Category Archives: Alzheimer’s

Those of you interested in advances in imaging for neurodegenerative disorders and the correlations between imaging studies (while a patient is alive) and brain pathology (seen on post-mortem autopsy) will LOVE this news.

The PET is a type of brain scan. Currently, nearly all PET scans employ FDG, which picks up on glucose in the brain. For the last several years, the latest in PET scans for Alzheimer’s or other dementia patients employs PIB, Pittsburgh Compound B. PIB picks up on amyloid plaques. (The dye is retained by the insoluble amyloid protein.) Alzheimer’s disease is a disorder of two proteins — amyloid (which forms plaques) and tau (which forms tangles).

Hopefully, one day, we’ll have PET scans that can detect tau tangles (which would help diagnose PSP and CBD). Also, PSP and CBD can co-occur with Alzheimer’s Disease, so this news may be relevant to some in the PSP/CBD community also. (I’ve forgotten the exact percentage but it’s something like 20-30% of the time.)

The Alzheimer Research Forum has a (mostly-understandable) summary of a recently published article in the December 13th issue of the journal Brain about a woman with Alzheimer’s Disease who “volunteered for the first PET-PIB scan ever performed. She received another PIB scan two years later, and over the course of her disease also got an MRI and three PET scans using fluorodeoxyglucose (FDG), a marker for glucose use and therefore brain metabolism.” The woman died at the age of 61. She donated her brain for autopsy.

“Over the eight years she was studied, the woman’s score on the Mini-Mental State Examination declined from a near-normal score of 27 down to five. The FDG data showed that her brain’s glucose metabolism decreased in parallel with her cognitive powers. By contrast, PIB retention, already high at first examination, showed little change over two years during which her cognition declined steeply. The amount of amyloid deposition seen at autopsy three years later also looked similar to PIB estimates…suggesting no further change in amyloid between the second PIB scan and death three years later. This pattern matches the data from numerous previous studies, in which PIB retention increases during mild cognitive impairment, then seems to plateau during AD.”

“Autopsy results confirmed the patient’s diagnosis of pure AD. … The results confirmed that in vivo PIB retention correlates quite well with amyloid deposits, but does not correlate closely with tau and neurofibrillary tangles, as previous studies have found. … In addition, the authors performed detailed studies not done before and turned up intriguing correlations between amyloid accumulation and synaptic receptor density, as well as a surprising lack of correlation with markers of inflammation.”

The summary on the Alzheimer Research Forum discusses four clinical trials with compounds targeting amyloid in Alzheimer’s patients. The trials were all negative. This PET-PIB study gives additional insight as to why that may be the case.

Here’s the summary on ARF about the recently-published study:
http://www.alzforum.org/new/detail.asp?id=2653

Note that some of the comments are well worth reading, though harder to understand than the summary. Some of the comments (posted in 2004) give historical info on PIB.

The recently-published study is available at no charge through the journal Brain. See:
http://brain.oxfordjournals.org/content/134/1/301.long (for HTML version)

This article is about whether people should be given tests that address their risk of getting Alzheimer’s, and whether they should be told the results of the tests. And it’s about physicians’ views on the same topics.

There was a related discussion about a year ago on the local PBS radio station. The interviewee was Dave Iverson, who has Parkinson’s Disease. His father had PD and his brother has PD. He was asked if he wanted to know whether he carried a genetic mutation associated with PD. He said he did not. He was willing to participate in research studies of his genetic profile but told researchers not to pass the results to him. I believe he also said that after he died, researchers could provide the info to his daughter, if she wanted to know.

There are obviously many viewpoints on these topics. Presumably medical ethicists will need to advise medical centers on how to proceed.

Robin

http://www.nytimes.com/2010/12/18/health/18moral.html

THE VANISHING MIND
Tests Detect Alzheimer’s Risks, but Should Patients Be Told?
By Gina Kolata
New York Times
December 17, 2010

This a very discouraging article about preventing Alzheimer’s Disease or delaying its progression in today’s New York Times (nytimes.com):

www.nytimes.com/2010/08/29/health/research/29prevent.html

Years Later, No Magic Bullet Against Alzheimer’s Disease
By Gina Kolata
The New York Times
Published: August 28, 2010

My online friend Ed Plowman pointed out that it would’ve been helpful if an update had been provided in the article about the pool of evidence found for genetics in AD.

Robin

Big news from the Alzheimer’s community. A test of someone’s spinal fluid for beta-amyloid and tau is 100% accurate in terms of predicting who has Alzheimer’s and who has significant memory loss on their way to developing Alzheimer’s.

“So the new results are giving rise to a difficult question: Should doctors offer, or patients accept, commercially available spinal tap tests to find a disease that is, as yet, untreatable?”

“Many…believe that when PET scans for amyloid become available, they will be used instead of spinal taps, in part because doctors and patients are more comfortable with brain scans.”

Thanks to over 300 people who had spinal taps for this research, and some number who donated their brains upon death.

What’s the connection to the disorders covered here? Tau is a protein involved in PSP and CBD (but not beta-amyloid).

Here’s a link to a New York Times article on this news and full text, plus a link to the editorial that accompanies the “Archives of Neurology” journal article and a link to the research journal article as well (all available for free online):

http://www.nytimes.com/2010/08/10/healt … pinal.html

Spinal-Fluid Test Is Found to Predict Alzheimer’s
By Gina Kolata
New York Times
Published: August 9, 2010

Researchers report 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.

Although there has been increasing evidence of the value of these tests in finding signs of Alzheimer’s, the study, which will appear Tuesday in the Archives of Neurology, shows how very accurate they can be.

“This is what everyone is looking for, the bull’s eye of perfect predictive accuracy,” said Dr. Steven DeKosky, dean of the University of Virginia’s medical school, who is not connected to the new research.

The study, said Dr. John Morris, a professor of neurology at Washington University, “establishes that there is a signature of Alzheimer’s and that it means something.It is very powerful.

A lot of work lies ahead, researchers say — making sure the tests are reliable if they’re used in doctors’ offices, making sure the research findings hold up in real life situations, getting doctors and patients comfortable with the notion of spinal taps, the method used to get spinal fluid. But they see a bright future.

The new study is part of a tsunami of recent findings on Alzheimer’s disease. After decades when nothing much seemed to be happening, when this progressive brain disease seemed untreatable and when its diagnosis could only be confirmed at autopsy, the field has suddenly woken up.

Alzheimer’s, investigators now agree, starts a decade or more before people have symptoms. And by the time there are symptoms it may be to late to save the brain. So the hope is to find good ways to identify people who are getting the disease, and use those people as subjects in studies to see how long it takes for symptoms to occur and in studies of drugs that may slow or stop the disease.

Researchers are finding simple and accurate ways to detect Alzheimer’s long before there are definite symptoms — in addition to spinal fluid tests they also have new PET scans that show the telltale amyloid plaques that are a unique feature of the disease. And they are testing hundreds of new drugs that, they hope, might slow or stop the relentless brain cell death that robs people of their memories and abilities to think and reason.

But the PET scans are not yet commercially available, while spinal fluid tests are. So the new results are giving rise to a difficult question: Should doctors offer, or patients accept, commercially available spinal tap tests to find a disease that is, as yet, untreatable? In the research studies, patients are often not told they may have the disease, but in practice in the real world, many may be told.

Some say it should be up to doctors and their patients. Others say doctors should refrain from using the spinal fluid test in their practices. It is not reliable enough — results can vary from lab to lab — and has only been studied in research settings where patients are carefully selected to have no other conditions, like strokes or depression, that could affect their memories.

“This is literally on the cutting edge of where the field is,” Dr. DeKosky said. “The field is moving fast. You can get a test that is approved by the F.D.A., and cutting edge doctors will use it.”

But, said Dr. John Trojanowski, a University of Pennsylvania researcher and senior author of the paper, given that people can get the test now, “how early do you want to label people?”

Some, like Dr. John Growdon, a neurology professor at the Massachusetts General Hospital who wrote an editorial accompanying the paper, said that decision is up to doctors and their patients.

Doctors might want to use the test in cases where they need to be sure a patient with symptoms of severe memory loss and loss of reasoning abilities has Alzheimer’s. And they might want to offer it to people with milder symptoms who really want to know if they have the devastating brain disease.

One drawback, though, is that spinal fluid is obtained with a spinal tap, and that procedure makes most doctors and many patients nervous. The procedure involves putting a needle in the spinal space and withdrawing a small amount of fluid.

Dr. Growdon and others say spinal taps are safe and not particularly painful for most people. But, Dr. Growdon said, there needs to be an education campaign to make people feel more comfortable about having them. He suggested that, since most family doctors and internists are not experienced with the test, there could be special spinal tap centers where they could sent patients.

The new study included more than 300 patients in their seventies, 114 with normal memories, 200 with memory problems, and 102 with Alzheimer’s disease. Their spinal fluid was analyzed for amyloid beta, which forms plaques in the brain, and for tau, another protein that accumulates in dead and dying nerve cells in the brain. To avoid bias, the researchers analyzing the data did not know anything about the clinical status of the subjects. Also, the subjects were not told what the tests showed.

Nearly every person with Alzheimer’s had the characteristic spinal fluid protein levels. Nearly three quarters of people with mild cognitive impairment, a memory impediment that can precede Alzheimer’s, had Alzheimer’s-like spinal fluid proteins. And every one of those patients developed Alzheimer’s within five years. And about a third of people with normal memories had spinal fluid indicating Alzheimer’s. Researchers suspect that those people will develop memory problems.

The prevailing hypothesis about Alzheimer’s says amyloid and tau accumulation are necessary for the disease and that stopping the proteins could stop the disease. But it is not yet known what happens when these proteins accumulate in the brains of people with normal memories. They might be a risk factor like high cholesterol levels. Many people with high cholesterol levels never have heart attacks. Or it might mean that Alzheimer’s has already started and if the person lives long enough he or she will get symptoms like memory loss with absolute certainty.

Many, like Dr. DeKosky, believe that when PET scans for amyloid become available, they will be used instead of spinal taps, in part because doctors and patients are more comfortable with brain scans.

And when – investigators optimistically are saying “when” these days – drugs are shown to slow or prevent the disease, the thought is that people will start having brain scans or spinal taps for Alzheimer’s as routinely as they might have colonoscopies or mammograms today.

For now, Dr. DeKosky said, the days when Alzheimer’s could be confirmed only at autopsy are almost over. And the time when Alzheimer’s could only be detected after most of the brain damage was done seem to be ending too.

“The new biomarkers in CSF have made the difference,” Dr. DeKosky said. “This confirms their accuracy in a very big way.”

Editorial: Sharpen That Needle
A. Zara Herskovits, MD, PhD; John H. Growdon, MD
Arch Neurol. 2010;67(8):918-920.
http://archneur.ama-assn.org/cgi/content/full/67/8/918 (as of right now, this is available for free)

Diagnosis-Independent Alzheimer Disease Biomarker Signature in Cognitively Normal Elderly People
Geert De Meyer, PhD; Fred Shapiro, MLS; Hugo Vanderstichele, PhD; Eugeen Vanmechelen, PhD; Sebastiaan Engelborghs, MD, PhD; Peter Paul De Deyn, MD, PhD; Els Coart, PhD; Oskar Hansson, MD; Lennart Minthon, MD; Henrik Zetterberg, MD, PhD; Kaj Blennow, MD, PhD; Leslie Shaw, PhD; John Q. Trojanowski, MD, PhD; for the Alzheimer’s Disease Neuroimaging Initiative
Arch Neurol. 2010;67(8):949-956.
http://archneur.ama-assn.org/cgi/content/full/67/8/949 (as of right now, this is available for free)