Monday 8 April 2013

ApoE4 - The Ancestral Allele | For ApoE4 carriers interested in primal diets and science

Googling for the rate of APOE4 among Native Americans, I found this paper on omega-3 fats and ApoE4:

The most recent statistics indicate that dietary intake of omega-3 PUFA is insufficient in >95% of Americans.

Deficits in omega-3s have been shown to contribute to inflammatory signaling, apoptosis, and neuronal dysfunction in all cause dementia, including Alzheimer’s disease.

DHA (22:6[n-3]), specifically, is a critical contributor to cell structure and function in the nervous system, and a recently identified DHA-derived messenger, neuroprotecting D1 (NPD1) has been found to regulate brain cell survival and to promote non-amyloidogenic processing of amyloid precursor protein, thus protecting against Alzheimer’s disease by inhibiting formation of β-amyloid.

Studies utilizing omega-3 supplementation to improve cognitive function in elders, however, have had mixed outcomes, an inconsistency which newly published research indicates is related to ApoE genotype. ApoE ε4 carriers have not been able to benefit from omega-3s. This article discusses why and what can be done to enable carriers of the ApoeE ε4 allele to receive the neuroprotective benefits of omega-3s.

The important thing for us is the dietary recommendations. Some highlights:

ApoE ε4 carriers are the canaries in the mine of the Western way of life.

Individuals with this genetic heritage cannot afford the “normal” level of dietary and lifestyle insults typical of life in the modern industrialized world because the ApoE ε4 allele magnifies the risks inherent in the Western diet and lifestyle.
…
Despite the disproportionately high prevalence of ApoE ε4, cardiovascular disease and diabetes among Native Americans, and the Pima Indians, specifically, research examining a Native American rural population in nearby New Mexico clearly shows that carrying the ApoE ε4 allele does not increase the risk for any of these conditions in people eating a low fat diet and following an active lifestyle.

Another important point the paper makes is that while O3s provide many benefits, they are also vulnerable to oxidative damage. Depending on the body’s redox state, O3s can be neurotrophic (good for the brain) or neurotoxic (not so good).

The paper seems to conflate a low fat diet with a plant-centered, unprocessed one. While it has some great information on omega-3s, it doesn’t have much to answer other key primal / e4 fat questions like whether saturated fats are good (as in primal) or bad (because of differences in lipid metabolism for e4s).

ApoE and HDL, and heart and cerebrovascular disease: LDL-apheresis therapy

Association of ApoE and HDL-C with cardiovascular and cerebrovascular disease:
potential benefits of LDL-apheresis therapy,
Clinical Lipidology, Future Medicine

June 2009, Vol. 4, No. 3, Pages 311-329 , DOI 10.2217/clp.09.21

Review

Association of ApoE and HDL-C with cardiovascular and cerebrovascular disease: potential benefits of LDL-apheresis therapy

Patrick M Moriarty

ApoE forms a lipid–protein complex with HDL-cholesterols (HDL-C) and remnant lipoproteins and is an important regulator of cholesterol and lipid clearance, transport and distribution. In the CNS, ApoE is strictly bound to HDL.

Unlike ApoE2 or ApoE3, the ApoE4 isoform is associated with both coronary artery disease and Alzheimer’s disease.

HDL-C levels may possess a U-shaped association with vascular diseases and HDL-C size might reflect an alteration in function.

Inflammation plays a key role in coronary artery disease and Alzheimer’s disease.

Elevated inflammatory markers such as C-reactive protein and serum amyloid A are associated with both diseases. Serum amyloid A, similar to ApoE, binds to HDL-C and may alter the lipoproteins size and function.

Familial hypercholesterolemia (FH) is a genetic disorder resulting in elevated plasma levels of LDL-cholesterol (LDL-C), xanthomas and premature coronary artery disease. FH patient’s plasma contains decreased levels of HDL-C with increased levels of ApoE4 and ApoE-bound HDL.

LDL-apheresis therapy lowers LDL-C and is designated for FH patients resistant to pharmacotherapy.

LDL-apheresis also lowers inflammatory HDL-C, ApoE4, and a host of inflammatory markers such as C-reactive protein and serum amyloid A. LDL-apheresis, adjunct to reducing cholesterol, may provide additional benefit to patients with cardiovascular and cerebrovascular diseases.

Full Text

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HDL, apoE4 and Alzheimer’s Disease » Alzheimer's Association | Blog

HDL Cholesterol and Alzheimer’s Disease » Alzheimer's Association | Blog

"This finding further advances the idea that the interplay between cholesterol, cholesterol-carrying proteins such as apoE and HDL, and beta-amyloid may be critical in the development of Alzheimer’s disease. "

According to researchers at Columbia University, people with high levels of HDL cholesterol (the “good” form) are 60 percent less likely to develop AD.

The researchers followed 1,130 seniors with no history of memory loss or dementia and measured their cholesterol levels every 18 months for four years. When the researchers compared the cholesterol levels of study participants with and without Alzheimer’s, they found that those with the highest HDL counts, greater than 55 mg/dL, had about a 60 percent reduced risk of developing the disease compared to those whose levels were less than 39 mg/dL.

Their findings support the theory that high levels of HDL cholesterol are correlated with lower incidence of AD. The study was published earlier this week in the Archives of Neurology and sheds more light on the interactions between cholesterol and AD.

Apolipoprotein E (apoE), as readers of this blog will recall, participates in the mobilization and distribution of cholesterol among various tissues of the body, including the brain. In humans, there are three common isoforms of apoE: apoE2, apoE3 and apoE4.

ApoE4 differs from apoE3, the most common isoform of apoE. A single e4 allele is sufficient to increase the risk of developing atherosclerosis, and also Alzheimer’s disease.

The e4 allele results in slightly elevated plasma LDL cholesterol levels and a small but significant decrease in plasma HDL levels. HDL is one of the major carriers of protein in and out of the brain, and also binds to beta-amyloid.

This finding further advances the idea that the interplay between cholesterol, cholesterol-carrying proteins such as apoE and HDL, and beta-amyloid may be critical in the development of Alzheimer’s disease.

This study has important strengths. It is a prospective cohort study designed for the diagnosis of cognitive decline that has complete clinical and neuropsychological evaluation at each interval.
Guidelines recommend that men raise HDL levels that are less than 40 mg/dL and that women increase HDL numbers less 50 mg/dL. An HDL of 60 mg/dL or higher is optimal.

Michael S. Rafii, M.D., Ph.D.
Associate Medical Director, ADCS Medical Core

This post originally appeared in Alzheimer’s Insights, an ADCS Blog.
* Association of Higher Levels of High-Density Lipoprotein Cholesterol in Elderly Individuals and Lower Risk of Late-Onset Alzheimer Disease. Christiane Reitz et al., Arch Neurol. 2010;67(12):1491-1497.

Thursday 4 April 2013

How Does ApoE4 Affect Alzheimer's Risk? New Clues

Editor's Choice
Main Category: Alzheimer's / Dementia
Also Included In: Genetics
Article Date: 21 May 2012 - 9:00 PST

Although there is a strong association between common mutations of the ApoE gene and the risk of developing late-onset Alzheimer's disease, researchers have not known what role this gene plays in the disease until now.

Of the three varieties of ApoE - ApoE2, ApoE3 and ApoE4, the team found that in mice, ApoE4 damages the blood vessels that provide nutrients to the brain.

The ApoE gene encodes a protein that helps regulate the levels and distribution of cholesterol and other lipids in the body. Researchers believe that ApoE2 helps protect against cardiovascular disease and Alzheimer's, ApoE3 is neutral and that ApoE4 confers a higher risk for both conditions.

The study, funded by the National Institutes of Health and published in the journal Nature, was conduced by Berislav Zlokovic, M.D., Ph.D., director of the Center for Neurodegeneration and Regeneration at the Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles.

Dr. Zlokovic explained:

"Understanding the role of ApoE4 in Alzheimer's disease may be one of the most important avenues to a new therapy. Our study shows that ApoE4 triggers a cascade of events that damages the brain's vascular system."

Normally mice only have a single version of ApoE. However, the researchers examined genetically engineered mice, including three lines that produce only human ApoE2, ApoE3 or ApoE4 and one line that lacks the ApoE gene.

They discovered that mice with the ApoE4 version or mice that produced no ApoE at all, had a leaky blood-brain barrier allowing harmful proteins to enter the mice's brains.

After several weeks, the team discovered that the mice had loss of small blood vessels, loss of connections between brain cells and alterations in brain function.

Roderick Corriveau, Ph.D., a program director of NIH's National Institute of Neurological Disorders and Stroke (NINDS), which helped fund the study, explained:

"The study demonstrates that damage to the brain's vascular system may play a key role in Alzheimer's disease, and highlights growing recognition of potential links between stroke and Alzheimer's-type dementia. It also suggests that we might be able to decrease the risk of Alzheimer's disease among ApoE4 carriers by improving their vascular health."

The team also discovered that unlike ApoE4, ApoE2 and ApoE3 help controlling levels of cyclophilin A (CypA), an inflammatory molecule.

They noted that in blood vessels of mice that produce only ApoE4, CypA levels were about five times higher. The excess CypA led to an activation of the MMP-9 enzyme, which destroys protein components of the blood-brain barrier. Cyclosporine A therapy, an immunosuppressant that blocks CypA, maintained the blood-brain barrier and reduced brain damage. According to earlier studies, the MMP-9 inhibitor had similar beneficial effects, decreasing brain damage after stroke in animal models.

Suzana Petanceska, Ph.D., a program director at NIH's National Institute on Aging (NIA), which also funded the study, said:

"These findings point to cyclophilin A as a potential new drug target for Alzheimer's disease.

Many population studies have shown an association between vascular risk factors in mid-life, such as high blood pressure and diabetes, and the risk for Alzheimer's in late-life. We need more research aimed at deepening our understanding of the mechanisms involved and to test whether treatments that reduce vascular risk factors may be helpful against Alzheimer's."

In the United States more than 5 million older adults are affected by Alzheimer's disease. Beta-amyloid is a hallmark of the disease and is a toxic protein fragment that accumulates in clumps, or plaques, within the brain. Gene mutations that result in increased levels of beta-amyloid are linked with a rare type of Alzheimer's that occurs between the age of 30 and 60.

According to the researchers, the ApoE4 gene variant is the most strongly associated to late-onset of Alzheimer's. People who inherit one copy of ApoE4 are three times more likely to develop Alzheimer's and people who inherit two copies, one from each parent, are 12 times more likely to develop the disease.

The researchers highlight that although beta-amyloid is known to accumulate in and damage blood vessels that cause bleeding into the brain, ApoE4 can destroy the vascular system independently of beta-amyloid. According to Dr. Zlokovic, this damage makes it more challenging to remove beta-amyloid from the brain. Some investigational therapies focus on destroying amyloid plaques, but therapies designed to compensate for ApoE4 might help prevent the plaques from forming, he said.

Written By Grace Rattue
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

The detrimental role of a high carbohydrate diet - Nutrition and Alzheimer's disease: EJIM01.pdf

Article history:

Received 29 October 2010

Received in revised form 8 December 2010

Accepted 27 December 2010

Available online 26 January 2011

Alzheimer's disease is a devastating disease whose recent increase in incidence rates has broad implications for rising health care costs. Huge amounts of research money are currently being invested in seeking the underlying cause, with corresponding progress in understanding the disease progression.

In this paper, we highlight how an excess of dietary carbohydrates, particularly fructose, alongside a relative deficiency indietary fats and cholesterol, may lead to the development of Alzheimer's disease. A first step in the pathophysiology of the disease is represented by advanced glycation end-products in crucial plasma proteins concerned with fat, cholesterol, and oxygen transport. This leads to cholesterol deficiency in neurons, which significantly impairs their ability to function.

Over time, a cascade response leads to impaired glutamate signaling, increased oxidative damage, mitochondrial and lysosomal dysfunction, increased risk to microbial infection, and, ultimately, apoptosis.

Other neurodegenerative diseases share many properties with Alzheimer's disease, and may also be due in large part to this same underlying cause.

Wednesday 3 April 2013

One in three dementia cases misdiagnosed | News.com.au

AAP
June 22, 2012 3:48Pm

ALMOST a third of dementia diagnoses in Australia are incorrect, a medical expert has said.

A federal inquiry into early diagnosis and intervention for dementia heard that 30 per cent of patients diagnosed with dementia were later found to be suffering from other conditions.

Dr Robert Prouse, from the Royal Australian College of Physicians, said other conditions such as depression could mimic the symptoms of dementia.

"There's a whole range of things that can present as cognitive decline that need to be tested along the way and that's where specialists come into it," Dr Prouse told the inquiry in Sydney.
"It's probably common enough to say a third of patients improve, lose their depression and have a new outlook on life."

He said he had also treated a number of patients who suffered from breathing problems during their sleep who had been able to move out of nursing homes and return to the community once their sleep apnoea had improved.

"We've had a number of people who have had significant cognitive decline," Dr Prouse said.
"By treating their sleep apnoea and improving nocturnal oxygenation, they've come back to normal."

The inquiry by the House of Representatives Health and Ageing Committee is examining whether dementia should be made a National Health Priority Area due to its growing prevalence in communities.

Bulletproof coffee. - Dave Asprey The Bulletproof Executive

Bulletproof coffee - Dave Asprey The Bulletproof Executive

By Dave Asprey

When people hear more than half my calories come from healthy fats, one of the most common questions after “Why?” is “How?”

I start the day with a cup of Bulletproof coffee. I learned about the power of butter at 18,000 feet elevation near Mt. Kailash in Tibet when I staggered into a guest house from the -10 degree weather and was literally rejuvenated by a creamy cup of yak butter tea. The biohacker in me asked, “why?” and that was the genesis of my recipe below, which is widely heralded as a cognitive enhancing recipe.

Dave Asprey near Mt. Kailash

It was John Patrick Henry’s 2nd cousin’s boyfriend Juan Valdez who said, “Give me high-end coffee or give me death.” That’s because toxins in cheap coffee (Starbucks included) will steal your mental edge and actually make you weak, but clean coffee actually fights cancer and provides antioxidants.
So I buy the best coffee there is, brew it, and then I blend unsalted grass-fed butter into it. Yes, butter. All the benefits of healthy milk fat with none of the damaging denatured casein proteins found in cream. It makes for the creamiest, most satisfying cup of coffee you’ve ever had. It will keep you satisfied with level energy for 6 hours if you need it. And because I’m having it for breakfast, I’m programming my body to burn fat for energy all day long!

Bulletproof Coffee Recipe

Start with 500 ml (2 mugs) of black coffee brewed with mold-free beans (important)
Add 2 Tbs (or more, up to 80 grams, about 2/3 of a standard stick of butter) of Kerry Gold or other UNSALTED grass-fed butter
Add 30 grams of MCT oil for max energy, weight loss and brain function (optional if you have none)
Blend with a pre-heated hand blender, Magic Bullet, or (best) counter top blender until there is a creamy head of foam. (It doesn’t work well if you mix it with a spoon)

It’s really fast and easy to prepare. Realize salted coffee is a crime. Do not do this with salted butter.
Bleah.

Kerrygold butter or another grass-fed brand of butter really matters because corn or soy-fed cows don’t make butter with the same fats. Those butters don’t blend well, don’t taste good, and don’t make you feel Bulletproof.

Grass-fed butter is much healthier than other butter. It doesn’t make cholesterol levels worse, it optimizes them! Starting your day with grass-fed butter will give you lots of energy and it will give your body healthy fats that it will use to make cell walls and hormones.

If you’re like most of my friends who try this, your body is so starved for healthy fats that you feel like you can’t get enough. It will take your body a week or two to fully turn on its fat digestion systems when you switch to a high healthy fat breakfast of Bulletproof coffee. If at first it is a little too rich, try using less butter at first and build up to the amount you like. Taking a betaine HCl or digestive enzyme supplement with your coffee will also help your body digest the butter.

Try this just once, with only 2 Tbs of butter, and have nothing else for breakfast. You will experience one of the best mornings of your life, with boundless energy and focus. It’s amazing.

After one drink of Bulletproof coffee, you’ll never be tempted to eat fat-free, insulin-raising, fat-storing toast and oatmeal breakfasts again!

P.S. If you benefit from this post, I’d really appreciate it if you tried my Upgraded Coffee beans. I created them for maximum mental performance and health, and they work, costing $2 more than Starbucks beans. The proceeds support the research that gets published on this site, and your brain really will notice the difference. Thank you.

About Dave Asprey

Dave Asprey is a Silicon Valley investor, computer security expert, and entrepreneur who spent 15 years and $250,000 to hack his own biology. He upgraded his brain by >20 IQ points, lowered his biological age, and lost 100 lbs without using calories or exercise. The Financial Times calls him a "bio-hacker who takes self-quantification to the extreme of self-experimentation." His writing has been published by the New York Times and Fortune, and he's presented at Wharton, Kellogg, the University of California, and Singularity University.

Harvard Medical School To Be Tried for Alzheimer’s Research Fraud | Health Impact News

by Vera Sharav
Alliance for Human Research Protection

The US Court of Appeals, 9th Circuit overturned a summary judgement by a lower court ordering a whistleblower lawsuit filed by Dr. Kenneth Jones against Harvard Medical School, its teaching hospitals, Brigham and Women’s and Massachusetts General Hospital, and Dr. Marilyn Albert (Principal Investigator) and Dr. Ronald Killiany to proceed to trial.

The case involves the largest Alzheimer’s disease [AD] research grants awarded by the National Institutes of Health (from 1980 through 2007) for a large project aimed at identifying early physical signs of Alzheimer’s by scanning certain regions of the brain with MRIs.

Dr. Jones was the chief statistician for the NIH grant. He blew the whistle after realizing that measurements used to demonstrate the reliability of the study had been secretly altered. Without these alterations, Dr. Jones explained, there was no statistical significance to the major findings of the study. When he insisted that the altered measurements be subjected to an independent reliability study, and that the manipulated results could not be presented as part of a $15 million federal grant extension application, he was terminated and his career came to an end.

The allegations in the suit concern multiple research fraud: data manipulation, significant deviations from the protocol, altered and re-traced MRI scans. To get positive results, Dr. Jones alleges, Dr. Killiany “fraudulently altered the MRI study data prior to 1998 to produce false results of a statistically significant correlation between conversion to AD and volume of the EC [entorhinal cortex].” US ex rel. Jones v. Brigham and Women’s Hospital and Harvard University.

He further alleged that Dr. Albert and Dr. Killiany violated federal regulations (43 CFR 50.103(c)(3) by making false statements in the NIH grant application. Statements that “were predicated on falsified data that the defendants, knowing of this falsity, failed to take corrective action or disavow the data.”

In overturning the lower court and ordering the case to proceed to trial, the Court of Appeals cited the lower court failure to consider substantial evidence of research fraud, and failed to consider relevant testimony from three expert witnesses presented by Dr. Jones:

A statistician who confirmed that the alterations were responsible for the statistical significance of the study results, a medical researcher who identified that the altered results could not be justified and were changed to establish a predetermined outcome, and a third expert who confirmed that NIH would not have funded the study had the falsity of the data been revealed during the application process and that Harvard failed to adequately investigate allegations of research fraud.

The Court of Appeals decision states:

”the essential dispute is about whether Killiany falsified scientific data by intentionally exaggerating the re-measurements of the EC to cause proof of a particular scientific hypothesis to emerge from the data, and whether statements made in the Application about having used blinded, reliable methods to produce those results were true.”

Michael D. Kohn, one of the lead attorneys for Dr. Jones said:

“This is a major breakthrough holding universities accountable for the integrity of reported research results. Fraud committed in order to obtain NIH funding not only robs taxpayers, but also sets back long-term medical research goals. The facts of this case indicate that the report of false data misdirected research efforts at other institutions.”

This case also underscores an inconvenient truth about the financial stakes that drive clinical trials. Those who are persuaded to serve as human subjects “for the good of humanity” and “to help medical progress” believe in the integrity and high mindedness of medical researchers–especially those at premier academic institutions. That trust, however, is all too often misplaced. Vulnerable human subjects are being shamelessly exploited in invalid, most often commercially driven experiments.

Indeed, the rationale behind the Harvard brain scanning experiment was to justify early interventions. Another example is Eli Lilly’s Alzeheimer’s imaging detection test (Amyvid) launched last month. http://www.ahrp.org/cms/content/view/842/98/

Inasmuch as no effective, safe treatment for Alzheimer’s exists, and ALL such screening tests have been demonstrably inaccurate and inconsistent, such an “early intervention” approach in clinical practice is unethical and controversial.

Read the Full Article Here: http://www.ahrp.org/cms/content/view/848/9/

Coconut Oil and Alzheimer’s Disease: The News is Spreading | Health Impact News

by Brian Shilhavy Health Impact News

The Failure of the Medical System to Treat Alzheimer’s

The news about how effective coconut oil is in treating Alzheimer’s Disease is spreading fast, as news about the failure of drugs in treating Alzheimer’s made huge headlines in 2012 in the mainstream media. These reports in 2012 coincided with news about the failures of drug companies to develop an effective Alzheimer’s drug. Drug companies Pfizer and Medivation admitted that the new drug they were developing for Alzheimer’s, dimebon, not only did not help patients in trials, but made patients worse. The expensive drug had already reached phase III trials. (See story here on ABC News)

In May 2012 a federal judge ruled that a case against Harvard Medical School and its teaching hospitals regarding fraudulent research using public funds for Alzheimer’s disease was to proceed. (Read the story here)

So as the development of this drug has now been abandoned, and so many other potential drugs have also failed (possibly due to fraudulent research?), many are beginning to look at the role of diet in Alzheimer’s and focusing on prevention. People are also beginning to see positive results in using coconut oil to reverse the effects of Alzheimer’s.

The harm of low-fat high-carbohydrate diets in cholesterol uptake in the brain

One of the most recent studies that looked at the role of nutrition in Alzheimer’s was published in the European Journal of Internal Medicine: “Nutrition and Alzheimer’s disease: The detrimental role of a high carbohydrate diet”¹.

The authors of this study have noted how researchers have begun to direct their energies towards understanding the earlier stages of AD, since drug research in later stages has not been very successful. They note that several researchers have noticed a strong correlation between insulin resistance in the brain and early AD, suggesting that AD might be considered a neuroendocrine disorder of the brain or so-called “type 3 diabetes.” Other observations have noted an association of AD with mitochondrial dysfunction, which is also common in Parkinson’s disease, and amyotrophic lateral sclerosis (ALS).

But the authors’ main conclusions regarding the early causes of AD center around the transport of cholesterol from the blood stream to the brain. They state that there is mounting evidence which suggests that a defect in cholesterol metabolism in the brain may play an important role in AD. They give a nice summary of the brain’s dependency on cholesterol:

The brain represents only 2% of the body’s total mass, but contains 25% of the total cholesterol. Cholesterol is required everywhere in the brain as an antioxidant, an electrical insulator (in order to prevent ion leakage), as a structural scaffold for the neural network, and a functional component of all membranes. Cholesterol is also utilized in the wrapping and synaptic delivery of the neurotransmitters. It also plays an important role in the formation and functioning of synapses in the brain.

They point to several studies that show a lack of cholesterol present in the brains of AD patients which is so vital for several functions, and also note that other studies show this cholesterol deficiency in dementia and Parkinson’s disease. In contrast, high cholesterol levels are positively correlated with longevity in people over 85 years old, and in some cases has been shown to be associated with better memory function and reduced dementia.

The authors go on to explain that the lipid theory of heart disease started by the work of Ancel Keys in the 1960s led to dietary beliefs that cholesterol was to be avoided in the diet, and with that belief came the “over-zealous prescription of cholesterol-reducing medications over the same decades in which there has been a parallel rise in AD prevalence.”

Another result of the low-fat dietary belief was the replacement of fats in the diet with refined carbohydrates, which leads to a rise in blood glucose levels and over time to insulin resistance and diabetes. They point out that the prevalence of fructose, mostly in the form of high fructose corn syrup, is ten times more reactive than glucose in inducing glycation. This impairs serum proteins, and they hypothesize that this leads to a depletion of much needed cholesterol and fat in the brain. Strong evidence in favor of their hypothesis is the fact that studies show patients with type-2 diabetes are at two to five times increased risk to AD.

Increased lipid peroxidation is also shown to be an early cause of Alzheimer’s disease. Liquid vegetable oils, the polyunsaturates, are highly prone to oxidation and rancidity, and it is now well known that in the form of trans fatty acids (through the process of hydrogenation) they are extremely toxic. (More research on polyunsaturated oils here.)

Dr. Raymond Peat has talked about the difference between polyunsaturated oils and saturated oils in their importance for brain tissue for years now:

Brain tissue is very rich in complex forms of fats. The experiment (around 1978) in which pregnant mice were given diets containing either coconut oil or unsaturated oil showed that brain development was superior in the young mice whose mothers ate coconut oil. Because coconut oil supports thyroid function, and thyroid governs brain development, including myelination, the result might simply reflect the difference between normal and hypothyroid individuals. However, in 1980, experimenters demonstrated that young rats fed milk containing soy oil incorporated the oil directly into their brain cells, and had structurally abnormal brain cells as a result. Lipid peroxidation occurs during seizures, and antioxidants such as vitamin E have some anti-seizure activity. Currently, lipid peroxidation is being found to be involved in the nerve cell degeneration of Alzheimer’s disease.²

How Coconut Oil Can Help Alzheimer’s

Coconut oil, by contrast, is highly saturated, and in its natural unrefined form has a shelf life of more than 2 years. Unlike unsaturated oils, it is not prone to oxidation.

Also, the study from the European Journal of Internal Medicine referenced above notes that Alzheimer’s, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS) all have an association with mitochondrial dysfunction. A study published in 2010 used coconut oil to show that a diet enriched in the saturated fatty acids of coconut oil offered strong advantages for the protection against oxidative stress in heart mitochondria.³

Much research is also being uncovered now on the advantages of high HDL cholesterol levels, besides the study we mentioned above in direct relation to Alzheimer’s. A study appearing in the American Journal of Cardiology in February 2011 showed that the higher men’s HDL cholesterol levels, the longer they lived and the more likely it was that they would reach the age of 85.⁴ A diet with adequate amounts of saturated fat is essential to keeping HDL high cholesterol levels. Those with deficiencies and suffering from neurological disorders need to consider a diet that is high in saturated fat, in stark contrast to the mainstream dietary advice for low-fat diets that might be causing many of these late-in-life diseases.

Another major advantage the saturated fat of coconut oil provides is its ability to provide the brain with an alternate source of energy in ketones. Ketones are high energy fuels that nourish the brain. Our body can produce ketones from stored fat while fasting or in starvation, but they can also be produced by converting medium chain fatty acids in certain foods. Coconut oil is nature’s richest source of these medium chain triglycerides (MCTs). A study done in 2004 took MCTs from coconut oil and put them into a drink that was given to Alzheimer’s patients while a control group took a placebo.⁵ They observed significant increases in levels of the ketone body beta-hydroxybutyrate (beta-OHB) 90 minutes after treatment when cognitive tests were administered. Higher ketone values were associated with greater improvement in paragraph recall with MCT treatment relative to placebo across all subjects.

As coconut oil’s use becomes more accepted and widespread, and as people begin to realize the dangers of the low-fat dietary belief, we are starting to see more testimonies in relation to diseases like Alzheimer’s. One of the most widely published reports is from Dr. Mary Newport as reported by the St. Petersburg Times on October 29, 2008⁶. Dr. Newport’s husband had been diagnosed with early onset Alzheimer’s and was watching her husband quickly deteriorate. After using drugs that slowed down the effects of Alzheimer’s, she looked into clinical drug trials and found one based on MCTs that not only slowed the progression of Alzheimer’s, but offered improvement. Not being able to get her husband into one of these trials, she began to give him Virgin Coconut Oil, and saw incredible improvement in his condition.

The coconut oil he’d ingested seemed to “lift the fog.” He began taking coconut oil every day, and by the fifth day, there was a tremendous improvement. “He would face the day bubbly, more like his old self,” his wife said. More than five months later, his tremors subsided, the visual disturbances that prevented him from reading disappeared, and he became more social and interested in those around him.⁷

You can read Dr. Newport’s entire case study here. You can also watch an interview with her done by CBN in 2012:

Read my commentary on this story regarding coconut oil and Alzhiemer’s from CBN here. While this is a great story showing how ketones and coconut oil can help with Alzheimer’s disease, it does not even address the whole issue of cholesterol uptake to the brain as I wrote about above. Dr. Newport admits that her husband Steve was taking statins (cholesterol lowering drugs) until she took him off of them in 2009, after studying the cholesterol issue. She stops short, however, in recommending that others suffering from Alzheimer’s do the same. Until the media and the general public wake up to the facts regarding all the serious side effects from cholesterol-lowering statin drugs, simply adding coconut oil to one’s diet might only have a minimal effect.

Carol Flett came across Dr. Newport’s research while praying for a solution to her husband’s worsening dementia. In her blog post Can God Use Facebook to Answer Prayers? she reports:

Within three or four hours after giving Bruce the first couple of tablespoons (of coconut oil) he was speaking in clear sentences again. He did have one relapse, shortly after starting, but it lasted only a day. After that he sprang right back and has been doing well ever since, taking care of many things himself that he hadn’t been able to do for a long time. The doctor came to see Bruce yesterday. He was amazed. He ordered another cognitive test, but he could see for himself that Bruce was much better. I told him about the answer to prayer. He believes in God. He didn’t scoff. He just said, “Keep doing what your doing because it’s is working.” I believe God can use whatever method he chooses. If He chooses to use part of his creation such as coconut oil, I won’t complain, and if He gives direction to His praying child through Facebook, that is His prerogative as well.⁸

She has since posted a video of Bruce thanking people for praying for him, and explaining how his condition changed dramatically after taking coconut oil. He reports how he was diagnosed with dementia and could no longer care for himself, and that the doctors recommended that he be put in a nursing home. Watch and listen to him now:

Ian Blair tells us in this video how “Coconut oil gave me my brain back” after he was diagnosed with Alzheimer’s:

Dietary Advice for Alzheimer’s Sufferers

Coconut oil does offer hope as nature’s most abundant source of MCTs, and it is an easily convertible fuel source for ketones. In addition, it is one of nature’s richest sources of saturated fat which is needed to produce HDL cholesterol to feed the brain. People suffering from Alzheimer’s should immediately start avoiding polyunsaturated forms of oil such as soy and corn oils, especially if they are hydrogenated and in the form of trans fatty acids. These are prone to oxidation and potentially mitochondrial dysfunction. Other healthy fats would include butter from the milk of cows that are grass-fed, and Omega 3 fatty acids from high quality fish oil, cod liver oil, or krill oil.

Refined carbohydrates in the form of refined wheat products and refined sugars should be strictly avoided! High protein foods such as eggs from pastured chickens (preferably fed a soy-free chicken feed), pastured poultry, and grass-fed meats are all desirable proteins for brain health.

I started checking into Coconut oil because I saw on the news that Alzheimers patients were dramatically improving after taking this oil. I bought some for my father who had recently been diagnosed and he now thinks the Alzheimers has gone away! I’m using it too and I feel so good, physically and MENTALLY better! Roxie (Coconut Diet Forums)

5 Medical Doctors with Gary Taubes and Robb Wolf Discuss Coconut Oil and Alzheimer’s Disease

– Article Here.

References:
1. Seneff S, et al, Nutrition and Alzheimer’s disease: The detrimental role of a high carbohydrate diet, Eur J Intern Med (2011), doi:10.1016/j.ejim.2010.12.017
2. 1996 Raymond Peat Newsletter, Eugene, OR -http://www.coconutoil.com/ray_peat_coconutoil.htm
3. Am J Cardiol. 2011 Feb 4. Relation Between High-Density Lipoprotein Cholesterol and Survival to Age 85 Years in Men (from the VA Normative Aging Study). Rahilly-Tierney CR, Spiro A 3rd, Vokonas P, Gaziano JM.
4. Mitochondrion. 2011 Jan;11(1):97-103. Epub 2010 Aug 5. Dietary fatty acids and oxidative stress in the heart mitochondria. Lemieux H, Bulteau AL, Friguet B, Tardif JC, Blier PU.
5. Neurobiol Aging. 2004 Mar;25(3):311-4. Effects of beta-hydroxybutyrate on cognition in memory-impaired adults. Reger MA, Henderson ST, Hale C, Cholerton B, Baker LD, Watson GS, Hyde K, Chapman D, Craft S.
6. Doctor says an oil lessened Alzheimer’s effects on her husband, St. Petersburg Times, October 29, 2008 - http://www.tampabay.com/news/aging/article879333.ece
7. Ibid.
8. Can God Use Facebook to Answer Prayers? Carol Flett EverydayChristian.com

More research and testimonies on Coconut Oil and Alzheimer’s Here.

About the authors: Unlike many people who write about coconut oil by simply reading about it, Marianita Shilhavy actually grew up on a coconut plantation in the Philippines and in a culture that consumed significant amounts of coconut fat in their diet. She later went on to earn her degree in nutrition and worked as a nutritionist in the Philippines. Brian Shilhavy also lived in the Philippines for several years with Marianita and their 3 children observing firsthand the differences between the diet and health of the younger generation and those of Marianita’s parents’ generation still consuming a traditional diet. This led to years of studying Philippine nutrition and dietary patterns first hand while living in a rural farming community in the Philippines. They are authors of the best-selling book: Virgin Coconut Oil: How it has changed people’s lives and how it can change yours!

BVCNOcover Coconut Oil and Alzheimer’s Disease: The News is Spreading

Keep up-to-date on the research regarding Alzheimer’s Disease and coconut oil, as well as other research on coconut oil, at CoconutOil.com.

Coconut Oil, Ketones and Alzheimer's: New brain metabolism and ketone review article

Friday, February 4, 2011

New brain metabolism and ketone review article

I recently received this new article that discusses in great detail what is known about brain metabolism as we age and the potential for alternative fuels to glucose to prevent or stabilize the progression of Alzheimer's disease:

"Brain fuel metabolism, aging, and Alzheimer’s disease",

Stephen Cunnane Ph.D., Scott Nugent B.Sc., Maggie Roy M.Sc., and others, Nutrition, January 2011

Here are some important excerpts from this article:

"The recent development of 11C-acetoacetate as a ketone tracer for PET studies opens a new window to compare brain metabolism of glucose and ketones in the same individual. If brain
ketone metabolism is not lower in AD or is less affected than glucose metabolism, one potential strategy to improve brain fuel availability and reduce the risk of AD that has already been targeted in clinical studies would be to develop a way to safely and reliably provide the brain with ketones as an alternative fuel to glucose..."

"Whether or not mitochondrial dysfunction reflects genetic or metabolic disturbances,
clinical trials attempting to redress the energy deficit in the AD brain suggest that cognitive function can be at least transiently improved if more fuel (glucose or ketones) can be
supplied to the brain."

"In carriers of apo E4, small areas of lower brain glucose metabolism are observed at an age
as young as 30 y old, e.g., 30-40 y before clinical onset. Indeed, we see an inverse relationship between CMRg in several brain regions and fasting plasma insulin, so brain metabolism
seems to be sensitive to even mild disturbances in systemic insulin control even if no clinical symptoms of cognitive decline are observed. Compared to non-carriers of apo E4, carriers have altered u3 [omega-3] fatty acid metabolism and higher measures of oxidative stress in the brain, both of which may contribute to a higher risk of early onset of brain hypometabolism. If brain hypometabolism can be present before clinical symptoms are apparent, this does not prove that hypometabolism is the earliest event in AD. However, to the best of our knowledge, hypometabolism is currently the earliest measurable abnormality in the brain that is connected to AD so its features and the reasons for it should shed light on the etiology of AD."

"The cerebral metabolic rate of ketones (CMRk) varies directlywith their blood concentration, starting at very low ketone concentrations...Hence, at a plasma b-hydroxybutyrate [one of the primary ketone bodies] concentration of 0.3-0.5 mM, such as can be achieved during 12-24 h fasting, b-hydroxybutyrate supplies 3-5% of whole brain energy requirements. As plasma ketones rise, CMRk also rises such that at a b-hydroxybutyrate of about 1.5mM, ketones provide about 18%, and at 6 mM, they provide about 60% of brain fuel." [Dr. Richard Veech's ketone ester can provide levels this high].

"Acute, controlled human experiments show that ketone infusion or ketogenesis inhibits the cognitive and behavioral sequelae of acute, experimental hypoglycemia, both in healthy
adults and in type 1 diabetes. It is generally assumed that the cognitive effects of hypoglycemia can be prevented by ketones because they seamlessly replace glucose to meet the brain’s energy requirements. However, acutely raising plasma ketones also increases cerebral blood flow in humans, an effect that may contribute to their beneficial impact on cognition during hypoglycemia. Studies in humans and animal models suggest further protective effects of ketones in the brain after ischemic insult [lack of oxygen/stroke] and other treatments damaging neuronal function."

"More recent controlled clinical trials confirm that short-term improvement can occur in cognitive tests when individuals with mild to moderate AD are provided with an exogenous source of glucose, ketones, insulin, or insulin sensitizers. These clinical studies show that the
affected brain regions in AD are at least partially viable and that cognition can improve when exogenous fuel supply to the brain is increased. In two of these studies, ketogenic supplements
based on medium chain triglycerides were used, thereby permitting a relatively normal choice of meals. Medium chain triglycerides have long been known to be ketogenic because they contain medium chain fatty acids (octanoic [8:0] and decanoic [10:0] acids), which do not require activation by CoA to enter mitochondria. The mild beneficial effects on cognition and relatively good tolerance to the doses of medium chain triglyceride used are promising, notwithstanding the possibility that carriers of apo E4 with AD derive little benefit from this treatment [Dr. Newport's comment: per one of the authors of the MCT oil studies, many of the ApoE4+ individuals did experience improvement, as a group when data was combined on the average they did not]. The explanation for the beneficial effect of mild, experimental ketonemia on cognition in AD may be as simple as exchanging one brain fuel for another as occurs in
fasting or starvation. It may also be due to the observation that although glycolysis may be impaired in the AD brain, CMRk and metabolic capacity to use a fuel other than glucose may
both be relatively normal in AD."

"...two observations in particular support the notion that the neurons affected in AD are still functional: (1) in AD, brain ketone uptake is apparently normal or at least less impaired than is glucose, and (2) there is a functional response to nutritional supplements that increase brain fuel
availability, particularly ketones. Hence, if brain fuel metabolism could be optimized or even partially returned toward normal, the risk of further cognitive decline may diminish. Raising plasma ketones to 0.4-0.5 mM would contribute to 5-10% of the brain’s energy requirements, which is equivalent to the early cortical glucose deficit in those genetically at risk AD. Such a mild, safe level of ketonemia is achievable with ketogenic supplements, so if implemented before symptoms develop, it seems plausible that they could diminish the risk of further metabolic deterioration and clinical onset of cognitive decline."

Regarding Omega-3 fatty acids:

"The u3 [omega-3] polyunsaturated fatty acid, DHA, is now widely understood to have an important role in mammalian brain development...Insufficient dietary intake of DHA and low levels of DHA in the hippocampus may have a role in cognitive decline in the elderly and/or AD. Hence, the low intake of DHA now widely but not universally reported in AD may contribute to the evolution of cognitive decline because of its role in brain glucose transport and in other aspects of brain function and structure. This emerging role of DHA in brain energy metabolism could be linked to the early presymptomatic onset of brain glucose hypometabolism in AD, at least in carriers of the e4 allele of apoE4. Nevertheless, such an effect probably involves relatively subtle changes in DHA metabolism because plasma DHA appears to be higher in the healthy elderly and is widely variable in AD."

Dr. Newport's comments:

The bottom line here, to try to prevent or stabilize AD, include medium chain fatty acids (coconut oil, palm kernel oil and MCT oil are the richest sources) in the diet to provide ketones as an alternative fuel to glucose AND eat fish (especially salmon) and/or take a supplement of marine based omega-3 oil (fish oil for most of us; algae based oil for vegans found in brands that are marketed to pregnant women).

Computers prevent dementia in older men | University News

Can Web Surfing Ward Off Dementia?

Gary Drevitch, Contributor

Most experts expect the rate of Alzheimer’s disease and other forms of dementia to rise rapidly worldwide in the years ahead, as the population ages and risk factors increase.

But new research from Australia, published in the science journal PLoSOne, found reason for guarded optimism about curbing the rise of Alzheimer’s and dementia in a surprising source: booming rates of computer use.

(MORE: Train Your Brain With Video Games)
As part of a longitudinal study of men’s health, researchers at Western Australia University report that having access to a personal computer appears to lower the risk of cognitive decline and dementia in older men by as much as 40 percent.

Their study of computer use analyzed more than 5,000 men age 65 or older over eight years and found that computer users were more successful in avoiding dementia. They also had more active social networks and were less likely to show signs of depression.

“If our findings are correct,” and regular computer use can help older men ward off the effects of dementia, said lead researcher Osvaldo Almeida of the university’s Center for Health and Aging, “the increase in the number of cases over the next 40 years may not be as dramatic as is currently expected.”

Almeida says he undertook the study after seeing widespread reports claiming that mentally stimulating activities decreased one’s risk of developing dementia. But, he noted, those studies did not analyze the specific impact of computer use. “It got us thinking,” he said in a statement. “Could it make a difference? We found that it did, and that there was a significant benefit.”

(MORE: Is Technology Helping or Hurting Us?)

The benefits found in the study could not be attributed to differing levels of education, incidence of depression or overall health among the subjects, Almeida says. Subjects told researchers how often they used computers and whether they used PCs for email, Web surfing, word processing, games or other activities.

In their paper, the Australian team noted that wider studies of larger groups could provide more definitive results. However, given the proliferation of computers, at least in developed Western countries, the researchers speculated that it would be challenging for other studies to produce similar results. The team was able to survey, over a reasonably long period of time, a group that was still old enough to include a significant number of non-computer users — an unlikely scenario for future studies.

While that may not bode well for further research, it’s potentially good news for aging Internet surfers. “In this context,” the researchers wrote, “the increasing ease of access to personal computers that has occurred over the past 20 years offers hope that the growing exposure of older adults to this technology will enhance their participation in mentally stimulating activities and contribute to maintain cognitive function and reduce the prevalence of dementia in the community.”

More on Next Avenue:

'Ram' memory saves real memory in older men | University News : University News : The University of Western Australia

Having access to a personal computer lowers or decreases the risk of cognitive decline and dementia in older men by up to 40 per cent, according to researchers at The University of Western Australia.
Winthrop Professor Osvaldo Almeida and his colleagues undertook an eight-year study of more than 5000 Perth men aged from 65 to 85. The results are published in the journal PLoSOne.

Professor Almeida is Research Director at the UWA-affiliate, the Centre for Health and Ageing.
"As the world's population ages, the number of people experiencing cognitive decline and dementia will increase to 50 million by 2025," he said. "But if our findings are correct, the increase in the number of cases of dementia over the next 40 years may not be as dramatic as is currently expected."
Professor Almeida said previous studies showed that cognitively-stimulating activities decreased the risk of dementia but there was little evidence on the likely effect of computer use over many years.
"So it got us thinking, with personal computer ownership on the increase, could it make a difference? We found that it did, and that there was a significant benefit," he said.

The researchers found that computer users were younger than non-users, had completed at least high school, had a more active social network and were less likely to show evidence of depression or poor physical health.

They found that the risk of dementia was about 30 to 40 per cent lower among older computer users than non-users and that their findings could not be attributed to age, education, social isolation, depression, overall health or cognitive impairment.

Older people should therefore be encouraged to embrace computer technology as long as they understand the dangers of prolonged physical inactivity and the many advantages of a balanced and healthy lifestyle, the authors write.

The research is part of Australia's longest-running longitudinal study of men's health and ageing. It has been following a group of more than 19,000 men since 1996.

Media references

Christianne White (WA Centre for Health and Ageing) (+61 8) 9224 2993 / (+61 4) 15 213 661
Michael Sinclair-Jones (UWA Public Affairs) (+61 8) 6488 3229 / (+61 4) 00 700 783

Alzheimer Research Forum - Current Hypotheses

CURRENT HYPOTHESES

Updated 27 October 2011 Important Notice: Alzheimer Research Forum does not provide medical advice nor promote any product or service. The contents are for informational purposes only and are not intended to substitute for professional medical advice, diagnosis or treatment. Always seek advice from a qualified physician or health care professional about any medical concern, and do not disregard professional medical advice because of anything you may read on this web site. The views of individuals quoted on this site are not necessarily those of the Alzheimer Research Forum.
We list here a collection of special seminars, on-line journal club discussions, recorded talks and other presentations on the Forum web site that describe a variety of scientific hypotheses about the pathogenesis of Alzheimer's disease. Over time, we intend to represent a more comprehensive range of theories. We hope that readers will be stimulated to think more broadly about this many-faceted disorder and to consider how this diversity of ideas and data may be integrated into a more complete picture of the disease.
We have also created the Hypothesis Factory that is devoted to the presentation and exchange of ideas regarding novel hypotheses, hunches, theories-in-progress, etc. The Hypothesis Factory is a forum where people with original or unconventional ideas can publicly present and discuss them.

See also The Forum Interviews.
Open Forum on Alzheimer's Disease: Q & A on Down Syndrome; Aluminum; Genetic basis, symptoms, and prevalence; Multi-infarct dementia; and Schizophrenia and Alzheimer's Disease

Submit a hypothesis. We invite your comments and questions.

AD, PD, HD, ALS, FTLD-U, CJD and RSA Are Autoimmune Disorders: A Unifying Hypothesis on the Function of Aß, Tau, a-Synuclein, Huntingtin, TDP-43, PrP, and AA in Innate Immunity
By Claudiu Bandea, Centers for Disease Control and Prevention, Atlanta, Georgia—Updated 27 October 2011

Aβ-mediated Crosslinking May Regulate TrkA-p75 Association and Cooperations of p75 With APP, Prion, and Synuclein
By Rudolf Bloechl, independent investigator, Germany—Updated 1 February 2010

Chronic Stress Hypothesis of AD
By Tohru Hasegawa, Saga Woman Junior College, Saga, Japan—Posted 7 April 2007

At a Crossroad of Amyloid-β Functional Pathways: Homeostasis of cholesterol and lipid peroxidation are integrated components of neural membrane neuroplasticity mechanisms and neurodegeneration —Updated 26 November 2005
By Alexei Koudinov and Natalia Koudinova

Apolipoprotein E, Alzheimer Disease, and Cerebral Amyloid Angiopathy: Effects of ApoE on Amyloid-β Metabolism Suggest Underlying Mechanisms and Potential Treatments (.pdf) —Posted 15 August 2005
By David M. Holtzman

Axonal Transport Dysfunction Hypothesis—Posted 7 July 2005
By John Trojanowski

"The Amyloid Cascade Hypothesis"—Updated 23 May 2005
By Dennis Selkoe.

Arguments Against the Amyloid Cascade Hypothesis Ipsen Foundation Symposium: "Connections, Cognition And Alzheimer's Disease"
A major theme in many of the speakers is that cognitive impairment in Alzheimer's disease is referable to loss of specific populations of projection neurons and the breakdown of highly vulnerable neural systems, especially those involved in memory formation. There is general consensus among these speakers that these neuronal alterations occur largely independent of amyloid deposition. "Alzheimer's disease: a re-examination of the amyloid hypothesis"
By R.L. Neve and N.K. Robakis. Live journal club discussion March 1998.
"Does beta amyloid kill from within the cell or from the extracellular space?"
A live debate by Steven Younkin and Dennis Selkoe. September 1997.
Debate: The Amyloid Cascade Hypotheses 10 Years Later
Chaired by Price, D. (Baltimore, MD, US) Wurtman, R.J. (Boston, MA,US).

Two Hits and You're Out? A Novel Mechanistic Hypothesis of Alzheimer Disease—Posted 23 October 2004
By Xiongwei Zhu, George Perry, Mark A. Smith, Institute of Pathology, Case Western Reserve University, Cleveland, Ohio, USA

The Pathogen Hypothesis—1 July 2004
By Brian Balin, Denah Appelt, Joseph Lyons, Ruth Itzhaki, and Curtis Dobson

Aluminosilicate Precipitation and Alzheimer's Disease—Updated 14 July 2005
By Colin Meyer

Is Alzheimer's an Autoimmune Disease?—Posted 12 February 2004
By Michael R. D'Andrea, Ph.D., Principal Scientist, J&J Pharmaceutical Research and Development

Disruption of Glial (oligodendrocyte and astrocyte) Cellular Function ...—Posted 19 August 2003
By Steven Brenner, Affiliated with Neurology Departments at the Saint Louis VA Medical Center and Saint Louis University Medical Center

The Combination of Nicotine with Galantamine Is Expected to Have Enhanced Therapeutic Effects in Patients with Alzheimer's Disease—Posted 5 December 2003
By Silvia Petrova

Viruses and Dementia, and the Role of Apolipoprotein E (ApoE)—Posted 15 June 2002
By Ruth Itzhaki, University of Manchester Institute of Science and Technology

Polymorphisms in Inflammatory Genes Enhance the Risk of Alzheimer Disease—Posted 11 February 2002
By P.L. McGeer and E.G. McGeer, Kinsmen Laboratory of Neurological Research, Department of Psychiatry, University of British Columbia, Vancouver, B.C., Canada

Advanced Aging Plus "Risk Factors" May Explain Late-Onset Spordic Alzheimer's Disease—Updated 8 May 2002
By Ming Chen, VA Medical Center, Bay Pines, Florida and University of South Florida.

"Calcium Signaling Deficit" Hypothesis for Alzheimer's Disease.—Updated 10 October 2001
By Ming Chen, VA Medical Center at Bay Pines, Florida.

The "Coblaminergic" Hypothesis—Posted October 2000
By Andrew McCaddon

Dementia as a neocortical disconnection syndrome: morphological and biochemical characterization of the vulnerable neurons
By Dr. Patrick Hof, Mt. Sinai School of Medicine

Alzheimer changes in hypothalamic nuclei: Their relationship to neuronal activity and clinical symptoms
By Dick Swaab and Ahmad Salehi, Netherlands Institute for Brain Research

"Apoptosis in Alzheimer's Disease"—Posted 5 May 1999
Panel discussion on with Paul Coleman, Carl Cotman, Mark Smith, George Perry, Mark Mattson.

"Frameshift mutants of beta amyloid precursor protein and ubiquitin-B in Alzheimer's and Down's syndrome patients"—Posted May 1998
By van Leeuwen FW, et al.

"Alzheimer Presenilins in the Nuclear Membrane, Interphase Kinetochores, and Centrosomes Suggest a Role in Chromosome Segregation"—Posted March 1998
By Li JH, Xu M, Zhou H. Ma J. and Potter H.

"Herpes simplex virus type 1 is a risk factor for Alzheimer’s disease"
By Ruth F. Itzhaki, Woan-Ru Lin and Gordon K. Wilcock.

"Towards an animal model of Alzheimer's disease: Can phorbol esters fan the flames?"
By N.R. Smalheiser.

"The cause of neuronal pathology in Alzheimer's disease"
By J.C. Vickers, et al.

"Oxidative Stress Is Central To The Pathogenesis Of Alzheimer Disease"
By M.A. Smith, G. Perry.

"The Role of the Carboxyl-Terminal fragment of APP in the Neurodegeneration and Cognitive Loss in Alzheimer Disease"—Posted September 1997
By Rachael Neve.

"NMDA Receptor Dysfunction And Alzheimer's Disease"—Posted September 1997
By John Olney.

Debate: Multi-Infarct Dementia: Disease Entity or Alzheimer's Lesion?

Alzheimer Research Forum - Hypothesis Factory

Hypothesis Factory

Updated 2 July 2010 Important Notice: Alzheimer Research Forum does not provide medical advice nor promote any product or service. The contents are for informational purposes only and are not intended to substitute for professional medical advice, diagnosis or treatment. Always seek advice from a qualified physician or health care professional about any medical concern, and do not disregard professional medical advice because of anything you may read on this web site. The views of individuals quoted on this site are not necessarily those of the Alzheimer Research Forum.

This page is devoted to the presentation and exchange of ideas regarding novel hypotheses, hunches, theories-in-progress, etc. All established hypotheses started out as someone's wild notion, and this page pays tribute to them by creating a forum where people with original or unconventional ideas can publicly present and discuss them. See also our AD Hypotheses page.

Submit a hypothesis. Comments are definitely encouraged!
(We also recognize that it is a subjective exercise to decide whether a hypothesis is still half-baked or fully formed and testable. Your opinions on this matter are also welcome.)

External Toxic Factors

Borrelia and AD

The Toxic Effects of Mercury and AD

Radiation Exposure and Alzheimer's Risk

Multiple Chemical Sensitivity

Refined Food Oils Contribute to AD and ADHD

Tellurium and Alzheimer's?

Nicotine and AD

Treatment-based Discovery

Folic Acid for Symptomatic Relief of “Sundowning” Syndrome

Agitation and Alerting Agents

Gingko Biloba and Yerba Mate Tea

Effect of Sleeping Pill Zolpidem in an AD Patient