The Tangled Neuron

Surgery, Anesthesia and Memory Loss

Summary:  After surgery, many people experience short-term delirium and/or longer-term cognitive decline.  Scientists are still studying how to prevent these problems.

Doctors, families and patients report that surgery seems to cause short-term delirium and/or longer term memory loss in some people.

In a recent Duke University study of 1064 patients undergoing major surgery (but not heart surgery), neuropsychological tests showed the following rates of post-operative cognitive dysfunction or POCD:

Age range                  Leaving hospital      3 Months After Surgery

18-39 year olds                 37%                                 6%     

40-59 year olds                 30%                                 6%

60 or older                         41%                               13%

Zhongcong Xie, M.D., Ph.D.

Even higher rates of POCD have been reported after heart surgery, but scientists still don't agree on how to measure these problems, or on whether the heart patients also had memory loss before their surgeries.

Dr. Zhongcong Xie, Assistant Professor at Massachusetts General Hospital and Harvard Medical School, is working with his colleagues to determine what causes POCD.

POCD seems to be worse among the elderly, but "the reason why age is a risk factor for POCD remains to be determined," Dr. Xie says.  In his lab, he and his colleagues are researching

Ibuprofen, Naproxen and other NSAIDs for Alzheimer’s

Large observational studies have linked regular use of painkillers such as ibuprofen (Advil) and naproxen (Aleve) with lowered risk of Alzheimer’s, but clinical trials have not backed this up. The publication of the results of two new studies this month didn’t do much to resolve this issue. In the first study, Boston University researchers analyzed the medical records of hundreds of thousands of military veterans, and found long-term use of NSAIDs (non-steroidal anti-inflammatory drugs), particularly ibuprofen, was associated with a reduced risk of Alzheimer’s.

A detailed analysis of the results of the second study, ADAPT (Alzheimer's Disease Anti-inflammatory Prevention Trial), was published this month. It showed that neither naproxen nor another NSAID, celecoxib, improved thinking and memory in more than 2000 men and women 70 years and older who had a family history of Alzheimer’s. Naproxen actually seemed to worsen cognition. The trial was stopped early because scientists worried about the side effects of the two painkillers.

Differences in study design could explain these conflicting results.

Constantine Lyketsos, MD, MPH

The various studies tested different NSAIDs at different dosages in different populations for different lengths of time. It’s also possible that there were “confounding factors” in the population studies – maybe people who take NSAIDs had later onset of Alzheimer’s because they had higher education levels or better overall health, for example.

So, what DO we know about NSAIDs and memory loss? “After the onset of dementia, anti-inflammatory treatment does not seem to work,” says Dr. Constantine Lyketsos, one of the researchers involved in ADAPT. “The data are pretty strong.” Dr. Lyketsos is Director of the Memory and Alzheimer’s Treatment Center at Johns Hopkins University and Chairman of the Department of Psychiatry at Johns Hopkins Bayview Medical Center. 

If treatment with NSAIDs does not seem to be effective, what about prevention?

Imaging with Pittsburgh Compound-B (PIB) – An Amyloid Surprise?

New imaging techniques have shown that many cognitively normal elders have as much amyloid protein (thought by some to cause Alzheimer’s) in their brains as do people diagnosed with Alzheimer’s. Does this mean that these cognitively normal elders are on the brink of developing Alzheimer’s, or does it mean that the amount of amyloid in the brain doesn’t always correlate to the amount of memory loss?

The Alzheimer Research Forum has now posted three parts of a four-part report from the Human Amyloid Imaging Conference. Their report covers the mixed results from studies using evidence Pittsburgh Compound-B (PIB) imaging of amyloid, and the potential effect on early diagnosis and clinical trials.

Does Depression Increase Your Risk of Memory Loss?

Summary: A new study provides more evidence that depression may be a risk factor for Alzheimer’s.

People with dementia often report they suffered from depression before they developed serious problems with memory and thinking. Study after study has shown a link between depression and memory loss. Researchers continue to debate whether depression increases the risk of developing serious memory loss or is simply a sign of brain changes underlying Alzheimer’s or other dementias.

Robert S. Wilson, Ph. D.

Dr. Robert Wilson, Professor of Neurological Sciences and Psychology at Rush University Medical Center, studies the neurobiology of the connection between depression and dementia. In an article in a recent issue of the Archives of General Psychiatry, he and his colleagues provide more evidence that depression may be a risk factor for Alzheimer’s.

The Alzheimer's Answer: a new book

Summary: Dr. Marwan Sabbagh’s new book The Alzheimer's Answer: Reduce Your Risk and Keep Your Brain Healthy is a handbook for baby boomers hoping to prevent serious memory loss.

Dr. Marwan Sabbagh is a geriatric neurologist and Alzheimer’s researcher at Sun Health Research Institute in Arizona. He spends his days seeing memory loss patients and their families, and supervising Alzheimer’s clinical trials. He helped care for his mother-in-law when she suffered from dementia. Like all of us who have watched family members struggle with memory loss, he worries about how it will affect his generation and his children’s.

Marwan Sabbagh, MD

For a man who admits to a fear of aging, he has deep personal relationships with the elders in his community. He calls Alzheimer’s “the embodiment of all that is sad and destructive about growing old,” and spends a lot of time thinking about what contributes to successful aging.

Looking at both the personal and the societal costs of Alzheimer’s, Dr. Sabbagh has come to the conclusion that our approach to memory loss must emphasize prevention. This is message of his new book The Alzheimer's Answer: Reduce Your Risk and Keep Your Brain Healthy.

The Myth of Alzheimer's?

We seem to be rethinking everything right now - the energy we use, the pollution we create, the foods we eat. Peter Whitehouse, a prominent Alzheimer’s researcher and doctor, is also rethinking the disease we call late onset Alzheimer’s.

In his new book, The Myth of Alzheimer's: What You Aren't Being Told About Today's Most Dreaded Diagnosis, written with Danny George, Dr. Whitehouse questions just about everything we think we know about Alzheimer’s and memory loss. Their book comes at a time when I’ve started to rethink my late father’s dementia after two years of blogging about Alzheimer’s research.

Education, Cognitive Reserve and Alzheimer's

Summary: A recent study confirms that higher levels of education seem to delay cognitive decline, but may increase the rate of decline once it starts. The results of this study don’t mean much for any one person. But they do mean that memory loss might not be readily apparent in people with Alzheimer’s, especially those with more education. The findings point to the need to detect changes in the brain before the symptoms of Alzheimer’s and other dementias appear. This will be especially important when treatments to delay progression are available.

The title of a recent press release from the American Academy of Neurology (AAN) caught my eye – “Educated People Who Develop Dementia Lose Memory At A Faster Rate.” The press release was based on study results published in the October 23, 2007 issue of the AAN’s journal Neurology.

Folate, Folic Acid and Alzheimer's

Summary: It’s unclear whether folate or folic acid supplementation can help prevent or treat Alzheimer’s and other dementias. Some evidence actually suggests the opposite: an association between high folate intake and increased cognitive decline. In more positive studies, the link between high folate and lower risk of Alzheimer’s may really be due to exercise.

Folic acid supplements can mask symptoms of Vitamin B12 deficiency, especially in older adults. The U.S. National Institutes of Health warns people 50 years of age or older to have their B12 status checked by a doctor before taking supplements containing folic acid.

Pretend you haven’t read the summary above, and take this short quiz:

1. Folate, a B vitamin found in leafy green vegetables and other foods is good for the brain.
_____Yes _____No _____Maybe

2. Folic acid, the synthetic form of folate found in supplements, is also beneficial.
_____Yes _____No _____Maybe

3. Taking a folic acid supplement can help prevent dementia.
_____Yes _____No _____Maybe

4. It’s OK to take a folic acid supplement just to be sure.
_____Yes _____No _____Maybe

A few days ago, I would have checked yes for every question. But it turns out the correct answer for all these questions is “maybe.” This is surprising, given the press reports:

“Folate shows promise in preventing Alzheimer’s” (USA Today, August 14, 2005)
“Higher Folate Levels May Lower Alzheimer's Risk: Study” (Forbes, January 9, 2007)
“Folic acid boosts elderly brains” (BBC, January 19, 2007).

With headlines like these, it’s no surprise that people worried about brain health have been taking folic acid supplements. When a news feed picked up a story on a study by Dalhousie University researchers in Canada suggesting folate may not reduce the risk of Alzheimer’s, this started an online discussion among members of Dementia Advocacy and Support Network International (DASN). One member wrote “I take folate and have had ‘cerebrovascular events’ in the past, now having vascular dementia.” She wondered what the study results meant for her. Several other members (most diagnosed with Alzheimer’s or dementia) responded that they take folic acid supplements in amounts ranging from 400 micrograms to 5 milligrams.

Some of the DASN members are taking folic acid on the advice of their doctors, or because they’ve heard it might be helpful for dementia. But what evidence is this based on?

Theories About Folate and Alzheimer’s

Scientists aren’t sure by what mechanism, if any, folate may prevent or treat Alzheimer’s. Theories about why folate may be linked to a lower risk of the disease center around homocysteine. Some studies have linked high blood levels of this amino acid to heart disease and Alzheimer’s. In 2001, an analysis of data for 1092 people in the Framingham Study by Boston University researchers showed that a high level of homocysteine in the blood was a strong risk factor for developing Alzheimer’s or other dementia. Folic acid appears to help lower homocysteine levels. So if there’s any protective effect from folate, it could be from lowering homocysteine levels.
There’s also a possible link among folate, homocysteine and beta amyloid, the protein many researchers think causes Alzheimer’s. Scientists at the U.S. National Institute of Aging have shown that brain cells without folate, or with added homocysteine, appear to be more vulnerable to damage from beta amyloid.

Lab studies and theories are tantalizing, but what do studies involving humans show?

Folate or Folic Acid for Prevention of Alzheimer’s?

The results of the study from Dalhousie University that generated discussion among DASN members were published in an article in the Journal of the American Geriatric Society. The lead author of the article, Laura Middleton, is a Ph.D. student studying the effects of lifestyle on the risk of Alzheimer's disease and dementia, with a particular focus on exercise.

Laura Middleton

“In our study, we looked at folate levels in the blood,” she says. “Low folate levels are associated with an increased risk of Alzheimer's disease. Conversely, supplementation with folic acid has not been consistently shown to decrease this risk, suggesting that there may be other factors at play. We suggest in our article that exercise may explain this paradox. In our study group, there were no exercisers who had extremely low folate levels. Folate levels may be associated with the risk of Alzheimer's disease because people who exercise both have higher levels of folate and less risk of Alzheimer's disease.”

Ms. Middleton doesn’t think other factors were at work. “We controlled for a number of other variables,” she says, “including age, sex, education, vascular risk factors, and folate/B12 supplementation.”

Folate’s effect on the risk of developing dementia has been the subject of several large studies, and the results have been mixed. Some studies tracking people’s food consumption, folate levels in the blood and health over several years have shown an association between higher folate intake (or higher levels of folate in the blood) and lower risk of developing Alzheimer’s. In 2001, the results of a study by researchers at Karolinska Institutet in Sweden were published in Neurology. The study found that people with low levels of folate in their blood had twice the risk of developing Alzheimer’s. In an article published in 2005, analysis of data from the Baltimore Longitudinal Study of Aging by the U.S. National Institute on Aging, the U.S. Department of Agriculture (USDA), Johns Hopkins University and the University of California showed a high folate intake was associated with a reduced risk of Alzheimer’s. Early this year (2007), a study by Columbia University researchers followed the dietary intake of 965 persons aged 65 or older over several years. These scientists also concluded that a higher folate intake was associated with a decreased risk of Alzheimer’s.

But as the Dalhousie University study suggests, just because high folate intake is sometimes associated with lower rates of Alzheimer’s doesn’t mean there is a cause and effect relationship. Researchers involved in the Baltimore Longitudinal Study of Aging caution that “additional studies are necessary to investigate whether folate or other(s) [sic] unmeasured factor(s) may be responsible for this reduction in risk,” and the authors of the 2007 article on the Columbia University study note “these results require confirmation with clinical trials.”

A systematic review of 24 studies by Tufts-New England Medical Center scientists published this month (July 2007) questions the value of some of these studies due to quality problems and to variations in the way cognitive function was measured and B-vitamin status was categorized.

Some recent studies have shown either no link between folate intake and the risk of developing dementia, or, more worrisome, that increased folate intake is actually associated with increased cognitive decline. At Rush University Medical Center in Chicago, Dr. Martha Clare Morris studies diet and dementia. She co-authored an article published last year in the Journal of Alzheimer’s Disease that describes a Rush study testing whether folate and other B vitamins can protect against Alzheimer’s. Using data from the Chicago Health and Aging Project (CHAP), she and her colleagues tracked 1041 people age 65+ for a median 3.9 years, and found no association between folate intake and the risk of developing Alzheimer’s.

Martha Clare Morris, Sc.D., Associate Professor, Internal Medicine, Rush Institute for Healthy Aging
Assistant Provost for Community Research, Rush University Medical Center

“We have much research to do in this area,” Dr. Morris says. “There is growing evidence to indicate that perhaps too little folate or too much folate can be harmful to our health…. There are some recent studies including our CHAP study that observed greater cognitive decline with high levels of folate intake.” These studies looked at the risk of developing Alzheimer’s; Dr. Morris and her colleagues plan to study the effect of folate on vascular dementia in the near future.

Can Folic Acid Treat Alzheimer’s and Dementia?

Evidence on the use of folic acid to treat dementia is as mixed as that about its use for prevention. A 2003 Cochrane Review of four double blind, placebo controlled, randomized trials found no beneficial effect of 750 micrograms of folic acid per day on measures of cognition or mood in people with mild to moderate cognitive decline and different forms of dementia.

A 2004 review by (London-based) King’s College researchers of six studies that met certain quality criteria concluded that “the evidence does not support a correlation between serum vitamin B (12) or folate and cognitive impairment in people aged over 60 years. Hence, there is little evidence to justify treating cognitive impairment with vitamin B (12) or folate supplementation.”

The results of two studies published in 2007 are more encouraging. In the first, a small trial of folic acid supplements with cholinesterase inhibitors in 57 patients with Alzheimer’s was conducted by researchers at the University of Dundee. They found adding folic acid to cholinesterase inhibitors improved the ability to carry out activities of daily living and “Social Behaviour” scores, but did not improve scores on the MMSE [Mini Mental State Exam]. In the second, Dutch researchers studied 818 participants in FACIT, a trial testing the effect of folic acid on hardening of the arteries. Their results, published in the January 20, 2007 edition of Lancet, showed that “folic acid supplementation for 3 years significantly improved domains of cognitive function that tend to decline with age.”

But in an editorial accompanying the Lancet article, Dr. Morris and her colleague Christine Tangney question whether the results of the FACIT trial apply to everyone. “By design,” they write, “the trial was focused on people whose folate status was inadequate…. The trial was well designed and unique in its approach of targeting individuals who might benefit from folate supplementation. But how well do the folate intakes of these highly selected trial participants correspond to intakes in more representative samples of the population?” They point out problems with measuring folate intake, as well as our lack of knowledge about what folate and homocysteine levels are optimal, and call for more randomized clinical trials.

Risks of Folic Acid Supplementation for Older Adults

So, the benefit of folic acid supplementation for dementia is unclear, and some studies show a link with increased cognitive decline. Are there other risks involved?

The U.S. National Institutes of Health warns in its folate fact sheet “Beware of the interaction between vitamin B12 and folic acid:”

Intake of supplemental folic acid should not exceed 1,000 micrograms (μg) per day to prevent folic acid from triggering symptoms of vitamin B12 deficiency. Folic acid supplements can correct the anemia associated with vitamin B12 deficiency. Unfortunately, folic acid will not correct changes in the nervous system that result from vitamin B12 deficiency. Permanent nerve damage can occur if vitamin B12 deficiency is not treated.

It is very important for older adults to be aware of the relationship between folic acid and vitamin B12 because they are at greater risk of having a vitamin B12 deficiency. If you are 50 years of age or older, ask your physician to check your B12 status before you take a supplement that contains folic acid. If you are taking a supplement containing folic acid, read the label to make sure it also contains B12 or speak with a physician about the need for a B12 supplement.

Many of us don’t know how much folic acid we get. Because low levels of folic acid are associated with certain birth defects, in the U.S., Canada and some other countries, folic acid is added to flour, breads and other grain products. “With the folic acid fortification program that was instituted in 1998, folate insufficiency is a rare occurrence in the U.S.,” says Dr. Morris. In addition, anyone taking a multivitamin is likely to be getting folic acid - mine contains 400 micrograms, the recommended dietary allowance for folate in the U.S.

So, what does all this mean for DASN members and anyone worried about brain health? It’s been hard to prove that folic acid or any supplement can prevent or treat Alzheimer’s and other dementias, but exercise may be helpful.

“So far, food sources of vitamin E and other antioxidant nutrients look promising for the prevention of dementia,” says Dr. Morris. But, she says, “there is little evidence to support protective benefit through vitamin supplement sources, except perhaps if one is deficient in dietary intake of certain nutrients. There are also a number of animal and observational studies that have shown that fish and n-3 fatty acids are protective against dementia. Verification of these relations through randomized clinical trials is needed before we can confidently recommend dietary intake of these foods and nutrients for dementia prevention.”

Laura Middleton points to the benefits of exercise instead of supplements. “In our studies to date, we have found that exercise not only delays dementia but can also slow the progression and increase the chances of improving even after you have been diagnosed with Alzheimer's disease,” she says. “It is never too late to start exercising. As little as walking three times a week can significantly reduce your risk of Alzheimer's disease and can slow or even pause cognitive decline.”

Chlamydia Pneumoniae and Alzheimer's

Summary: Infection with a common bacterium called Chlamydia pneumoniae may increase the risk of developing Alzheimer’s. The bacterium has already been linked to heart disease and hardening of the arteries. Work to investigate the role of viruses and bacteria such as Chlamydia pneumoniae in chronic diseases is in the early stages, but researchers hope it will help identify and treat the underlying causes of Alzheimer’s.

More study is needed to confirm the bacterium’s relationship with dementia, and rigorous clinical trials would be necessary before any treatments based on this research could be recommended.

I’ve written before about how viruses and bacteria can contribute to chronic diseases not previously linked to infections. It is now accepted that a type of bacteria contributes to ulcers, and that human papillomaviruses are the major cause of cervical cancer. A common bacterium called Chlamydia pneumoniae (also called Chlamydophila pneumoniae and C. pneumoniae) has been linked to atherosclerosis (hardening of the arteries) and other chronic diseases.

Dr. Brian Balin, a professor at the Philadelphia College of Osteopathic Medicine and Basic Science Director of the school’s Center for Chronic Disorders of Aging thinks that same bacterium may also contribute to many cases of Alzheimer’s. As the name indicates, the bacterium causes a type of pneumonia - it’s not the same as the sexually transmitted type of Chlamydia.

Although the link between C. pneumoniae and Alzheimer’s is not well-accepted, Dr. Balin has been researching the relationship for years. At a 1995 meeting he attended, talk turned to the possible link between the bacterium, hardening of the arteries and heart disease.

“I asked whether anyone had ever looked for the organism in brain tissue,” he remembers. “My background in neuropathology dealt with the blood brain barrier, and I had for some time believed that damage to the blood vessels in the brain could be involved in Alzheimer’s disease. My beliefs were not widely held….”

“Anyway, after asking the question, I performed a search of the literature and found that no one had ever looked in brain tissues for the presence of this infection.... So, I went to our -80 C freezers and pulled out frozen brain tissues from both AD [Alzheimer’s disease] and non-AD brains. I sent these samples in a coded or blinded fashion to Dr. Alan Hudson for analysis by polymerase chain reaction (PCR), which is a way of testing whether the DNA of the organism was in the tissue samples.” [Dr. Hudson is a Wayne State University School of Medicine professor whose lab focuses on Chlamydia research.]

It turned out that the AD tissue samples contained the DNA from the bacterium, while the non-AD tissues did not. The two researchers repeated the experiment with different samples, and got the same results.

“This then led to our expanded experiments to determine whether C. pneumoniae could be detected using a variety of methods,” says Dr. Balin. “All in all, we used six different techniques which gave consistent results. The first publication of our work was in 1998 in Medical Microbiology and Immunology.”

Chlamydia Pneumoniae - An Elusive Bacterium

All these different testing methods were necessary because Chlamydia pneumoniae is the Loch Ness Monster of the bacteria world – hard to categorize, and even harder to find.

“Because of the nature of this organism, one cannot take a ‘quick and dirty’ approach to this problem,” says Dr. Balin. The bacterium is hard to categorize because it acts more like a virus than a bacterium, growing inside cells and using the resources of the cell to reproduce. Even worse, he says, it keeps changing form. “C. pneumoniae has multiple developmental phases in its life cycle and expresses genes and proteins variably depending on things such as life cycle, environment, and tissue in which it is located.”

This may be why some labs report they have not found C pneumoniae in Alzheimer’s brains. But Dr. Balin thinks the extensive testing he and his colleagues have done is accurate. “There are a number of techniques used to detect C. pneumoniae in clinical samples… What we do, and which is not consistently done in other labs, is use multiple techniques with many different types of probes to detect the presence or not of C. pneumoniae in a clinical sample. We have used at least 15 different antibodies specific either to Chlamydia genus or Chlamydophila pneumoniae on our brain samples to determine if antigens from the bacterium can be detected in the tissues. In addition, multiple PCR primer sets have been used to detect different genetic sequences of C. pneumoniae. We also have used biochemical techniques, electron microscopy, and tissue culturing to demonstrate C. pneumoniae in brain samples. We believe the most thorough sampling is required to truly rule in or rule out presence of the organism in brain tissues.”

He received some confirmation of his findings this year, when scientists at the Wroclaw Medical University in Poland reported finding Chlamydia pneumoniae in the spinal fluid of 44 percent of the Alzheimer’s patients they tested, but only 11 percent of a control group. The Polish researchers suggested that testing for the bacterium in spinal fluid could be useful in the diagnosis of Alzheimer’s.

How Chlamydia Pneumoniae May Trigger Alzheimer’s

How could a type of pneumonia affect the brain? “My group has found that C. pneumoniae, once inhaled, infects white blood cells, in particular the monocytes that circulate throughout the blood stream,” Dr. Balin explains. “These cells can enter through the walls of the blood vessels and can carry the organism into different tissues, including the brain.”

“We also have evidence that the cells in our upper noses known as the olfactory neuroepithelial cells (those cells controlling our sense of smell) are infected by C. pneumoniae.” The olfactory neuroepithelial cells are close to the olfactory bulb region of the brain and to the hippocampus, where short term memory is formed. These areas of the brain are among the first to be affected by Alzheimer’s. This suggests there may be a link between infection with C. pneumoniae and the reported association between the loss of sense of smell and the onset of Alzheimer’s.

Finally, there is some tantalizing evidence that the bacterium may actually trigger the formation of the amyloid plaques characteristic of Alzheimer’s brains. When mice in Dr. Balin’s lab were infected with C. pneumoniae, they developed amyloid plaques in their brains. Adding to the evidence of the link between the bacterium and Alzheimer’s pathology, the bacterium was found near plaques and tangles in human Alzheimer’s brains studied in his lab.

C. Pneumoniae – Another Piece of the Dementia Puzzle?

Dr. Balin points out that the connection between C. pneumoniae and Alzheimer’s is consistent with other research on the disease. Some scientists think inflammation causes the brain damage seen in Alzheimer’s. “Quite possibly the inflammatory response due to a chronic persistent infection with C. pneumoniae and/or other infectants causes much of the cellular damage in the brain,” he says. “Also, genetic risk factors such as having the ApoE 4 variant which has been correlated with Alzheimer’s disease may actually increase one’s risk for being infected with C. pneumoniae and other infectants such as Herpes Simplex Virus 1. The interrelationship of ApoE with infectants may be how this variation confers greater risk for getting both infections and Alzheimer’s disease. Our data have shown that Alzheimer’s brains that express the ApoE4 variation actually have greater concentrations of C. pneumoniae than Alzheimer’s brains not expressing the variant.”

He thinks the connection between C. pneumoniae and hardening of the arteries may also be relevant to dementia. Of course, arteries are a type of blood vessel. Once white blood cells infected with C. pneumoniae reach the brain, Dr. Balin theorizes, they may damage the blood vessel walls there. This would contribute to vascular dementia and brain tissue damage.

But if exposure to Chlamydia pneumoniae is common, as indicated by the antibodies in many people’s blood, why don’t we all develop Alzheimer’s? “Exposure to an infectious agent does not necessarily translate into a specific disease,” says Dr. Balin. “There are many other factors, both genetic and environmental, that would dictate why some get a disease and others do not, even when you have a large percentage of the population exposed to the infectious agent. One example is exposure to the common cold viruses, which are very ubiquitous. Not everyone exposed gets a cold. …so, not everyone exposed to C. pneumoniae would develop Alzheimer’s, but the potential for the disease would be ever-present.”

Potential Treatments for Alzheimer’s and Dementia

Dr. Balin cautions against rushing to treat Alzheimer’s based on the possibility that C. pneumoniae could trigger the disease. “The dilemma that we face is that without current long-term effective treatments for AD, many people may want to try, even experimentally, other types of drug regimens based on the work that we and others are doing with infection,” he says. “Obviously, without clinical trials first, we cannot know for sure who would be most likely to benefit. We have to determine who is infected with which organism(s) and try to treat appropriately. This is why we really need a concerted effort to develop controlled clinical trials.”

He’s done some thinking about what types of therapies a clinical trial could test. “We know that Herpes Simplex Virus 1 may be involved in a significant number of AD cases and this may also have to be considered in a therapeutic regimen. All in all, I think that infection data (even at this point in time), suggests that using combination therapy of an anti-inflammatory, anti-chlamydial and an anti-viral for Herpes could be beneficial."

The “cocktail” he is proposing for trials includes anti-inflammatory medicines or NSAIDs (non-steroidal anti-inflammatory drugs such as aspirin and ibuprofen). Although some population studies have shown a link between NSAID use and decreased risk of Alzheimer’s, evidence from clinical trials using NSAIDs to slow progression of the disease is not very encouraging. If inflammation is caused by infection with C. pneumoniae, Dr. Balin says, it’s unlikely that it could be controlled in the long run by NSAIDs alone.

Antibiotics targeted to Chlamydia bacteria are also part of the proposed cocktail. At least one study has shown antibiotics may slow progression of mild to moderate Alzheimer’s, but more research is needed. “Our research suggests that treating individuals who have Mild Cognitive Impairment, and those who have newly diagnosed and/or existing Mild AD, with anti-chlamydial antibiotics may have a positive effect by either stopping a trigger for the disease or preventing disease onset in the case of MCI,” Dr. Balin says.

But antibiotics don’t always wipe out C. pneumoniae, and as with other infectious disease, there are worries that the bacterium will become resistant to treatment. These worries have scientists searching for alternative therapies, Dr. Balin says. “The use of more novel anti-infection compounds, and potentially the development of a vaccine for these infectants could result in combating dementia-causing organisms.”

Hopes For Finding And Treating The Causes Of Alzheimer’s

“I believe that we have uncovered a non-conventional infectious agent that likely is
increasing the risk for the development of Alzheimer’s,” Dr. Balin says. “We don’t yet have all the answers. However, there is hope because we are still discovering and studying how this actually works. Similar to how the discovery of a bacterium is the cause of gastric ulcers and some types of gastric cancers, we are hopeful that our findings result in expanded efforts by others to consider how infection may be causing many diseases in the nervous system not currently considered to be infectious. This understanding is vital to proceeding in a rational fashion to treat the problem based on the evidence. This will take us from simply trying to treat the symptoms of disease to actually treating the causes. This is why I have great hope that we will defeat this and other neurodegenerative diseases in our lifetimes.”

Alzheimer's Risk Factors, Genetics, Family History and Prevention

“I don’t know why I can’t remember words lately,” my maternal grandmother said to my mother. Grandma Ben (shown here at her college graduation in 1924) was then in her early 80’s, brisk and competent. Around the same time, my paternal grandmother (right) started getting lost while driving around our small town. “Kilo,” as we called her, was in her early 70’s. And when my father (below, on the Pamlico River with his dog Beau) was in his late 60’s, he too had trouble finding words. They all went on to develop dementia. So it isn’t surprising I had a personal interest in a presentation called “Family History as a Risk Factor for Alzheimer’s” at the Wisconsin State Conference on Alzheimer’s Disease and Related Disorders earlier this month. The talk was given by Dr. Mark Sager, Director of the Wisconsin Alzheimer’s Institute at the University of Wisconsin. For early onset Alzheimer’s disease, family history is a huge risk factor. But the majority of people who develop dementia do so later in life, and it’s not clear what role family history plays in these cases. One genetic variant (APOE4) is associated with increased risk of late onset Alzheimer’s, and researchers are working to confirm the risk associated with another gene, SORL1. But these weakly associated genes don’t allow us to predict with any accuracy who will develop Alzheimer’s. Are there other inherited or family risk factors? This isn’t clear, says Dr. Sager. “We know nothing about the adult children of Alzheimer’s disease - we don’t really understand the risk.” By tracking these adult children through a program called WRAP (Wisconsin Registry for Alzheimer’s Prevention), Dr. Sager and his colleagues hope to address this knowledge gap. The average age at enrollment of the more than 1000 WRAP volunteers is 53, much younger than when the first symptoms of Alzheimer’s typically appear. Why study people before they develop dementia? “Alzheimer’s is labeled an old person’s disease because the brain is so resilient that the disease manifests when people are in their 60’s, 70’s and 80’s,” says Dr. Sager. “But actually, the brain begins to fail much earlier.” Scientists hope that within a few years, Alzheimer’s will be more like heart disease in that we will be able to identify who is at risk, and begin treatment before symptoms appear. “The presence of symptoms means the disease is at an advanced stage,” Dr. Sager says. “We want to intervene before that.” What does data from the first wave of testing in the WRAP program show? On average, the neuropsychological test scores of the adult children of Alzheimer’s are the same as those of volunteers whose parents didn’t have the disease. But even though they have no apparent cognitive problems, the brains of volunteers whose parents had Alzheimer’s seem to work differently. During functional MRIs, participants with a family history of Alzheimer’s show less activity in the part of the brain called the hippocampus when viewing new items. A second wave of testing, funded by a grant from the U.S. National Institutes of Health, will determine if the Alzheimer’s children’s thinking and memory has declined over the four year interval between evaluations. These tests will include PET scans using the new Pittsburgh Compound B imaging to map amyloid deposits in the volunteers’ brains. WRAP data is also being used to study risk factors besides family history, including: - previous surgeries (often associated with post-operative memory problems) - high cholesterol (and the use of statins) - hormonal status (along with the use of hormone therapy). Even before we understand how to prevent or delay Alzheimer’s, the staff at WRAP is developing a pilot study of interventions based on the available research. Study volunteers who develop Mild Cognitive Impairment will be offered these interventions in an attempt to slow or prevent further decline. Interventions will probably involve the lifestyle factors that research has shown may lower the risk for Alzheimer’s, such as cognitive and leisure activities, moderate alcohol consumption and physical exercise, as well as reducing psychological stress or untreated depression. Dr. Sager and his colleagues are also following the research on substances that may delay onset or slow progression of Alzheimer’s. It’s too early to recommend them for prevention, and some have bad side effects. You should check with your doctor before considering any of these treatments on Dr. Sager’s watch list: - estrogen - ginkgo [but many formulations contain contaminants – I’ll write more about this soon] - medicines that lower blood pressure - folic acid - non-steroidal anti-inflammatory drugs - Dr. Sager notes side effects including kidney damage have caused trials of these medicines for Alzheimer’s to be discontinued. - statins - trials are ongoing - selegiline [I plan to write more about this over the summer] - vitamin E - supplements are controversial, so it’s best to try to get this vitamin from foods, Dr. Sager says. - cholinesterase inhibitors [but there’s not enough evidence that these help before symptoms appear]. Want to help? You don’t have to live in Wisconsin to volunteer for WRAP, but you must be able to travel to Madison for testing every four years. People whose parents did not have Alzheimer’s are also needed for comparison. If you’re interested, contact Janet Rowley at 608-829-3306 or jsrowley@wisc.edu. If all of us with family histories of dementia can work with researchers in programs like WRAP, maybe our children and grandchildren will never experience the first symptoms of a failing brain.

Herpes Simplex Virus Type 1 and Alzheimer's

Summary: A British scientist, Dr. Ruth Itzhaki, has shown that the combination of latent Herpes Simplex Virus Type 1 (HSV1) in the brain and the type 4 form of the APOE gene could account for 60 percent of all cases of late onset Alzheimer’s disease. Almost all elderly brains are infected with HSV1, which often causes no symptoms. Dr. Itzhaki’s lab found the virus in areas of the brain most damaged by Alzheimer’s, and has data relating HSV1 to plaques and tangles.

The idea that a viral infection could underlie Alzheimer’s is part of an emerging understanding of the role of bacteria and viruses in chronic diseases. This kind of research is neither well-accepted nor well-funded, so don’t expect any Alzheimer’s treatments targeting HSV1 to be on the market anytime soon.

I have only a vague understanding of viruses and bacteria. Most of what I know is based on personal experience and on what little I remember from high school biology class. I know that viruses and bacteria are infectious, and that illnesses caused by them are often short-lived. Until recently, I thought scientists understood and could control most harmful viruses and bacteria.

The leading causes of death in the U.S. seem to be in a different category: the top ten list is dominated by chronic diseases like heart disease and stroke, cancer, and diabetes. Alzheimer’s has moved up to number seven on the list. These illnesses are not infectious, not short-lived, not well-understood and not well-controlled.

But it looks like the two categories might overlap more than I knew - the idea that viral or bacterial infections might contribute to chronic diseases not previously linked to infections is gaining ground. One bacterium called helicobacter pylori has been found to cause ulcers, and another called Chlamydophila pneumoniae (Cp), is linked to coronary artery disease. Human papillomaviruses are now recognized as the major cause of cervical cancer.

These discoveries hint at the possibility of a fundamental shift in the way we view diseases, including Alzheimer’s. In his book Plague Time: The New Germ Theory of Disease, Dr. Paul Ewald, Professor of Biology at University of Louisville in Kentucky, argues that bacteria and viruses are behind many chronic diseases, including Alzheimer’s, cancer and some forms of mental illness.

Herpes Simplex Virus Type 1 Linked to Alzheimer’s

For almost twenty years, Dr. Ruth Itzhaki, Professor of Molecular Neurobiology at the University of Manchester in England, has been exploring possible links between viruses and Alzheimer’s. Viruses are tiny infectious particles that attach themselves to and penetrate cells, then use the capabilities of those cells to reproduce. They can cause diseases like colds, flu and AIDS, or they can just sit there, remaining dormant or latent for long periods of time. A latent virus can become active when triggered by stress, other infections or environmental factors.

Ruth Itzhaki, Ph.D.

For a virus to contribute to the development of Alzheimer’s, Dr. Itzhaki reasoned, it would have to be very common in humans. And because Alzheimer’s appears to develop over a long period of time, it would make sense to look for a virus that has long periods of latency, but could periodically be reactivated and cause damage.

One family of viruses fits her criteria: herpes. There are over 100 types of herpes, of which eight infect humans, causing diseases ranging from chickenpox and shingles to cold sores and mononucleosis. Most people have some type of herpes, even though they may have no symptoms.

When Dr. Itzhaki and her colleagues examined the brains of older people, they found signs of latent Herpes Simplex Virus Type 1 (HSV1) in the areas most affected by Alzheimer’s. Traces of the virus were present in both Alzheimer’s and non-Alzheimer’s brains. Because HSV1 is not prevalent in the brains of younger people, the researchers hypothesize that the virus infects the brain in older age, as the immune system declines.

HSV1 is especially common in humans. The virus, which can be transmitted via skin contact and saliva, infects approximately 58% of people between the ages of 14 to 49, and in older people, almost everyone. Often, there are no symptoms.

Even though the presence of the virus in areas of the brain damaged by Alzheimer’s was intriguing, it was clear that not everyone with HSV1 develops Alzheimer’s. “‘Infect’ doesn’t always mean ‘affect,’ Dr. Itzhaki notes. “With many sorts of infection, some people show no symptoms.” As with other viruses, perhaps an unrelated illness or stress could activate latent HSV1. But Dr. Itzhaki wondered if a combination of HSV1 and some other factor could be involved.

The APOE Connection

The APOE4 genetic variant has already been identified as a risk for developing Alzheimer’s, but is “neither necessary nor sufficient to cause Alzheimer’s,” Dr. Itzhaki points out. She wondered if HSV1 and APOE4 could together trigger a series of events leading to brain damage and degeneration. The idea that APOE status could determine the effect of a virus not new. For example, studies in her own lab had determined the risk for cold sores from HSV1 is higher in people with the APOE4 mutation. Also, her lab found that APOE status determines susceptibility to, or severity of, infections in various other diseases.

When Dr. Itzhaki and her colleagues tested for both HSV1 in brain tissue and APOE4, their data indicated that the combination of these two factors could account for 60 percent of all sporadic Alzheimer’s cases (late onset Alzheimer’s that does not run in families).

It’s interesting that a small study of the brains of three people with familial Alzheimer’s disease by scientists at Aichi Medical University School of Medicine, Aichi, Japan showed signs of active HSV1 in areas with beta amyloid deposits. This would suggest that HSV1 is involved with the type of Alzheimer’s that runs in families, not just the sporadic Alzheimer’s Dr. Itzhaki studied.

How Does HSV1 Damage the Brain?

Just how HSV1 might damage the brain is not known. It could be via inflammation and oxidation. Oxidation is when unstable molecules called oxygen free-radicals combine with other molecules. In the same way that rusting damages metal, oxidation can damage brain cells. Dr. Itzhaki says that oxidation has been found in HSV1 infected cells in the lab and in brain cells harboring latent HSV1.

“We think inflammation must be a major factor,” she says. She lays out the hypothesized chain of events: “When HSV1 is latent (i.e. in a dormant state) in the brain, it can be activated by inflammation of the brain. The latter can occur when somebody has an infection, or is stressed, or immunosuppressed. The virus then augments the inflammation there. So other viral or bacterial infections (not necessary in the brain) can cause indirect trouble.”

What About Other Herpes Viruses?

Dr. Itzhaki and her team have investigated whether other types of herpes might be linked to Alzheimer’s. Their research shows HSV2 (genital herpes) and a type of herpes called cytomegalovirus are not as prevalent as HSV1, and not associated with Alzheimer’s disease. However, cytomegalovirus was found to be present in a high percentage of brains of people who had had vascular dementia. More research is needed to understand this connection.

HSV6 (a virus that is common in infants, but often causes little or no illness), was prevalent in the brains the researchers tested, and was associated with Alzheimer’s. Because it overlapped with the presence of HSV1, it’s not clear whether HSV6 could be a cause or a consequence of Alzheimer’s.

A Unifying Theory?

Dr. Itzhaki’s theory that a combination of HSV1 and the APOE4 genetic variant underlies many cases of Alzheimer’s is appealing because it could explain several factors already linked to an increased risk of the disease:

*Age (the older you are, the more chance you have of having HSV1 in your brain)
*APOE4 (see above)
*Cholesterol (HSV1 is associated with increased cholesterol levels)
*Beta amyloid (Dr. Itzhaki has data [not yet published] linking HSV1 to increased levels of beta amyloid. In addition, increased cholesterol levels seem to increase formation of beta amyloid plaques.)
*Tau (Dr. Itzhaki also has unpublished data linking HSV1 with abnormal tau, the protein in Alzheimer’s tangles).

The hypothesis is also appealing to me because it addresses possible underlying causes of the plaques and tangles that have been the focus of Alzheimer’s research for more than 100 years.

Before this theory is widely accepted, more research in Dr. Itzhaki’s lab and in other labs is needed. Money is tight for any Alzheimer’s research now, with only a small percentage of proposed studies funded. For a theory that’s not “mainstream,” funding is even more difficult.

Future Treatment

What if Dr. Itzhaki’s hypothesis about HSV1’s role in Alzheimer’s proves to be true?

“It would have enormous consequences,” she says, “as antiviral agents, which are currently available and which have relatively small side effects and are cheap, could be used to treat patients and should stop further deterioration.”

A good way to test of the role of HSV1 in Alzheimer’s “would probably be to use antiviral treatment for a year,” Dr. Itzhaki says, “and measure cognitive decline during that year and compare the rate with the patient’s rate a year before and a year after treatment. This would take into account the different rates of decline in different people. Scanning too would be very useful in indicating the course of brain damage during each of the three years.”

This type of clinical trial of antiviral drugs sounds good, but “as antiviral agents are off-patent, pharmaceutical companies have little profit motive in using them thus, especially as trials are hugely costly,” she points out.

In addition to antiviral drugs to stop progression of Alzheimer’s, vaccination against HSV1 could potentially prevent the disease. Dr. Itzhaki and colleagues have shown that vaccination of mice can protect against latent HSV1 infections of their brains.

But right now, she says, there’s no interest in developing Alzheimer’s therapies targeting HSV1. It’s a kind of “Catch-22” – more research is needed to confirm HSV1’s role in dementia, but there’s no funding for that research without confirmation of that role. “The trouble again is not just cost, but also the hostility of many people in the field…as a result, neither we nor others who want to repeat our research can get adequate or even any funding. It’s incredibly frustrating and disheartening. But until funds are available to extend the work, resistance to it will continue,” Dr. Itzhaki says.

Cholesterol, Statins and Alzheimer's: Part 3 of 3

Summary: A new study shows that a decline in total cholesterol may be associated with the early stages of dementia. More research is needed to understand what this means.

When Dad was in his mid-60’s, the results of his annual physicals were straight out of an advertisement about healthy aging. His weight and blood sugar were normal, and his blood pressure and cholesterol were low.

Now it seems Dad’s low cholesterol levels weren’t such a good sign after all. Some research links high cholesterol in mid-life to increased risk of heart problems and dementia. But later in life, low cholesterol levels, not high, are linked to increased risk of dementia and even death.

A new study, published in the Archives of Neurology, shows that a decline in total cholesterol may be associated with the early stages of dementia. Researchers at King’s College London Institute of Psychiatry looked at 26 years of total cholesterol readings for over 1000 Japanese American men participating in the Honolulu-Asia Aging study. They found that “cholesterol levels in men with dementia, and, in particular, those with Alzheimer disease had declined at least 15 years before the diagnosis and remained lower than cholesterol levels in men without dementia throughout that period.”

What do the results of this study mean? I fired off a list of questions to the study’s lead author, Dr. Robert Stewart, Head of Section of Epidemiology at the Institute of Psychiatry at King’s College.

Robert Stewart, MD, MRCPsych

Q: Should Dad have been worried about his low cholesterol readings? Could the drop in cholesterol seen in the new study be a “biomarker” for Alzheimer’s or dementia?

Dr. Stewart: This is a possibility. However, the drop in cholesterol in our study occurred quite a long time before the onset of dementia and so you would have to wait a long time to know if such a ‘biomarker’ was accurate. This is a finding that needs further investigation.

Q: Did the men in the Honolulu-Asia Aging Study who developed dementia have high cholesterol levels at the beginning of study?

Dr. Stewart: The analysis was designed to measure change in cholesterol over time, so it’s not strictly possible to comment on differences in initial levels. There have been a few studies which have suggested that high cholesterol levels in middle age may predict a higher risk of developing dementia later on in life, but this is still a slightly controversial issue.

Q: Is a drop in cholesterol an underlying cause of dementia and death, or simply a sign of some disease process such as heart disease or a disease process in the brain?

Dr. Stewart: We really can't be sure what it was due to. In the paper we mention that a drop in cholesterol can be caused by an inflammatory event or possibly a nutritional deficit, but you are right in that it could be secondary to cardiovascular disease or secondary to some early brain change. We simply don't know and need to investigate this issue further.

Q: Finally, what does this study say about the potential use of statins to treat dementia?

Dr. Stewart: I don't think that our findings have any particular implication for statin trials. It is likely that the drop in cholesterol in our study was secondary to other processes and was not a direct cause of later dementia. It is also highly unlikely that it was related to cholesterol lowering treatment as these medications were not widely available at the early stages of this study when the cholesterol decline occurred.

We may never know whether Dad’s low cholesterol was a bad sign, or whether taking Mevacor affected his dementia. With the ongoing studies on the use of statins to treat Alzheimer’s, and further research into late-life drops in cholesterol, we should have a better picture of the relationship between cholesterol and dementia in the next few years.

Cholesterol, Statins and Alzheimer's: Part 1 of 3

Summary: Cholesterol is the Anna Nicole Smith of the Alzheimer’s world – it’s always in the news, and its relationships are hard to understand. High cholesterol in mid-life may be a risk factor for developing dementia. Studies on whether cholesterol-lowering drugs called statins can reduce that risk have had mixed results, with more recent research finding no effect. As with the men claiming to be the father of Ms. Smith’s baby, further tests will determine the role cholesterol-lowering drugs will play.

Going through my father’s medical records, I found a 2004 notation from his first neurologist: The recent total cholesterol (on Mevacor) was only 139 (LDL 81). Therefore, the Mevacor will be decreased to 10 mg. daily beginning today.

Mevacor is a statin, prescribed to lower cholesterol levels. But as far as I know, Dad’s cholesterol was always low – why was he taking Mevacor?

In the last few years, headlines on the use of statins to prevent dementia have swung from wild optimism to flat-out skepticism, and it seems Dad was dragged along for the ride.

In early 2000, when Dad started calling himself “stupid,” Loyola University researchers announced their analysis of hospital records showed patients taking statin drugs had a lower prevalence of probable Alzheimer’s. A paper by Boston University scientists that same year showed that British patients taking statins seemed to have a reduced risk of developing dementia. Dad probably saw the headlines: “Cholesterol drug may prevent Alzheimer’s” and “Statins Take On the Brain: Cholesterol-lowering drugs may also treat or prevent Alzheimer's disease.”

By 2001, he was combing through newsletters from Mayo Clinic and Harvard Medical School looking for ways to improve his memory. That year, Finnish researchers at the University of Kuopio published an article in BMJ that seemed to confirm the Alzheimer’s/cholesterol link. In their study of 1449 Finns followed over 21 years, high cholesterol levels at midlife were a risk factor for Alzheimer’s disease later in life. Shortly after that, studies in several labs showed a relationship between cholesterol and beta amyloid plaques and suggested that, at least in a test tube, high cholesterol leads to increased beta amyloid production. Surely the newsletters Dad subscribed to carried stories about these studies.

In 2003 or 2004, his family doctor must have prescribed Mevacor, but none of us know why. Maybe both Dad and his doctor had read about these studies, and agreed to give a statin a try.

By early 2005, Dad wasn’t reading much at all. But when I called to say hi one day, he was exasperated by a headline he’d seen in the local paper. “Did you see that?” he asked. “Now they say those drugs don’t help your brain.” The story was about a study by Johns Hopkins University researchers. After following approximately 5000 people over a period of five years, they found “no association between statin use and subsequent onset of dementia or AD”. Later that year, University of Washington scientists said that their analysis of statin use and dementia prevalence among 2798 participants in the Cardiovascular Health Study showed the use of statins was not associated with decreased risk of dementia. They wrote that the results of their investigation and similar studies depended on how they looked at the data, and that more research is needed.

After these negative results were published, the excitement about using statins to prevent Alzheimer’s had died down. Dad had stopped taking Mevacor anyway, and had definitely developed dementia.

Although statins may not prevent Alzheimer’s, studies are underway to see if they can be used to treat the disease after onset. I’ll write more about that in my next post.

Dreaming About A Cure, Talking About Care: Part 4 of 4 - New Ideas for Care and Cure

Whether we view Alzheimer’s as a disease, or as part of aging, most of us know from personal experience that the way we deal with it is terribly inadequate. In the past three posts, I’ve written about the growing recognition that Alzheimer’s isn’t a single disease, and the controversy about whether we should spend our limited resources on trying to find a “cure.”

Maybe if we give up our fantasies of a single “cure” for Alzheimer’s, we can start talking about better ways to view and treat dementia. These discussions have already begun in labs, at conferences, on email lists, and in homes around the world. While preliminary, they provide us with a glimpse of how Alzheimer’s care might look in the future.

Dr. Peter Whitehouse’s work is an example. Earlier in his career, he focused on drug development. Now he’s more interested in prevention and in intervention studies aimed at improving quality of life for dementia sufferers.

“We need to re-evaluate what’s important,” he says. “Regardless of cure, care needs more attention. Trying to find a cure is part of caring, but there’s an imbalance. We have a great obligation to think clearly about the condition, then do things to improve it. We need to think about ethical considerations – for example, there are still children whose brains are being damaged by lead. Addressing this problem is important for future generations. And instead of focusing on degeneration, we should be focusing on renaissance and legacy.”

Dr. Whitehouse’s recent work includes research on using electronic aids for reminiscence therapies (LifeBook) and archiving individual stories of people’s experiences with disease (including dementia) and medical treatment (StoryBank). His main intervention studies will be at The Intergenerational School, a Cleveland public school serving learners of all ages. He founded the school with his wife Catherine. “The IG school represents one way of pulling it all together,” he says. “Purpose, a sense of community, remaining cognitively active, leaving a legacy, being engaged and valued - these things are much more important to quality of life.”

In labs and at conferences, other scientists are discussing new approaches to Alzheimer’s research, such as more accurate “sub-typing” for identifying different types of dementia, and focusing on investigating potential causes of dementia other than beta amyloid. I’ll write more about this in another post.

And within DASN, members are talking about how to improve care:

- “I think the 'person-centered' model is the ideal for both the care partner and the person with dementia. Each of us has different needs, so no care plan would suit even the majority of folks touched by this disease.” (Shirl Garnett, western Australia, diagnosed with early onset dementia at 59)

Shirl Garnett

- “The mind-body-spirit approaches developed by new age physicians to address those other diseases must be brought to bear on AD. Further, I believe that new era medicine - consciousness and healing - could inform the research being done in the AD research centers and private laboratories.” (Jay Smith, California, diagnosed with early onset Alzheimer’s)

- “Services in the form of support for caregivers and those of us with dementia can often be provided in part by volunteers. I am convinced that there are many more volunteers who are qualified and would contribute if given the opportunity.” (Charley Schneider, Missouri, diagnosed with early onset Alzheimer’s)

- “I think that the key to finding a better medication for treatment and possibly a cure lies in the minds (no pun intended)of those that ARE diagnosed in their 30's, 40's and 50's. If they were open to allowing us to be a part of research in clinical trials I personally think that this would speed up the process for their goal of a cure. So, so many of us work so diligently with great urgency to make this happen as we don’t have the time that the associations and researchers do to plan this all out as our time is running out. Why not focus on those under 50? They might be surprised how much money is saved in research if they would just broaden their horizons so to speak.” (Tracy Mobley, Missouri, diagnosed with early onset Alzheimer’s disease at the age of 38)

Tracy Mobley

- “What makes the best sense of all is empowering people with dementia to care for themselves as much as possible and for as long as possible. People with dementia absolutely can learn some things far into the disease. I truly believe that people with early dementia can be taught to better understand and manage their own disease and behaviors. I further believe that a society which allows people with dementia to stay involved in their chosen activities also prolongs life and emotional health.” (Carole Mulliken, Missouri, diagnosed with vascular dementia)

Dr. Whitehouse sees hope in this kind of open-minded discussion. “If we can think through Alzheimer’s in a deeper way, will have insights into how the brain works. Underneath Alzheimer’s is a re-thinking about what it means to be human, and science’s role in society.”

Dreaming About A Cure, Talking About Care: Part 3 of 4 - The Fantasy of "Cure"

When Dr. Peter Whitehouse of Case Western Reserve University says we should redirect Alzheimer’s funding to emphasize care over “cure,” the idea isn’t very popular (see previous two posts). But he’s not really suggesting we should stop funding research – it’s just that he doesn’t like how that research is presented to the public. “I’m not saying we don’t need bio research,” he explains. “But using the word “cure” is irresponsible.”

“I’m more of a psycholinguist than a physician, so I’m interested in words,” he continues. “In the discourse about Alzheimer’s, our field needs to be more honest. It’s unlikely we’ll fix the problem in the sense of a cure. Care is more complicated to appreciate than finding a drug that blocks pathways, and it involves ethical and cultural implications. It’s easy to say ‘give me half a billion dollars to find a cure,’ but asking for half a billon for better long term care is more difficult. But we keep saying ‘give us more money to find a cure.’ This is a fantasy – people are starting to realize the emperor has no clothes.”
Looking back, I think my dream of finding a cure for Dad really was a fantasy. I kept reading that we were making great progress towards a cure for Alzheimer’s, but the reality was that my father’s doctors were unsure why he had dementia, and unsure what to do about it.

This is part of the massive information disconnect surrounding Alzheimer’s and dementia, and a source of anger for many persons with dementia and their families. I think most of us dealing with dementia can understand the kind of complexity Dr. Whitehouse talks about. We will continue to support both research and care efforts even when the hype about a cure is replaced by careful discussion about how we should view and treat dementia.

“It’s our obligation to think through what “Alzheimer’s” is and how to address it,” Dr. Whitehouse says.

Dreaming About A Cure, Talking About Care: Part 2 of 4 - More Care, Less "Cure"?

In my last post, I wrote about how researchers are beginning to question whether Alzheimer’s is really one disease. A different view of the definition of Alzheimer’s naturally leads to a different view of what we should do about it:

1. If Alzheimer’s is a disease, we need to continue to try to find the cure for it.

2. If Alzheimer’s is cognitive dysfunction caused by multiple aging-related conditions, we should shift our focus to steps we can take to prevent those conditions.

Dr. Peter Whitehouse, Professor of Neurology at Case Western Reserve University, is one of those who holds the second view. Because he doesn’t think Alzheimer’s is a single disease, he believes it’s unlikely that researchers will find a “cure.” He’s concluded we should focus resources on care and services for people with cognitive impairment, and on prevention, rather than searching for a “magic bullet” cure. “Care needs to be dominant over cure,” he says.

Richard Taylor, a retired psychologist, DASN member and author of the book Alzheimer's from the Inside Out, was diagnosed three years ago with dementia. He agrees there should be a shift in funding.

Richard Taylor, Ph.D

“This disease creates turmoil in 99.9% of the families who are dealing with it,” he says. “While ‘bench’ researchers run around chasing their molecular tails, people who are living with the disease as carers and carriers battle with themselves and each other.

When will more attention be paid to this real problem and less to the conditions of nude mice? I realize both areas need research, lots of research. In the mean time millions of people are struggling with the psycho-social consequences of the disease.

The vision of a world without Alzheimer's is compelling. Shouldn't the cries for help from people confronting it be just as compelling? There needs to be a more equitable split in research dollars between tomorrow's and today's issues.”

As I think through the care versus cure question, I wonder what a decision to shift resources away from research would have meant for my dad, whose cerebral amyloid angiopathy (CAA) caused microbleeds in his brain that led to his dementia and death. I don’t think the preventative measures we talk about now (healthy diets, exercise, staying engaged, etc.) would have made a difference for him. Basic research into the causes of and treatments for CAA and Alzheimer’s would have helped him more.

But in the last few years, research facilities have been forced to delay Alzheimer’s-related experiments and lay off scientists because they can’t get funding. With money already scarce for Alzheimer’s research, do we really want to shift resources from cure to care?

Lisa Genova, the neuroscientist and author mentioned in my earlier post, doesn’t think so. “As a neuroscientist who understands the biology of this disease and as someone who knows the researchers who are driven and dedicated to finding a cure, I honestly believe that a cure for this disease is within grasp, and to take funding away would be a crazy, horrific mistake,” she says.

Jeanne Lee, a DASN member living in Hawaii, and author of the book Just Love Me: A Life Turned Upside-down by Alzheimer’s, doesn’t want research funding reduced, but would like to see it redirected. “I do agree too much money is spent on the later stages of Alzheimer's or dementia,” she says. “The research monies need to go towards the other end of the disease when WE are still capable of knowing what is happening in our lives. We have medicines for early stages of cancer, diabetes and other diseases, and sometimes they’re caught early enough to be cured. This is what we need for Alzheimer’s and dementia, so why would you say research is not necessary?” Jeanne was diagnosed with dementia of the Alzheimer’s type in 1995.

Jeanne Lee

Many scientists agree with Jeanne that research must focus on stopping dementia long before onset. Dr. Whitehouse has specific ideas of how we should address research on early medical interventions. “I’d prefer to see research on healthy aging, and understanding the value of basic preventative measures, such as physical exercise,” he says. “Many of these measures are good for a lot of things besides Alzheimer’s, so the money would be better spent.”

On this aspect, Jay Smith, another DASN member mentioned in my last post, agrees with Dr. Whitehouse. “More research should be done to identify and isolate the various environmental and lifestyle causes of the disease - diet, nutrition, life style, stress, genetics, environmental toxins, etc. - as has been done in diabetes, heart disease and cancer over the past twenty years,” he says.

Wrong Question?

Other DASN members don’t like the care versus cure question. Carole Mulliken, a former teacher and school counselor diagnosed with vascular dementia at 59, says that, “…in most cases, framing a question in ‘either or’ format guarantees a false conclusion. To tie ourselves up in deciding which of the two is more important eliminates the possibility of putting energy in to multi-faceted responses.”

Carole Mulliken

Chuck Jackson another DASN member who has been diagnosed with early onset dementia agrees. “If we have a medical cure,” he says, “or medical treatment that stops progress of the disease in early stages, then we won’t need expensive care facilities after a certain amount of time. The bottom line is how to facilitate both care research and medical research.”

Richard Taylor feels the same way. “It's the wrong question to ask. The crucial question is why are there so few dollars that a choice has to be made. It's tragic, it's irresponsible, and everyone should be ashamed and angry we all aren't doing more to address the consequences of this plague.”

But if the current trend of reduced government spending for Alzheimer’s research continues, and private donors don’t step up with more donations, we’ll have to make a choice between cure and care.

Dreaming About A Cure, Talking About Care: Part 1 of 4 - Is Alzheimer's Really A Disease?

Last night, I dreamed Dad was getting better. He called to say he was back home, and sounded upbeat. He was finding words more easily than when we last had talked. I immediately started thinking about things we could do to speed his recovery: green tea, meditation, maybe even a little red wine. More than a year after Dad died, I'm still dreaming about a cure.

I'm not alone in my dreams. "I really thought that we would have a cure before I had to worry about onset. I was terribly wrong," says Chuck Jackson, a former employment counselor whose mother and nine of her siblings had early onset Alzheimer's. Four of his cousins have died of the disease, and how he, his brother and three of his cousins have been diagnosed with it.

This talk of a cure is echoed around the world in hundreds of labs and millions of homes. But I don't think we're anywhere close.

If you are diagnosed with Alzheimer's today, your doctor may prescribe Aricept, Namenda or other medicines. The most these drugs will do is delay symptoms in some people; they have no effect in others. Treatment won't change the underlying degeneration of your brain, or halt progression. If your family can't care for you, there's little chance you'll get good care in a nursing home, at least in the US.

This bleak reality has prompted Chuck Jackson and other members of the Dementia Support and Advocacy Network (DASN) to speak out about Alzheimer's. The majority of DASN members are persons with dementia or their care partners. Individual members of the group are working with organizations, the media and lawmakers to raise awareness about Alzheimer's.

"If doctors themselves would be more aware, I think they'd find there are a lot more afflicted with Alzheimer's disease than they realize," says Sarah Christianson, a DASN member and former office manager diagnosed with early onset Alzheimer's and frontotemporal dementia.

Sarah Christianson

But Dr. Peter Whitehouse advocates something different: a complete redefinition of Alzheimer's and how we treat it.

Dr. Whitehouse is Director of Integrative Studies and Professor of Neurology at Case Western Reserve University, and author of the forthcoming book The End of Alzheimer's [St. Martin's Press]. He is one of several scientists and doctors who have mentioned to me that they don't think Alzheimer's is a single disease.

Peter J. Whitehouse, M.D., Ph.D

"People suffer enormously from what I used to call Alzheimer's," he says. "But as a clinician, I'm aware of the variability of dementia symptoms and progression, so I'm suspicious of the claim that this is one disease and that it's different than aging."

Expressing doubts about Alzheimer's status as a disease is controversial, both among researchers and among persons with dementia. "Terribly wrong-headed," says Jay Smith, a DASN member from California who is working to organize a conference for people with dementia. "That kind of thinking (simplistic, not based in reality) is just dang