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Thursday, October 20, 2011

Could Hypertension Drugs Help People With Alzheimer's? FTD?

So, since I have been taking an ACE Inhibiter for a few years, specifically Enalapril, this article was particularly interesting. Though I take a sub-clinical 5mg dosage as a prophylactic to protect my kidneys from the ravages of Type II Diabetes,  any extra benefits are just fine with me. I think the absolutely coolest thing about this whole class of drugs is that they are all originally synthesized from compounds found in pit viper venom, they inhibit angiotensin-converting enzyme (ACE), a component of the blood pressure-regulating renin-angiotensin system. This article is about Alzheimer's Disease, but may certainly have other implications.

Science Daily (Oct. 17, 2011) — Within the next 20 years it is expected the number of people with Alzheimer's disease (AD) will double from its current figure of half a million to one million. A new study has looked at whether certain types of drugs used to treat high blood pressure, also called hypertension, might have beneficial effects in reducing the number of new cases of Alzheimer's disease each year.

The team of researchers from the University of Bristol have looked at whether drugs already being used to treat hypertension, particularly ones that specifically reduce the activity of a biochemical pathway, called the renin angiotensin system, might reduce the occurrence of Alzheimer's and another common type of dementia called vascular dementia.

The study, conducted with the support from North Bristol NHS Trust and published online in the Journal of Alzheimer's Disease, stems from work by one of the team's members, Dr Patrick Kehoe. Dr Kehoe, who is a Reader in Translational Dementia Research and co-leads the Dementia Research Group at Frenchay Hospital, Bristol, is a leading authority on the possible role of the renin angiotensin system in Alzheimer's.
This pathway is very important in blood pressure regulation and, for at least a decade, links between hypertension and dementia have been known but poorly understood.

In more recent years it has been shown that certain signals produced by this pathway contribute to a number of the damaging effects often seen in the brains of people with Alzheimer's. These include memory loss, lowered blood circulation in the brain, higher levels of brain inflammation and increased levels of brain cell death due to reduced oxygen circulation.

Dr Patrick Kehoe said: "Drugs that can prevent Alzheimer's occurring at all, or delaying its onset would have a substantial benefit on the lives of future sufferers, their families, as well as an overstretched health care system.

"Current Alzheimer's drugs treat memory loss by attempting to correct chemical imbalances in the brain but these only work for a limited time. This limited treatment period is because the drugs are unable to stop the underlying mechanisms that cause the disease. Therefore the need to find new ways of stopping Alzheimer's goes on."

Dr Kehoe's research led him to experts in the study of risk factors for disease in large populations and datasets. Professors Richard Martin and Yoav Ben-Shlomo, and researcher Neil Davies in the University's School of Social and Community Medicine, used the General Practice Research Database, which holds anonymised data on approximately ten million people who attend General Practitioner surgeries around the UK. The research team made some very interesting observations in what is one of the largest studies of its kind on dementia in the UK.

The researchers found people over 60 years, who had ever taken one of two different groups of drugs that target the renin angiotensin system in the previous ten years, had a 50 per cent lower risk of developing Alzheimer's with a more modest 25 per cent reduced risk for forms of vascular dementia compared to patients on any other types of hypertension drugs. This suggests that these benefits, if truly causal, are not merely due to a blood pressure lowering effect and may involve specific biochemical alterations.
Professor Richard Martin added: "Whilst our findings are interesting, these are not conclusive findings. We now need to do the clinical trials to properly test our observations."

Dr Kehoe and colleagues are now currently in the process of trying to obtain funding to undertake this necessary further research. If found to be successful, these treatments could be relatively quickly entered into Alzheimer's care since these drugs are already used for other conditions and are thought to have reasonably low side effect issues.

Friday, October 14, 2011

Could Alzheimer's Dementia Be Caused by a Virus?

The following is an article from Psychology Today, and is closely related to the concept of dementias being contagious or transmissible. I would not be at all surprised if in the future some pathogen were linked to all of the tauopathies, but for now it is just speculation. Nothing more than something to make you say, "Hmmmm!"


Could Alzheimer's Dementia Be Caused by a Virus?

Evidence links several common infections to the development of dementia.
Alzheimer's Disease is a slowly progressive illness of neuron loss leading to memory problems, cognitive impairment, and eventually death.   Since there appear to be no conventional medicine ways to prevent Alzheimer's and there is no known cure, there is a flurry of research trying to figure out what may cause the condition (besides genetics, which we can't do much about) and what might help the symptoms.
Today, we will take a peek at one of the more compelling theories about the cause of Alzheimer's -- it may well be due to an infection. Meaning exposure to certain parasites, bacteria, or viruses, particularly those that tend to inhabit the central nervous system, could bring on the disease. Even if you don't find Alzheimer's that compelling, if infectious agents contribute to its pathology, then you have to open your mind to the idea that many neurodegenerative processes could be due to (or accelerated by) infection.  Neurodegenerative diseases include many neurological illnesses, but also depression, bipolar disorder, schizophrenia, autism, and some other psychiatric illness.

What is the argument against infection as an ongoing contributing factor?  Well, where's the bug? Do a spinal tap - does the fluid grow any bacteria in culture?  Are there white blood cells (sign of active infection)?  Is there an elevated level of protein (a sign of viral infection)?  Over the last hundred years we've become pretty good at finding bugs.  It's hard to imagine them hiding from us, even in the protected environment of the human skull.  So if you bring up the idea of infections causing Alzheimer's disease to a physician friend and he or she scoffs at you -- that's why.  Where's the bug?
With that in mind, let's plunge forward into a very good review by Urosevic and Martins from the Journal of Alzheimer's Disease, "Infection and Alzheimer's Disease: The Apoe epsilon4 Connection and Lipid Metabolism."

The whole theory is based on the following premise: there's a continuous, chronic infection supplying persistent live microorganisms, and their toxic products stimulate the host's (that's you) inflammatory response.  The pathogen itself damages the neurons, and the brain's inflammatory response also damages the neurons.

ApoE4 is the  Alzheimer's vulnerable genetic variant of apolipoprotein. ApolipoproteinE is basically a molecular key that helps cholesterol and triglycerides go from the circulation into the brain. Since we know that being a carrier of ApoE4 makes one more likely to get Alzheimer's, any theory postulating an infectious origin of Alzheimer's will have to explain why ApoE4 will leave more vulnerable as well. Fortunately, the infectious theory meets that criteria, as you will see below.

What infectious agents are we talking?  Some viruses immediately come to mind, specifically herpes viruses.  These little guys are exceedingly common and come in lots of different flavors, and are well known to hide out in nerve cells for the duration of the host's life (an easy example of "There's the bug.")  HSVI, associated with cold sores, infects people early in life and hangs out in the trigeminal ganglia (the nerve root of the trigeminal nerve that innervates a good part of the face).  Some people get cold sores, some people don't, but those who do are more likely to be ApoE4 carriers.  People infected with HSVI are also more likely to develop Alzheimer's.  ApoE4 mice were more likely to carry invasive HSVI and have brain colonization of the virus.
Other viruses implicated include human herpes virus 6 (cause of roseola, a common childhood illness of high fever followed by a characteristic rash), HIV, hepatitis C, and cytomegalovirus (a cause of mononucleosis-like illness and fatigue symptoms).  It is well known that HIV causes a form of AIDS dementia (which happens to be more common in carriers of ApoE4), so it would make sense that other common viruses that infiltrate the neurons might lead to other types of dementia.

All the common inflammation players (TNFalpha, IL-6, nitric oxide synthase) are involved in fighting off viral infections.  We know these players have a role in Alzheimer's pathology and in depression and bipolar disorder.  Interestingly, as we get older, our immune response becomes less aggressive, and it is perhaps then that the infectious agents hold sway, leading to Alzheimer's pathology.  Other inflammation-mediated brain disease occurs at different developmental stages - late adolescence and early adulthood for schizophrenia, and infancy for autism.

In this very recent study of mice, scientists were able to inject the extracts of mouse brains from mice with Alzheimer's (or an experimental mouse version of it) into mice with no signs of Alzheimer's Over time, the injected mice began to develop plaques and mouse dementia, while mice that weren't injected didn't develop the problem.

There are also suspected bacterial causes.  The "spirochetes" are a type of sneaky bacteria that are known to infect nerves (as in syphillis and Lyme disease).  Some spirochetes that cause gum disease are found in the mouths of Alzheimer's patients and healthy folks, but in the Alzheimer's patients, they are found in the brain more often than in healthy folks.  Certain spirochetes have been found in the amyloid plaques in the brains of patients with Alzheimer's (once again - there's the bug).

Chlamydia pneumoniae is an intracellular bacterial pathogen also implicated in Alzheimer's dementia.  Not surprisingly, it is better known as a common cause of pneumonia and other acute respiratory infections, but infected immune cells could presumably carry Chlamydia pneumoniae from the upper respiratory tract to the brain if the blood brain carrier is compromised in some fashion.  Chlamydia pneumoniae has been injected into mouse brains and causes amyloid deposits, which anyone will agree is suspicious behavior.  Once again, ApoE4 comes up, as ApoE4 seems to allow for greater bacterial load and numbers of infected cells.

ApoE4 is not only a bad guy when it comes to Alzheimer's in the modern world.  Carriers are at greater risk of atherosclerosis, stroke, and poor recovery from head injury.  And ApoE's role as a molecular marker and director of where lipoproteins go is key.  Lipoproteins are how fat and antioxidants are carried throughout the body.  It is probably not a coincidence that major conditions leading to weight loss without any particular effort are infectious disease and Alzheimer's (along with cancer and melancholic depression).   ApoE4 in particular is associated with poor clearance and recycling of lipoprotein particles.  It's just not a very efficient key.  If everything is going along just fine, maybe we don't need a particularly efficient key.  Add stress or infection, though, and you have a greater need for metabolic efficiency.  If you fall behind on cleanup and recycling, garbage builds up in the brain, causing major problems.

Wednesday, October 5, 2011

Alzheimer's Might Be Transmissible - Or It May Not Be!

The following story from Science Daily is being reported by nearly every news service.  I am very skeptical for several reasons. First, and foremost, caregivers don't seem to have an abnormally higher risk of developing the disease. Second - they actually transplanted brain tissue. That is akin to transplanting a tumor, and saying cancer is contagious ...oh Wait! Some forms of cancer do seem to be contagious. Hmmm... In any case hopefully it will shed some light on the process, and maybe open some new research pathways into the tauopathies. Here is the whole article:

Alzheimer's Might Be Transmissible in Similar Way as Infectious Prion Diseases, Research Suggests

ScienceDaily (Oct. 4, 2011) — The brain damage that characterizes Alzheimer's disease may originate in a form similar to that of infectious prion diseases such as bovine spongiform encephalopathy (mad cow) and Creutzfeldt-Jakob, according to newly published research by The University of Texas Health Science Center at Houston (UTHealth).

"Our findings open the possibility that some of the sporadic Alzheimer's cases may arise from an infectious process, which occurs with other neurological diseases such as mad cow and its human form, Creutzfeldt-Jakob disease," said Claudio Soto, Ph.D., professor of neurology at The University of Texas Medical School at Houston, part of UTHealth. "The underlying mechanism of Alzheimer's disease is very similar to the prion diseases. It involves a normal protein that becomes misshapen and is able to spread by transforming good proteins to bad ones. The bad proteins accumulate in the brain, forming plaque deposits that are believed to kill neuron cells in Alzheimer's."

The results showing a potentially infectious spreading of Alzheimer's disease in animal models were published in the Oct. 4, 2011 online issue of Molecular Psychiatry, part of the Nature Publishing Group. The research was funded by The George P. and Cynthia W. Mitchell Center for Research in Alzheimer's Disease and Related Brain Disorders at UTHealth.

Alzheimer's disease is a form of progressive dementia that affects memory, thinking and behavior. Of the estimated 5.4 million cases of Alzheimer's in the United States, 90 percent are sporadic. The plaques caused by misshapen aggregates of beta amyloid protein, along with twisted fibers of the protein tau, are the two major hallmarks associated with the disease. Alzheimer's is the sixth leading cause of death in the United States, according to the Alzheimer's Association.

Researchers injected the brain tissue of a confirmed Alzheimer's patient into mice and compared the results to those from injected tissue of a control without the disease. None of the mice injected with the control showed signs of Alzheimer's, whereas all of those injected with Alzheimer's brain extracts developed plaques and other brain alterations typical of the disease.

"We took a normal mouse model that spontaneously does not develop any brain damage and injected a small amount of Alzheimer's human brain tissue into the animal's brain," said Soto, who is director of the Mitchell Center. "The mouse developed Alzheimer's over time and it spread to other portions of the brain. We are currently working on whether disease transmission can happen in real life under more natural routes of exposure."

UTHealth co-authors of the paper are Rodrigo Morales, Ph.D, postdoctoral fellow, and Claudia Duran-Aniotz, research assistant. Other co-authors are Joaquin Castilla, Ph.D., Basque Foundation for Science, Bilbao, Spain; and Lisbell D. Estrada, Ph.D., Universidad Catolica de Chile, Santiago, Chile. Duran-Anoitz is also a doctoral student at the Universidad de los Andes in Santiago, Chile. Soto, Morales, Castilla and Estrada did a portion of the research at The University of Texas Medical Branch at Galveston.

Comments are welcome.

Monday, October 3, 2011

Frontotemporal Degeneration: Rare Brain Disorder Is Highly Hereditary

Frontotemporal Degeneration: Rare Brain Disorder Is Highly Hereditary

ScienceDaily (Nov. 4, 2009) — New research shows that a rare brain disorder that causes early dementia is highly hereditary. The study is published in the November 3, 2009, issue of Neurology®, the medical journal of the American Academy of Neurology.

The brain disorder, called frontotemporal dementia, is formerly known as Pick's disease and destroys parts of the brain, leading to dementia, including problems with language or changes in behavior and personality. The disease often affects people under the age of 65.

"Knowing your family's health history may be one way for people to better predict their risk of developing dementia," said study author Jonathan Rohrer, MRCP Clinical Research Fellow at the Dementia Research Center at the University College London in the United Kingdom.

For the study, blood was drawn from 225 people who were diagnosed with frontotemporal dementia. The people were asked about family history of dementia and given a score of one through four. A score of one represents a person who had at least three relatives with dementia and an autosomal dominant inheritance, meaning that an affected person has one mutant gene and one normal gene and has a 50-percent chance of passing the mutant gene and therefore the disorder on to their offspring. A score of four represents a person with no family history of dementia.

The study found that nearly 42 percent of participants scored between a one and a 3.5, meaning they had some family history of dementia. However, only 10 percent had an autosomal dominant gene history.

The people in the study also had their DNA tested for five gene mutations thought to cause frontotemporal dementia. Mutations were found in two of the five genes.

"Many people were still found to have a strong family history of dementia even without having any of the five known gene mutations, suggesting that there are still unknown genes that cause frontotemporal dementia," said Rohrer.

"Discovering new genes and gene mutations could provide another key to unlocking the doors to new treatments and prevention strategies for dementia."

The study also found that behavioral problems associated with frontotemporal dementia were the most likely to be hereditary, while language problems were the least likely to be hereditary.

The study is supported by the United Kingdom Department of Health's NIHR Biomedical Research Centers, the Medical Research Council UK and the Alzheimer's Research Trust in the United Kingdom.

Comments are welcome.

Thursday, September 29, 2011

Fish Oil Reviseted

The following is from the Dementia Weekly web site. We are not mice! however, Fish Oil is a very inexpensive supplement. Also, and even better - real fish makes a tasty dinner!

Fish oil researchers are making headlines in Quebec and Rhode Island. Read how DHA in fish oil's omega-3 creates an anti-inflammatory, neuroprotective environment in the brain. In more news, learn why fish oil protects brain volume in 2 critical areas utilized in memory & thinking.
Stroke Severity Reduced By Omega-3s
A diet rich in omega-3s reduces the severity of brain damage after a stroke, according to a study conducted by Université Laval researchers. The team, co-directed by professors Jasna Kriz and Frédéric Calon, showed that the extent of brain damage following a stroke was reduced by 25% in mice that consumed DHA type omega-3s daily. Details of the study can be found on the website of the journal Stroke.
Researchers observed that the effects of stroke were less severe in mice that had been fed a diet rich in DHA for three months than in mice fed a control diet. In mice from the DHA group, they saw a reduction in the concentrations of molecules that stimulate tissue inflammation and, conversely, a larger quantity of molecules that prevent the activation of cell death.
Frédéric Calon of Université Laval's Faculty of Pharmacy, underscored,
"This is the first convincing demonstration of the powerful anti-inflammatory effect of DHA in the brain."
This protective effect results from the substitution of molecules in the neuronal membrane: DHA partially replaces arachidonic acid, an omega-6 fatty acid known for its inflammatory properties.

Jasna Kriz, of Université Laval's Faculty of Medicine, summarized,

"The consumption of omega-3s creates an anti-inflammatory and neuroprotective environment in the brain that mitigates damage following a stroke. It prevents an acute inflammatory response that, if not controlled, is harmful to brain tissue."
Professor Calon believes that this anti-inflammatory effect is likely transferable to humans. He concluded:

"Since DHA is readily available, inexpensive, and reduces the risk of a number of health problems without causing significant side effects, the risk-benefit ratio tends to favor the regular consumption of fish or DHA."
Fish Oil’s Impact On Cognition And Brain Structure
Researchers at Rhode Island Hospital’s Alzheimer’s Disease and Memory Disorders Center have found positive associations between fish oil supplements and cognitive functioning as well as differences in brain structure between users and non-users of fish oil supplements. The findings suggest possible benefits of fish oil supplements on brain health and aging. The results were reported at the recent International Conference on Alzheimer’s Disease, in Paris, France.
The study was led by Lori Daiello, PharmD, a research scientist at the Rhode Island Hospital Alzheimer’s Disease and Memory Disorders Center. Data for the analyses was obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), a large multi-center, NIH-funded study that followed older adults with normal cognition, mild cognitive impairment, and Alzheimer’s Disease for over three years with periodic memory testing and brain MRIs.
The study included 819 individuals, 117 of whom reported regular use of fish oil supplements before entry and during study follow-up. The researchers compared cognitive functioning and brain atrophy for patients who reported routinely using these supplements to those who were not using fish oil supplements.

Daiello reports that compared to non-users, use of fish oil supplements was associated with better cognitive functioning during the study. However, this association was significant only in those individuals who had a normal baseline cognitive function and in individuals who tested negative for a genetic risk factor for Alzheimer’s Disease known as APOE4. This is consistent with previous research.
The unique finding, however, is that there was a clear association between fish oil supplements and brain volume. Consistent with the cognitive outcomes, these observations were significant only for those who were APOE4 negative.
Daiello says,
“In the imaging analyses for the entire study population, we found a significant positive association between fish oil supplement use and average brain volumes in two critical areas utilized in memory and thinking (cerebral cortex and hippocampus), as well as smaller brain ventricular volumes compared to non-users at any given time in the study. In other words, fish oil use was associated with less brain shrinkage in patients taking these supplements during the ADNI study compared to those who didn’t report using them.”
Daiello continues, “These observations should motivate further study of the possible effects of long-term fish oil supplementation on important markers of cognitive decline and the potential influence of genetics on these outcomes.”

...like I said. We are not mice, but might be worth trying now and then.

Comments are welcome.

Tuesday, August 23, 2011

Treatment With Vitamin C Dissolves Toxic Protein Aggregates in Alzheimer's Disease

Treatment With Vitamin C Dissolves Toxic Protein Aggregates in Alzheimer's Disease, but could it work for bvFTD (Frontotemporal Degeneration) also? Ummmmm ...maybe!

It would be a pleasant addition to any diet.
There have been so many outrageous claims made over the years about the benefits of vitamin C that I am very skeptical. It does seem that almost any antioxidant is beneficial in treating tauopathies. Of course, one cannot soak a living brain in orange juice, so a little more research needs to be done on how much, how long, and what forms can be absorbed by humans.

ScienceDaily (Aug. 18, 2011) — Researchers at Lund University have discovered a new function for vitamin C. Treatment with vitamin C can dissolve the toxic protein aggregates that build up in the brain in Alzheimer's disease.
The research findings are now being presented in the Journal of Biological Chemistry.

The brains of people with Alzheimer's disease contain lumps of so-called amyloid plaques which consist of misfolded protein aggregates. They cause nerve cell death in the brain and the first nerves to be attacked are the ones in the brain's memory centre.

"When we treated brain tissue from mice suffering from Alzheimer's disease with vitamin C, we could see that the toxic protein aggregates were dissolved. Our results show a previously unknown model for how vitamin C affects the amyloid plaques," says Katrin Mani, reader in Molecular Medicine at Lund University.

"Another interesting finding is that the useful vitamin C does not need to come from fresh fruit. In our experiments, we show that the vitamin C can also be absorbed in larger quantities in the form of dehydroascorbic acid from juice that has been kept overnight in a refrigerator, for example."

There is at present no treatment that cures Alzheimer's disease, but the research is aimed at treatments and methods to delay and alleviate the progression of the disease by addressing the symptoms.

That antioxidants such as vitamin C have a protective effect against a number of diseases, from the common cold to heart attacks and dementia, has long been a current focus of research.

"The notion that vitamin C can have a positive effect on Alzheimer's disease is controversial, but our results open up new opportunities for research into Alzheimer's and the possibilities offered by vitamin C," says Katrin Mani.

Comments are welcome.

Any Drug Which Controls Brain Cell Death Will Probably Have Potential To Treat FTD

Alzheimer's Disease Drug Treats Traumatic Brain Injury

ScienceDaily (July 14, 2009) — The destructive cellular pathways activated in Alzheimer's disease are also triggered following traumatic brain injury, say researchers from Georgetown University Medical Center (GUMC). They say this finding suggests that novel therapy might successfully target both conditions.

In an oral presentation at the Alzheimer's Association 2009 International Conference on Alzheimer's Disease, the scientists will show that deactivating these pathways in part by using a gamma secretase inhibitor - a class of Alzheimer's disease drugs currently being tested - reduced loss of neurons in animal models of traumatic brain injury and protected the animals against motor and cognitive deficits.

"The goal for both diseases is to prevent neuronal cell death, and this study suggests that one therapy could possibly work for both," says the study's lead author, neuroscientist Mark Burns, PhD, an assistant professor at GUMC.

Both disorders are associated with build-up of beta amyloid, a toxic brain peptide. This substance is commonly found in the brains of elderly patients who died from Alzheimer's disease, but has also been found in a third of traumatic brain injury victims, some of whom are children, Burns says. It is also known that people who experience such a brain injury have a 400 percent increased risk of developing Alzheimer's disease.

Burns says that buildup of beta amyloid occurs in a second wave of damage that follows immediate "necrotic" death of nerve cells after traumatic brain injury. This secondary injury can last months, if not years, resulting in large holes within brain tissue.

Amyloid peptides are produced when a long brain protein known as the amyloid precursor protein (APP) is cut in two by the enzyme beta secretase, and then cut once again by a second enzyme known as gamma secretase. Agents that inhibit the activity of gamma secretase are now being studied as treatment for Alzheimer's disease.

In this study, researchers used mice that were either treated with DAPT, an experimental gamma secretase inhibitor, or mice which were "BACE knock-outs" – so called because they were genetically altered in such a way that they could not produce beta secretase. In unaltered and untreated "normal" mice, brain injury resulted in a rapid accumulation of beta amyloid, along with cognitive and motor deficits. But DAPT and BACE knock-out mice had brain lesions that were as much as 70 percent smaller than control animals and they experienced minimal impairment.

The findings further cement the connection between Alzheimer's disease and traumatic brain injury, Burns says, and show that "modulation of beta and gamma secretase may provide novel therapeutic targets for the treatment of traumatic brain injury."

The study was funded by grants from the National Institutes of Health and by the Klingel Family Foundation. The scientists report no potential financial conflicts in this research. Georgetown University has filed a patent application for the technology involved in this research.

Sunday, July 31, 2011

Point Of No Return - Crossing The Rubicon ...or RUBYKON, as the case may be

The idiom "Crossing the Rubicon" means to pass a point of no return, and refers to Julius Caesar's army's crossing of the river in 49 BC, which was considered an act of insurrection. Because the course of the river has changed much since then, it is impossible to confirm exactly where the Rubicon flowed when Caesar and his legions crossed it. Since someone else already had taken the license plate, I spelled it RUBYKON. A nice plate for a red Rubykon.

Yeseree! That is a trail. The Bracken Fern was as tall as my Jeep.

Affectionately known as, "Ruby"
So I got to thinking. Always dangerous for someone with FTD. Ya never know where it might lead.

I figured I needed a vacation. I also figured I might not be able to take one next year, or the next. My future is very uncertain. So, somehow I got motivated. Actually someone else motivated me to get my butt in gear, and finally make a trip up North into Michigan.

So, my Jeep was coming off its lease. It is expensive, and has a huge carbon footprint. Yeah, but I love it. It is red. It is the most fun I have ever had driving. Well, due to some deceit by a formerly trusted friend, I was no longer able to get the financing approved to refinance my Jeep at the end of its lease. This was unfortunate because it had about $12,000 worth of equity in it. The dealership was more than happy to get it back, and there was no motivation for them to extend me any breaks. They were looking at a hefty profit when they resold it, and I would take the loss.

So, I figured I might as well take my Jeep up into Michigan, go off-roading, and beat the snot out of it before I had to give it back. Seemed like a good plan to me. And so it was. And so I did.

I planned the whole trip myself. I only got lost once - kinda - my GPS had me going in circles for a little while until I figured out that I should do what it was telling me to do, and not what I thought it was telling me to do. Yes, there is a difference between right and left. Round trip I ended up driving about 1500 miles, and only about 60 miles of that could be considered off-road. I got to see a lot of Michigan. I started around the lower end of Manistee National Forest near Fremont, spent a whole day exploring Manistee National Forest near Cadillac, and then headed on up to the Upper Peninsula to the Pictured Rocks area, and the Hiawatha National Forest.

The trip was a total success. I broke my Jeep, and had a great time. I ended up coming home early because the shifter for the 4WD became disconnected from the linkage to the transfer case. In short, my Jeep wasn't a Jeep anymore, so I packed it in. I was so far out in the boonies that the nearest dealership was 450 miles away, and it was about the same distance to get back home. So, that morning I got my feet wet in Lake Superior, that afternoon I was wading in Lake Michigan, and that evening I was floating around in my pool. Long day.

I got back, and figured I had to fix the Jeep. While I had it in to the service center, I decided to test-drive a few new cars. I tried a Compass, and a Liberty, and a couple others. That was enough fore me. They were ...ummmm ...how to put this nicely. Sub-standard? They were definitely NOT a Jeep Wrangler JK 4 door Rubicon!!! I am spoiled. So, I talked to the new car sales person, and she managed to get me financing. It cost me more than I would have liked, but it is the price I had to pay for someone else's actions. Lesson learned. I kept the Jeep. The repairs needed are minor. A bushing fell off the bottom of the shift lever, and a cable became disconnected so I could not shift into 4WD.

I do not know how much longer I will be able to drive. I have discussed this with my doctors. The best evaluation is from my Neurologist. When he saw what I was driving, and that it is a 6-speed manual transmission, his comment was, "You will have trouble driving it, before you can't drive." I think he is probably right. In any case, I am doing OK for now. I am very careful.

So, that is how I spent my Summer vacation. So far... and the best part is that except for gas one can visit the National Parks for free. Camping is allowed almost anywhere as long as you are 200 feet away from the roads. I hope my vacation pictures weren't too boring. I kept the top up on the Jeep because the flies were bad, and the temperature was around 96 degrees with a heat index in the hundreds. I have air conditioning. Sweet Jeep!

Mud! Mud! Gotta love the MUD!!!!

End of the trail. Literally! Had to turn around, but not before a good cigar and a mug of Stout.

Lake Superior. Minor's Castle is the name of the rock formation.

Minor's Falls. The only one that is is legal to hike down to, and get under. Yes I DID!

Lake Superior. I was here in the morning, and home that night.

Comments and questions are welcome.

The Roller Coaster - Medication Update

Yeah! Kinda like this... only FAST!
"Fun is like insurance. The older you get, the more it costs."

I went for 16 days without any medication. This is because of a lapse in my insurance coverage. COBRA is a really expensive pain in the necessity. Everything finally seems to be caught up ...for now.

The first few days were OK. I really didn't notice any change. I was thinking, "Maybe I really don't need to be taking all this stuff anyway."
Hah! Shows what I know.

The "stuff" I am referring to in particular is Aricept 23, Namenda, and Ritalin. Quite a mental cocktail.

Before the first week was over, the changes started. I did not have any noticeable physical withdrawal. Yay! But wait! There's more.

I will try to describe what it felt like to me. Imagine you are on a roller coaster. A really fast, high, furious roller coaster. We have all been there at some time or other. Hanging on for dear life as the coaster careens down and around, and maybe upside down. Slamming our bodies right and left, up and down. Weightless, then extra gravity. It only lasts a few minutes. Then it is over.

What do you remember of the ride?

What kind of trees were nearby. Were there houses. Was it a sunny day? Birds? Who knows. Everything went by to fast to notice. All you can concentrate on is your hands gripping the bar, and the sensations, and maybe forcing yourself to let go now and then, and wave your arms in the air like an idiot. You may remember the coaster. It was probably red. Mine always was.

Well, that is kinda what it was like without the medications. The whole world was coming at me so fast all I could do was hang on. Either that, or I was moving so slowly that it seemed like the whole world was moving faster. Not much difference from my perspective.

I don't remember much of the 16 days I was without my medications. Seriously. When you are on a roller coaster how much of it do you remember afterwards? Not much of what was going on around you. Just you, trying to "get through it."

So it was for me. I obviously am not a roller coaster thrill seeker type. I got through it. My way of coping was to close the doors, and hibernate for most of 2 weeks. I think it was my way of limiting the external stimulus. Cutting down the stress levels. I guess it worked.

So, after 16 days, I got back on all of my medications. I suppose I could have eased back into them, but I figured my body would remember, and I would not have all of the side effects like I did when I first started taking the medications.

I was sorta right. I had a couple rough days, one in particular the day after I started taking all of my medications again. Most of my problems were gastrointestinal. I never made it out the door that second day. I never made it off the couch. I caught up on a lot of TV programs I had recorded. It was fine. I got through it. I really don't think my friends had clue what was going on, and at the time I really couldn't explain it to them.

Being without the medications was very informative. I learned that the Ritalin does help, and that it helps a lot. I was thinking of discontinuing it. It is actually what made things bearable for me. I had an extra months supply, and started taking it after the first week when things got really hard to cope with. The world was coming at me too fast. I took the Ritalin, and the world slowed down, or maybe I sped up. It was as if it anchored me to my surroundings, and I could function.

I also learned that my initiative is worse than a year ago, and my attention deficit is a major impairment. My cognitions didn't change much - I could still do mental arithmetic - but my Dysexecutive Syndrome is probably slightly advanced overall. But I also learned that I could still cope. I got through it.

I have been back on my medications for a couple of weeks now, and things are back to normal. I now realize just how dependent I am on these medications - none of which are approved for FTD. Well ...I approve of them!

Comments and questions are welcome.

Thursday, July 28, 2011

The Keto-Dementia Diet

“What? Ridden on a horse?'
'You're using coconuts!'
'You've got two empty halves of coconuts and you're banging them together!'

                    ~Monty Python

The Dementia Weekly web site has several articles on this diet. I tried working some Coconut Oil into my regular diet last Spring, and will do so again after my next shopping trip. It has no taste, and is not thick or greasy, so it can be added to almost any hot food. It melts at a very low temperature. I gotta repeat this - it has no taste. It floats on top of hot beverages, and that is pretty disgusting no matter what claims are made about it dissolving in coffee. Coffee is water, and oil is oil. Go figure! It would be fine in soup, though.

The Keto-dementia Diet, usually known as the ketogenic diet for people with dementias such as Alzheimer’s, is based on the science of ketosis. Ketogenic diets have been in clinical use for over 80 years.

Glucose is our brains' primary energy source. Like an athlete too weak to run due to hunger, a brain with too little glucose can experience cognitive decline. That means a person will have problems thinking and remembering.

As our brains age, they "burn" glucose less efficiently. Furthermore, research has shown that a drop in glucose metabolism usually occurs in people with dementias such as Alzheimer's. This glucose-drop often occurs years before people begin to exhibit symptoms.

To address this problem, scientists began studying ketones as an alternative energy source to glucose.

In 2008, the medical journal "Neurotherapeutics" published the study, Ketone Bodies as a Therapeutic for Alzheimer's Disease. The groundbreaking research demonstrated the brain's apparent ability to use ketones as an alternative energy source.

With this new evidence regarding ketones' benefits for the ailing brain, scientists began taking a closer look at the "Ketogenic Diet." The ketogenic diet activates the "ketosis" process in our bodies, generating these energy-giving ketones.

Indeed, researchers found the ketogenic diet to have neuroprotective effects, breathing new life into brain cells. In uncontrolled clinical trials and animal studies, the ketogenic diet provided "symptomatic and disease-modifying activity in a broad range of neurodegenerative disorders."(1) This includes:

* Alzheimer’s disease
* Parkinson’s disease
* Traumatic brain injury
* Stroke (Vascular dementia) (1)
* Huntington's Disease(2)
* Lewy Body Dementia(3)

The ketogenic diet is complex, usually involving a professional nutritionist, such as when it is administered for its proven benefits for epileptics. When not strictly supervised or adhered to, it can have undesirable side effects.

To make its benefits more accessible to the millions of people with dementias such as Alzheimer's, the biotechnology company Accera introduced Axona®.

Axona® is a brand-name high-quality FDA-recognized prescription-only medical food. It comes in clean, easy-to-use one-a-day packets. For those who can afford it, clinical trials have shown it to be a promising supplement. At about a hundred dollars a month, though, it is not for everyone.

The most important ingredient in both the ketogenic diet and Axona® seems to be MCTs (Medium Chain Triglycerides). MCTs are one of the quickest and easiest molecules for our liver to convert into ketones. Fortunately, they are available in a variety of foods.

Coconut Oil
Virgin coconut oil is available at health food stores, food co-ops, many grocery stores and even on Amazon.com . It is inexpensive and contains about 60 percent MCTs.

The most famous advocate of coconut oil for dementia is Dr. Mary Newport. Dr. Newport almost gave up hope on treating her husband's Alzheimer's. After doing her own research, she began giving him a daily dose of coconut oil. He showed immediate improvement. After two years of regular use, she has carefully documented that he:

* improved dramatically
* jogs once more
* reads again and remembers what he read
* gets distracted less
* has had a stable MRI for the entire two-year period.

Dr. Newport says, "I do believe that, overall, the use of coconut oil has taken us back in time at least two years. I don't know if we will beat it, but we have at least gotten a reprieve from this disease."

Coconut oil dissolves easily in anything from coffee to hot breakfast cereal. Although it is an ordinary food that does not need a prescription, taking a lot of anything can have side-effects or interactions, so be sure to ask your doctor.

Tuesday, July 12, 2011

Busy Summer, And No Medications - Yipes!

Well, it has been a while since I have written anything. For me it does not seem very long at all. It feels like a week or maybe a little more. It is only when I look at the calendar, and see the date of my last post that I realize it has been over a month. That is how what I refer to as "time compression" works. Things in the past don't seem as far back as they should because so much in between is "Missing Time".

There are several reasons I have not written as often. First, it is Summer, and I am lazing in the pool, gardening, and enjoying the nice weather.

Second, Nemanda. This is one very strong medication. Once I reached the full dose around the beginning of June, I felt "stoned" all the time. I was content to laze in the pool, and watch the Fabbits, and Hummingbirds from my deck. I was woozy most of the time, and very unsteady walking. I did not feel comfortable driving much at all. After about a month it got better. As with the Aricept, the side-effects went away as my body got used to operating under the influence of the drug.

Third, my insurance lapsed for a few weeks when I had to switch to COBRA, and I did not take any medications at all. No Aricept, Nemanda, or Ritalin. Cold Turkey! I was only without medications for 16 days, but it seems to me much longer. The opposite of "Time Compression", but I remember very little from those 16 days so there is still plenty of "Missing Time". Time just dragged on, and on. I was incapable of doing any serious writing during those couple weeks.

I started my medications again yesterday, and am hoping my body will remember them so I won't have to endure all of the side-effects again. I want to write more on this whole incident with the insurance in the near future.

Fourth, I have had a lot of pain in my right foot. I guess it is time for me to finally see a doctor about it because it is starting to limit the few activities I have.

For all of those who were concerned because I hadn't written in a while, "Thank You!" I am as well as can be expected, and maybe even better.

Some days are better than others.

Comments and questions are welcome.

Monday, June 6, 2011

Cancer Drug SAHA Holds Potential to Fight Frontotemporal Dementia

Dr. Joachim Herz Dr. Joachim Herz

I found this article at the Dementia Weekly website, and thought it may hold some real promise.

DALLAS  – A drug already approved for people with cancer shows early potential as a therapy for a common form of dementia, UT Southwestern Medical Center researchers report.

"Suberoylanilide hydroxamic acid (SAHA) holds promise as a first-generation drug for the prevention and treatment of familial frontotemporal dementia (FTD), a progressive, inherited neurodegenerative disease for which there is no treatment," said Dr. Joachim Herz, director of the Center for Alzheimer's and Neurodegenerative Diseases and the study's senior author.

"SAHA is already approved for clinical use in an unrelated condition, which should make it easier to move quickly to human trials," added Dr. Herz, professor of molecular genetics and neuroscience at UT Southwestern.

FTD – usually diagnosed around age 60 – trails only Alzheimer's disease among non-elderly dementias. The as-yet untreatable condition is marked by a progressive deterioration in decision-making ability, behavioral control and/or language skills.

In a study available online and in the current issue of the Journal of Biological Chemistry, UT Southwestern researchers from the Alzheimer's Center, the Harold C. Simmons Comprehensive Cancer Center and the Protein Chemistry Technology Center showed that SAHA increased the cell-signalling protein progranulin (GRN) levels in a dose-dependent way in cultured mouse cells and also demonstrated that it restored near-normal GRN production in cells from human subjects with FTD.

Up to 25 percent of patients with FTD have an inherited form of the disease that is thought to be caused by one of several genetic mutations that reduce production of GRN, Dr. Herz said. Because familial FTD patients inherit one working copy of the GRN gene and one mutated one, the researchers wanted to identify a drug that would make the working copy of the gene work harder.
Dr. Gang YuDr. Gang Yu
In an attempt to move as quickly as possible from basic science to clinical trials, the team established a method to quickly screen 1,200 drugs that already had Food and Drug Administration approval. SAHA emerged as the most active of the chemicals they screened, said lead author and graduate student Basar Cenik, who works in the laboratories of both Dr. Herz and co-senior author Dr. Gang Yu, associate professor of neuroscience.

SAHA is in a class of drugs called histone deacetylase inhibitors, and is approved for use in a cancer called cutaneous T-cell lymphoma.
"We found a drug that can overcome the chemical deficiency associated with the condition, and we showed that it worked in cells taken from humans with FTD," Dr. Yu said.

It is not yet known if the drug will efficiently cross the blood-brain barrier, a biologically protective system that keeps many chemicals from reaching the brain, Dr. Yu said. The next research step, he said, will be to screen larger chemical libraries in an effort to find other promising GRN-stimulating drugs for human trials.

Drs. Herz and Yu are both investigators for the Consortium for Frontotemporal Dementia Research and are working toward human trials with that national network, which is based at the University of California at San Francisco.

Comments welcome.

Monday, May 23, 2011

Public Citizen Wants FDA to Ban Aricept 23

I found this article on the Dementia Weekly website. I cannot say that I agree since I have seen some dramatic results from taking Aricept 23. Yes, there are side effects, but most of the the side-effects go away after a few weeks. Why should some interfering pseudo do-gooders want to make it more difficult for those of us impacted by dementia to make our own decisions. Nobody is forcing anyone to take Aricept. We need to have more, not fewer, choices.  If it works for even a few of us it should be available.

They are not saying that Aricept does not work. They are just saying that there isn't a benefit to taking 23mg over 10mg. I must disagree. In my case I think I did see a difference. Of course Aricept is not approved for FTD anyway, so I guess that doesn't count.

WASHINGTON, D.C. – A drug used to treat moderate or severe cases of Alzheimer’s disease should be removed from the market immediately because of its risk of serious adverse effects and its lack of effectiveness, Public Citizen and an eminent geriatrician from Johns Hopkins said in a petition filed today with the Food and Drug Administration (FDA).

Donepezil, also known as Aricept, has been approved by the FDA in a dose of 5 to 10 milligrams (mg) for patients with mild to moderate cases of Alzheimer’s disease and in a dose of 10 or 23 mg for patients with moderate to severe Alzheimer’s. Public Citizen is calling for the 23-mg dose to be immediately pulled from the market.

“Data show that the 23-mg dose of donepezil is significantly more toxic than the 10-mg dose,” said Dr. Sidney Wolfe, director of Public Citizen’s Health Research Group. “Combined with its lack of improved clinical benefits, this leads to only one conclusion: that the 23-mg dose should be immediately withdrawn from the market.”

Public Citizen is also asking the FDA to warn doctors and patients against taking 20 mg of the drug (two 10-mg pills) a day, even if Aricept 23 is removed from pharmacy shelves.

Dr. Thomas Finucane, professor of medicine in the Division of Gerontology and Geriatric Medicine at The Johns Hopkins University School of Medicine and staff physician at the Johns Hopkins Bayview Medical Center, stated that “Cholinesterase inhibitors such as Aricept have gained multibillion-dollar success due primarily to two factors: the understandable desperation of those who care for patients with Alzheimer’s disease, and a relentless promotional campaign by drug companies.” Finucane is a co-petitioner with Public Citizen to ban Aricept 23.

“When clinicians consider whether to initiate a therapeutic trial of a largely ineffective drug, the risk of harm should be a prominent consideration,” Finucane said. “The clearly increased risk of harm from Aricept 23-mg compared to Aricept 10-mg is so great, coupled with the lack of any evidence of improved benefit, that I believe it should not have been approved for sale to the families and caregivers of Alzheimer patients.”

The only clinical trial of donepezil submitted to the FDA for approval of the 23-mg dose compared it to the 10-mg dose and failed to prove that the higher dose was more effective. In three of four tests, on either a cognitive or functional level, there was no significant difference between the 10- and 23-mg doses. In the fourth test, the improvement over the 10-mg dose was only two points on a 100-point scale, which is not clinically important, Wolfe said.

Increased adverse effects of the 23-mg dose of donepezil compared to the 10-mg dose include a slowed pulse rate, nausea, vomiting, diarrhea, urinary incontinence, fatigue, dizziness, agitation, confusion and anorexia. Vomiting – which occurred more than 3.5 times as often in patients taking the 23-mg dose than those taking the 10-mg dose – is a particularly dangerous side effect for patients with Alzheimer’s disease because it can lead to pneumonia, massive gastrointestinal bleeding, esophageal rupture and even death, Wolfe said.

Overall, patients taking the 23-mg dose stopped taking the drug because of adverse effects more than twice as often as those taking the 10-mg dose. Additionally, because of the drug’s very long half-life, it can stay in patients’ systems for about two weeks after they stop taking the drug. So, those who suffered adverse effects may not have immediate relief after they stop treatment, Wolfe said.

“With no evidence of an added advantage in benefit to patients, the clear increase in risk should have been more than adequate grounds for denying approval, a conclusion reached by both the FDA medical officer and statistician,” Wolfe said. “It is inexcusable that the FDA approved this higher dose. Its prompt removal would belatedly fulfill the agency’s mission to allow only drugs whose benefits outweigh their risks to be marketed.”

Here is a video of this story.

Comments and questions are welcome.

Monday, May 16, 2011

Niacin - Vitamin B3 and Dementia - Alternative Medicine

Vitamin B3 Reduces Alzheimer's Symptoms, Lesions: Clinical Trial On Nicotinamide Effect In Alzheimer's Patients

ScienceDaily (Nov. 5, 2008) — An over-the-counter vitamin in high doses prevented memory loss in mice with Alzheimer's disease, and UC Irvine scientists now are conducting a clinical trial to determine its effect in humans.

Nicotinamide, a form of vitamin B3, lowered levels of a protein called phosphorylated tau that leads to the development of tangles, one of two brain lesions associated with Alzheimer's disease. The vitamin also strengthened scaffolding along which information travels in brain cells, helping to keep neurons alive and further preventing symptoms in mice genetically wired to develop Alzheimer's.

"Nicotinamide has a very robust effect on neurons," said Kim Green, UCI scientist and lead author of the study. "Nicotinamide prevents loss of cognition in mice with Alzheimer's disease, and the beauty of it is we already are moving forward with a clinical trial."

The study appears online Nov. 5 in the Journal of Neuroscience.

Nicotinamide is a water-soluble vitamin sold in health food stores. It generally is safe but can be toxic in very high doses. Clinical trials have shown it benefits people with diabetes complications and has anti-inflammatory properties that may help people with skin conditions.

Nicotinamide belongs to a class of compounds called HDAC inhibitors, which have been shown to protect the central nervous system in rodent models of Parkinson's and Huntington's diseases and amyotrophic lateral sclerosis. Clinical trials are underway to learn whether HDAC inhibitors help ALS and Huntington's patients.

In the nicotinamide study, Green and his colleague, Frank LaFerla, added the vitamin to drinking water fed to mice. They tested the rodents' short-term and long-term memory over time using water-maze and object-recognition tasks and found that treated Alzheimer's mice performed at the same level as normal mice, while untreated Alzheimer's mice experienced memory loss.

The nicotinamide, in fact, slightly enhanced cognitive abilities in normal mice. "This suggests that not only is it good for Alzheimer's disease, but if normal people take it, some aspects of their memory might improve," said LaFerla, UCI neurobiology and behavior professor.

Scientists also found that the nicotinamide-treated animals had dramatically lower levels of the tau protein that leads to the Alzheimer's tangle lesion. The vitamin did not affect levels of the protein beta amyloid, which clumps in the brain to form plaques, the second type of Alzheimer's lesion.

Nicotinamide, they found, led to an increase in proteins that strengthen microtubules, the scaffolding within brain cells along which information travels. When this scaffolding breaks down, the brain cells can die. Neuronal death leads to dementia experienced by Alzheimer's patients.

"Microtubules are like highways inside cells. What we're doing with nicotinamide is making a wider, more stable highway," Green said. "In Alzheimer's disease, this highway breaks down. We are preventing that from happening.

Abstract of original article:
Nicotinamide Restores Cognition in Alzheimer's Disease Transgenic Mice via a Mechanism Involving Sirtuin Inhibition and Selective Reduction of Thr231-Phosphotau

Memory loss is the signature feature of Alzheimer's disease, and therapies that prevent or delay its onset are urgently needed. Effective preventive strategies likely offer the greatest and most widespread benefits. Histone deacetylase (HDAC) inhibitors increase histone acetylation and enhance memory and synaptic plasticity. We evaluated the efficacy of nicotinamide, a competitive inhibitor of the sirtuins or class III NAD+-dependent HDACs in 3xTg-AD mice, and found that it restored cognitive deficits associated with pathology. Nicotinamide selectively reduces a specific phospho-species of tau (Thr231) that is associated with microtubule depolymerization, in a manner similar to inhibition of SirT1. Nicotinamide also dramatically increased acetylated α-tubulin, a primary substrate of SirT2, and MAP2c, both of which are linked to increased microtubule stability. Reduced phosphoThr231-tau was related to a reduction of monoubiquitin-conjugated tau, suggesting that this posttranslationally modified form of tau may be rapidly degraded. Overexpression of a Thr231-phospho-mimic tau in vitro increased clearance and decreased accumulation of tau compared with wild-type tau. These preclinical findings suggest that oral nicotinamide may represent a safe treatment for AD and other tauopathies, and that phosphorylation of tau at Thr231 may regulate tau stability

A general dose of 1,000 milligrams taken three times a day is recommended - this dose is actually the "human equivalent" of the amount given to the mice who recovered from the symptoms of Alzheimer's in the study mentioned above.

All B Vitamins are not the same. Another study showed B vitamins were inneffective which included supplementation with folic acid and vitamins B6 and B12 for 18 months in 409 individuals with mild to moderate Alzheimer's disease. "Participants were randomly assigned to two groups of unequal size; to increase enrollment, 60 percent were treated with high-dose supplements and the remaining 40 percent treated with identical dosages of placebo. A total of 340 participants (202 in active treatment group and 138 in placebo group) completed the trial while taking study medication. Cognitive abilities were measured via testing with the Alzheimer Disease Assessment Scale (ADAS-cog).

The researchers found that the ADAS-cog score did not differ significantly between treatment groups, but that symptoms of depression were more common in the high-dose supplement group.

"Our study does not support the treatment of individuals with mild to moderate Alzheimer's disease and normal vitamin levels with B vitamin supplements," the authors conclude." This study did not include vitamin B3m only B6 and B12.

Vitamin B3 (Niacin)
Vitamin B3 is one of 8 B vitamins. It is also known as niacin (nicotinic acid) and has 2 other forms, niacinamide (nicotinamide) and inositol hexanicotinate, which have different effects from niacin.

All B vitamins help the body to convert food (carbohydrates) into fuel (glucose), which is "burned" to produce energy. These B vitamins, often referred to as B complex vitamins, also help the body metabolize fats and protein. B complex vitamins are necessary for healthy skin, hair, eyes, and liver. They also help the nervous system function properly.

Niacin also helps the body make various sex and stress-related hormones in the adrenal glands and other parts of the body. Niacin is effective in improving circulation and reducing cholesterol levels in the blood.

All the B vitamins are water-soluble, meaning that the body does not store them.

You can meet all of your body's needs for B3 through diet; it is rare for anyone in the developed world to have a B3 deficiency. In the United States, alcoholism is the prime cause of vitamin B3 deficiency.

Symptoms of mild deficiency include indigestion, fatigue, canker sores, vomiting, and depression. Severe deficiency can cause a condition known as pellagra. Pellagra is characterized by cracked, scaly skin, dementia, and diarrhea. It is generally treated with a nutritionally balanced diet and niacin supplements. Niacin deficiency also results in burning in the mouth and a swollen, bright red tongue.

Very high doses of B3 (available by prescription) have been shown to prevent or improve symptoms of the following conditions. However, taken at high doses niacin can be toxic, so you should take doses higher than the Recommended Daily Allowance only under your doctor's supervision. Researchers are trying to determine if inositol hexanicotinate has similar benefits without serious side effects, but so far results are preliminary.

Because of the potential for side effects and interactions with medications, you should take dietary supplements only under the supervision of a knowledgeable health care provider.

High doses (50 mg or more) of niacin can cause side effects. The most common side effect is called "niacin flush," which is a burning, tingling sensation in the face and chest, and red or "flushed" skin. Taking an aspirin 30 minutes prior to the niacin may help reduce this symptom.

At the very high doses used to lower cholesterol and treat other conditions, liver damage and stomach ulcers can occur. Your health care provider will periodically check your liver function through a blood test.

People with a history of liver disease or stomach ulcers should not take niacin supplements. Those with diabetes or gallbladder disease should do so only under the close supervision of their doctor.

Niacin should not be used if you have gout.

Taking any one of the B complex vitamins for a long period of time can result in an imbalance of other important B vitamins. For this reason, it is generally important to take a B complex vitamin with any single B vitamin.
Possible Interactions:

If you are currently taking any of the following medications, you should not use niacin without first talking to your health care provider.

Antibiotics, Tetracycline -- Niacin should not be taken at the same time as the antibiotic tetracycline because it interferes with the absorption and effectiveness of this medication. (All vitamin B complex supplements act in this way and should therefore be taken at different times from tetracycline.)

Aspirin -- Taking aspirin before taking niacin may reduce flushing associated with this vitamin, but should only be done under your doctor's supervision.

Anticoagulants (blood thinners) -- Niacin may make the effects of these medications stronger, increasing the risk of bleeding.

Blood Pressure Medications, Alpha-blockers -- Niacin can make the effects of medications taken to lower blood pressure stronger, leading to the risk of low blood pressure.

Cholesterol-lowering Medications -- Niacin binds bile-acid sequestrants (cholesterol-lowering medications such as colestipol, colesevelam, and cholestyramine) and may decrease their effectiveness. For this reason, niacin and these medications should be taken at different times of the day.

Recent scientific evidence suggests that taking niacin with simvastatin (a drug that belongs to a class of cholesterol-lowering medications known as HMG-CoA reductase inhibitors, or statins), appears to slow down the progression of heart disease. However, the combination may also increase the likelihood for serious side effects, such as muscle inflammation or liver damage.

Diabetes Medications -- Niacin may increase blood glucose (sugar) levels. People taking insulin, metformin, glyburide, glipizide, or other medications used to treat high blood sugar levels should monitor their blood sugar levels closely when taking niacin supplements.

Isoniazid (INH) -- INH, a medication used to treat tuberculosis, may lower levels of niacin in the body and cause a deficiency.

Nicotine Patches -- Using nicotine patches with niacin may worsen or increase the risk of flushing associated with niacin.

Alternative Names:
Inositol hexaniacinate; Niacin; Niacinamide; Nicotinamide; Nicotinic acid

So, maybe I am grasping at straws, but adding a Niacin Supplement seems like it couldn't hurt, and may help. Once again, as with the Pomegranate Juice mentioned in another post, there is some evidence in the research of a recovery, and clearance of the tau protein clumps - at least if you happen to be a genetically-altered mouse. The jury is still out for us human-folk. I am not going to sit around and wait for the verdict. This morning I washed my 1000 mg of B3 down with a nice cold glass of Pomegranate Juice. Something seems to be working. I feel good.

Everything here is my account of what happened to me, or my interpretation of stuff. Every case of FTD is different. Keep in mind as you read this that the person who wrote this has Frontotemporal Degeneration. That would be ME.  Medical Disclaimer.

Comments and questions are welcome.

Tuesday, May 10, 2011

Namenda and Aricept

What follows is a little information I found on Namenda(Memantine).
This starter pack increases the dosage over the first month
I started taking it about 2.5 weeks ago using a starter pack I received from my Neurologist. So far I have not had any severe side-effects other than being a little "woozy" at times. From what I can find in the research a combination of Aricept (Donepezil) and Nemanda (Memantine) is more effective than taking either one of them alone. Though some improvement of the symptoms may be expected, the main reason I am taking this combination is to slow the disease progress.

A recent research study was being conducted investigating the effectiveness of the drugs Aricept and Namenda in treating Alzheimer's disease. The study shows that both drugs combine to slow down the degeneration caused by Alzheimer's to its patients. After only a year's treatment, the test subjects indicate a reduction in the progress of the disease with the patients not exhibiting any side-effects from the combination.

The researchers report that the combination of the two drugs is more effective in slowing memory and intellectual function degradation than taking either one of the two drugs or none at all. The study shows how the mix of cholinesterase inhibitors like Aricept, Exelon and/or Razadyne and the drug Namenda (Memantine) taken by patients markedly slows down the rate of memory function decline better than those receiving only a single type of cholinesterase inhibitor or even no drug at all.

In earlier stages of the disease, Alzheimer patients are most commonly treated with a single type of cholinesterase inhibitor. Depending on the diagnosis, it can be either Aricept, Exelon or Razadyne. On the other hand, for advanced stages of the disease are typically treated with the medicine Namenda.

The research was conducted on more than 350 patients in a span of 15 years beginning 1990. The patients were separated into three groups with varying treatments. The first group of more than a hundred patients wasn't treated with any medications while the second group received an FDA approved cholinesterase inhibitor. The last group was treated with the inhibitor augmented with memantine, a drug that aids patients and allows them to think better. Every 2 1 years the patients are given tests that indicate their mental abilities as well as their capability to perform normal daily tasks. Results clearly show a significant decrease in the rate of decline for the third group.

The research was still incomplete. However, since during the time of testing, only cholinesterase inhibitors were the most commonly used and mematine was not tested by itself.

Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial.
Tariot PN, Farlow MR, Grossberg GT, Graham SM, McDonald S, Gergel I; Memantine Study Group.
Source: Department of Psychiatry, University of Rochester Medical Center, Monroe Community Hospital, Rochester, NY 14620, USA. pierre_tariot@urmc.rochester.edu. JAMA. 2004 Jan 21;291(3):317-24.

Memantine is a low- to moderate-affinity, uncompetitive N-methyl-D-aspartate receptor antagonist. Controlled trials have demonstrated the safety and efficacy of memantine monotherapy for patients with moderate to severe Alzheimer disease (AD) but no controlled trials of memantine in patients receiving a cholinesterase inhibitor have been performed.

The change in total mean (SE) scores favored memantine vs placebo treatment for SIB (possible score range, 0-100), 0.9 (0.67) vs -2.5 (0.69), respectively (P<.001); ADCS-ADL19 (possible score range, 0-54), -2.0 (0.50) vs -3.4 (0.51), respectively (P =.03); and the CIBIC-Plus (possible score range, 1-7), 4.41 (0.074) vs 4.66 (0.075), respectively (P =.03). All other secondary measures showed significant benefits of memantine treatment. Treatment discontinuations because of adverse events for memantine vs placebo were 15 (7.4%) vs 25 (12.4%), respectively.

In patients with moderate to severe AD receiving stable doses of donepezil, memantine resulted in significantly better outcomes than placebo on measures of cognition, activities of daily living, global outcome, and behavior and was well tolerated. These results, together with previous studies, suggest that memantine represents a new approach for the treatment of patients with moderate to severe AD.

Treatment Effect Size of Memantine Therapy in Alzheimer Disease and Vascular Dementia

Smith, Matthew BASc*; Wells, Jennie MSc, MD†; Borrie, Michael MB, ChB

The purpose of this paper is to assess the clinical relevance of the significant results reported in clinical trials of memantine therapy for Alzheimer disease (AD) and vascular dementia. We sought to understand what clinically detectable changes would be evident to the patient with dementia, their caregivers, and the treating physician during a trial of memantine therapy. A literature search was performed on MedLine, PsycInfo, and the Cochrane database. The statistically significant findings from the memantine literature were reviewed using treatment effect size as a measure of clinical meaningfulness. There have been 3 phase 2 studies of memantine in dementia, and 6 phase 3 studies published as of August 1, 2005. Of the 6 published phase 3 trials of memantine in dementia; 2 were in mild-moderate vascular dementia, 1 in mild-moderate AD, 2 in moderate-severe AD, and 1 in severe dementia (both AD and vascular dementia). The most convincing evidence of a clinically meaningful treatment effect of memantine therapy is in the moderate-severe AD patient population. Cognition, as measured by the Severe Impairment Battery, had an effect size of 0.32 and 0.49 in the 2 published trials, indicating a small-to-medium effect of the medication. Global, functional, and behavioral scales also showed a small-to-medium response to memantine.

Everything here is my account of what happened to me, or my interpretation of stuff. Every case of FTD is different. Keep in mind as you read this that the person who wrote this has Frontotemporal Degeneration. That would be ME.  Medical Disclaimer.

Questions and Comments are welcome.

Friday, April 22, 2011

Progress - A year Later - Aricept And My bvFTD

It Has Been A Year Since I Was Diagnosed With Frontotemporal Degeneration (Dementia), bvFTD

Can it really dissolve tau clumps?
I have not written anything this month. It isn't because I didn't want to, and it isn't because I didn't have anything to say. For the past several weeks it has been more difficult than usual to get motivated. I have been keeping busy doing other things, but that is no excuse. Motivation, initiating actions, and "doing things" are my major behavioral symptoms. I also tend to be reclusive, and not answer my phone or stay in contact with others. I may go a couple weeks without much contact with other people. If a few close friends did not take the initiative and keep in contact with me, I probably would not talk to, or see, anyone at all. All of these symptoms seem to have changed quickly and be more severe over the past few weeks.


I have a theory. Aricept!

The main reason that Aricept is not approved for use in people with bvFTD is because it can make the behavioral symptoms of FTD worse. Since I am now taking Aricept 23, the highest recommended dosage for someone with advanced Alzheimer's Disease, it is a pretty good bet that it is making my behavioral symptoms more pronounced.

All of the physical side-effects have gone away. I occasionally feel a little dizzy, but that is very likely due to a blood pressure medication I take (Enalapril), and not the Aricept 23. Once in a while I have some minor gastrointestinal distress, but again that is probably from something else.

The purpose of my taking the Aricept is to slow, or arrest, the progression of my FTD
. Hopefully it will, but I have no way to evaluate that in the short term. Only time will tell. My neurologist is hopeful, as is my family doctor.

An unexpected benefit of taking the Aricept is that my Executive Functions have improved tremendously. A year ago I was totally incapable of doing even the simplest mental arithmetic. Today I am able to add, and subtract, and do simple mental calculations. I have no way to objectively test it, but my overall thinking is improved. I feel like I am sharper, and more like my "old self".

I am reading a book! OK, this isn't a big deal. I have (had?) always been a reader. Sometimes a couple of books a week. The last book I tried to read was one I started in November of 2008. I finally gave up on it about a year-and-a-half later! I was so frustrated, I threw it in the trash. I simply was not capable of concentrating, and following the complexities of the story. Of course at the time I had no idea why.

I am currently reading, and enjoying, a novel in a continuing science fiction series I started years ago. I am having no problems concentrating, or following the plot. The only difference I see is that I tend to read for shorter periods at a time than I used to. But ...I am reading a book!

A year ago I was totally dependent on making lists, and reminders, to do everything. I still use lists, and make reminders for things, but I am not nearly as dependent on them as I was last year at this time. That may be partly because I have developed a daily routine, but I think I am remembering things much better.

So, it has been almost a year to the day since my diagnosis of Behavioral Variant Frontotemporal Degeneration (Dementia). In my own subjective evaluation, my behavioral symptoms are marginally worse, and my cognitive functions are markedly improved. With bvFTD everything is a trade-off. The only halfway objective evaluation I have is from the few friends who still take the initiative to keep in contact with me. They all say they have seen a huge difference, and that I seem much more like my "old self". A good friend did observe recently that I seem to be having some noticeable ADHD-like symptoms. She said I tend to skip around more in my conversations - enough so that she noticed a change.

I think that something I am doing is working. Maybe it is the Aricept, and maybe it is the other supplements I am taking. In any case, I am not giving up. I even drink some of that awful pomegranate juice every now and then.

Some days are better than others, but there are more good days than bad days. I think a year ago it was the other way around.

Comments and questions are welcome.

Friday, April 15, 2011

WOW! Over 15,000 visits.

There were visitors from the following countries in the past month. Thanks for reading!

United States, Australia, Canada, United Kingdom, India, France, Germany, New Zealand, Malaysia, Pakistan, Switzerland, Slovenia, Netherlands, Brazil, Italy, Turkey, Greece, Sweden, Latvia, Chile, Russia, Saudi Arabia, South Africa, Spain, Indonesia, Armenia, Ireland, Georgia, Fiji, Belarus, El Salvador, Lebanon, Poland, Denmark, Bulgaria, Taiwan, Colombia, Philippines, Nigeria, Qatar, Japan.

What strikes me is that we are not alone. For a disease which is supposedly so rare, we are all over the world, and we are many. Too many! We are Legion!

Saturday, March 26, 2011

Aricept - Aricept 23 and My bvFTD - Update 2

More about Aricept (Donepezil) 23, the benefits, and my side effects.

“The reason people find it so hard to be happy is that they always see the past better than it was, the present worse than it is, and the future less resolved than it will be”     ~Marcel Pagnol

"How poor are they that have not patience! What wound did ever heal but by degrees?"    ~William Shakespeare

First a short review from my previous post about taking Aricept . I started taking Aricept (Donepezil) 5 mg on September 13, 2010. I increased the dosage to 10 mg after about 6 weeks, and on December 13, 2010, I increased the dosage to 23 mg. My Neurologist is very supportive of this treatment, and reports having very good results in other patients with FTD.

Though not approved for use with bvFTD, Aricept is frequently prescribed off-label. It has a large enough effect on cognition that it is a highly sought-after drug by students taking exams such as the BAR, or Medical Boards. Well, if the wannabe doctors are taking it to help pass their exams there is probably something to it. That is worth more than a pill manufacturer's advertising any day.

For the first few days at the lowest dosage of 5mg I did not notice any side effects, or any improvement. Then I developed a sore throat, and a head cold. This actually may have been a side effect, but there is really no way to tell. By Thursday I had insomnia, and nausea. These are definitely side effects of the Aricept. Though I did not seem to have any adverse behavioral issues, I did have some gastrointestinal problems when I increased the dosage to 10mg. The most bothersome of which eventually was heartburn. The insomnia was not too bad to cope with, but the itching was horrible, and almost caused me to discontinue taking the drug. It started suddenly on the bottoms of my feet one night, and then got worse. Much worse! I cannot express in words how severe the itching was - think poison ivy on top of mosquito bites... and add a few chiggers! Then multiply by two! Everywhere! It moved around. Then, after a particularly uncomfortable drive back from chasing Elk around Pennsylvania, the itching abruptly stopped. So far it has not recurred, but it was a miserable couple of weeks.

Overall most of the side effects lasted about 6 - 10 weeks after each dosage increase, but were considerably more manageable near the end of that period. There may still be a little nausea and insomnia now and then, but that may have nothing to do with the Aricept because of some other medications I occasionally take which also can cause both nausea and insomnia. In any case it does not happen often, doesn't last more than a few minutes, and is not severe.

So, back on December 10, 2010, with the support of my neurologist, I increased the dosage to see if I could tolerate the higher 23 mg dosage of Aricept without having a return of the adverse side effects. It is now the end of March 2011. I have been taking the higher dosage Aricept for more than 12 weeks, and "Yes!" - there are side-effects!

Just like when I first started taking Aricept, I got sick again. I had Strep Throat, and then a couple of head colds. I have a runny nose most of the time - kinda like a slight case of hay-fever, but no sneezing or itchy eyes. The runny nose is listed as a pretty common side effect, so is to be expected. I mostly felt pretty lousy for about 5 weeks catching one thing after another, and still have a slight cough. I even got a skin infection on my nose that lasted a full 2 weeks. Looked pretty awful, but was nothing serious. It is finally healing, and should be gone in another few days. It seems that Aricept really gives your immune system a challenge fighting off infections of any kind. I have had more sickness in the past few months than I have in the past 10 years.

I also have the same gastrointestinal problems with the Aricept 23 as when I first started taking Aricept 5mg, but the nausea is not as severe, and the rest is worse. I don't want to dwell on it, but constipation and diarrhea can occur all in the same day, or for a few days at a time. Sometimes unpleasant, but something I can tolerate. It is getting better, but is still unpredictable.

For a couple of weeks I had some pretty bad incidents of vertigo. The worst was one morning when I actually fell down in the shower. How trite is that? At least I didn't break a hip or anything. I just got dizzy, grabbed onto the sliding door of the tub for balance, and gradually blacked out and slid-half-fell into the tub as the shower door rolled open. OK, so maybe it wasn't the best thing to grab on to, but it was all I had within reach at the time. I was a little sore the next day, but not bruised. It shook me up though, and made me very careful. At least a couple other times I had to sit down, or fall down. I spoke to my Neurologist about it on the insistence of my then girlfriend (actually, she told him all about it), and his advice was, and I quote, to "Be more careful!", and "don't worry! It will go away." Gotta like that guy ; )

Another side-effect is blurred vision
. This is rather subtle. I noticed it when I increased my dosage to 10mg because one day I walked outside onto my deck, and the morning was clear. Everything looked sharp. It was then that I realized that I had been having blurred vision, and just didn't notice it. Well, I have it again with the 23mg dose of Aricept. It isn't very bad, but when I am driving, the street signs are a little blurry and harder to read. This is already getting better, and may be completely gone already.

I forgot to mention, I have also gained about 10 pounds since I started taking Aricept. It seems that no matter what I eat, and even if I severely cut down on my calories, I cannot seem to lose this extra weight. Both "Weight Gain", and "Weight Loss", are listed as known side-effects of taking Aricept, so my guess is that my weight gain is related. I have also been taking Ibuprofen, and that can cause a weight gain also, but my best guess is that it is the Aricept. Though I am still at an acceptable weight for my height, I don't like the extra pounds around my middle. But hey! Even though my brain is turning to Lime Jello - I am still "lookin' good"!

According to the research I found, the biggest problem with taking Aricept with bvFTD is the possibility of it making the behavioral symptoms worse. This is difficult for me to evaluate in myself, but I may notice a slight increase in some of my behavioral symptoms. I think I may be having even more difficulty than before initiating actions which translates into just "doing stuff", or getting things done. I am even better than before at procrastinating. Thinking about doing something is just as good as actually doing it. Part of the symptom is that I am happy not doing stuff, so though frustrating after-the fact sometimes, it hasn't been horrible. I still manage to go shopping, and pay the bills on time ...mostly. My attention issues may also be slightly worse. Of course, that may all be due to the normal progression of my disease. There is no way for me to tell for sure.

So, except for some insomnia, and gastrointestinal distress occasionally, I think I am doing well taking the Aricept 23. Some may ask, "Why put up with all the discomfort?" The answer is that for me the benefits far outweigh the minor inconvenience of the side-effects.

As I mentioned in my earlier post, some beneficial changes in me that I and others have noted in the first 12 weeks when I started taking Aricept included: being able to do mental math again, not using a daily to-do list, quicker thinking and speech. I am generally more like my "old self".  All of those benefits have continued, or even improved with the increased dosage.

I still don't really have too many ways to objectively evaluate any benefits. I can still say that without a doubt I feel like my thinking is sharper, and my cognition has improved. Subjectively I think I have seen a huge improvement regarding my Dysexecutive Syndrome, and maybe a slight improvement in attention. As I recounted in my earlier post, the only objective test is that I can now add a couple numbers in my head, and do other mental math. The example I gave then was: "I was at a store a couple days ago, and as I was being checked out I was adding the stuff up in my head as it was being tallied into the cash register. When the total was given, I was confident enough in my math capability to question it because it was about $22 higher than what I had added it up to be. I was right! I had been double charged for a bag of a hundred wine corks!"

Additionally, I was out counting frogs again last week. It is finally Spring, or it was there for a few days at least, and the frogs were happily singing. At the end of the count, I tallied up the sheet. My friend, whom I have been counting frogs with for the past 10 years was astounded. According to her, last year I was unable to tally up the count sheets at all, and had great difficulty with even the simplest arithmetic. I zipped through the sheet easily last week totaling the counts. It seemed effortless to me, and I loved it! It made me feel really good to see such a positive change.

I could not add up the tally sheet a year ago, and another person also noticed the change! So, in my opinion, Aricept is helping. Aricept is helping a lot! I am also still taking a couple of herbal supplements as well, specifically Ginkgo and Melatonin. I strongly believe that the combination of the Ginkgo and the Aricept is having a huge impact. The two have been shown to interact in numerous studies, and as soon as I started taking the Ginkgo Biloba I noticed an increase in the effects of the Aricept. Of course, it may also increase the adverse side-effects. Maybe it is a coincidence... if you believe in that sort of thing. I take 120mg Ginkgo Biloba in the morning and again at night. There is more about  Ginkgo Biloba here.

But remember, all of that is just a bonus. I am not taking Aricept to improve my FTD symptoms. My purpose in taking it is to slow or stop the progression of my bvFTD. If I can gain even a couple years any nasty side-effects (except the itching!) would be well worth it. Unfortunately there is no way I can think of to objectively measure if it is working to slow the progression or not. Only time will tell.

 So, I am going to continue taking the Aricept 23 as long as I can afford it - it is expensive even with my current insurance - and there are no other adverse effects. I am also going to continue to explore other options such as Alternative Medicine, and Namenda (Memantine) in the coming weeks.

Everything here is my account of what happened to me, or my interpretation of stuff. Every case of FTD is different. Keep in mind as you read this that the person who wrote this has Frontotemporal Degeneration. That would be ME.  Medical Disclaimer.

Questions and Comments are welcome.