Fair warnings: this episode is deeply technical and scientific, but during the last 15 minutes of the interview Dr Grant speculates on how NAD+ might be beneficial directly to Alzhiemer's (and Parkinson's patients). ALSO, we apologize for the sound quality of this episode. we are working to bring you better quality sound with each episode.

NAD+ or Nicotinamide Adenine Dinucleotide is a molecule necessary for a huge number of biological processes supporting human life. NAD+ levels decrease as we age. The body produces NAD+, but in addition to the natural decline in production, as we age there is also likely an increased need for NAD+ that is beyond our bodies ability to produce.

Key Biologic Processes where NAD+ is involved

1. Repair of the DNA (single base pairs) via PARP (Poly-ADP ribose polymerase)
2. Energy Production Enzymes
3. Redox-Repair Enzymatic activity
4. Epigenetical Switch - controlling gene expression especially of SIRT1 activity.
5. Immune system regulation/repair - especially relevant in Alzheimers where the immune systems and inflammation appear to be overactive making self repair more difficult.
6. Activate Tankyrase in order to extend telomeres.
7. It may act as a direct neurotransmitter in the brain and nervous system.

In an aging brain, inflammation and susceptibility to oxidative stress increase. As this happens, NAD+ levels drop and the brain loses NAD+'s sponsorship of longevity genes and mitochondrial support via sirtuin activity all contributing to eventual cell death.

Taking or using an outside source of NAD+ seems less likely to help someone if they have a lot of free radical damage (super oxide activity where oxygen free radicals are doing damage) occurring.

Caloric Restriction is one of the only scientifically proven methods to reduce damage from oxidative stress. When there is excess caloric intake (i.e. eating too much) or eat poor quality food our usable NAD+ is "tied up" in a less usable form called NADH.

Intake of excess and/or poor quality calories (i.e. bad food) gives rise to excess free radicals in the body. This occurs as cell turnover and reproduce themselves over time. Each "generation" of cells in our bodies (sometimes just hours or days later) will be made with increasing damage from these free radicals being made from a poor diet, so when this generation of cells is produced they are produced as damaged goods and effectively tie up NAD+. This increasing injury over time is known as "aging" and it depletes the body of its usable NAD+.

SIRT1 - Sirtuin (Silent Information Regulators) are able to switch on and off genes, including those that produce anti-oxidant capabilities in the body. When the body gets too many calories or the wrong kind of calories these genes - through an epigenetic mechanism known as acetylation - get down shifted and aren't able to protect us like they are designed to because the NAD+ and materials that turn them on are "busy" (ie they take the form of NADH). Being busy renders them unable to "hit the activation switch" as it were.

In general, mitochondria (energy producing parts of cells) seem to function less efficiently over time (ie aging). Some of the earliest changes in Alzheimer's occur in the mitochondria. The brain has an inordinate number of mitochondria relative to the rest of the body. NAD picks up electrons through a mitochondrion in a fairly efficient way to create energy currency in the body. Over time, this process can breakdown and become "leaky." Nutrient rich, energy limited diets (healthy, modest portions) seems to be one way to minimize these inefficiencies over time (i.e caloric restriction).

Mitochondrial Biogenesis -is the process of adding mass and function to the mitochondria (energy producing parts of our cells). Mitochondria are known to "crash" and are susceptible to damage early on in Alzheimer's. You can increase available NAD by increasing the bodies production of NAD 1) from Tryptophan 2) from over the counter forms of NAD.

Practically- these 3 forms can be bought over the counter:

1) Nicotinamide Riboside

2) Nicotinamide mononucleotide

3) Niacin

Dr Grant mentioned about 350mg may be a responsible dose, but also cautioned that some oral forms of Nicotinamide may end up stacking up and having the opposite effects that are intended (eg blocking sirtuin and PARP pathways), so you will - as always - definitely want to consult with your healthcare practitioner before trying this.

Each one of these three forms can increase the NAD inside our cells. But just supplementing with NAD without addressing other lifestyle factors of a good diet, proper sleep, enough exercise and stress reduction can lead to a build up of a recycling chemical in the body called, homocysteine which is associated with Alzheimer's, heart disease and other health issues.

Currently, there are only a few research institutions in the world that can truly measure NAD. It is unfortunately not widely available outside a research setting. According to Dr Grant, Dr Charles Brenner lab at the University of Iowa is the most reliable in the United States

IV (intravenous) NAD+ is being administered through a variety of clinical outlets in the US under medical supervision. This might be the most useful way to use it in neurodegenerative diseases like Alzheimer's and Parkinson's.

To learn more about NAD+

https://medicalsciences.med.unsw.edu.au/people/dr-ross-grant

http://www.springfieldwellnesscenter.com/

http://www.nadtreatmentcenter.com/nad-research/

On the cusp of her 50th birthday Julie Gregory started to experience symptoms of cognitive decline. Feeling alone and terrified, and given her family history of Alzheimer's, Julie sought to do something. Julie learned that she was an ApoE-4 homozygote - in other words she has both genetic copies of the ApoE4 gene which increased her chance of developing Alzheimer's by 50% - 90%. This episode discusses Julie's health journey and what she done to improve her cognitive and general health.

Along with a few other people, Julie founded ApoE4.Info Inc. - a crowdsourced website that brings people info in science and self-experimentation for those with one or two copies of the high risk gene for developing Alzheimer's (ie the ApoE4 gene).

Important NOTE: not everyone that is diagnosed with Alzheimer's has copies of the ApoE4 gene.

Julie's Most Effective Strategies for Brain Health

1. Exercise 60 minutes per day - low and moderate intensities.
2. "Super clean diet" - no grains, high numbers of natural colors, high vegetables, healthy fats (she focuses on plant fats and less so on the saturated animal fats).
3. Reduced cerebral glucose utilization - ketones can create alternate fuel (mild ketosis) you can do this by reducing sugar intake and ingesting MCT oil
4. Optimizing sleep - blue blocker glasses 3 hours before bed (to ramp up melatonin production)
5. Meditation - any kind for any amount of time
6. Impeccable tooth care- coconut oil pulling (10 minutes per day). Julie uses non-fluoride toothpaste
7. "Skin Deep Database" by the Environmental Working Group- to find safe skin care products

Minute 22:30 - Discussion about Babesia Duncani, Lyme related infections, chronic microbial infections (ie potential infectious micro-organisms) and how the research seems to suggest that these may lead to some of the proteins (beta amyloid in specific) that we know our causally related to Alzheimer's. Also, Julie tells her story about getting tested and treated for some of these infections.

Minute 32:01 On why talking about Alzheimer's or Pre-Alzheimer's is such a touchy subject and the goal of APOE4.INFO - the crowd-sourced website that Julie and others founded to help those looking for accurate information. They have an active forum and facebook page that you can interact with. We also discuss the ethical controversy of genetic testing to understand your Alzheimer's risk (spoiler alert: Julie and I are both fans of checking) and the controversy around talking about the view that Alzheimer's is potentially reversible and preventable.

Find out more about Julie's organization to help you understand your risk: apoE4.info

In this episode we explore emerging radiology technologies and the new field of Preventative Radiology The info in this show will help you understand your risk for Alzheimer's and cognitive impairment and possibly even concussion related brain changes - and what to ask your doctor to get it ordered correctly.

Our guest, Cyrus Raji MD PhD, is a clinical fellow at the University of California - San Francisco. He completed his combined MD and PhD at the NIH-funded Medical Scientist Training Program at the University of Pittsburgh School of Medicine in 2010. He has worked with leaders in the field including Dr Bennet Omalu (the pathologist played by Will Smith from the movie, Concussion). His current research involves Diffusion Magnetic Resonance Imaging based Edge Density Connectome Mapping for Prediction of Alzheimer's Disease. He is an advisor to the NeuroReader.

Neuroradiology is the branch of radiology focusing on the brain and spinal cord. Ironically, very few radiologists actually have deep expertise in neurodegenerative conditions like Alzheimer's.

An MRI of the Brain- looks at brain structures and is readily available to most anyone through a local doctor. Typically they are simply interpreted by an individual radiologist which may or may not be useful in assessing your risk of Alzheimer's.

A better assessment may be the individual radiologist joining forces with computer programs that perform volumetric analyses of specific brain regions (explained in min 26:38). These volumetric analyses programs assist the radiologist by comparing domains of your brain to a database of normal brains and may give you a more detailed analysis and detect areas of early concern before it is obvious to the naked eye (even a trained one sometimes!). It can also identify other patterns of brain shrinkage - like vascular disease (e.g. strokes, mini-strokes, and suboptimal blood pressure issues), alcoholism, and psychiatric disorders.

The Different Types of Imaging Used for Alzheimer's

1) MRI (Magnetic Resonance Imaging). Looks at the structure of the brain alone. Does not look at function. A brain MRI contains no radiation if it is done without IV contrast.

2) fMRI (functional MRI) measures oxygen reflecting blood flow in the brain. Can identify problematic areas before structural changes are evident. It is overall a more sensitive tool than regular MRI, but for the most part is only available in research setting.

3) "Nuclear imaging" - looks at metabolism in the brain using radioactive tracers that have patterns consistent with Alzheimer's and other dementias. 2 examples of nuclear imaging a) PET-fdg assesses glucose utilization, high cost if not covered by insurance and not as available as MRI b) SPECT scans - not widely available and cost is somewhat prohibitive at this time.

What insights imaging can give you about Alzheimer's Brains

Classic brain atrophy (shrinkage) in Alzheimer's happens in the hippocampal regions in the medial temporal lobes near the middle of the brain. The hippocampi are important in the making (encoding) of new memories. The hippocampi start to shrink up to 3 years before actual symptoms of Alzheimer's begins. And in that area one can get a loss of volume in the temporal lobe.

Posterior cingulate gyrus and precuneus in the brain's parietal lobes can develop problematic changes as well. These areas are important in tracking information and cognitive integration.

What do my MRI volumetric numbers mean?

To be considered abnormal and potentially consistent with Alzheimer's diagnosis - the "magic number" for hippocampal volumes on MRI of the brain (using the Neuroreader or Neuroquant tool) is a number below the 25 percentile (this information is included in the report provided by Neuroreader or Neuroquant). Ventricular volumes, if higher than 75th percentile, may be too big and suggestive of Alzheimer's or another disorder as well.

An Introduction to the field of "Preventative Neuroradiology" (discussed at minute 23:30).

Knowing your risk for Alzheimer's with imaging. It's not the whole story but its good data.

If your MRI is read as "normal" but is noted to have some "periventricular white matter" or white matter changes suggesting "chronic ischemia" and low blood flow - this may not be exactly normal. Remember T2 FLAIR (one way the radiologist views the MRI images where fluids lights up brighter) is the easiest place to see these changes on your MRI. These changes may represent issues like hypertension, diabetes, or artery disease. When there is white matter problems then gray matter disease (or problems with brain cells like neurons) is probably not far behind.

Lifestyle changes seem to be able to impact the hippocampus in a positive direction.

Brain changes classic for CTE (Chronic Traumatic Encephalopathy) that happen as a consequence of concussion/traumatic brain injury may be found within the brain stem. Ventral diencephalon and frontal lobe may be affected as well.

How to Get a Volumetric MRI of your Brain

To get a Volumetric Brain MRI study done so that it can be computer-read by Neuroreader (by the Brainreader company) or NeuroQuant (by Cortechs labs). Make sure to have it done in a "volumetric acquisition" (ie really "thin slices"). Ask the imaging center's MRI technologist:

if the MRI Volumetric scan is done in the "sagittal" orientation with General Electric machine- "acquisition in SBGR" or if the machine is a Siemens machine-acquisition ask for it to be done in "MP-RAGE" or whatever settings the institution uses for volumetric acquisitions.

Lisa Feiner is a co-founder of the grassroots, not-for-profit organization - Sharp Again Naturally - focused on preserving memory and restoring minds.

SharpAgain's "roadmap" to reversible causes of memory loss is really quite impressive. They advocate working on your own and in partnership with your healthcare practitioner to look for reversible causes of Alzheimer's, dementia, and memory loss. Here is the list and you can find this on www.sharpagain.org - check out the "roadmap."

10 REVERSIBLE CAUSES OF MEMORY LOSS (PER SHARP AGAIN NATURALLY)

1. Nutritional imbalances and deficiencies
2. Toxins in food, water, air, work/home environments
3. Effects of prescription medications
4. Mercury and other heavy metal toxicity
5. Hormonal imbalances (thyroid, estrogen, testosterone and others)
6. Inflammation from low-level infections, mold, food allergies, and Lyme Disease
7. Inadequate physical activity, mental stimulation, and social interaction
8. Stress, especially from life changes and how we process information
9. Sleep and breathing problems related to oxygen deficiency
10. Traumatic Brain Injury

We also touch on the roles of meaning and spirituality and prevention (min 22:43).

We discuss the importance of oxygen and the airway on brain health (Min 30:24). Interestingly, there is a role for proper nutrition (including MCT oil) in terms of airway development.

Listen to stories of people that have improved using the the concepts advocated by Lisa's organization (Min 33). Treatment may take several months or longer to really see the powerful impacts.

Show Resources:

Lisa's organization's website: Sharp Again Naturally

LA TIMES Article linking pollution and Alzheimer's

"The Polluted Brain - Evidence builds that dirty air causes Alzheimer's dementia"

"GASP - The Hidden Path to Wellness" by Michael Gelb DDS and Howard Hindin DDS. This is a book that explains many of the complexities around sleep disorders, airway problems and how to assess and treat them. It connects the concept of airway and sleep to problems with cognition.

BrainHQ by Posit Neuroscience.

Get ready because this episode takes us 5-10 years into the future - where Big Data meets Alzheimer's. But the future is already here!

Dr Nathan Price PhD is the associate director of the highly esteemed Institute for Systems Biology (ISB) and co-founder of it's spin-off company Arivale - a leading company in the Scientific Wellness space. ISB and Providence St. Joseph Health, a 50 hospital system to which ISB is affiliated, have particularly focused on solving Alzheimer's and have invested millions of dollars into research in finding both cures and prevention programs.

Dr Price gives us an intro to the concept of "Scientific Wellness" and it's role in creating health and predicting and preventing disease. Scientific Wellness - refers to technologies that quantify and assist to enhance health in the human body. Using methods of measurement called "Computational Biology" this approach builds models to make sense of disease and resilience states and gain insights from vast amounts of information generated using computer technology. This information can be from a person's genes or gene expression products or even the bugs in their stool and saliva. In some cases these methods may even try to make sense of data streams collected by a variety of sensor-based information (for example, from a FITBIT).

All of this information can be overwhelming to handle and requires "supercomputing" capacity which companies like Arivale and ISB possess. Dr Price and I discuss how all of this information comes together in the case of Alzheimer's disease in the form of "dense dynamic personal data clouds" and how this will likely be important in solving the Alzheimer's puzzle. Dense dynamic personal data clouds - refer to huge data sets that are followed on individuals over time to help predict and prevent disease. The first such project was called the "Pioneer 100." While some of these data collections are investigational at this time, the near term goal is to leverage these data to practical help people get better or possible prevent Alzheimer's.

In order to make sense of an individual's information, his/her genome need to be compared against what is know about Alzheimer's in the highly touted Genome Wide Association Studies (GWAS). GWAS data are important because they tell you about gene variations that are associated with a variety of aspects of Alzheimer's disease. Fortunately, there is good GWAS data for Alzheimer's and based on this, Dr Price and his team at Arivale believe that this will help track the manifestation of Alzheimer's disease based on tracking way the way genes express in a variety of other measurable data from a human being. This information is collected from multiple levels of a person including stool, saliva, urine, blood and potentially more. The variety of levels of "Omic" information is aggregated then with the assistance of computer technology is made sense of in the form of a "dense dynamic personalized data cloud."

Other Interesting Topics discussed in this episode

• Connections between diabetes type 2 and Alzheimer's a
• Where stem cells might have a role in treatment.
• CRISPR technology - the benefits and ethical questions of gene-editing technology.

I want to highlight CRISPR in this summary because of how significant it appears it will be in the future of achieving real health on multiple levels. CRISPR is a gene-editing tool - that Dr Price calls one of the most exciting developments in biology in his generation. CRISPR is a simple technique for gene editing that allows someone to effectively "pull out" risky genes at the stem cell level, fix them, and put them back. But, Dr Price also considers the ethics and potential unintended consequences.

Changing the paradigm of how clinical research is done in the Information Age. In the age of Personalized Medicine the paradigm of the single pill for a single ill is being challenged and a new approach for clinical trials is emerging with ISB amongst the leaders of this emerging paradigm.

Find out more about Dr Price's work here:

The Institute for Systems Biology

Arivale

Today's Guest is, Dr Majid Fotuhi of the Neurogrow program and Johns Hopkins University. He is the author of 3 books and multiple academic as well as popular scientific articles. Dr Fotuhi's work has been featured in Time Magazine and Reuters and he has been seen on PBS, CNN, NBC, ABC and FoxNews.

Show Summary:

The hippocampus is an area in our brain that - when smaller than average compared to those our age - seems to be highly related to Alzheimer's. The hippocampus is partially responsible for storing and processing memories. it is highly susceptible and sensitivity to toxicants and the ongoing effects of stress. Over time this area can get penetrated resulting in leaks through the blood brain barrier (a protective lining of cells that protects the brain from harmful elements in the blood). This "leaky brain" has an effect on over all brain function and is associated with Alzheimer's disease and poor brain functioning.

Hippocampal "size matters" - hippocampal volumes of the brain correlate with better brain function and seem to protect against memory loss and Alzheimer's. and you can impact the size of your hippocampus.

Poor diet, obesity, lack of activity/exercise, poor sleep/uncorrected sleep apnea, high stress all seem to impact the hippocampal size either positively or negatively.

Ask your institution about getting an MRI of your brain with "quantitative volumetrics" with software like Neuroquant or Neuroreader (listen to episode with Dr Cyrus Raji for more information) that can tell you how large or small your hippocampus is compared to those your age.

Dr Fotuhi published an article that showed 84% of participants improved their in memory and positively increased the sizes of their hippocampi after participating in a 12 week brain health program.

The Key Practical elements of Dr Fotuhi's program are:

• adherence to a Mediterranean diet with the additional of omega 3 fatty acids
• stress reduction and meditation
• regular exercise
• identifying and treating sleep apnea
• memory and brain training
• brain mapping with qEEG and neurofeedback

Significantly positive EEG (brainwave formation) changes were shown on the "brainmapping" portion of his program within just 6 weeks. This was due to the use of neurofeedback, a way of training the brainwaves using EEG-related biofeedback technology. The result...better brain function!

Walking 10,000 steps per day seems to be more effective than at least one FDA approved medication for Alzheimer's.

Practice Makes Cortex Article

Dr Fotuhi's Brainfitness Calculator - take this test and score your own brain fitness

Dr Majid Fotuhi's website: www.neurogrow.com for information or to enroll as a patient

Books by Dr Fotuhi:

Boost Your Brain: The New Art and Science Behind Enhanced Brain Performance

The Memory Cure : How to Protect Your Brain Against Memory Loss and Alzheimer's Disease

The New York Times Crosswords to Keep Your Brain Young: The 6-Step Age-Defying Program

Dr Dale Bredesen is an internationally recognized researcher in Alzheimer's. His incredible resume includes being the Director of the Easton Center for Alzheimer's Research at UCLA as well as founding president and CEO of the Buck Institute on Aging in Novato, California. He has worked in the lab of 2 nobel prize winners and has run his own labs for 28 years looking at neurodegenerative diseases - focusing on Alzheimer's. Dr Bredesen's fundamental theory is that Alzheimer's is actually a protective brain response to different classes of insults.

Classes of Insults Leading to Alzheimer's

1. Inflammation and the brain's response to pathogens/infections – these trigger the creation of amyloid beta, a key chemical in the brain that destroys brain cell connections and is believed to be a key factor in the development of Alzheimer's. Amyloid Beta is a part of the Innate Immune system which seems to be over stimulated or dysregulated in most cases of Alzheimer's. Dr. Bredesen explains the connection of immune activation in Alzheimer's.
2. Inadequate amounts OR withdrawal of support of brain-"growing" chemicals like B12, vitamin D, and other hormones. This results in a downsizing of the networks of brain cell connections.
3. Sugar toxicity – damages via:
   1. advanced glycation end products (AGEs) acting to damage through inflammation as well as,
   2. loss of cell supports because of shoddy insulin signaling necessary for healthy brain activity.
4. A protective response by amyloid that bind to things that the brain perceives as a toxin – things like: copper, iron, mercury, biotoxins, infections.
5. People in their 50s and early 60s tend to have the more "toxic" form.
6. Problems with blood vessels and leakiness in the protective blood-brain-barrier which result in lower support chemicals and toxicity.
7. Trauma, e.g., from things like concussions – which also lower chemical and hormone support as well as make the brain susceptible to all the insults mentioned above.

The story of "Patient Zero" (Minute 28:53) Dr. Bredesen describes the first success he had with his program.

Things that induce Alzheimer's a.k.a. "Dementogens"

• Biotoxins
  • Exposures to water building and the harmful effects of mold
  • Tick exposures
• Heavy Metals Exposure
  • Aluminum, copper, mercury
• Water damaged building, mycotoxins
• Certain types of infections
• Concussions
• The effects of diabetes and poor diet
• Certain types of pollution
• Not enough time asleep or insufficient oxygen when you sleep.\
• Not enough exercise

Elements of a "Cognoscopy"Because the brain changes in Alzheimer's can creep in 20 years or more before symptoms start prevention makes a whole lot of sense. Though a cognoscopy doesn't really exist yet in a conventional medical setting, Dr. Bredesen's thinks that one should probably be done around age 45 to assess the risk of developing Alzheimer's and might include the following:

1. Genetic markers and blood work that elucidates Dr. Bredesen's three metabolic subtypes (see an MPICognitions.com to find a doctor trained in the protocol).
2. Functional cognitive testing using BrainHQ, Lumosity, Cog-state, CNS vital signs to see where your brain function is in a "testing environment".
3. Brain MRI with volumetrics (listen to Evolving Past Alzheimer's podcast with Dr. Cyrus Raji episode #6 for full explanation) if someone has symptoms.

The Role of Sleep in Alzheimer's

• Time of repair (don't eat 3 hours before bed)
• Time for autophagy (brain cell "pruning")
• There is a slight change in the microanatomy of the brain where some of the accumulated toxicants get "washed away"
• Sleep hygiene is important

Who typically improves with the Bredesen Program?Dr. Bredesen mentions the "MoCA" which refers to the Montreal Cognitive Assessment. This is a screening test that won't tell you if someone has Alzheimer's but can give you a general indication of different levels of cognitive impairment. Dr. Bredesen mentioned that people that score 22 or greater (out of 30) are seeing improvements with his methodology. These are people that are typically early on in their disease.

Who typically does not improve with the Bredesen Program?

• People that are more "frail" (less able to exercise, etc.)
• People that are further along with the disease and have had symptoms for longer periods of time.

How much improvement do people see with the Bredesen Program?Some people seem to get just a bit better in terms of mood, outlook, and brain function. Others get much better and almost completely back to their best brain function. Too early to say how many, but more than half of the people using the methodology report some sort of improvement.

A discussion of an upcoming Documentary of the impact on people's lives using Dr. Bredesen's program.

Resources

• Dr. Brdesen's Book: The End of Alzheimer's
• To find a Bredesen trained physician, visit Dr. Bredesen's website – MPI Cognition
• Website: Institute for Functional Medicine

Our show and website is here to help you or someone you know with a problem that is destroying minds and families all over the world. This problem is Alzheimer's disease. Our fundamental belief is that Alzheimer's is generally preventable and reversible (especially if discovered in the early stages).

My name is, Nate Bergman, your host on the "Evolving Past Alzheimer's" Podcast. I am a physician in Cleveland Ohio. Listen to this episode to hear my own story of memory loss and how I coped with feeling like I was losing my mind...and how I have gotten better. The Evolving Past Alzheimer's podcast covers Alzheimer's issue from many angles. This show is focused on preventing Alzheimer's, or at least identifying the disease as early as possible (if not before it starts...yes that may be possible). But our greatest desire is to help our listeners avoid the disease and "get better" from Alzheimer's. This show will explore the latest research and technologies with an emphasis on what you can do yourself or bring to your healthcare provider. Everything from diet, exercise, stress, medications, genetics, genomics, brain games, "Big Data', Artificial intelligence (AI), and gene therapies. At times we will sidebar into the spiritual and futuristic sides of Alzheimer's and aging. These are exciting times...come learn with us, interact, transform, and get better!!