testing the dependent variable, decline in mental abilities, as a function of the independent variable, age, shows no correlation at all.
Ted Nettlebeck and Nicholas Burns at the University ofAdelaide recently investigated what causes both the improvement of reasoning ability (fluid intelligence) in children between the ages of 8 to14 and the decline in reasoning ability in adults from 50 years onwards.
They took a large sample of children aged 8–14 years and adults aged 18–87. They all completed the same set of IQ tests, which measured their abilities in processing speed, working memory and reasoning ability. Even though each of these abilities is partly distinct, they are all positively linked with overall intelligence and IQ level.
They found that for children as they age from 14 to 18 years old, their processing speed increases. This increased speed improves their working memory, and their working memory improves their reasoning ability/fluid intelligence.
The links between processing speed, working memory and reasoning/fluid intelligence was different for adults however. They found that between the ages of 18 to 87, processing speed steadily declines. Slower information processing reduces working memory capacity. They also found that from the age of 55 onwards working memory declines independently from processing speed.
This is partly due to the steady loss of brain cells that is known to occur in the memory brain structure called the hippocampus during aging. The overall reduction in working memory causes poorer reasoning skills in older age.
The 55 plus group performed at 72% the level of the 18-45 year olds on working memory (memory span)
The 55 plus group performed at 75% the level of the 18-45 year old group in reasoning (matrices)
This kind of reduction in cognitive function is called ‘cognitive aging’. This study shows that the decline in fluid intelligence during aging is due to poorer working memory capacity.
It is worth noting that this decline sets in from our 30s onwards – but it is more pronounced in middle age and older.
http://www.highiqpro.com/recent-iq-research/what-causes-loss-of-reasoning-ability-from-middle-age
http://www.sciencedirect.com/science/article/B6V9F-4XT2CH7-2/2/90014e5ed743eb0af4e791ff5af54864
When does age-related cognitive decline begin?
Timothy A. Salthouse, PhD
To summarize, the results of the current project, together with results from research on non-human animals and on neurobiological variables, suggest that age-related cognitive decline begins relatively early in adulthood, but that it may not be detected in longitudinal comparisons until effects of prior test experience are taken into consideration. Not all aspects of cognitive functioning exhibit early age-related declines because measures based on accumulated knowledge, such as performance on tests of vocabulary or general information, are consistently found to increase until at least age 60. However, only those variables exhibiting negative age-related differences in cross-sectional comparisons are directly relevant to the question of when age-related cognitive decline begins.There is some evidence that the magnitude of age-related decline accelerates at older ages. To illustrate, a sample of about 800 adults between 61 and 96 years of age in my laboratory had cross-sectional slopes of about -.04 to -.05 SD units per year compared to the slopes of -.02 to -.03 SD units per year for adults under age 60. In absolute units, the decline in speed variables was about twice as great in this age range compared to adults under age 60, and the decline in the memory variables was nearly 4 times greater. What is not yet known is whether these quantitatively different age trends reflect changes in the same set of influences, or the operation of qualitatively different types of influences. However, what does appear clear is that several different types of results converge on the conclusion that age-related cognitive decline begins relatively early in adulthood, and certainly before age 60 in healthy educated adults.
Neurobiol Aging. 2009 April; 30(4): 507–514.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2683339/
The New York Times
June 23, 2010
Promise Seen for Detection of Alzheimer’s
By GINA KOLATA
Dr. Daniel Skovronsky sat at a small round table in his corner office, laptop open, waiting for an e-mail message. His right leg jiggled nervously.
A few minutes later, the message arrived — results that showed his tiny start-up company might have overcome one of the biggest obstacles in diagnosing Alzheimer’s disease. It had found a dye and a brain scan that, he said, can show the hallmark plaque building up in the brains of people with the disease.
The findings, which will be presented at an international meeting of the Alzheimer’s Association in Honolulu on July 11, must still be confirmed and approved by the Food and Drug Administration. But if they hold up, it will mean that for the first time doctors would have a reliable way to diagnose the presence of Alzheimer’s in patients with memory problems.
And researchers would have a way to figure out whether drugs are slowing or halting the disease, a step that “will change everyone’s thinking about Alzheimer’s in a dramatic way,” said Dr. Michael Weiner of the University of California, San Francisco, who is not part of the company’s study and directs a federal project to study ways of diagnosing Alzheimer’s.
Still, the long tale behind this finding shows just how difficult this disease is and why progress toward preventing or curing it has been so slow.
Ever since Alzheimer’s disease was described by a German doctor, Alois Alzheimer, in 1906, there was only one way to know for sure that a person had it. A pathologist, examining the brain after death, would see microscopic black freckles, plaque, sticking to brain slices like barnacles. Without plaque, a person with memory loss did not have the disease.
There is no treatment yet to stop or slow the progress of Alzheimer’s. But every major drug company has new experimental drugs it hopes will work, particularly if they are started early. The questions though, are who should be getting the drugs and who really has Alzheimer’s or is developing it?
Even at the best medical centers, doctors often are wrong. Twenty percent of people with dementia — a loss of memory and intellectual functions — who received a diagnosis of Alzheimer’s, did not have it. There was no plaque when their brains were biopsied. Half with milder memory loss, thought to be on their way to Alzheimer’s, do not get the disease. And with such a high rate of misdiagnosis, some who are mistakenly told that they have Alzheimer’s are not treated for conditions, like depression or low levels of thyroid hormone or drug side effects and interactions, that are causing their memory problems.
Brain scans that showed plaque could help with some fundamental questions — who has or is getting Alzheimer’s, whether the disease ever stops or slows down on its own and even whether plaque is the main culprit causing brain cell death.
Dr. Skovronsky thought he had a way to make scans work. He and his team had developed a dye that could get into the brain and stick to plaque. They labeled the dye with a commonly used radioactive tracer and used a PET scanner to directly see plaque in a living person’s brain. But the technology and the dye itself were so new they had to be rigorously tested.
And that is what brought Dr. Skovronsky, a thin and eager-looking 37-year-old, to his e-mail that recent day.
Five years ago, Dr. Skovronsky, who named his company Avid in part because that is what he is, had taken a big personal and professional gamble. He left academia and formed Avid Radiopharmaceuticals, based in Philadelphia, to develop his radioactive dye and designed a study with hospice patients to prove it worked.
Hospice patients were going to die soon and so, he reasoned, why not ask them to have scans and then brain autopsies afterward to see if the scans showed just what a pathologist would see. Some patients would be demented, others not.
Some predicted his study would be impossible, if not unethical. But the F.D.A. said it wanted proof that the plaque on PET scans was the same as plaque in a brain autopsy.
The Avid study was designed to provide that proof. And the full results, contained in the e-mail message sent that day, May 14, were the moment of truth. When he saw them, Dr. Skovronsky said they were everything he had hoped for.
“This is about as good as it gets,” he said that day.
He went into a rotunda that serves as Avid’s lunchroom to tell the company’s 50 employees. “This is a big day for us,” he continued. “I thought about what I would say, but I have totally forgotten it.”
His employees applauded. Then they had champagne in blue plastic cups.
A First Dye
The type of scans used in this study, PET scans, are expensive and patients have to go to a scanning center, get injected with a radioactive dye, wait for the dye to reach their brain and then have a scan.
Other tests are being studied — ones that look for amyloid in cerebrospinal fluid that bathes the brain; MRI scans that look for shrinkage of the brain in areas needed for memory and reasoning; PET scans that look for uptake of glucose, a cellular fuel, to show areas where the brain was active and where it was not. The tests, though, were not necessarily specific for Alzheimer’s and none had been studied to see if they accurately predicted plaque on autopsy.
Earlier this decade, two scientists at the University of Pittsburgh developed an amyloid dye that while not practical for widespread use, stunned scientists by showing it seemed possible to see amyloid in a living brain.
The researchers, Chester Mathis and William Klunk, began their work two decades ago, persevering even though they had no research money. In the first 10 years, they tested more than 400 compounds. When they finally found one that seemed promising, they tested more than 300 variations.
“On and on it went,” Dr. Mathis said.
Finally, in late 2001, they began working with collaborators in Sweden to test their dye in humans.
On Valentine’s Day 2002, the Swedish researchers injected the first Alzheimer’s patient with the dye, known as Pittsburgh Compound B, and scanned the patient’s brain.
It worked, the Swedish doctors told Dr. Mathis in an excited phone call.
A PET scan showed amyloid exactly where it would be expected. The Swedish doctors were convinced they were seeing actual plaque. They told Dr. Mathis it was time to celebrate.
But Dr. Mathis worried. What if the same pattern occurred in people without Alzheimer’s?
Two weeks later, he got another call from Sweden. His colleagues had scanned a person without Alzheimer’s. There was no sign of telltale plaques.
His sweet reward came in July 2002, when the scans were shown to an audience of 5,000 scientists at an international conference on Alzheimer’s.
“There was an audible gasp,” Dr. Mathis said. “The field was taken aback.”
“The rest is history,” he added.
Yet there was a problem. Pittsburgh Compound B used carbon 11 as its radioactive tracer. And its half-life is 20 minutes. Researchers have to make it in a cyclotron in the basement of a medical center, quickly attach it to the dye, dash over to a patient lying in a scanner, and inject it.
And a critical question remained: Was a PET scan with the Pittsburgh dye really equivalent to a brain autopsy?
Meanwhile, others, including Dr. Skovronsky, had another idea — use fluorine 18, with a half-life of about two hours. It could be made in the morning, and used that afternoon. And fluorine 18 is made routinely for two million cancer PET scans each year.
Dr. Skovronsky, starting at the University of Pennsylvania and then at Avid, worked with a University of Pennsylvania chemist, Hank Kung, for nine years to find and develop the radioactive dye. The university had the patent; Avid licensed it. Finally, on June 8, 2007, a patient at Johns Hopkins had a scan with their compound. Plaque lit up.
Most of the time, the scans were as expected — those with Alzheimer’s had lots of plaque, those with normal memories had little if any and those with mild memory impairment were in between.
But about 20 percent of people over 60 with normal memories had plaque.
“Then we looked more carefully,” Dr. Skovronsky said. “The 20 percent who had amyloid, though they were still statistically in the normal range, did worse on every memory test than the control group.”
What, Dr. Skovronsky asked, did that mean? Were they starting to develop Alzheimer’s? If so, could dementia be stalled if there were drugs to stop amyloid from accumulating?
The definition of Alzheimer’s is plaque plus memory loss and other symptoms of mental decline. But what is not known because no one could follow the development of plaque before a person died, was whether people with plaque and normal memories were developing Alzheimer’s.
“We’ve always assumed the pathology has been there, that the plaque has been there years before symptoms,” said Dr. Steven T. DeKosky, an Alzheimer’s researcher who is vice president and dean at the University of Virginia School of Medicine. “But we never had a way to detect plaque in living persons,” he said. And so plaque in the brains of people with normal memories has been a puzzle.
“Over the next couple of years, we will find out what it means.”
A Request of the Dying
On Oct. 23, 2008, Avid and two other companies, Bayer and General Electric, that are developing fluorine 18-based dyes for amyloid scans, got a pointed question from an advisory committee to the F.D.A.: How do you know that what you are seeing on scans is the same as the amyloid you see on autopsy?
It seemed impossible to answer. If researchers wait for their subjects to die before comparing scans with autopsies they can be waiting a long time.
But Avid had a plan, and the committee agreed in principle that it would work. Hospice patients would be study subjects, some with dementia, some without. All would have memory tests and brain scans. After death, their brains would be autopsied. Avid suggested that after the first 35 died, there should be enough data to know if the scans gave a true picture of the pathology. Then the F.D.A. could decide if the results were convincing enough to approve the dye for marketing.
Some doctors had misgivings, wondering how they could ask people who were sick and dying to be scanned just to help Alzheimer’s research. But, they found, most patients and their families agreed and said they were grateful to have been asked.
That was evident on May 19, when Dr. Skovronsky gave a lunch for patients’ families in Sun City, Ariz., to thank them for participating.
They thanked him.
“It really touched my heart to be in this,” said Dorothy Wall, whose husband, Claude E. Wall, died of liver cancer in Sun City on March 3.
“Something bad happens, and now something good happens.”
Answers
Late last year, Avid saw the initial results of its hospice study — data from the first six patients. Then, as more patients were studied, the data from them were held by a company that would analyze it. Avid did not see the results until the study was completed. But those first six were encouraging.
A man diagnosed with Alzheimer’s and cancer had a scan showing no plaque. His autopsy did not show it, either. The diagnosis was wrong. Another man with Parkinson’s disease and dementia had been diagnosed as having dementia solely due to Parkinson’s. His scan showed amyloid. So did the autopsy. He had Alzheimer’s. A woman with mild memory loss had a scan showing no amyloid. Her autopsy also found none. Three others had clinical diagnoses of Alzheimer’s, confirmed by scans and autopsies.
Finally, on May 14, 35 patients had been scanned and autopsied. The Avid study was complete, and the full data will be presented at the meeting next month. Other companies, still doing their studies, did not yet have data to examine.
And Dr. Skovronsky got that e-mail message.
“This is going to have a big impact on Alzheimer’s disease, guys,” he told his staff that day.
http://www.nytimes.com/2010/06/24/health/research/24scans.html?_r=1&scp=1&sq=PET%20scans%20and%20Alzheimer's&st=cse
& 
There is a simple blood test (CRP, for c-reactive protein) that can be done by any lab. It predicts fairly accurately probability of onset of Alzheimer's, other dementias, and many other diseases
Researchers in Germany found that those with high CRP levels had brain changes associated with problems in so-called executive function, or the ability of the brain to plan and execute tasks and behave in an appropriate manner.
High levels of CRP, however, were not associated with problems in memory or language skills, which are often a prominent feature of Alzheimer’s disease.
http://www.alzinfo.org/newsarticle/templates/newstemplate.asp?articleid=406&zoneid=10
Reported July 1, 2010
Best Tests for Predicting Alzheimer's
(Ivanhoe Newswire) -- People with abnormal results on both PET scans and episodic memory tests were nearly 12-times more likely to develop Alzheimer's disease than those who scored normally on both measures. Researchers found that, of five tests, these two most accurately predicted the onset of Alzheimer’s disease.
http://www.ivanhoe.com/channels/p_channelstory.cfm?storyid=24659
Soon, 'Holy Grail' Blood Test to Predict Alzheimer's Disease
by Kathy Jones on July 06, 2010 at 10:36 PM
Following the discovery of a protein called clusterin, a simple blood test could soon be developed to predict Alzheimer's disease up to ten years before the appearance of symptoms.
Scientists have suggested that levels of clusterin rise 'many years' before symptoms of Alzheimer's disease first appear.
Thus high levels of clusterin, which can be detected in a blood sample, could be used as an early warning sign that the body is already fighting Alzheimer's disease.
An early test for the condition could allow those patients could have early treatment and make improvements to their lifestyle to minimise the impact of the disease.
http://www.medindia.net/news/Soon-Holy-Grail-Blood-Test-to-Predict-Alzheimers-Disease-70947-1.htm
DNA As Crystal Ball: Buyer Beware
When it comes to predicting risk of disease, Alzheimer’s genes—and others—strike out.
When James Watson, codiscoverer of the double helix, had his genome fully sequenced in 2008, there was one piece of DNA he insisted the lab not tell him about: whether he had a genetic variant that significantly increases the chance of developing Alzheimer’s disease. Called apoE, the gene comes in three variants, of which APOE4 increases the risk of Alzheimer’s between 10- and 30-fold. Different people have different feelings about learning what lies in their medical future, especially if it is something for which there is neither cure nor treatment. If studies coming out over the last few months are any indication, however, most of us can postpone making this difficult decision: the revolution in using DNA to read people’s medical future is turning out to be more hype than hope.
The latest research to throw cold water on the crystal-ball powers of DNA is a paper in the current issue of the Journal of the American Medical Association. It starts out as a standard genomewide association study (GWAS) in which scientists sequence genomes of people with and without particular diseases and identify genetic variants associated with those illnesses. In this case, Monique Breteler of the University Medical Center in Rotterdam and her colleagues analyzed the genomes of just over 35,000 people, some healthy and some with Alzheimer’s, and found that four DNA misspellings (or, in the vernacular, single-nucleotide polymorphisms) were connected to Alzheimer’s in that they were common to people with the disease but were not found in healthy people.
Until recently, that would have been that: a rigorous, thorough analysis—just over 35,000 genomes—leading to headlines about newly discovered genes linked to this dreaded disease. (Two of the four identified misspellings were previously known, and two are new.) But to their credit, Breteler’s team took the next step. They used the four misspellings, along with individuals’ age and sex and whether or not they carried the apoE4 genetic variant that so frightened Watson. The results were not pretty. Adding the newly discovered genes “did not improve the ability of a model that included age, sex, and apoE to predict” whether someone would develop Alzheimer’s. The genes, concluded the scientists, were “not clinically useful.”
In a phone interview, Breteler went further. “Adding these genes to traditional risk factors, such as age and sex, does nothing to aid prediction” of whether someone will develop Alzheimer’s, she told me. “Knowing your genetic status will not help. We may still be in the Stone Age when it comes to gene-based prediction.” Identifying risk genes isn’t pointless, however: they can identify new causes of the disease, and therefore new ways to treat it.
http://www.newsweek.com/2010/05/18/dna-as-crystal-ball-buyer-beware.html
While testing for predisposition to Alzheimer's is becoming very popular, there is no hard science that these test are accurate.
In addition, predisposition is an elusive term. Are you predisposed to Alzheimer's by 20 percent or by 40 percent? Are your chances of contracting Alzheimer's disease one in five or two in five?
We already know you have a one in eight chance at age 65. And, about a 42 percent chance if you live to the age of 85?
So what exactly is the test going to tell you? Accuracy issues aside.
If you are worried about Alzheimer's you should be making dramatic and important health and life style changes. If the already known statistics are not enough to get you to start trying to reduce the risk of Alzheimer's via lifestyle and healthy living, go ahead and get the test. Maybe it will convince you to do what you should already be doing.
If you are worried about Alzheimer's then start doing: real exercise that gets your heart rate up, eating Mediterranean style diet, and get your cholesterol down and reduce the size of your belly.
http://www.alzheimersreadingroom.com/2010/05/is-cheap-dna-test-for-alzheimers-coming.html
I used to do CRPs, indeed a simple test.
I knew it as a good indicator of several disease syndromes, but didn't know re the alzheimer's connection. ...
Alzheimer's earliest sign might be an imbalance in the body's immune system. This shows up as an inflammatory reaction that occurs not just in the brain cells, but throughout the body. The net effect of this imbalance is a build up of the toxic amyloid protein, which is poisonous to brain cells and triggers their progressive death.....He was also able to compare his test against autopsy confirmations, which were available for 20 of the samples. Among those, he says, the enzyme screen was 100% predictive.
Read more: http://www.time.com/time/health/article/0,8599,1226497,00.html?iid=sphere-inline-sidebar#ixzz0wy9graNo
Proof of CRP or other (simple and general) inflammation tests as 100% Alzheimer's predictors was finally publicly announced couple of days ago
Are you quite sure about that? -You do realize the date on that article you posted is 2006 and this is the year 2010.
Time
A Skin Test for Alzheimer's
By Alice Park Monday,
Aug. 14, 2006
So far, Alkon has used his test on 60 samples from patients with both the hereditary form of Alzheimer's, which hits patients earlier in life, and the more common, sporadic version that strikes in older age. He was also able to compare his test against autopsy confirmations, which were available for 20 of the samples. Among those, he says, the enzyme screen was 100% predictive.
http://www.time.com/time/health/article/0,8599,1226497,00.html?iid=sphere-inline-sidebar#ixzz0wy9graNo
The New York Times
August 17, 2010
Lilly Stops Alzheimer’s Drug Trials
By DUFF WILSON
Eli Lilly halted two late-stage clinical trials of an experimental Alzheimer’s treatment on Tuesday, representing a setback to one leading theory on treating the degenerative disease and a new blow to Lilly’s business prospects.
The company said patients who had taken the drug, intended to reduce plaque in the brain, actually showed worse cognitive functioning and less ability to perform daily living tasks than patients who had taken a placebo.
“A completely unexpected result,” Dr. Eric R. Siemers, medical director for the Alzheimer’s team at Lilly, said in an interview. The patients also had a higher risk of skin cancer. The trials involving the drug, semagacestat, began in 2008.
The price of shares in the company, which is based in Indianapolis, has fallen 5 percent in the last week, as Lilly has had problems involving some of its most popular drugs.
Lilly officials said that they would still follow the more than 2,600 Alzheimer’s patients in 31 countries who were enrolled in the trials for six more months. The company is conducting a separate test of a biologic therapy aimed at Alzheimer’s.
Dr. Ronald C. Petersen, director of the Alzheimer’s Disease Research Center at the Mayo Clinic in Rochester, Minn., and a member of the executive committee of the Alzheimer’s Association, said the drug failure highlighted the need to try to attack multiple targets related to dementia, not just plaque on the brain. He compared the approach to developing several drugs for hypertension.
“When one like this fails, it’s discouraging to the field, but it’s not the end of the day,” Dr. Petersen, who was not involved with the trials, said in an interview. “We have other targets out there and other ways to attack the same target.”
Still, Lilly’s announcement quashed one hope, and an effective prevention or cure, if possible, remains years away.
While hundreds of drugs are under study, Lilly’s effort was one of only five to reach late-stage clinical trials, said Dr. Paul S. Aisen, director of the federally financed Alzheimer’s Disease Cooperative Study and a professor of neuroscience at the University of California, San Diego.
“It is a significant disappointment,” he said, “but there’s still a lot to be optimistic about.”
Dr. Aisen, who also consults widely for the drug industry, said he was excited about brain scans and spinal fluid tests that may help to identify people most at risk of Alzheimer’s before they show any symptoms — the time a treatment may be most effective.
Lilly shares fell 2.3 percent to $34.75 on Tuesday, the latest of several blows to the company. Lilly said it would charge 3 cents to 4 cents a share against third-quarter earnings for the Alzheimer’s test failure but reaffirmed earlier guidance for 2010 profits.
“We are clearly disappointed by the results we are announcing today,” John C. Lechleiter, Lilly’s chairman, said in a statement. “However, Lilly’s innovation strategy, based on advancing a pipeline of nearly 70 molecules currently in clinical development, does not rest on the success or failure of any single compound.”
Lilly’s failure in the final phase of an Alzheimer’s trial follows misses by Myriad Genetics and by the team of Pfizer and Medivation. Another closely watched drug being developed by Pfizer, Johnson & Johnson and Elan has had mixed results in a middle-stage clinical trial. Several prescription drugs are approved to treat symptoms of Alzheimer’s, but none stop its progression.
Lilly’s drug was intended to reduce production of so-called amyloid beta plaques in the brain by inhibiting the activity of an enzyme called gamma secretase.
Dr. Siemers of Lilly said the failed trials might indicate that too much reduction in amyloid beta unexpectedly harms cognitive functions, or it may be that the problems arose from the drug’s effect on some 20 other proteins.
“It’s certainly a setback, but no one’s developed a treatment to slow the rate of progression of the disease,” Dr. Siemers said. “This was I think a very good shot on goal, but not Lilly’s only potential treatment.”
Lilly is also testing an intravenous monoclonal antibody that reduces amyloid beta, the plaque, by a different and more focused mechanism in late-stage clinical trials. “They’re actually going quite well,” Dr. Siemers said of those trials.
Alzheimer’s affects an estimated 5.3 million Americans. Dr. Steven T. DeKosky, an Alzheimer’s researcher and dean of the University of Virginia’s School of Medicine, said Lilly’s failure may show that plaque reduction does not help patients with full-blown symptoms but it could still help to prevent the disease.
“It’s too soon to say,” said Dr. DeKosky, who has consulted for Lilly and other companies. “Having the drug fail doesn’t say the hypothesis is wrong that amyloid causes the disease.” Some researchers are less certain about the role that plaque may play in the onset of the disease.
http://www.nytimes.com/2010/08/18/business/18lilly.html
NIH SENIOR SCIENTIST PEARSON SUNDERLAND SENTENCED
ON CONFLICT OF INTEREST CHARGE
Accepted $300,000 For Consulting Services on Research Projects
He Supervised in His Official Government Capacity
