The Tangled Neuron

Biomarkers: Some Thoughts from Richard Taylor

       Richard Taylor, PhD

Note:  as a person with dementia and a retired psychologist, Richard is uniquely positioned to think about Alzheimer's and dementia.  Here are some of his thoughts about what the headlines on biomarkers mean for people with dementia and their families.

Will I "get" Alzheimer's Disease/Dementia? How can I know before even my brain knows, or at least shows any signs of knowing? The answers claim the usual gang of suspects turns out to be in a bag of bodily fluids (mostly blood and spinal fluid), DNA, Genes, and stuff I spilled on myself while eating lunch just before I went in to the "create your own bag of bio markers" get-together.

Change comes and goes fast, very fast. For someone living with the symptoms of dementia the change I have experienced since my diagnosis about nine years ago would even spin the head of someone whose cognitive skills are not slipping. For me, since my skills are slipping and the change is literally overwhelming. Now comes the claim there is a bag of biomarkers that predicts Alzheimer's (or is it dementia) with a 90% accuracy rate, and can predict it way, way before our brain is effected by the biology of dementia (if indeed there is such a freestanding biology).

Should You Ask for One of the New Alzheimer's Diagnostic Tests?

Summary:   A Swedish study questioned the accuracy of the proposed “Dubois criteria” for diagnosing Alzheimer’s.  Professor Dubois says the criteria are very specific, and so will miss some cases, but will result in few false positive diagnoses.

Researchers are still working to validate the biomarkers included in the proposed criteria.  If you are considering requesting one of these tests before researchers can confirm its accuracy, there are some practical considerations you may want to discuss with your doctor.

I wrote last month about a Swedish study questioning the accuracy of the proposed “Dubois criteria” for diagnosing Alzheimer’s. These criteria incorporate biomarkers such as results of imaging scans and spinal fluid tests.

Commenting on the Swedish study, Bruno Dubois, leader of the group of experts who developed the criteria, says other research has shown “a high accuracy of the new proposed criteria.”  Professor Dubois is Director of the Memory and Alzheimer’s Institute at the Salpêtrière Hospital in Paris.

New Alzheimer's Diagnostic Techniques: Not Ready for Widespread Use?

Summary:  A recent study questions the accuracy of proposed biomarkers for diagnosing Alzheimer’s. 

Doctors currently make a diagnosis of Alzheimer’s based on symptoms and by ruling out other medical causes for those symptoms.  Two groups of researchers have proposed new diagnostic criteria that add certain "biomarkers" -- physical or biochemical characteristics that are signs of disease.  One set of criteria was developed by panels convened by the Alzheimer’s Association and the U.S. National Institute on Aging.  A similar set, the "Dubois Criteria," was developed by the International Working Group for New Research Criteria for the Diagnosis of AD.

The goal of these new criteria is more accurate diagnosis, which hopefully will lead to earlier and better treatment.  More accurate diagnosis would have been enormously valuable for my family, eliminating the long diagnostic roller coaster that my father endured. 

But at least initially, these new criteria may cause more confusion than clarity. Researchers at the Karolinska Institute in Stockholm recently compared the diagnoses of memory clinic patients via the current methods with diagnoses of the same patients using the Dubois criteria.  Use of the new criteria drastically decreased the number of people diagnosed with Alzheimer’s.

Alzheimer's and Dementia Screening

Summary:  As part of the new health care reform law in the U.S., Medicare will begin covering dementia screening next year.  Researchers who developed a new screening questionnaire called AD8 at Washington University in St. Louis believe it is the right tool for screening.  No matter which tool is best, screening all older adults for dementia may not be practical or useful. 

Along with more than 100 other participants, I listened to Tuesday’s Alzheimer Research Forum webinar about a new paper and pencil test to screen for dementia.  The new screening tool, called AD8, was developed by researchers at Washington University in St. Louis.  It consists of eight questions about changes in behavior that could be caused by problems with memory and thinking, and is meant to be answered by a family member or close relative or friend.  It can also be filled out by the person being screened.

A good portion of the webinar was a presentation by one of the tool’s developers, Dr. James Galvin (now at New York University).  He presented research showing AD8 is better at detecting early dementia than some other tools.  But the panel discussion and questions towards the end of the hour got at the more fundamental question:  is screening all older adults for dementia a good idea?

Correction to New York Times Article

The New York Times has published a much-needed correction to its article on a spinal fluid test that "can be 100 percent accurate" in predicting which patients with memory loss would go on to develop Alzheimer's.

The Trouble With Expectations

You’ve probably seen recent media reports on the proposed changes to the guidelines for diagnosing Alzheimer’s, along with an article claiming that “a spinal fluid test can be 100 percent accurate in identifying patients with significant memory loss who are on their way to developing Alzheimer’s disease.”   Today’s headlines include a story about a blood test for predicting whether you’ll develop Alzheimer’s.

Although most professionals are careful to say the proposed guidelines and tests aren’t ready for widespread use, public expectations seem very high.   On a flight last month, I sat next to a man in his 20s whose stepfather is showing signs of memory loss.  My seatmate wasn’t terribly concerned about his stepfather, he said, because he had seen the recent reports of progress in Alzheimer’s research and believed that a cure is around the corner. 

Expecting Improved Diagnosis and Treatment

        Mary Kay Baum

Two of my friends diagnosed with young onset dementia also have high expectations.  They sent me their thoughts supporting the proposed guidelines for diagnosis, particularly the guidelines for a diagnosis of “preclinical Alzheimer’s.”  Their strong support is based on the long and difficult process each went through to get diagnosis and treatment, and the relative success of treatments in stabilizing their conditions.   It’s also based on their assumption that they would have been diagnosed with some form of Alzheimer’s if the proposed guidelines were used when they first sought answers about their symptoms.

“Consider me,” wrote Mary Kay Baum, who has a strong family history of dementia.   “I am a 63 year-old woman who was a lawyer and pastor with two graduate degrees, thirty years of public service, and ten years of cognitive challenges. The old Alzheimer’s disease criteria ignored me. It did not have a vocabulary for my issues. Doctors did not know what to do with me! The criteria from 25 years ago did not advise practitioners to help me prevent the dementia we had seen in my mother and my aunt while in their mid-fifties. Most research excluded me…. Many in my situation fear we won’t be treated until we are really demented.”

Aspirin, Brain Bleeding and Memory Loss

I’ve written before about how bleeding in the brain is more common than previously thought, especially for people diagnosed with Alzheimer’s.  Bleeding in the brain (which can be detected by a type of MRI) may be a sign of the cerebral amyloid angiopathy my father had, and is linked to memory loss. 

A new study suggests that if you’ve already had bleeding in your brain, aspirin may increase the risk of further bleeding.  This adds to the evidence that you should check with your doctor before taking aspirin on an ongoing basis.

Early AD Symposium: John Morris Makes the Case for "Preclinical Alzheimer's Disease"

            John Morris, MD

Dr. John Morris is a Professor at Washington University in St. Louis and Director of the Alzheimer’s Disease Research Center  there.  One of his areas of interest is detecting “preclinical Alzheimer’s disease.”  He made the case for this relatively new concept in the first day’s keynote address at the Symposium on Early Alzheimer’s Disease in Miami Beach earlier this month.

Alzheimer’s should be viewed more as a chronic disease, he said, and this concept includes a “preclinical” phase where there are changes in the brain, but no noticeable symptoms.  Despite some studies showing people with large amounts of Alzheimer’s pathology (plaques and tangles) can have normal memory and thinking, he does not believe that pathology is harmless.  He and his colleagues have shown that people with Alzheimer’s pathology who seem cognitively normal already have brain shrinkage in some areas.  Tests show that their memory and thinking has already declined over time.  They will develop dementia if they live long enough, he thinks.

The Father of the MMSE

Marshal Folstein, MD

Marshal Folstein, who along with his wife Susan, developed the Mini-Mental State Examination (MMSE) used to screen for cognitive impairment was at the Symposium on Early Alzheimer’s Disease in Miami Beach this year.

How Do People React to a Diagnosis of MCI?

         William Haley, Ph.D.

In my last report from the Mild Cognitive Impairment (MCI) Symposium, I wrote about research on disclosing a diagnosis of dementia.  But what if the diagnosis is MCI, not dementia?  Bill Haley, Professor at the School of Aging Studies at the University of South Florida, gave a presentation focusing specifically on this topic.  This next report summarizes his presentation on recent USF research in this area.

Disclosing a Diagnosis of Dementia

Alexandra Zaleta and Brian Carpenter, Ph.D.

My last few reports from the Mild Cognitive Impairment (MCI) Symposium were about the symptoms seen in people with MCI and the conditions that may underlie it.  These are researchers' views.  But what do patients think about MCI?

There were no patients or family members at the Symposium, but two presentations began to deal with that question.  The first, by Brian Carpenter, Associate Professor of Psychology at Washington University, was about disclosing a diagnosis of dementia.  Dr. Carpenter and his colleagues (including Alexandra Zaleta, a graduate student pictured here with Dr. Carpenter at the MCI Symposium) have been examining how doctors tell patients and families about a diagnosis, and what patients and families hear.  You can find details of his presentation in the latest report from the MCI Symposium.

Mild Cognitive Impairment in Parkinson's?

Alexander Tröster, Ph.D.

There is a growing recognition that people diagnosed with Parkinson’s disease may have cognitive impairment in addition to their physical symptoms.  Another report from the Mild Cognitive Impairment (MCI) Symposium covers Dr. Alexander Tröster's presentation on the challenges in considering MCI in someone with Parkinson's.

Lewy Body Disease and MCI

  Brad Boeve, MD

At autopsy, pathologists often find Lewy bodies in the brains of people who had Mild Cognitive Impairment (MCI).  But doctors may be able to tentatively diagnose Lewy body disease in MCI patients when they're still living.  Check out a summary of Dr. Brad Boeve's presentation from the Mild Cognitive Impairment Symposium for details.

The 7th Annual Mild Cognitive Impairment Symposium: Part 4

The criteria for diagnosing Mild Cognitive Impairment (MCI) are not very specific, so whether or not you are diagnosed with MCI depends somewhat on your doctor’s judgment.   Scientists are working to determine which tests are best for detecting MCI, and whether the current criteria for the diagnosis can firmed up.

The fourth report on last month’s Mild Cognitive Impairment Symposium in Miami is about new neuropsychological tests and brain scans for diagnosing MCI.

The 7th Annual Mild Cognitive Impairment Symposium: Part 3

There’s a great deal of interest in genetic testing to assess the risk of developing Alzheimer’s and other common diseases.  Although some scientists argue that we don’t yet know enough to really estimate risk based on a genetic test, some companies offer testing and risk assessment now.

Should someone diagnosed with Mild Cognitive Impairment undergo genetic testing to find out if he has a neurodegenerative disease such as Alzheimer’s or Parkinson’s?  The third report from the Mild Cognitive Impairment Symposium is a summary of a presentation on this topic by Dr. Owen Ross, Assistant Professor of Neuroscience at Mayo Clinic College of Medicine.

The 7th Annual Mild Cognitive Impairment Symposium, Part 2

The term Mild Cognitive Impairment (MCI) is used to describe a level of memory loss that is somewhere between normal aging and dementia.  It doesn’t specify what might be causing the impairment, so it’s not surprising that symptoms vary widely among people diagnosed with MCI.  

The second report from the Mild Cognitive Impairment Symposium is a summary of presentations on these symptoms and a discussion of how the symptoms are classified.

The 7th Annual Mild Cognitive Impairment Symposium

Ranjan Duara, MD

Last week, researchers gathered in Miami for the 7th Annual Mild Cognitive Impairment Symposium, organized under the direction of Dr. Ranjan Duara, Medical Director at the Wien Center for Alzheimer’s Disease and Memory Disorders at Mount Sinai Medical Center in Miami Beach and Associate Professor of Medicine, Neurology and Psychiatry at the University of Miami.

The first of a series of Tangled Neuron reports on the Symposium covers the keynote speech of Dr. Ron Petersen, Director of the Mayo Alzheimer’s Disease Research Center.  I’ll be posting more information on this meeting in the next few days.

CAA, Microbleeds and Dementia: A New In-Depth Report

In the three years since my father died, I’ve often felt like there’s been little progress in dementia research.  This week, I was reminded that the complexity of the topic sometimes hides the progress that has been made.

A good example of this is the research on the cerebral amyloid angiopathy (CAA) and microbleeds Dad had.  When he died, awareness about CAA and microbleeds was low, even among doctors.  Lately, though, I’ve been getting more emails from people whose family members have those conditions, and new research shows they are much more common than we thought.

Given the new interest in the topic, I thought I’d do a quick update.  I found so much new information that my quick update grew into a longer report (see CAA, Microbleeds and Dementia:  An Update). 

We still don’t know how to prevent or treat CAA or microbleeds – some of the new information brings more questions than answers.  But it’s still progress.

New Lewy Body Dementia Publication

 A new publication, "Introduction to Lewy Body Dementia," is now available from the Lewy Body Dementia Association.  Written for people newly diagnosed with Lewy body dementia as well as for those who don't yet have a diagnosis, this brochure covers symptoms, treatments, prognosis and frequently asked questions.

The Association has also developed a Medical Alert Wallet Card to alert medical professionals to sensitivity to certain medicines in people with Lewy body dementia.

Lewy Body Dementia: The Importance of the Right Diagnosis

Every day is a great day for Harry Lewis.  “He’s so plugged into life that he wakes up singing 'You Are My Sunshine,'” says his wife Sue.  “He tells me ‘there’s nothing wrong with me – I feel great!’” she says.

It wasn’t always this way.  When he was diagnosed with Alzheimer’s several years ago, Harry was anxious and depressed.  When his doctors prescribed an antipsychotic medicine to control his hallucinations, he started having seizures.  There weren't any great days in the Lewis household back then.

Once Harry’s diagnosis was changed to dementia with Lewy bodies (DLB), Sue says, she was able to educate herself and work with his doctors to improve their quality of life.  Although there’s no treatment to stop progression of DLB, the medicines Harry takes have reduced his symptoms considerably.

   Angela Taylor

“Getting the right diagnosis and treating the many LBD symptoms correctly can make a significant difference in the quality of life of both the patient and his primary caregiver,” says Angela Taylor, board member and chair of the Science Committee for the Lewy Body Dementia Association.  Along with Sue Lewis and Joseph Friedman, M.D., she talks about why an accurate diagnosis is so important in Part 3 of the Tangled Neuron series on Lewy body dementia.

In addition to the right diagnosis and treatments, Sue thinks a good attitude is the key to living with the disease.  She focuses on the positive, and tries not to give in to what she sees as a common and deep-seated fear of dementia. 

“As I’ve grown as a caregiver and thrived through dementia, we’ve lost that mask - that bored look Harry used to have on his face,” she says.  “I’ve refused to let him be ‘unplugged.’  When he was mobile, I took him to concerts and potluck suppers, and everyone helped entertain him. He told everyone dementia made him a better dancer - he lost his inhibition!   Even now that he’s in a wheelchair, we’ve stayed social.  And I bought two guitars - it’s not pretty, but we play the blues.” 

Despite her positive attitude, Sue finds the fluctuations in Harry’s symptoms maddening, and she worries about how they would handle any change in the environment and routines she's created for her husband.  “I live with the fear that everything can crumble every day,” she says.  “What if our house burns down?  I can’t go live in a motel with Harry.  What if we need a new roof or a new furnace?  Harry couldn’t deal with that right now.”