Issue 2 December 2018

Can’t-Miss Research from November Chemical Effects of Coffee Researchers studied the chemical effects of coffee and some of the specific chemicals found in coffee on Amyloid Beta and Tau protein in the lab. They found that several chemicals helped stop Amyloid Beta from aggregating, and one chemical, phenylidanes, inhibited both Tau and Amyloid Beta aggregation.  As the study was performed outside of human or animal models, the actionable results are limited. It is not known if these chemicals make it into a coffee drinker's the bloodstream unaltered or if these chemicals can cross the blood-brain barrier in order to act on Amyloid Beta and Tau in the brain. Phenylidanes are more common in dark roasts, but the evidence does not support making the switch to dark roast yet.Study. Related Press Articles: Forbes, USA Today and many more.

Artificial Intelligence Can Help Diagnose Alzheimer'sAn AI deep learning model and radiologists separately analyzed PET scans from 40 patients to predict if those patients would develop Alzheimer's disease. At a follow-up about 6 years after the scans, the AI model predicted 7/7 (100%) of Alzheimer's diagnosis and the radiologists predicted 4/7 (57%). However, the radiologists had fewer false positives than the AI model on people without a later Alzheimer's diagnosis. Radiologists predicted 30/33 (91%) people that did not get diagnosed with AD vs the AI model's prediction of only 27/33 (82%). With testing on wider datasets, the AI model could become a good clinical tool for physicians, but in the near term, it may have limited impact due to the small number of people having this type of PET scan outside of research studies.Study and press release. Related Press Articles: Being Patient. Further reading on AI: Could Artificial Intelligence Catch What Doctors Miss? Precision Medicine’s Role in Brain Health - Being Patient.

Potential Alzheimer’s VaccineA vaccine was studied in mice that were genetically modified to have Alzheimer's disease. The vaccine succeeded in three ways: it reduced Amyloid Beta peptides and plaques, it reduced Tau protein, and it was noninflammatory. The noninflammatory result is particularly important because a previous vaccine clinical trial was ended due to 6% of human patients experiencing encephalitis (brain inflammation). Many headlines inaccurately suggest that the vaccine could cure half of dementia cases. In reality, the researchers suggest that the vaccine could delay onset of Alzheimer’s by enough time that people die from other causes before they develop the disease. That said, any delay in Alzheimer's onset would be a huge development. The researchers are optimistic about moving to human trials with the vaccine after having already completed safe testing in three mammals.Study and press release. Related Press Articles: Forbes and many more.

December Newsletter Knowing Alz �1

Holidays & Family

Holiday Gift Ideas for Seniors with Dementia - the common wisdom is time is the best gift to give your loved one, but there are many gifts that can bring small joys to them.

Family Gatherings - dementia can present added challenges to holiday gatherings, but planning and a few tips can help improve everyone’s experience of the holidays.

Travel - can be tough. The top tip is to not be afraid to ask for help or use special accommodations like boarding early or using a wheelchair through security.

Politics

$100 Million BOLD Act passed unanimously in committee. The act provides resources to translate “research into practice” with the goal to “create a modern infrastructure for the prevention, treatment and care of Alzheimer’s”

KNOWING ALZ Prevention | News | Resources

Issue 2 December 2018

Alzheimer’s PreventionA groundbreaking paper from the Alzheimer's Prevention Clinic "describes a very nice, rigorous approach toward reducing risk for Alzheimer's."1 The paper outlines the steps that a patient and doctor can take to identify their specific Alzheimer's disease risk and begin the prevention process. This paper is by the same author as the main study examined in the November and December Knowing Alz Deep Dives and can be viewed as the practical guide to risk reduction based on the understanding of Alzheimer's disease mechanisms from the original paper. The work of Dr. Isaacson (the paper's lead author), Dr. Bredesen (featured in this month's guide), and other Alzheimer's prevention researchers are behind a growing wave of attention focusing on prevention.Study and video (1). Related Press Articles: Discover Magazine on AD and Lifestyle and San Diego Tribune on AD and Sleep.

Fruits, Vegetables and DietIn a study of 27,000 male health professionals, researchers found that the top 20% of fruit and vegetable consumers were 34% less likely to be categorized as poor thinkers than the bottom 20% of fruit and vegetable consumers. The top 20% consumed 6 servings of vegetables and 3 of fruit per day on average and the bottom 20% consumed 2 servings of vegetables and 1/2 servings of fruit on average.  These findings align with existing evidence for what constitutes a brain-healthy diet. The MIND diet, a combined Mediterranean and heart-health diet, is an evidence-based set of guidelines that the current study reinforces and a good place to start for people looking to make dietary changes with Alzheimer's prevention in mind.Study and MIND Study. Related Press Articles: Being Patient and Web MD on the MIND Diet.

Genetic RiskA study of 1.5 million people found 90 genes associated with both Alzheimer's disease risk and cardiovascular disease risk. According to the researchers, the genes associated with Alzheimer's disease were primarily associated with the lipid metabolism aspect (think high cholesterol) of cardiovascular risk. Drawing any conclusion about the exact relationship between cholesterol, Alzheimer's disease, cardiovascular disease, and these genes is not possible due to the nature of the study. For example, determining if cardiovascular disease causes Alzheimer's disease, vice versa, or if the genes separately cause each disease cannot be done, but if you have these genes, you may be at risk for both. The study’s findings should spark more research into these genes, adding to the existing AD genetics knowledge base focused on ApoE4.Study and press release. Related Press Articles: Medical News Today and many more.

Diabetes Treatment and Alzheimer’sThe study shows that people with type 2 diabetes and Alzheimer's disease who were being treated for diabetes had more normal gene expression and small blood vessels in the brain than people with just AD. As the research stands, the causal relationship is not clear between diabetes treatment and the reduction in these markers of Alzheimer's Disease; Medscape reports, "What it can't show is whether Alzheimer's is causing these changes in gene signaling, whether it's the other way around, or whether there is some other factor entirely affecting both." It is likely too early for this research to suggest diabetic treatments will help treat Alzheimer's, but it is an interesting result that could lead to fruitful research. Much of the excitement around this finding stems from the idea that the diabetic treatments could be employed with less FDA trials if they're found to provide a benefit, as they are already used safely in humans on a large scale.Study and Press Release. Related Press Articles: Medscape, Being Patient and UPI.

Deep Dive: Chronic Inflammation and AD Prevention The following characterization does away with a lot of nuance, including the fact that the exact nature of the

causes of chronic inflammation, how the chronic inflammation results in damage, and the effects of the damage are either not known or not entirely understood. The goal here is to the give the reader a useful model for understanding inflammation, because understanding it, even broadly, can be a useful first step to managing it.

December Newsletter Knowing Alz �2

Issue 2 December 2018

What are inflammation and chronic inflammation?Inflammation is part of the body's immune response to damage, bacteria, viruses, or irritants.  The immune response is complex and so is inflammation, but there are relatable aspects of the process. The redness, swelling, heat, and pain associated with inflammation from a cut or injury are due to increased blood flow to the area and the chemicals released by white blood cells. The body's goal is to get white blood cells to the area to help kill pathogens, remove irritants or damaged cells, and start the healing process. Collateral damage to the body's cells can be caused by immune processes meant to kill and remove pathogens. Normally this is ok because after the body removes the source of the inflammation, the processes turn to healing. However, when the source does not get removed, the damaging processes continue to happen. This is called chronic inflammation and over time that damage adds up, causing larger problems.   What causes chronic inflammation? knows many causes, but likely not all. Broadly, these causes fall into five categories:

1. Failure to eliminate a pathogen -- e.g., bacteria, mold, or viruses.

2. Exposure to a low-level irritant -- e.g., pollution, industrial chemicals, or dietary issues.

3. Autoimmune disorders, the body mistaking itself for a foreign invader then attacking itself -- e.g., rheumatoid arthritis, systemic lupus erythematosus (SLE).

4. Recurring acute inflammation -- e.g., multiple bouts with a virus like herpes.

5. Oxidative Stress and related processes, which will be covered in a future deep dive.

  Age, Obesity, Diet (high in saturated fats, trans fats and sugars), smoking, low sex hormones, stress, and sleep disorders are all associated with higher risk of chronic inflammation.  

Section Source: Chronic Inflammation by Roma Pahwa and Ishwarlal Jialal.   How does this relate to Alzheimer's Disease? There is evidence of inflammation in the brains of Alzheimer's patients. As with everything involved with AD, the role of the brain cells that manage inflammation, microglia, is complicated. Microglia and immune processes, simultaneously, help clear away Amyloid Beta, increase Amyloid Beta production, and create chemicals that can damage/kill neurons. Ideally, an AD prevention intervention would keep the good and stop the bad, but there is no perfect solution yet.   Section Source: Mechanisms of Risk Reduction in the Clinical Practice of Alzheimer’s Disease Prevention Schelke, Matthew W et al.   What can be done to reduce Inflammation-related AD risk?Lifestyle: • Diet: Avoid refined starches, refined sugar, artificial trans-fats, and saturated fats with carb heavy meals. • Sleep: Get 7-8 hours of sleep per night. • Social Engagement: Increase time with others and strengthen relationships. Medications: • NSAID: Long-term NSAID use to control inflammation is associated with reduced AD risk. • TNF Alpha Inhibitor: Only included here to bring up with a doctor as desired. “In humans, a small study of

perispinal administration of the TNF-a inhibitor etanercept demonstrated cognitive improvement in patients with AD (Tobinick, 2007), suggesting that modulation of cytokines and microglial activation may also modify the disease course.”

December Newsletter Knowing Alz �3

Wikipedia

Issue 2 December 2018Section and Quote Source:  Mechanisms of Risk Reduction in the Clinical Practice of Alzheimer’s Disease Prevention Schelke, Matthew W et al.   Further Reading: For ideas on fighting general inflammation, there is a good list here. General Inflammation: Wikipedia, Khan Academy, Osmosis. Chronic Inflammation: Johns Hopkins Health Review,  Chronic Inflammation by Roma Pahwa and Ishwarlal Jialal.

Guide: The End of Alzheimer’s by Dr. Dale Bredesen

The End of Alzheimer's: The First Program to Prevent and Reverse Cognitive Decline is the first item to come up in a search for "Alzheimer's" on Amazon. My first thought upon seeing the title was, 'That feels a bit scammy. If there were a way to completely prevent, much less reverse, Alzheimer's, it'd be front page news everywhere." I read it anyways, and the guide below is everything I wish I'd known before reading it. More specifically, the goal of this guide is to provide a preview of and give context to Dr. Bredesen's theory of Alzheimer's and his reversal/prevention protocol. Understanding the context around the book upfront should make it significantly more useful because the reader won't be wondering 'who is this guy?', 'is this theory plausible or BS?' and 'is any of this well supported by studies?'. Additionally, due to its popularity, The End of Alzheimer's might be someone's first exposure to much of the science and prevention strategies, and one data point makes it hard to know what to believe.   Who is Dr. Dale Bredesen? Far from a quack, Dr. Bredesen was the founding President and CEO of the Buck Institute on Aging and is a UCLA School of Medicine professor.  Dr. Bredesen's qualifications require his hypothesis about Alzheimer's disease mechanisms to be taken seriously. Many people have interviewed him, and in my opinion, he seems to deeply believe in his protocol's virtues. The press tour, which initially made me wonder if he was just trying to make a buck from the book, is about trying to help people by informing them about the protocol and trying to change attitudes about his research in pursuit of more research funding.   What are the theory and the protocol?Theory

  Summary: Put simply, Bredesen hypothesizes that AD is the brain's natural way of handling poor conditions that make it impossible to sustain the health of all neurons in the brain. Each individual's cause of their poor brain environment varies, but Bredesen categorizes causes into three types: atrophic (low hormone levels, nutrient deficiencies, insulin resistance etc.), inflammation (dietary, infection etc.), and toxins (metals, molds etc.)  Due to these poor conditions, the brain cannot maintain itself and begins to manage its own decline. The memory loss and other symptoms associated with Alzheimer's are the brain's way of degrading in an orderly fashion.     Commentary: I know the idea that Alzheimer's disease is really the brain working correctly seems a bit absurd, but it makes sense that the human brain could have this type of mechanism. If the brain doesn't have a mechanism to prioritize loss of brain functions, temporary problems could be fatal.  For example, our evolutionary ancestors might have missed a few meals due to poor hunting, started starving, and the first brain function lost could be breathing control. Without the ability to prioritize brain functions, relatively minor issues could quickly cascade into lethal issues. However, if the brain has a way of prioritizing brain functions, starving would mean the loss of a few memories or the failure to form memories. In the hierarchy of things the brain does, memories are important to us and our identities, but they are not as important for survival as breathing. Human bodies are hardwired for survival at the most basic level, not necessarily quality of life.

December Newsletter Knowing Alz �4

Amazon Book Cover

Issue 2 December 2018  Protocol

Summary: According to Bredesen, people can stop their brain from deteriorating by testing the 24 brain health factors he identified and improving them with his ReCODE protocol. The book outlines normal and optimal levels for each factor and strategies for working towards a fix. Factors include pathogens, leaky gut, insulin resistance, suboptimal nutrient/hormone/trophic support, and toxin exposure.  In short, find out the specific reasons for each person's poor brain conditions and work to fix those factors.   Commentary: Similar principles underlie other prevention protocols, but the novel concept from Bredesen is that these changes can reverse decline.  The consensus among practitioners of Bredesen's protocol seems to be that there is little harm in cultivating a healthier brain, even if the underlying disease mechanism turns out to be wrong with continued research.   What does the broader scientific community think about the protocol and theory?It is very easy to be skeptical about the entire book, and readers should have a healthy dose of skepticism. However, there are several reasons to be less skeptical or, really, to be skeptical of parts but not all of the book. In late October, a new study of 100 people across many doctors and regions of the US showed improvements using Bredesen's protocol. Additionally, the types of improvements involved in the protocol are corroborated in many other studies, and the factors in the protocol are in line with other prevention methodologies. In my opinion, skepticism should focus on Bredesen's view of the disease mechanism, because it is not proven yet. There should also be some skepticism for the specificity of the targets proposed for the 24 factors because the level of evidence supporting each individual recommendation in the book varies widely. A point made in the book and by some practitioners of the protocol is that there are no other viable prevention or treatment options, which is partly true. There are several prevention clinics around the country, but the main actionable insights coming out of those institutions are along the same lines as Bredesen's protocol. My perspective is to be skeptical of the disease mechanisms and the specificity of the advice, but not the results. The evidence from the latest study suggests that his protocol helps people improve Alzheimer’s symptoms.   Should I read this book?  Can I understand the theory and protocol without reading? If you are interested in the book, beware that it can be dense and takes some slogging through. I recommend reading this very detailed summary first to get an overall picture of the theories and protocol before reading. If you want some motivation when starting the book, start by reading the "How to Give Yourself Alzheimer's: A Primer" chapter; the chapter provides some insight into what of your lifestyle factors might have room for improvement. If you don't want to read the book, you can get a lot of information by reading the summary and listening to the Found My Fitness interview.   You read the book…now what?

What's new • The new study of 100 people, discussed above, across many doctors and regions of the US showed

improvements using Bredesen's protocol. • The ReCode protocol was acquired by

AHNP Health. The protocol appears to be the same and Dr. Bredesen is part of the team. The pricing is below, which you will not be able to see without registering.

What can I do now? • Sign up for the protocol at AHNP

Health, the company that now owns and administers the ReCode program.

• See table for pricing (November 2018)

• Visit Dr. Bredesen's Website • Find a ReCode trained doctor or health

coach. This can be easier said than done. Start here, if you have not signed up for the protocol, or use the tools provided by AHNP, if you have signed up.

December Newsletter Knowing Alz �5

ReCode Report Pricing - November 2018

Report Options One-time Monthly

Price $1399 $900 annually

Lab Testing Yes No

Protocol Report One Report Unlimited Reports

Issue 2 December 2018• Visit one of the five prevention clinics in the USA. If you know of other Alzheimer's or prevention clinics

around the world, please, email me. • UAB Alzheimer's Disease Center• Alzheimer's Prevention Clinic - Richard Isaacson• Brain Health Center - Northshore Chicago• Dementia Prevention Initiative - Jim Glavin, Boca Raton • Pacific Brain Health Center - David Merrill

• Listen to these interviews of Dr. Bredesen. • Found My Fitness - Dr. Dale Bredesen on Preventing and Reversing Alzheimer's Disease• Bulletproof Radio - The Quest To End Alzheimer’s: Dale Bredesen #522

• Join ApoE4.info: an online community with many people on the ReCode protocol. • Read the studies that are the basis of the protocol.

• Bredesen's Original Study from 2014• The new study with 100 people

December Newsletter Knowing Alz �6

Issue 2 December 2018

About the Newsletter Feedback and Questions are Greatly AppreciatedPlease feel free to email me at steve@knowingalz.com or fill out this form with any questions or feedback you may have. My goal is to help make your experience learning about and dealing with Alzheimer’s or other dementias easier, so let me know how I can do that better.

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The “Origin Story”Having loved three grandparents with dementia, I know just caring for and about them can take up all the extra space in your life. It takes up time, mental space, and sometimes even physical space (I know some of you have a basement full of a loved one's things). Putting even more effort into dementia is just simply the last thing on your mind. It's because of this that even after a decade of having loved ones suffer from dementia, I knew very little about Alzheimer's or dementia beyond seeing its first-hand effects. After my third grandparent passed away with dementia, I threw myself into learning everything I could about the disease. All of a sudden, I was neck-deep in the thousands of resources out there. I was reading news that I barely understood and didn't know where to go to get good answers to my questions. Many hundreds of hours of research later, I'm still finding new things every day. The amount of resources and attention Alzheimer's Disease (AD) and dementia is getting is awesome, but it's also overwhelming. It's too late to help my grandparents, but I can still help my parents, myself and now you. My goal is simple: reduce the amount of time it takes to learn what you want to know about Alzheimer's and dementia. Here's how:• News: All the Alzheimer’s- and dementia-related news is now gathered in one place. I've coded a program

that aggregates news stories on Alzheimer's and dementia from across the web. I review the articles daily and post links to the best ones. Occasionally, I'll provide a summary or review of a study that I think didn't get good coverage. BUT, I think reading news on AD every day or every week isn’t the best way to learn.

• Monthly Newsletter: There's a lot of news, but not a lot that you NEED to read. The newsletter gives you the top news items from the month, prioritizing prevention and caregiving research. It includes deep dives into broader topics around those news items, guides on important non-news topics, and anything else I think is interesting or worth knowing from the month. The purpose is to provide a single document with a lot of value in a short amount of time, without you having to do anything more than open your email. For the overachievers, it also has a lot of further reading suggestions. Subscribe here if you haven’t already.

• Questions Answered: One of the biggest frustrations when trying to understand Alzheimer’s is finding answers to your questions. The sheer number of resources out there means there are often many different answers to one question, or the answer is buried deep in a forum somewhere. Instead of wasting your time, fill out this form, and I'll help you find what you're looking for.

December Newsletter Knowing Alz �7

KNOWING ALZ