The Tangled Neuron

A Quick and Easy Biomarker for Alzheimer's?

Summary:  A new method of visually assessing shrinkage of certain areas of the brain using standard MRIs may improve the diagnosis and treatment of Alzheimer's.

ICAD was all about biomarkers.  Biomarkers are physical or biochemical characteristics that are signs of an ongoing disease process in a living person.  They include genetic variations, molecules in blood or spinal fluid, and patterns seen on imaging tests.  To be useful in screening for a disease or monitoring the progress of a disease, they should be easy to obtain.  This typically involves collecting blood, urine, stool or saliva samples, or performing a radiological test. The use of biomarkers for certain diseases is well-accepted - for example, blood tests are used to indicate the presence of certain cancers or the risk of heart disease.

But for Alzheimer's, diagnosis is currently based on neuropsychological tests and medical histories showing cognitive impairment.  Brain scans (MRI and CT scans) are not typically used to diagnose Alzheimer's, but instead are used to exclude other conditions that can cause cognitive problems.

Speaker after speaker at ICAD explained that we need biomarkers to:

• diagnose [and eventually treat] Alzheimer's in early stages, perhaps even before symptoms appear

• diagnose Alzheimer's more accurately, at any stage

• measure the effect of drugs on disease progression in clinical trials.

This concept sounds good, but there are practical problems:

• studies have not yet confirmed the accuracy of many of the biomarkers proposed; a high percentage of false positive results seems possible

• new technologies to measure potential biomarkers like amyloid protein in the brain are expensive and not yet available outside of research facilities

• some studies have shown that the levels of certain proteins in spinal fluid may be an accurate biomarker, but the required spinal tap is unappealing to many patients.

Ranjan Duara, MD

Dr. Ranjan Duara, Medical Director of the Wien Center for Alzheimer's Disease and Memory Disorders in Miami Beach, Florida and Associate Professor of Medicine, Neurology and Psychiatry at the University of Miami, thinks we already have a biomarker that is accurate, inexpensive and doesn't require drawing spinal fluid.  He has developed a system for visually measuring and rating the atrophy, or shrinkage, of three areas within the medial temporal lobe of the brain.  He and his colleagues recently completed a study showing that this method can help differentiate among people who are cognitively normal, those with Mild Cognitive Impairment and those with Alzheimer's.  The study also showed that this assessment can help predict which patients will progress from Mild Cognitive Impairment to Alzheimer's.

Beyond Drugs: Other Ways To Treat Alzheimer's and Dementia (Part 1)

Summary:  Nondrug treatments such as aromatherapy, bright light therapy and caregiver support can complement drug treatments and benefit people with dementia and their caregivers.

Almost all the presentations at ICAD were about molecular biology.  They dealt with proteins like amyloid and tau, with genes like APOE and SORL1, and with the inner workings of brain cells.  Sitting in dark conference rooms watching these presentations, it was easy for me to lose sight of the real-life problems of people with dementia and their caregivers.

The last session I went to brought my focus back to these real-life problems.  It's too bad these presentations were given when many conference attendees were already on their way home -  "Psychosocial Issues and Neuropsychology" was one of the most interesting sessions at ICAD!  Four of the six presentations were specifically about nondrug treatment of dementia, and it's those presentations I'll focus on in the next few posts.

First up was Dr. Alistair Burns, a Professor and Deputy Dean of Clinical Affairs at The University of Manchester in the UK.  He is involved in trials of both drug and nondrug treatments for people with dementia and their caregivers.  Some of the nondrug treatments he has studied include:

Rember: "Breakthrough" Alzheimer's Drug?

Summary:  results of Phase 2 clinical trials of a new Alzheimer's drug called rember look promising.  The drug is thought to reduce tau, the protein that makes up Alzheimer's tangles.  Drugs that look effective in Phase 2 trials have a low chance of proving effective in Phase 3, so we'll have to wait for the results of the Phase 3 trials before calling rember a "breakthrough." 

The positive results of this Phase 2 trials lend credibility to those who would like to broaden Alzheimer's research beyond the amyloid hypothesis.

I estimate there were 5400 minutes of presentations at ICAD, last month's Alzheimer's research conference in Chicago.  There were also around 2000 poster presentations.

One twenty minute presentation on a potential Alzheimer's drug called rember, along with six related posters, generated more excitement than all the other presentations put together.

Flurizan Clinical Trial Results at ICAD

I walked into the Tuesday afternoon Clinical Trials session at ICAD half an hour early, and got one of the last seats in the room.  Conference attendees were literally running into the room to try to get a seat.  The press was there in full force.  Women complained about having to choose between using the restroom (which given the long lines would have meant a 10-15 minute delay) and getting in to this session.  A film crew was roving around, blocking the aisles and adding to the carnival atmosphere. 

This was definitely the best-attended session of the conference, and the Alzheimer's Association set up an overflow room with a video feed for those who could not get in. 

The Alzheimer's Action Plan: Book Review

Summary: The Alzheimer's Action Plan is a comprehensive resource for patients and families. It's not likely that most people with memory loss will get the standard of care the authors would want for their own parents, but the guidelines in the book will help patients and families get as close to that standard as possible.

The scenario at the beginning of The Alzheimer's Action Plan will be familiar to many adult children whose elderly parents have memory problems:  warning signs, denial of problems by both your parent and his doctor, increasing problems, seemingly sudden diagnosis of Alzheimer's, no advice or support.  While this scenario doesn't exactly reflect my family's situation, I wish we had had this book when my father was alive.

Lisa Gwyther, M.S.W.

I met the authors at ICAD last week.  Dr. Murali Doraiswamy is Chief of Biological Psychiatry and past Director of Psychiatry Clinical Trials at Duke University Medical Center.  Lisa Gwyther is Director of the Alzheimer's Family Support Program at Duke's Center for Aging and current President of the Gerontological Society of America.  The combination of the viewpoint of a doctor involved in clinical trials and that of a social worker who has worked with thousands of families makes The Alzheimer's Action Plan a comprehensive resource.

Dr. Doraiswamy and Ms. Gwyther wrote the book to answer the question they often hear:  "what would you do if your mother was starting to have memory problems?"  To get a flavor for how the book is structured around real-world concerns, read the last chapter, "Our Top 40 Questions and Answers," first.  You'll find thoughtful answers to other questions they hear, including:

• "How do I get my father to go to the doctor when he thinks nothing is wrong?"
•  "Is it worth it to get a second opinion?  The doctor said my dad's CAT scan was normal, but he just isn't himself anymore."
• "Is there anything I can do now to keep from getting Alzheimer's like my mom and her mom?"

This book has something for everyone - people with memory loss, their families, and anyone worried about cognitive problems.  But at 400+ pages, it might be best-suited for the adult children audience the authors had in mind.  Parts one and two of the book cover what you need to know when you're in the doctor's office:  the latest diagnostic tests, what you can and can't expect from treatment, the pros and cons of participating in clinical trials and patients' rights.  Parts three and four are about life outside the doctor's office:  living well with early-stage Alzheimer's, dealing with changes in behavior and emotions, and finding peace of mind in later stages.  Part five contains advice for a brain-healthy lifestyle.

The real achievement of the book is laying out guidelines or standards for diagnosis and care.  If I had had this resource when my father was alive, I wouldn't have had to spend so much time researching diagnosis and treatments.  I would have been more comfortable asking Dad's doctors questions.

"Knowledge is power," Dr. Doraiswamy says.  "We wrote this book to give families the highest quality information which we hope will empower them to become their own best advocates for better brain and memory health."

But if I had had this book, would my father's diagnosis, treatment or care have been any different?  I don't think so.  Despite our best efforts, and those of numerous doctors inside and outside of a university-based memory clinic, we were not able to get the kind of diagnostic work, treatment or care described in The Alzheimer's Action Plan.  I suspect that is true of many families.

In between sessions at ICAD, I asked Lisa Gwyther if the book raises expectations too high.  "I hope not," she said.  "What we're trying to do is talk about what's possible, what to aim for as an advocate for yourself or your family member."  To be fair, Dr. Doraiswamy and Ms. Gwyther write frankly about the shortcomings of the medical system and the limits of treatments.  But what can be done to move toward their vision of excellent care?

From Ms. Gwyther's point of view, the answer may lie in a chronic disease management team approach, where overall patient care is coordinated among a variety of healthcare professionals.  "You can't expect to get all of your information from one physician," she said.  "Sometimes we need translators or interpreters, and we can get more time and more in-depth answers from experienced geriatric nurse specialists, social workers or other members of the healthcare team.  Geriatricians know a lot about dementia, and they are more likely to focus on enhancing function and comfort by treating excess disabilities or other chronic conditions.  Sometimes the most important thing you can do is get a 'tune-up and oil change' - go to a geriatrician or your regular doctor and make sure the things you can fix, treat or manage are treated.  Then look at what can be done to make your environment safer, and your daily routines and relationships more pleasant and meaningful."

It's not likely that most people with memory loss will get the care Dr. Doraiswamy and Ms. Gwyther would want for their parents, but the guidelines in The Alzheimer's Action Plan will help patients and families get as close to that standard as possible.

 

 

International Conference on Alzheimer's Disease (ICAD) 2008

Summary:  the majority of presentations at ICAD focused on Alzheimer's as a disease, and what we can do to cure it.  But the presentations on healthy brain aging (even in people with Alzheimer's plaques and tangles in their brains) were just as interesting.  From my layperson's point of view, we may learn as much from exploring healthy brain aging as we do from looking for an Alzheimer's cure.

It's hard to summarize ICAD 2008, held last week in Chicago.  The majority of the hundreds of oral presentations and thousands of poster presentations focused on molecular biology (genes, proteins, etc.), and on amyloid protein in particular.  But the three presentations in the plenary session on the last day highlighted that there are at least two ways to look at Alzheimer's: 

1. as a disease, with the focus on what can we do to cure it
2. as the opposite of successful aging, with the focus on what keeps our brains healthy as we age.

Paul Aisen, MD, now at University of California - San Diego, gave a presentation called "The Evolution of Alzheimer's Disease Clinical Trial Design."  His presentation was from the view of Alzheimer's as a disease, and what we can do to cure it.