The Tangled Neuron

Flurizan, Lipitor and Alzhemed: Negative Study Results

On Monday, Myriad Genetics Inc. announced the failure of Flurizan in Phase III trials.  This news follows the results from the LEADe study showing the cholesterol drug Lipitor did not benefit Alzheimer's patients, and the failure of Alzhemed in Phase III trials last year.

With all this disappointing news, it seems more important than ever for professionals, with input from patients and their families, to talk about new approaches to Alzheimer's research and care.  Maybe implementing some of the ideas discussed at the National Institute on Aging 2006 conference would help.  I'll be at ICAD (the International Conference on Alzheimer's disease) in late July - it will be interesting to see whether new approaches are widely discussed.

8 Practical Tips for Living with Memory Loss

I turned 50 last year.  Given my family history of dementia, I was not happy to read that as many as half of people my age and older have some memory loss. 

I've noticed my already poor navigation skills have declined lately, and I can't multitask the way I used to.  It's not just me - my friends complain about missing appointments, bouncing checks and forgetting words.  Even worse, they lose the calendars and smartphones that are supposed to keep them on track!

Modern medicine doesn't have a cure for memory loss, at least not yet.  Without a medical fix, are there things we can do to make living with memory loss easier?  I posed that question to some of my friends with more serious memory loss.  Here are some of their practical ideas that make sense to me:

1.  Experiment with a whiteboard for orientation and reminders. Use to record the date, where family members are, appointments, reminders, etc.

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?

Webcast: The Myth of Alzheimer's

If you want to congratulate Dr. Peter Whitehouse and Danny George for writing their book The Myth of Alzheimer’s, let them know how wrong you think they are, or are just plain curious, here’s your chance. They’ll be featured on a HealthTalk webcast tomorrow night (Wednesday, May 14th) at 7 PM eastern. Details are on the registration page at the HealthTalk site.

Chuck Jackson to Testify at U.S. Senate Hearing on Alzheimer’s

My friend Chuck Jackson, who along with many family members has early onset Alzheimer’s disease, will testify at a U.S. Senate hearing on Alzheimer’s tomorrow (Wednesday May 14th). The hearing starts at 10:30 AM eastern time. A link to the live webcast will be available at http://aging.senate.gov/.

Note:  you can now watch the webcast of the full hearing at any time, or read a transcript of Chuck's testimony.

Orien Reid Nix: Alzheimer’s Disease International and Baby Boomers at the Crossroads

Orien Reid Nix is a baby boomer with a family history of dementia. She is also Chair of Alzheimer’s Disease International.

Last week, she gave a keynote address at the Wisconsin State Conference on Alzheimer’s Disease and Related Disorders in Milwaukee. In her talk, she focused on the devastating effects of Alzheimer’s on baby boomers, both as they care for their elders and as they develop their own memory problems.

Orien Reid Nix and Corinne Reid Owens

Ms. Reid Nix was accompanied by her aunt, Corinne Reid Owens, a civil rights activist in Wisconsin. Ms. Owens is 95, and does not have Alzheimer’s. But several of Ms. Reid Nix’s family members, including her mother, had the disease. In her speech, she talked about the challenges of caring for her mother while still caring for her children – a common situation these days. Estimates of the number of Americans in the “sandwich generation” run as high as 20 million. There’s even a new term, “club sandwich generation,” to describe people who are caring for three generations.

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 Great Forgetting"

David Brooks’ April 11th New York Times opinion piece, “The Great Forgetting,” could have been a thoughtful look at the social consequences of memory loss and aging. Instead, his keen observations on "the memory haves and the memory have-nots" were followed by silly jokes.

He missed the opportunity for a more serious discussion about how our hyper-cognitive society measures a person's value by the speed and accuracy of his recall.

AAFP-ACP Guidelines for Drug Treatment of Dementia: What Do You Think Of The AAFP's Photo?

When my father was struggling with memory loss, his doctors prescribed both Aricept and Namenda. If they helped his memory and thinking, I couldn’t tell. For Dad, the side effects of these medicines didn’t seem to be worth any benefit.

Dad and my nephew Chris play the piano

But for other people with memory loss, these drugs seem to be very helpful, and the side effects are generally tolerable. This wide variety in benefits and side effects may be what the American Academy of Family Practitioners (AAFP) and the American College of Physicians (ACP) were trying to address when they published new guidelines about drug treatment of dementia last month.

CADASIL: Young Onset Dementia Caused by a Stroke Disorder

Summary: CADASIL is a type of stroke disorder that can cause young onset dementia. Two web sites have been developed by women whose families are affected by the disease.

Billie Duncan-Smith’s husband Steve’s first symptom came when he was 38. He woke up with an excruciating headache, and started vomiting because the pain was so bad. Over the next few years, he would suffer many such migraines, some lasting for several weeks. An MRI of his brain showed a high number of white matter lesions, but Steve’s doctors weren’t sure what was causing his headaches.

Billie and Steve in 2004

While Steve suffered, Billie searched the internet and contacted medical experts all over the world. She sent his records and test results to those who offered to help. Finally, someone at the U.S. National Institutes of Health called her to suggest Steve might have CADASIL (Cerebral Autosomal Dominant Arteriopathy with Sub-cortical Infarcts and Leukoencephalopathy), a type of stroke disorder.

Does Loss of Memory Mean Loss of Self? A Webcast

My friend Don Moyer, who blogs about his wife Jenny's memory loss and about memory loss in general, will be one of the guests on a HealthTalk webcast Wednesday (April 9, 2008) at 4 pm Pacific time. He, Jenny and Dr. Renee Beard, a geriatric sociologist at the University of Illinois Chicago, have published a paper about the rich and meaningful lives people with memory loss lead.

You can read more about this webcast, and register to participate here.

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.

Amyloid Inhibitors for Alzheimer's: Less Promising Than Thought?

Summary: Amyloid inhibitors, a type of Alzheimer’s drug under development, may not be as promising as once thought. A cheap and easy test early in the drug development process should help researchers focus on the most promising compounds. This finding does not apply to the vaccines being developed to clear amyloid.

If you’re one of the millions waiting for Alzheimer’s drugs now under development, you’ll want to know that researchers at the University of California, San Franciso (UCSF) have come to some interesting conclusions about one type of potential treatment. Which do you want first - the good news or the bad?

UCSF researchers Brian Shoichet, Ph. D. (left) and Robert Fletterick, Ph.D

Let’s start with the bad news. It looks like “amyloid inhibitors” may not be as promising as once thought. Some Alzheimer’s researchers are focused on developing these compounds to prevent beta amyloid proteins from clumping together to form the fibrils and plaques thought to be harmful to your brain. But as with other diseases, the trick is to find compounds that will affect only the beta amyloid “target,” without affecting other proteins your body and brain might need.

Research conducted in the lab of Brian Shoichet, a professor in the Department of Pharmaceutical Chemistry at UCSF, suggests that amyloid inhibitors often affect too many other proteins to be safe and effective Alzheimer’s treatments. The results of his work on this topic were published in late January in Nature Chemical Biology online.

Alzheimer's Research at a Crossroads: a new conference report

Summary: A new conference report from the U.S. National Institute on Aging summarizes the presentations, discussions and recommendations of top Alzheimer’s researchers. From my layperson’s point of view, the report shows three reasons why Alzheimer’s research is at a crossroads:

1. We don’t really understand what causes memory loss and dementia.
2. Every brain is different, and multiple factors and diseases may underlie any one person’s memory problems.
3. Overall, research to date has not yielded the hoped-for answers.

Of the many recommendations made to the NIA, the ones involving broadening the concept of Alzheimer’s and collaborating with scientists in other fields make the most sense to me. The NIA meeting and report seem like good first steps towards consensus on which road to take.

Over the weekend, I’ve been reading through an excellent report on a conference on Alzheimer’s convened by the U.S. National Institute on Aging (NIA). The conference took place in October 2006, on the 100th anniversary of Dr. Alzheimer’s discovery of plaques and tangles in the brain of his patient Auguste D.

Two Articles on Early Onset Alzheimer's

Two of my friends are featured in recent articles about Alzheimer's. An article in the Appleton, Wisconsin Post-Crescent tells the story of the dementia that runs in Chris VanRyzin's family, and how a combination of prescription medicines, supplements and lifestyle changes have gradually improved her health. Chris is the founder of forMemory, a non-profit working to share information to prevent and treat early onset Alzheimer's and related disease.

Jim Cook's work to help identify people under age 65 with memory loss in the Lincoln, Nebraska area is profiled in the Kearney, Nebraska Hub article. Jim was diagnosed with probable Alzheimer's when he was 55.

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.

Creativity and Memory Loss

Are people with memory loss more creative? It seems many have taken up painting, writing or playing an instrument. Donna Beveridge has taken up all three.

Donna, 65, is a retired elementary school teacher diagnosed last year with early stage probable Alzheimer’s. She lives with her partner Betsey and their two cats, Shadow and Idgy, near the coast of Maine. Her three children and their families live close by.

Enbrel – an Alzheimer’s “Miracle” and Irresponsible Reporting

When I started blogging about Alzheimer’s and dementia, people began sending me links to information about miracle cures for memory loss. I’ve received entire books about “hidden discoveries” and Alzheimer’s conspiracies in the mail. So far, none of the information (including an analysis I received a few weeks ago explaining how oral sex causes Alzheimer’s!) has been backed up by careful research. So when I saw excerpts of a press release about a new “miracle” cure for Alzheimer’s early this month in the Alzheimer’s Daily News (“Alzheimer’s Treatment Shows Promise”), I didn’t pay much attention.

But it turns out other media outlets were repeating the words of the press release, and attaching sensational headlines. ScienceDaily’s headline read “Reversal of Alzheimer’s Symptoms Within Minutes In Human Study” and FOXNews.com said “Study: Arthritis Drug Shows Promise in Reversing Symptoms of Alzheimer’s.”

It’s no surprise that Alzheimer’s message boards are full of emails about this “study,” which is really a case report published in The Journal Of Neuroinflammation. The case report tells about a man with probable Alzheimer’s who appeared to show immediate improvement (“within minutes”) when the arthritis drug Enbrel was injected into his spine. This “study” is not a clinical trial, and involved only one patient. The journal also published a link to a video [look under Additional Material - requires Apple QuickTime to view] “depicting family’s description of change in patient.”

Articles about this report were published with little or no investigative journalism or analysis. Many appear to simply repeat, word for word, a press release from the University of Arkansas. [This was weird in and of itself - why would we rely on a University of Arkansas press release about research supposedly conducted at UCLA and USC?] Most of us still harbor hopes for a cure for memory loss, and we want to believe Alzheimer’s headlines. Irresponsible reporting may drive advertising revenues, but it doesn’t help us sort through what might be helpful and what’s simply hype.

Gabrielle Strobel has published a careful analysis of this case and the circumstances surrounding the report on the Alzheimer Research Forum site. I also like Dr. Peter Whitehouse’s comments during an ABC interview, published on his Beyond The Myth blog.

Terry Pratchett Diagnosed With Alzheimer's: Overlooking the Best Source of Information?

Bert Piedmont at Had A Dad writes that one of her favorite authors, Terry Pratchett, has been diagnosed with early onset Alzheimer's. His doctors had originally diagnosed him with stroke.