Tag Archives: alzheimer’s disease

The MEND Program Shows Promise for Reversing Cognitive Decline

Background

In September 2014, researchers from the University of California reported the development of the MEND protocol, short for Metabolic Enhancement for Neurodegeneration. MEND was designed to combine the results of multiple studies to create a comprehensive set of guidelines for enhancing cognitive function in elderly adults. The program was also intended to be personalized to each patient based on his or her lifestyle and medical history. The MEND protocol includes the following guidelines, among many others:

  • Eat a diet rich in high-antioxidant foods, such as blueberries and kidney beans, and anti-inflammatory foods, such as tumeric and salmon.
  • Minimize or eliminate simple carbohydrates, such as white bread and pasta, as well as foods with a high glycemic index, which are quickly digested and cause blood sugar spikes.
  • Fast for 12 hours each night, including at least 3 hours before bedtime. For example, if you typically eat breakfast at 7am, you should not eat anything after 7pm the previous night.
  • Reduce stress through yoga, meditation, or other methods.
  • Get 8 hours of sleep every night. Seek treatment for insomnia or sleep apnea. (See: How Sleep “Cleans” Your Brain and Fends Off Alzheimer’s)
  • Maintain healthy digestion using prebiotics and probiotics. (See: Probiotics May Improve Cognitive Function and Alzheimer’s Disease)
  • Optimize oral hygiene through regular, thorough brushing and flossing. (See: How Oral Hygiene Protect Your Brain from Dementia)

A small clinical trial was created to test the effects of the MEND program on cognitive function. Ten middle-aged or elderly adults with Alzheimer’s disease or other forms of cognitive impairment worked with the researchers to develop personalized plans based on MEND’s guidelines. Most of the subjects and their families began noticing improvement within three to six months of starting the program, and several were able to return to work after previously having to discontinue. Though promising, the evidence of this study was short-term and anecdotal, requiring confirmation by additional data.

New Results

The study published this month reports on follow-up exams of the original ten subjects after following the MEND protocol for between 5 and 24 months. The researchers used MRI scans as well as neuropsychological testing to evaluate the subjects’ cognitive function. For two of the subjects, the results were dramatic. The volume of one patient’s hippocampus (the part of the brain most associated with memory) went from the 17th to the 75th percentile after following the program for only 10 months. Another patient with diagnosed Alzheimer’s disease experienced substantial improvement on cognitive exams after 22 months on the program, even moving from the 3rd to the 84th percentile on one of the tests. Though the changes observed in the other eight subjects were more modest, all ten subjects showed some level of improved cognition during the follow-up exams, and none of them experienced any cognitive decline. Additionally, most of the subjects had at least one copy of the APOE4 allele, a strong genetic risk factor for Alzheimer’s, demonstrating that we may be able to combat the effects of our genes through healthy lifestyle choices (see The Genetics of Alzheimer’s Disease).

Due to the very small sample size, larger trials need to be conducted before broad conclusions can be drawn. It also remains to be seen whether this cognitive improvement is permanent or temporary. However, these results give new hope to the prospect of reversing cognitive decline, which previously was deemed impossible for people already experiencing cognitive impairment. If you or a loved one is noticing memory troubles or has been diagnosed with dementia, consider implementing some of the MEND guidelines to possibly reverse the effects of cognitive decline. For more details on reducing your Alzheimer’s risk, see How to Reduce Your Dementia Risk in 2018.

 

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Book Review: “100 Simple Things You Can Do to Prevent Alzheimer’s”

“100 Simple Things You Can Do to Prevent Alzheimer’s and Age-Related Memory Loss” is a nonfiction book written by Jean Carper, a former medical journalist best known for her award-winning 1996 book “Stop Aging Now!” Carper’s most recent book lists and describes 100 tips for reducing your risk of dementia backed up by scientific data. These include having regular eye exams, eating berries every day, and learning a second language.

“100 Simple Things” is written in jargon-free language that any reader can easily understand while also presenting scientific evidence to back each claim without exaggerating the predicted results. Carper demonstrates a deep understanding of the science of Alzheimer’s disease and following even a few of her tips are quite likely to improve the health of your brain as you age. The back of the book provides an excellent guide for creating “Your Anti-Alzheimer’s Plan,” describing how to incorporate these tips into your lifestyle successfully.

One possible conflict of interest with this book is the fact that Jean Carper is the founder of a vitamin and supplement company called Stop Aging Now, best known for the anti-aging multivitamin that Carper designed. Carper sold the company before publishing this book and no longer has any financial connections, but it’s worth keeping this in mind when reading her advice on supplements. Many experts agree it’s best to get nutrients from your diet rather than from a pill whenever possible, although some supplements such as fish oil are still recommended for brain health. My only other criticism is that the book chapters can be a bit redundant. For example, at least five of the tips essentially described the importance of keeping your brain stimulated through mental activity, several others all discussed social interaction, etc. In my opinion, the book could have easily been condensed into 50 or 75 tips.

Overall, I would highly recommend this book to anyone who is experiencing or at risk of dementia, has a loved one with dementia, or simply wants to learn more about brain health. It is easy to follow, scientifically valid, and realistic for anyone to incorporate into their lifestyle.

Rating: 4.5 stars

 

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The Strange Link Between Alzheimer’s and Cancer

Two of the most common causes of death in America are Alzheimer’s disease and cancer. To most of us, these seem like completely unrelated diseases. However, this intuition is far from the truth. For reasons that puzzle scientists, having Alzheimer’s actually seems to protect you from cancer, while having cancer may protect you from Alzheimer’s.

This counterintuitive relationship was first discovered in 2005 by the Washington University Alzheimer’s Disease Research Center. This study of 882 elderly participants reported that the people with Alzheimer’s disease were significantly less likely to be diagnosed with cancer during the course of the study, and that those who did develop cancer did so at an older age. In 2012, the Framingham Heart Study reported that participants with Alzheimer’s disease were less than half as likely to be diagnosed with cancer during the course of the study compared to dementia-free subjects of the same age, sex, body mass index, and smoking status. A 2014 meta-analysis summarized the results of six independent papers to conclude that Alzheimer’s patients have a 42% reduced risk of cancer in their lifetime, while cancer survivors have a 37% reduced risk of Alzheimer’s. These differences remained statistically significant even after accounting for the effects of reduced life expectancy and demographic factors.

Interestingly, this inverse relationship does not seem to apply to other diseases of the central nervous system, including vascular dementia, Parkinson’s disease, amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), or Down’s Syndrome. This suggests that the cancer-protective mechanism is specific to Alzheimer’s disease. Weirdly, the naked mole rat is immune to both cancer and Alzheimer’s, which may help to shed light on this strange connection. (Read more: What Naked Mole Rats Can Teach Us About Alzheimer’s Disease)

Scientists are still unsure as to why cancer and Alzheimer’s are inversely related, although several theories have been suggested. One possibility is that proteins that are needed for cells to divide and reproduce might be under-produced in Alzheimer’s patients, causing a reduction in neurogenesis (the formation of new brain cells, important for learning and memory) while also protecting from cancer by preventing uncontrolled cell division. Another theory is that amyloid beta, the protein that forms toxic clumps in the brains of Alzheimer’s patients, may fight cancer by suppressing the growth of tumors. The APOE4 allele, which increases the risk of Alzheimer’s disease, has also been associated with a reduced risk of certain cancers. Further research is needed to establish a definite mechanism.

One of the main consequences of this relationship applies to clinical trials of drug candidates to treat Alzheimer’s disease (see Where’s our cure to Alzheimer’s disease?). Several trials have had to discontinue prematurely due to an increased risk of cancer among the participants, especially skin cancers. In other words, the drugs that were supposed to be combatting Alzheimer’s disease ended up causing some participants to develop cancer. Though only a subset of trials have reported this problem, it’s worth being aware of the possibility when considering whether to participate in a clinical trial, particularly if your family has a history of skin cancer or other cancers.

References

Catala-Lopez, F., et al. Inverse and direct cancer comorbidity in people with central nervous system disorders: a meta-analysis of cancer incidence in 577,013 participants of 50 observational studies. Psychother Psychosom. 2014;83(2):89-105. Link
Driver, J.A., et al. Inverse association between cancer and Alzheimer’s disease: results from the Framingham Heart Study. BMJ. 2012;344:e1442. Link
Ma, L.L., et al. Association between cancer and Alzheimer’s disease: systemic review and meta-analysis. J Alzheimer Dis. 2014;42(2):565-573. Link
Roe, C.M., et al. Alzheimer disease and cancer. Neurology. 2005;64(5):895-898. Link
Roe, C.M., et al. Cancer linked to Alzheimer disease but not vascular dementia. Neurology. 2010;74(12):106-112. Link
Slattery, M.L., et al. Associations between apoE genotype and colon and rectal cancer. Carcinogenesis. 2005;26(8):1422-1429. Link

 

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Where’s our cure to Alzheimer’s disease?

(This article was originally written for the Junior Committee of the Central Ohio Alzheimer’s Association’s blog. Click here to view the original on their website.)

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Deaths from Alzheimer’s have increased dramatically, while other diseases have reduced death rates. Source

Biomedical research has made great strides in the past several decades. Our death rates for most major diseases have decreased significantly, including heart disease, cancer, stroke, and HIV. However, one conspicuous exception to this trend is Alzheimer’s disease, for which total deaths increased by nearly 70% between 2000 and 2010. Why does research on Alzheimer’s disease seem to be bearing meagre fruits, and when can we expect the next breakthrough?

To answer these questions, we need to have a bit of background on the science of the disease (for more detailed background, see Alzheimer’s Disease: A General Overview). Alzheimer’s disease is differentiated from other types of dementia by the presence of abnormal protein deposits in the brain known as amyloid beta (AB) plaques. Several studies have demonstrated that genetic mutations that increase production of the AB protein increase the risk of developing Alzheimer’s, while a rare mutation that decreases AB production is protective against Alzheimer’s (see The Genetics of Alzheimer’s Disease). This led most researchers to adopt the amyloid cascade hypothesis, which proposes that the gradual accumulation of AB in the brain is the main cause of Alzheimer’s disease. This hypothesis suggested that a cure to Alzheimer’s lay in discovering a drug that could prevent or reverse the buildup of AB plaques.

Between 2002 and 2012, more than 400 drug candidates were discovered that could dissolve AB plaques in mice. However, despite these promising results, the drugs consistently failed in human clinical trials. The patients’ symptoms improved only marginally, if at all. Even worse, many drugs came with a host of severe side effects, including skin cancer (see The Strange Link Between Alzheimer’s and Cancer), gastrointestinal problems, and micro-hemorrhaging, which forced the trials to be canceled prematurely. Hundreds of millions of dollars were spent searching for new ways to destroy the plaques, yet each new drug met the same fate.

Following this torrent of failed clinical trials, some researchers began to wonder if there was a serious problem to the way we were studying Alzheimer’s disease. The long-dogmatic amyloid cascade hypothesis was brought into question when new studies showed that nearly 1 in 3 cognitively normal people have high levels of AB in their brains, suggesting that the plaques could not be the only factor contributing to dementia symptoms.

The scientific community was initially slow to react to criticisms of the amyloid cascade hypothesis. However, in recent years, new areas of research have begun to open up that consider new mechanisms for Alzheimer’s disease development. Many exciting theories have been suggested, including the tau protein, neuroinflammation, microbial infection, mitochondrial dysfunction, and oxidative DNA damage, among others. It’s likely that all of these factors, in conjunction with Ab accumulation, contribute together to this complex disease.

With this new generation of neuroscientists approaching the problem with a fresh perspective, it’s likely that our understanding of Alzheimer’s will be radically transformed in the coming years. Though it’s impossible to predict exactly when the next breakthrough will come, the scientific community’s shift away from the amyloid cascade hypothesis toward more nuanced theories will bring our search for a cure that much closer.

 

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Alzheimer’s Disease: A General Overview

There’s a lot of misinformation floating around about Alzheimer’s disease, and sometimes it feels like you need to be a neuroscientist to sort through it all. This article will give you a brief primer on this disease and help you to understand the basics.

Discovery

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A portrait of Dr. Alois Alzheimer

In the year 1906, Dr. Alois Alzheimer took the stage at a meeting of German psychiatrists to present his findings on “a peculiar disease.” An fifty-year-old patient named Auguste D. had come to Dr. Alzheimer experiencing memory loss, paranoia, personality changes, and difficulty sleeping. He was baffled by her symptoms and could do little to help her. Following Auguste’s death five years later, Dr. Alzheimer performed an autopsy on her brain and discovered that it was greatly shrunken in volume. Closer inspection revealed that Auguste’s brain was full of abnormal protein deposits located in and around the neurons. Dr. Alzheimer concluded that the pathology of her brain had caused his patient’s symptoms, a revolutionary idea at a time when mind was seen as completely separate from the physical body.

To Dr. Alzheimer’s dismay, the other physicians at the conference seemed uninterested in the findings–it’s said that they were anxious to hear the next speaker, who was to discuss “compulsive masturbation,” and as a result paid little attention to Dr. Alzheimer. When he died in 1915, he had no idea of the enormity of his discovery, or that a century later the disease bearing his name becoming the sixth leading cause of death in the U.S. Amazingly, had his patient Auguste been alive today, we could do no more to slow the progression of her disease than Dr. Alzheimer could more than a hundred years ago (see Where’s our cure to Alzheimer’s disease?).

 

Symptoms

Alzheimer’s disease has many symptoms aside from the well-known progressive memory loss. Personality and mood changes, such as depression and apathy, are common. Many patients experience reduced executive function, a broad category of cognition which includes attention, self-control, and problem solving. As the disease progresses, motor problems can appear, especially difficulty with speaking, swallowing, and walking. On average, patients with Alzheimer’s pass away within 4 to 8 years of diagnosis. The direct cause of death is often aspiration pneumonia, an infection of the lungs caused by food being improperly swallowed into the windpipe rather than the esophagus. Other common complications include bedsores, falls, urinary tract infection, malnutrition, dehydration, and organ failure.

In Our Brains

Some areas of the brain are affected more than others by this disease. Two areas of the brain that undergo particularly high levels of atrophy (i.e., tissue death) are the hippocampus and the entorhinal cortex. These two regions are most associated with declarative memory. Declarative memories are things that you can describe out loud, such as personal experiences or factual information. Conversely, procedural memory, also known as “muscle memory,” is the unconscious kind of memory that allows you to tie your shoes or play the piano. Interestingly, since procedural memory is handled by different brain systems, it is largely spared by Alzheimer’s disease. In other words, the inability of these patients to do basic tasks like dressing themselves is likely due to disruptions in motor function, and not from forgetting how to do so.

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The left panel shows a cross-section of a healthy brain, while the right panels shows a brain with advanced Alzheimer’s disease. The hippocampus and entorhinal cortex are the brain regions most affected by this disease.

In addition to the hippocampus and entorhinal cortex, Alzheimer’s causes atrophy in various other brain regions involved with vision, mood, stress, language, movement, and proprioception (the sense of our body’s position in three dimensions, which is important for movement and coordination).

In Our Cells

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Amyloid plaques and tau tangles inside the brain of an Alzheimer’s patient. Source

When Dr. Alzheimer examined his patient’s brain, he characterized the protein deposits into two types: those inside the neurons and those outside the neurons. The protein deposits inside neurons are known today as neurofibrillary tangles. They’re made of a protein called tau. When tau becomes hyperphosphorylated, meaning it has a large number phosphate groups attached to it, it becomes “sticky” and begins to adhere to other tau molecules. The protein deposits outside of neurons are called senile plaques, which are made of the amyloid beta protein. Like tau, amyloid beta can stick to itself to form large clumps in the brain. Both tangles and plaques are toxic to neurons in high concentrations, and are believed to be some of the main drivers of the disease’s progression.

In Our Genes

The genetic factors involved with Alzheimer’s disease is a very complicated topic (see The Genetics of Alzheimer’s Disease for a more detailed look). However, a brief overview will suffice for the purposes of this article. Alzheimer’s is typically classified into two types: familial, a rarer form that usually affects people younger than 65, and sporadic, which affects older patients and accounts for around 95% of Alzheimer’s diagnoses. Familial Alzheimer’s usually results from one of three genetic mutations: APP, which encodes a protein that is the precursor to amyloid beta; and PSEN1 and PSEN2, which encode an enzyme that helps turn APP into amyloid beta. These genes are highly penetrant, meaning that if you have one it’s very likely that you will develop familial Alzheimer’s disease. Additionally, a person who has one of these genes has a 50% chance of passing it on to each of their children.

The causes of of sporadic Alzheimer’s disease are more complicated. One gene that we know to be involved is APOE4. One copy of this gene increases your chances of getting the disease by about 2 to 3 times, while two copies increases your risk by nearly 15 times. This gene is actually fairly common, with 1 in 5 people possessing at least one copy. Many of these people never develop Alzheimer’s, and not all people with sporadic Alzheimer’s have APOE4. This tells us that other factors, which may be genetic or environmental, must also be involved.

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Nearly 15% of the U.S. population has two copies of the APOE4 variant. Source

Learn More

Now that you’ve learned some basics about Alzheimer’s disease, here are some more articles for you to read and learn more:

References

n.a. What APOE means for your health. Alzheimer’s Drug Discovery Foundation. n.d. http://alzdiscovery.org/cognitive-vitality/what-apoe-means-for-your-health
Alzheimer’s Association. 2016 Alzheimer’s disease facts and figures. Alzheimer’s & Dementia. 2016;12(4):459-509.
Herrup, K. The  case for rejecting the amyloid cascade hypothesis. Nature Neuroscience. 2-15;18(6):794-799.
Hippius H, Neundörfer G. The discovery of Alzheimer’s disease. Dialogues in Clinical Neuroscience. 2003;5(1):101-108.
Hirono, N., et al. Procedural memory in patients with mild Alzheimer’s disease. Dementia and Geriatric Cognitive Disorders. 1997;8(4):210-216.
Leonard, W. Alzheimer’s Disease Complications. Healthline. 2014. https://owl.english.purdue.edu/owl/resource/560/10/

 

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