News of plaque-clearing drug tops week of major advances against Alzheimer's disease

In the last eight days, scientists have delivered a powerful one-two punch in the fight to defeat Alzheimer's disease. At the same time, the White House and members of Congress are proposing increases in Alzheimer's research funding. This has been a big week for all who seek to end this disease, says the CEO of the American Health Assistance Foundation.

11 feb 2012--"In the last eight days, scientists have delivered a powerful one-two punch in the fight to defeat Alzheimer's disease," said Stacy Pagos Haller, President and CEO of the American Health Assistance Foundation (AHAF), a nonprofit that identifies and funds exceptionally high-impact research worldwide through its Alzheimer's Disease Research program.

"We are excited about today's announcement by Case Western University researchers that a cancer drug, used in mice studies, appears to help clear out the excess plaque found in the Alzheimer's-disease brain and it does this by enhancing the body's natural defense mechanisms," noted Haller. "This follows last week's announced discovery of how Alzheimer's disease spreads in the brain. The timing of these findings coincides with new proposals in Congress and the White House to increase federal funding for Alzheimer's research. This has been a big week for all who seek to end this disease."

In a study of mice, a research team headed by Case Western University scientist Gary Landreth, Ph.D., found that bexarotene—a drug currently used to combat T cell lymphoma— helped the body clear out amyloid beta proteins. Alzheimer's disease arises in large part from the body's inability to clear these naturally occurring proteins. As amyloid beta levels increase they tend to aggregate and contribute to the so-called brain "plaques" found in Alzheimer's disease.

Bexarotene appeared to improve brain function in these mice. Study results were published in the journal Science.

"Although this is a mouse study, the results are encouraging, and the drug did its job with unprecedented speed, by targeting ApoE, the primary genetic risk factor for Alzheimer's disease," said AHAF Vice President for Scientific Affairs Guy Eakin, Ph.D.

"This announcement is particularly exciting because bexarotene achieved regulatory approval by the U.S. Food and Drug Administration more than a decade ago for the treatment of cancer. That earlier approval could speed up the prospects for human clinical trials of the drug as an Alzheimer's treatment."

AHAF, which had also supported Landreth earlier in his career, started funding the preliminary work leading to this line of research in 2007. Currently, AHAF is funding follow-up studies in which the Landreth team is testing the latest findings on other "mouse models" that may better represent the human form of Alzheimer's disease. Positive findings could help pave the way towards human clinical studies.

"While it is still too early to make predictions, if these findings can be replicated in additional preclinical studies, and then later in human clinical trials, we may have a powerful new weapon in the battle to halt this disease," noted Eakin.

This latest news comes only one week after an AHAF-funded research team in Boston and another team in New York announced a major breakthrough in understanding how Alzheimer's disease spreads in the brain. By learning that toxic "tau" proteins jump from nerve cell to nerve cell, scientists can now focus on ways to target and stop this cell-to-cell spread.

Although these reports are coming in rapid succession, the overall progress of Alzheimer's disease research has been slower than that of other major diseases, due in part to comparatively meager financial support for Alzheimer's disease research. "We hope this funding scenario will improve, as promising study results stimulate our national resolve to defeat this disease," said Haller.

This week the Obama Administration announced it will provide an additional $130 million in Alzheimer's research funding over the next two years. Last week a bipartisan group in Congress unveiled the Spending Reductions through Innovations in Therapies (SPRINT) Agenda Act of 2012. The legislation, introduced by Senators Barbara Mikulski (D-MD) and Susan Collins (R-ME) and Representatives Chris Smith (R-NJ) and Ed Markey (D-MA), would spur public and private research funding and streamline the regulatory review of treatments.

More information: http://www.science … ence.1217697

Provided by AHAF-American Health Assistance Foundation

ICAD: Pondering Over Woes in Middle Age May Save the Brain in Later Life

By Peggy Peck
CHICAGO, 02 aug 2008-- Men who spend their 40s and 50s focusing on the difficulties of daily life may be rewarded with a dementia-free old age, researchers reported here.
A study of Israeli men found that those who ruminated -- going over and over worrisome details -- during midlife were about 30% to 40% less likely to develop dementia in their 80s, Ramit Ravona-Springer, M.D., of Sheba Medical Center in Ramat Gan, Israel, told attendees at the International Conference on Alzheimer's Disease.
The cohort were 9,000 participants in the Israeli Ischemic Heart Disease study, which is a longitudinal look at incidence and risk factors for cardiovascular disease among Jewish male civil service workers, who were assessed for "rumination" in 1963.
At the initial assessment, the men ranged in age from 40 to 60. The mean age at follow-up in 1999 was 82.
Rumination was defined as the "unintentional process of repetitively focusing attention on one's depressed mood and potential causes and implications of it," said Dr. Ravona-Springer.
To gauge rumination, men were asked, "when your wife/ children/peer/superior hurts you, do you forget this, tend to forget, tend to ruminate, or usually ruminate."
Men who said they forgot or tended to forget scored low on the rumination scale with a one (forget) or two (tended to forget), while those who said they tend to ruminate received a three, and those who usually ruminate were given a four.
In 1999, the researchers conducted follow-up examinations on 1,715 of the 2,600 survivors of the original cohort.
At follow-up, 24% of the men who forgot about hurts inflicted by co-workers or superiors and 21% of those who forgot a hurt by a child or wife had developed dementia.
But only 14% of the men who usually ruminated over hurts inflicted by spouses or children and 15% of those who ruminated about hurts inflicted by peers and bosses had developed dementia.
There were no differences in blood pressure, cholesterol levels, diabetes, or tobacco use by rumination status.
Men with the highest rumination score had a slightly higher survival rate after age 70 -- 63% -- but it was not significantly different from the survival rate for men with low rumination scores.
Dr. Ravona-Springer said that, on first glance, the findings differ from other studies that have linked rumination with depression, and neuroticism, both of which are believed to increase the risk of dementia.
One possible explanation would be the type of rumination -- reflection or brooding.
Reflection, she said, "consists of contemplation, which is proposed to be adaptive, and not associated with increased risk of depression."
Brooding, by contrast, consists of what she called "moody pondering" and it is considered a maladaptive tendency that does increase the risk of depression.
The ruminating men in this study may have been men who were given to reflective pondering, "leading to problem solving, a cognitive activity that may be protective."
No funding source was disclosed. Dr. Ravona-Springer disclosed no financial conflicts.
Primary source: International Conference on Alzheimer's DiseaseSource reference:Ravona-Springer R, et al "Tendency for rumination as a psychological cognitive style in midlife is associated with decreased risk for dementia three decades later" ICAD 2008; Abstract O8-A-2763_ALZ.

Alzheimer's Research Holds Promise

By ALICE PARK

01 aug 2008--When it comes to Alzheimer's disease, there hasn't been much to celebrate in recent years. Efforts to develop a vaccine against the brain disorder have stalled, and no drugs have been able to reverse the slow death of neurons that robs people of their memories and thoughts. For the first time in many years, however, researchers in the field are genuinely excited about the potential for effective drug treatments and helpful new risk factors.
Scientists gathered this week at the Alzheimer's Association's International Conference on Alzheimer's Disease in Chicago, presenting a slew of promising results from drug trials, a new understanding of how the neurological disease works and insights into the way social and lifestyle factors may affect its progression. "On the one hand, Alzheimer's disease is a complex pathologic process, and that is daunting," says Dr. Ronald Petersen, chair of the Alzheimer's Association's medical and scientific advisory council and director of the Mayo Clinic Alzheimer's Disease Research Center. "But now we are beginning to segregate out different therapeutic targets and develop drugs that have an impact on each target, so in combination they may handle the disease better than any single approach."
The potential success of the combination strategy was borne out in some of the conference's most exciting papers. Researchers from Mount Sinai School of Medicine reported, for example, that compared with other Alzheimer's patients, those who had diabetes and took insulin plus another anti-diabetes medication to control blood sugar had 80% fewer amyloid plaques - the sticky brain-clogging masses that, together with protein tangles, are the hallmarks of Alzheimer's disease. Although the mechanism wasn't entirely clear, researchers think the drugs may work by normalizing the brain's communication network of insulin receptors, which goes awry in the Alzheimer's brain, while clearing away the damaging plaques.
In a separate trial, an experimental drug called rember, developed by a Singapore-based company, also showed some promise in a safety study. Among 321 patients, rember appeared to stall advancement of the disease, degrading the protein tangles that build up in Alzheimer's brains. Potentially, a combination of drug therapies - designed to prevent both plaques and tangles - may prove effective in slowing the progression of the disease.
But future approaches won't stop with drug treatments. Petersen notes that researchers are also forging ahead with innovative screening tests to identify Alzheimer's patients sooner - before too much deterioration occurs in the brain. Better screens could also potentially identify patients by the specific type of brain buildup - plaques vs. tangles - that is causing them the most severe problems. That kind of triage early on could help doctors target the right patients with the most effective therapies.
Alzheimer's doctors also reported new discoveries about certain lifestyle factors that may accelerate or slow the dementia that often precedes Alzheimer's. Swedish psychologists studied rates of the disease in a sample of 1,449 people over a period of 21 years. They found, as previous research has suggested, that single people have up to twice the risk of developing Alzheimer's as their married counterparts. But what was unexpected was the finding that the reason for a person's singlehood impacts his or her risk. Compared with other singletons, people who were single as a result of divorce or widowing had a three times and six times greater risk, respectively. "This was quite unexpected," says Krister Hakansson, who led the study and is a lecturer in psychology and a Ph.D. candidate at Vaxjo University and the Karolinska Institute. "We established the association, but when it comes to explaining it, we can only speculate at this state."
One reason for the higher risk could be that those who had the cognitive protection and social benefits of a relationship but lost them may be worse off than those who never enjoyed those benefits at all; or perhaps the emotional toll of losing a close partner damages cognitive functions in a way that puts these people at greater risk for dementia and Alzheimer's down the line. Either way, says Hakansson, the results suggest that "if you are looking for interventions to prevent Alzheimer's, one way may be to identify people who have been divorced or widowed, and who haven't adapted or gotten back into the social circle, and give them support with the aim of giving them new structure and social networks in their lives."
As more discoveries are made, researchers hope they'll develop a better understanding of who is most at risk of Alzheimer's disease, how each patient's case is unique, and how best to treat specific patients with the drug and lifestyle changes that will be most effective for them. Taken together, these approaches could one day make the long goodbye of Alzheimer's a thing of the past.

ICAD: Investigational Alzheimer's Drug Found Beneficial in Extension Trial

By Todd Neale
CHICAGO, 01 aug 2008 -- For patients with mild to moderate Alzheimer's disease, the investigational drug dimebon continued to show benefits and safety in a six-month, open-label extension of a placebo-controlled trial, researchers reported here. Earlier this month, Rachelle Doody, M.D., of Baylor College of Medicine in Houston, and colleagues reported in The Lancet that after one year, Alzheimer's patients who received dimebon had significantly improved cognitive function, memory, activities of daily living, and behavior compared with those on placebo, who progressively worsened. Participants in both groups were then eligible to enroll in the six-month open-label extension and 104 patients -- 54 who had been taking dimebon and 50 who had received placebo -- entered the study.
As expected, those who had originally been taking dimebon began to decline to below baseline values on the various measures through the extension phase, but the declines were delayed compared with the estimated drop in function with placebo.
"We did not arrest the disease permanently," said co-author Jeffrey Cummings, M.D., of the University of California Los Angeles, at the International Conference on Alzheimer's Disease. "Eventually the mechanisms of the disease, whatever they are, overwhelm the benefits of dimebon."
Patients who had been on placebo stabilized when they crossed over to treatment with dimebon for the extension phase, but at a lower level of function than those who were originally taking the active treatment.
"This emphasizes the benefit of earlier treatment, and suggests the possibility that dimebon may slow the progression of Alzheimer's," Dr. Cummings said.
"However," he added, "open-label extensions are not the same as placebo-controlled trials, and extrapolation of the treatment results should be done with caution."
The researchers are currently enrolling patients for a phase III clinical trial to be conducted in multiple countries, including the U.S.
According to Dr. Cummings, the FDA has said that the trial will provide enough evidence to move forward with a new drug application. He said that dimebon could be on the market by 2011.
Dimebon works by repairing mitochondrial function at sites of cellular stress, such as beta-amyloid plaques. The repair might help prevent cell death and increase signaling between neurons, according to Dr. Cummings.
In the six-month extension phase, the 104 participants were all given 20 mg of dimebon three times a day; 92 (88.5%) completed treatment.
The mean age of the participants at the beginning of the extension phase was 69. Those who had been taking dimebon in the one-year study had a higher mean score on the Mini-Mental State Examination compared with those who had been taking placebo (19 versus 17).
The projected decline on various assessments if a patient was to take placebo was estimated using a linear regression analysis of data from the one-year study.
Those who received dimebon in the one-year study preserved function close to baseline values after 18 months and continued to show an advantage over the predicted decline with placebo.
On the Alzheimer's Disease Assessment Scale -- cognitive subscale (ADAS-cog), patients who had received dimebon for 18 months had a significantly smaller decline than those who had crossed over from placebo (P<0.05).
On the Alzheimer's Disease Cooperative Study -- Activities of Daily Living (ADCS-ADL) scale, patients who were on dimebon dropped 2.40 points through 18 months, compared with a 4.3-point decline in those who had been taking placebo.
On the Neuropsychiatric Inventory (NPI), patients who were taking dimebon declined by 0.68 points at 18 months, compared with 3.2 points in those who were taking placebo.
On the Clinician's Interview-Based Impression of Change plus Caregiver Input (CIBIC-plus), 57.4% of patients on dimebon improved or showed no change at 18 months, compared with 39.1% of placebo patients.
Dr. Cummings said that dimebon was well tolerated, although dry mouth, sweating, and depressed mood and sadness were more common in patients taking active treatment compared with placebo.
He said that the rates of depression with active treatment (about 15%) were not high enough to halt the phase III trial that is being planned.
The study was funded by Medivation, maker of dimebon.
Dr. Cummings and three of his co-authors reported serving as consultants for Medivation. Two of his co-authors are employees, shareholders, and board members of Medivation.
Primary source: International Conference on Alzheimer's DiseaseSource reference:Cummings J, et al "18-month data from an open-label extension of a one-year controlled trial of dimebon in patients with mild-to-moderate Alzheimer's disease" ICAD 2008; Abstract P4-334.

ICAD: Monoclonal Antibody that Binds to Amyloid Found Safe in Alzheimer's

By Todd Neale
CHICAGO,01 aug 2008-- An investigational monoclonal antibody that binds to beta-amyloid was well tolerated by Alzheimer's patients in a 12-week phase II study that was too short to establish meaningful clinical efficacy endpoints.
With a goal of enabling the body to more easily clear beta-amyloid42, from which plaques are predominantly made, LY2062430 was given IV to 52 Alzheimer's patients, said Eric Siemers, M.D., of Eli Lilly in Indianapolis, maker of the antibody, at the International Conference on Alzheimer's Disease here.
Dr. Siemers said the increased clearance of beta-amyloid could potentially slow the progression of Alzheimer's by preventing the build-up of plaques.
The antibody was well tolerated, he said, with no infusion reactions or evidence in the cerebrospinal fluid or on MRI scans of meningoencephalitis, microhemorrhage, or edema through 112 days of follow-up.
There was a slight immune response to the antibody in five patients, but it did not affect the pharmacokinetics or binding of beta-amyloid, Dr. Siemers said.
On the basis of the results, a phase III trial will be conducted starting in 2009.
Dr. Siemers and colleagues recruited patients diagnosed with mild-to- moderate Alzheimer's disease (mean age 71.2, mean baseline Mini-Mental State Examination score 20.2).
They were given infusions of the antibody for 12 weeks at one of four doses -- 100 mg per week (10), 100 mg every four weeks (11), 400 mg per week (11), or 400 mg every four weeks (10) -- or placebo (10).
All doses of antibody increased mean plasma concentrations of beta-amyloid to about 100,000 pg/mL for beta-amyloid40 and 10,000 pg/mL for beta-amyloid42.
About a 10th of a percent of the antibody entered the cerebrospinal fluid and similar increases in beta-amyloid concentration were found.
Surprisingly, as the dose increased, the amount of beta-amyloid42 -- the form of the protein found primarily in plaques -- that was not bound to the antibody also increased in the cerebrospinal fluid.
According to Dr. Siemers, that finding suggested that the antibody was not simply binding free beta-amyloid, which would cause the amount of the protein to decrease, but was also dissolving plaques in the brain.
Two other types of protein found primarily in plaques also increased in the plasma and cerebrospinal fluid with higher doses of the antibody, further strengthening the evidence that plaques were dissolving, he said.
However, MRI scans did not show any reduction in the amyloid plaque load in the brain through 12 weeks. The scans and the tracer used may not have been sensitive enough to detect the changes, Dr. Siemers said.
As expected, he said, there were no significant differences between the treatment groups or the placebo group in cognitive function measured using the Alzheimer's Disease Assessment Scale -- cognitive subscale.
The study was funded by Eli Lilly, maker of the antibody.
Dr. Siemers and four of his co-authors are employees of Eli Lilly. The other four co-authors have received grants or research support from the company.
Primary source: International Conference on Alzheimer's DiseaseSource reference:Siemers E, et al "Safety, tolerability, and biomarker effects of an Abeta monoclonal antibody administered to patients with Alzheimer's disease" ICAD 2008; Abstract P4-346.

Advances Made Against Alzheimer's Disease

By Ed Edelson
01 aug 2008--New reports on very different approaches to treating Alzheimer's disease could one day lead to better therapies for the mind-robbing condition, experts say.
A trio of studies that were presented Wednesday at the Alzheimer's Association 2008 International Conference on Alzheimer's Disease in Chicago noted progress made on three different treatment fronts.
The first involves a drug called Dimebon, with positive results being reported from tests in Russia. Dimebon is an antihistamine, and data from the Russian trials indicated that Dimebon might have value in treating Alzheimer's.
This buttressed American research reported earlier this year that showed improvements in Alzheimer's patients given Dimebon in a controlled study. The drug is believed to prevent the death of brain cells.
Researchers at the University of California, Los Angeles, studied 183 people who had mild to moderate Alzheimer's disease. Mental function remained stable in those taking the drug, while it declined in those given a placebo. Mental function also stabilized in people who were first given a placebo after they began taking Dimebon.
Another trial used the body's immune system to prevent the mental deterioration suffered by people with Alzheimer's disease. The immune attack is aimed at the deposits of beta-amyloid protein that accumulate in the brains of patients.
"The idea has been around for almost a decade now," Nixon. "The initial notion was to use the vaccine approach to prevent amyloid deposition, injecting amyloid so the body would attack the deposits. Now we are into phase two, injecting the antibody itself."
Researchers at Eli Lilly & Co. reported on 52 people with mild to moderate Alzheimer's. Some were given weekly injections of a monoclonal antibody that binds to beta amyloid, while others were injected with a placebo.
Detailed measurements showed an increased level of beta amyloid in both blood and cerebrospinal fluid after 12 weeks in those getting the antibody, an indication that the beta amyloid in the brain might be starting to dissolve, the researchers said. New studies of the therapy are planned.
Nixon viewed the results with "tempered optimism." One interesting finding was the response to the therapy was greatest in people who did not have a known genetic marker for Alzheimer's risk, he said. "What is the significance of this? Why do carriers not respond?" Nixon asked. The answer might help explain Alzheimer's disease better, he said.
A third study using a broad spectrum of antibodies was reported by a team at Weill Cornell Medical College in New York City. The treatment, originally developed by Baxter International to treat autoimmune conditions, was given to 24 people with mild to moderate Alzheimer's disease in a set of trials extending as long as 18 months. Statistically significant increases in mental function were seen in those getting the treatment, the researchers said. A large-scale, 18-month follow-up trial will be done.

ICAD: Marriage May Protect Against Dementia

By Todd Neale

CHICAGO, 31 july 2008-- The give and take of marriage may be enough to stave off Alzheimer's disease and other cognitive impairment, a prospective population-based study suggested. People living alone from midlife on were almost three times as likely to develop some level of cognitive impairment as those who were living with a partner (OR 2.89, P<0.001).
Krister Hakansson, of Vaxjo University in Vaxjo, Sweden, and the Karolinska Institute in Stockholm, reported at the International Conference on Alzheimer's Disease here. There were similar greater risks of mild cognitive impairment (OR 3.17, P<0.001) and Alzheimer's disease (OR 2.83, P<0.05) for those living alone.
"This study points to the beneficial effects of a married life," Hakansson said, "consistent with the general hypothesis of social stimulation as a protective factor against dementia."
It has been suggested that remaining socially active may protect against the development of dementia, and Hakansson reasoned that a partner relationship would form the most intense form of social interaction because of the necessity of dealing with another's needs or perspectives, enhanced communication, and joint problem-solving.
So he and colleagues turned to the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study, which randomly selected middle-age participants from the general population of Finland. Baseline measurements were taken from 1972 to 1987.
In 1998, after a mean follow-up of 21 years, 1,432 of the participants ages 65 to 79 were evaluated for signs of cognitive impairment. At baseline, 1,147 were married or cohabitating, 111 were single, 63 were separated or divorced, and 111 were widowed.
At the end of follow-up, 139 were diagnosed with some form of cognitive impairment, including 82 with mild cognitive impairment -- which may represent a transitional phase between normal age-related memory decline and Alzheimer's disease -- and 48 with Alzheimer's.
Those who were not living with a partner at midlife were twice as likely to have some level of cognitive impairment (OR 2.09, P<0.01) or mild cognitive impairment (OR 2.14, P<0.01) later in life than those who were married or cohabitating, regardless of their late-life living status.
The association with an increased risk of Alzheimer's disease did not reach statistical significance.
Widowed participants at midlife who did not remarry had the highest increased risk of any cognitive impairment (OR 3.53, P<0.001), mild cognitive impairment (OR 3.10, P<0.01), and Alzheimer's disease (OR 7.70, P<0.001) later in life.
Having the APOE-e4 genotype -- a risk factor for Alzheimer's -- was particularly damaging for those who were widowed or divorced from midlife through late life. Those who were married and had the high-risk genotype had a 3.44-fold (P<0.05) increased risk of Alzheimer's disease, compared with a 25.55-fold (P<0.001) greater risk for those who were divorced or widowed.
This suggested, Hakansson said, that other factors beyond cohabitation were involved in the associations.
All analyses were adjusted for education, body mass index, cholesterol, blood pressure, occupation, physical activity, smoking habits, and depression at midlife, as well as APOE e4 status, age at follow-up, and gender.
Hakansson speculated that those who were widowed or divorced -- and remained so -- were at a greater risk than those who were single because the loss of a partner destabilized the psychobiological system, enhancing vulnerability to disease.
Hakansson made no disclosures.
Primary source: International Conference on Alzheimer's DiseaseSource reference:Hakansson K "Unmarried life: paving the way for dementia?" ICAD 2008; Abstract O2-07-01.

ICAD: Biomarkers May Help Identify Pre-Clinical Alzheimer's

By Todd Neale
CHICAGO, 31 july 2008-- Several biomarkers may be useful in detecting the pre-clinical stages of Alzheimer's disease or in evaluating the effectiveness of therapies in development, researchers said here.
Four studies presented at the International Conference on Alzheimer's Disease explored the usefulness of biomarkers in blood and cerebrospinal fluid and a new tracer for positron emission tomography (PET).
"There's been a focus on moving the detection threshold for this disease into earlier symptomatic phases and ultimately into asymptomatic individuals," said Ronald Petersen, M.D., Ph.D., of the Mayo Clinic in Rochester, Minn., and vice chair of the medical and scientific advisory council of the Alzheimer's Association, who moderated the session at which the results were presented.
Biomarkers are needed to do the latter, Dr. Petersen said.
"It is greatly preferable that these markers be easy to obtain, such as in samples of blood or urine, or through readily available imaging technologies, such as MRI and PET," said William Thies, Ph.D., vice president of medical and scientific relations at the association.
One such biomarker -- increased expression of the protein CD-69 in peripheral blood lymphocytes -- was identified by researchers at the University of Leipzig in Germany.
Measuring the expression of CD-69 differentiated patients who were diagnosed with Alzheimer's from patients with normal cognitive function with 88% and 82% accuracy, respectively, said Louis Kirby, M.D., chief medical officer for Provista Life Sciences, which oversees the company that licensed the assay, called the LymPro test.
It also differentiated those who were diagnosed with Alzheimer's from demented Parkinson's patients with 91% accuracy when the diagnosis was Alzheimer's and 92% accuracy when the diagnosis was Parkinson's.
A larger trial is underway to verify the results, Dr. Kirby said, and the test could be on the market in October.
Two other studies explored biomarkers in cerebrospinal fluid.
The first, presented by Anne Fagan, Ph.D., of Washington University in St. Louis, looked at beta-amyloid42, a form of the protein that is particularly likely to create plaques characteristic of Alzheimer's disease.
In an earlier small study, Dr. Fagan and her colleagues had shown that the level of beta-amyloid42 in cerebrospinal fluid was inversely associated with plaques in the brain, as measured with PET scans using Pittsburgh Compound B (11C-PIB) as a tracer. (See: Another Avenue for Detecting Early Alzheimer's)
The researchers repeated the study in a larger cohort of 132 patients (mean age 65.7) who had no to mild dementia, and found similar results.
Of 37 patients who had a large amount of plaques, 36 (97%) had low levels of beta-amyloid42.
Of 95 patients with low levels of plaques, 80 (84%) had high levels of the protein in their cerebrospinal fluid.
"Our analyses suggest that a decline in [beta-amyloid42 in cerebrospinal fluid] may effectively identify non-demented individuals who are in the preclinical stage of Alzheimer's, even before they are PIB positive," Dr. Fagan said.
The second study examined the presence of another protein, beta-secretase (BACE1), in cerebrospinal fluid.
Past studies have shown that the protein is involved in the processing of amyloid precursor protein and the production of toxic beta-amyloid, and that it is over-expressed in the brains of Alzheimer's patients.
So Harald Hampel, M.D., of Trinity College Dublin, and colleagues examined the presence of BACE1 in the cerebrospinal fluid of 47 patients with mild cognitive impairment.
After a mean of 2.3 years of follow-up, 15 of the patients had developed Alzheimer's disease.
Cox-regression analysis showed that BACE1 levels and APOE e4 genotype -- a risk factor for Alzheimer's disease -- were the strongest predictors for progression to Alzheimer's.
The technique requires further study, Dr. Hampel said, but it may eventually be used as an outcome biomarker in clinical trials of anti-amyloid therapies for Alzheimer's.
A fourth study evaluated the effectiveness of a new tracer for PET scans of amyloid plaques.
The first tracer developed, 11C-PIB, has a relatively short half-life -- 20 minutes -- making it suited mostly for larger medical centers that can produce the compound on-site.
Michael Pontecorvo, Ph.D., of Avid Radiopharmaceuticals in Philadelphia, reported that a new tracer, called 18F-AV-45, has a longer half-life -- about two hours -- and therefore, would not necessarily have to be made on-site.
The tracer was retained in the brains of patients diagnosed with Alzheimer's but not in older individuals with normal cognitive function and showed rapid uptake and steady levels in the brain from 50 to 90 minutes after administration.
The compound "has the potential to aid in the diagnosis and early detection of Alzheimer's in a community setting and may be a useful biomarker for the development and monitoring of novel amyloid reducing therapies," Dr. Pontecorvo said.
Phase II trials with the compound have been initiated, he said.
Dr. Fagan's study was supported by grants from the NIH and the National Institute on Aging and by the Dana Foundation and the Charles and Joanne Knight Alzheimer's Initiative.
Dr. Hampel made no disclosures.
Dr. Pontecorvo is an employee of Avid Radiopharmaceuticals.
Dr. Petersen has participated in previous studies with Avid.

ICAD: IV Immunoglobulin Therapy Shows Early Signs of Efficacy in Alzheimer's

By Peggy Peck
CHICAGO, 31 july2008 -- Mild-to-moderate Alzheimer's disease can be safely and effectively treated with intravenous immunoglobulin (IVIG) therapy, according to preliminary results from a trial reported here. Over nine months, patients randomized to IVIG demonstrated significant improvement on a number of cognitive measures compared with placebo, with no evidence of toxicity, said Norman Relkin, M.D., of Weill Cornell Medical College in New York, discussing an interim analysis of the first double-blind phase II trial of the therapy. "The key points," said Dr. Relkin at the International Conference on Alzheimer's Disease, "are that this was the first time that a controlled clinical trial of this treatment demonstrated benefit at what we believe to be an optimal dose."
He said an 18-month phase III trial was scheduled to begin this fall, recruiting at 35 clinical sites. IVIG is an appealing therapy option because "it is obtained from the plasma of healthy humans and, as such, it has the advantage of having an established safety record."
Moreover, it is literally loaded with antibodies, including antibodies against beta amyloid, he said. Asked how he could be sure that the benefit was the result of IVIG targeting beta amyloid and not attributable to other antibody activity, Dr. Relkin said that there was a dose-dependent decrease in both plasma and cerebrospinal fluid beta amyloid.
One drawback of the treatment is cost. Dr. Relkin said IVIG costs about $100 per gram and "we use 20 to 30 grams per treatment."
Another consideration is time and accessibility. Patients need to travel to a clinic where they receive infusion that typically takes at least two hours.
The trial randomized eight patients to placebo and 16 to IVIG at 0.4 g/kg every two weeks. All patients were in their early 70s and all had mild-to-moderate Alzheimer's disease. Five of the placebo patients and seven of the IVIG patients were women.
All patients were taking acetylcholinesterase inhibitors.
Efficacy endpoints were the Alzheimer's Disease Assessment Scale and the Clinical Global Impression of Change.
At six months, there was no significant difference on the Alzheimer's Disease Assessment Scale (P=0.054) but at nine months, IVIG patients performed significantly better than placebo patients (P=0.009), Dr. Relkin said.
On the Clinical Global Impression of Change, the benefit was significant and apparent at six months (P=0.017), and was sustained at nine months (P=0.003), he said.
The trial was funded by the National Institutes of Health and Baxter, which is developing IVIG for Alzheimer's disease. Dr. Relkin disclosed support from Baxter Bioscience, Pfizer, Eisai, Myriad, and Smart Genetics.
Primary source: International Conference on Alzheimer's DiseaseSource reference:Tsakanikas D, et al "Effects of uninterrupted intravenous immunoglobulin treatment of Alzheimer's disease for 9 months" ICAD 2008; Abstract 08-A-3147.

New Alzheimer's predictors advance earlier detection

NEW YORK, 31 july 2008 – The following news tips are based on poster and oral presentations at the Alzheimer's Association 2008 International Conference to be held in Chicago from July 26 to July 31. Each presentation is embargoed for a specific date and time.
Brain Atrophy and Biomarkers May Help Identify People at Risk for Alzheimer's Susan de Santi, Ph.D., Associate Professor, Department of Psychiatry, NYU Langone Medical Center EMBARGOED FOR RELEASE UNTIL TUESDAY, July 29, 2008 at 12:30 p.m. CT
By combining MRI brain scans and measurements of certain compounds in the cerebrospinal fluid, NYU researchers were able to distinguish individuals who would develop Alzheimer's disease over a two-year period. In a study of 23 people, they found atrophy in areas of the brain involved in learning and memory, and significantly higher CSF levels of phosphorylated tau and other compounds among individuals who would develop Alzheimer's compared to those individuals who didn't progress from mild cognitive impairment over the two-year period. This preliminary study suggests that combining these tests could help predict which individuals with mild cognitive impairment are at the highest risk for developing Alzheimer's disease.

Presentation # P3-067
Big Immune Response to Common Mouth Bacteria Linked to Alzheimer's. Angela R Kamer, D.M.D., M.S., PhD., Assistant Professor, College of Dentistry, New York University EMBARGOED FOR RELEASE UNTIL SUNDAY, July 27, 2008, at 12:30 p.m. CT
In a study investigating the link between Alzheimer's disease and a heightened inflammatory-immune response, NYU researchers found that twice as many subjects with probable Alzheimer's disease tested positive for antibodies in their plasma against a type of bacteria that is commonly found in the mouth. The pioneering study supports a growing body of evidence that associates notable immune changes with a means of predicting and classifying Alzheimer's disease. Together with other immune markers associated with Alzheimer's disease, antibodies to these periodontal bacteria could serve to better understand the causes and mechanisms of the disease, the researchers say.

Presentation # P1-348
Signs of Brain Disease among Healthy Individuals Lidia Glodzik, MD, PhD, Research Physician, Center for Brain Health at NYU Langone Medical Center EMBARGOED FOR RELEASE UNTIL TUESDAY, July 29, 2008 at 12:30 p.m. CT
NYU researchers identified signs of pathology before the clinically noticeable stages of mild cognitive impairment that normally precede Alzheimer's disease. The study involved a cognitively normal group of people ages 40 to 86. It found that higher levels of tau protein in the cerebrospinal fluid correlated with lower grey matter density in brain regions that are important for learning and memory, and are susceptible to Alzheimer's. Combining cerebrospinal fluid measurements and imaging markers to identify normal subjects who are more vulnerable to the neurodegenerative disease opens an opportunity to explore early detection in the service of prevention, the researchers report.

Presentation # PS-070
Couples Counseling Helps the Spouse Caregiver Mary S. Mittelman, Dr.P.H., Research Professor in the Department of Psychiatry at New York University School of Medicine EMBARGOED FOR RELEASE UNTIL WEDNESDAY July 30 at 2:30 p.m. CT
When the patient with Alzheimer's and their spouse caregiver are counseled separately, they are expected to go home and live together. Can couples counseling help stabilize their relationship as they grapple with the disease? Early results show that it can. In a pilot study, researchers at NYU's Silberstein Center offered six counseling sessions focused on the new needs of each member of a couple brought about by the illness. Each of the ill spouses was in the early stages of dementia and could still participate in a counseling session. The NYU researchers report that all caregivers were surprised by how much the person with dementia could communicate in the session. They also report that relationships improved as a result of the counseling, and the caregivers became less depressed.

Presentation # P4-429
Subjective Memory Complaints a Predictor of Further Cognitive Decline Barry Reisberg, MD, Professor, Department of Psychiatry at NYU Langone Medical Center EMBARGOED FOR RELEASE UNTIL TUESDAY, July 29, 2008 at 12:30 p.m. CT
An NYU study that followed 213 healthy adults over an average of 7 years found that subjects with subjective memory complaints at the first evaluation were almost 7 times more likely to experience cognitive decline to mild cognitive impairment or dementia compared to adults without initial complaints. This is the first prediction study to link subjective cognitive impairment to both mild cognitive impairment and dementia and underlines the importance in studying early, non-specific symptoms that arise before mild cognitive impairment is apparent, the researchers report. Such efforts are critical to preventing the disease. To develop preventive interventions it may be necessary to accurately identify the disease in its earliest manifestations, when symptoms are first emerging, say the NYU researchers. These subjective symptoms appear to occur as early as twenty or more years before the overt dementia of Alzheimer's appears.

Presentation # PS-043
A Decreasing Ability to Learn Among Aging Healthy Carriers of APOE 4 Nunzio Pomara, M.D., Professor in the Department of Psychiatry, NYU Langone Medical Center; Director of the Geriatric Psychiatry Program, Nathan S. Kline Institute EMBARGOED FOR RELEASE WEDNESDAY, July 30, 2008, at 1 PM CT
A new study by NYU researchers at the Nathan Kline Institute suggests that a major genetic risk factor for Alzheimer's disease, apoE 4, may exert its adverse effects long before clinical symptoms of the disease emerge. During this critical period they believe there may be a gradually decreasing ability to learn new material, and subsequently form new memories. The scientists evaluated 184 healthy adults, ages 38 to 80 (64 people carried the apoE4 allele), using standardized measures of verbal learning and memory, such as learning a list of words. At younger ages, surprisingly, those with the apoE 4 genetic risk factor significantly outperformed those without it. By ages 60 to 64 and older, however, performance in the apoE 4 group dropped below the non-apoE 4 group.

Presentation # HT-3577
Genetic Mutation Linked to a More Abundant Form of Alzheimer's Protein Allal Boutajangout, PhD, Research Assistant Professor, Department of Medicine and Psychiatry at NYU Langone Medical Center EMBARGOED FOR RELEASE UNTIL WEDNESDAY July 30, 2008 at 4:00 p.m. CT
NYU researchers found that a specific gene mutation previously associated with an increase in production of an Alzheimer's disease-causing protein, amyloid beta, also promotes the entanglement of another protein, tau, which also is associated with the neurodegenerative disease. Mice that produced human types of tau while expressing the gene mutation showed a significant increase in the harmful form of the tau protein in the brain. The research provides a new model for Alzheimer's onset and progression.

Presentation #04-01-05
Study Further Ties Digestion of Harmful Protein to Alzheimer's Disease Dun-Sheng Yang, PhD, Assistant Professor, Department of Psychiatry, NYU Langone Medical Center; Research Scientist, Center for Dementia Research, Nathan S. Kline Institute EMBARGOED FOR RELEASE UNTIL SUNDAY, July 27, 2008 at 12:30 p.m. CT
NYU researchers genetically enhanced the activity of digestive enzymes in the nerve cells of mice that were susceptible to producing an overabundant amount of amyloid beta, the abnormal protein found in the plaques littering the brains of people with Alzheimer's. The mice showed lower amounts of the protein in parts of the brain responsible for advanced thinking, learning and memory—evidence that their brain cells were more efficient at digesting and expelling the toxic, misfolded protein, the researchers report. The study shows that the failure to degrade amyloid beta in lysosomes containing the digestive enzymes is an important factor in Alzheimer's disease. Amyloid beta and another protein called tau are associated with the disease, but it hasn't yet been proven definitively that either actually causes the disease.

Presentation # P1-059
Study Suggests a Link Between Amyloid and Memory Paul M. Mathews, PhD, Assistant Professor, Department of Psychiatry, NYU Langone Medical Center; Research Scientist, Center for Dementia Research, Nathan S. Kline Institute EMBARGOED FOR RELEASE UNTIL SUNDAY, JULY 28, 2008 at 3:00 p.m. CT
By manipulating levels of the beta amyloid peptide, which accumulates in brain plaques in people with Alzheimer's disease, NYU researchers have found that the peptide not only plays a toxic role in the neurodegenerative disease but also is crucial in modulating learning and memory consolidation in the normal brain. The rat study, which controlled peptide levels in a region of the brain that is important in learning and memory, suggests that its disruption may be one of the underlying causes of nerve dysfunction during Alzheimer's disease pathogenesis.

Presentation #02-02-01
Dysfunctional Transporters in Nerves Related to Alzheimer's Seonil Kim, Ph.D student, Sackler Institute for Graduate Biomedical Sciences, NYU Langone Medical Center, Graduate Training Program in Cellular and Molecular Biology, Nathan S. Kline Institute and Ralph Nixon, M.D., Ph.D., Professor of Psychiatry and Cell Biology, NYU Langone Medical Center EMBARGOED FOR RELEASE UNTIL TUESDAY, JULY 29, 2008 at 12:30 p.m. CT
An NYU study found that membrane vesicles that are essential for the trafficking of materials across nerve cells are an important factor in the pathology of Alzheimer's disease. Mouse neurons which over-produce a precursor to the amyloid protein closely linked to Alzheimer's disease development were unable to shuttle the vesicles to their proper destinations in nerve cells, causing them instead to enlarge abnormally and accumulate. The impeded transport of these vesicles, according to the researchers, may affect communications within and between nerve cells that are critical for cognition and when disrupted can lead to the neurodegeneration of Alzheimer's disease.

Presentation # PS-410
Early Phases of Creating a Vaccine against Prion Disease Thomas Wisniewski, MD, Department of Pathology at NYU Langone Medical Center EMBARGOED FOR RELEASE UNTIL TUESDAY, July 29, 2008 at 11:30 a.m. CT
In an animal study, NYU researchers bolstered immunity against a toxic and infectious version of the prion protein, which causes a group of brain diseases, including mad cow's disease. By injecting a safe, reconfigured form of the protein into the body cavity of mice, in addition to orally delivering a neutral bacterial booster, animals could produce more antibodies against the prion protein in the mouth and blood system, preventing access of the infectious prions to the brain. The inoculated mice remained symptom free for 400 days after exposure to infectious prion, while their brains were free from the disease causing protein. The finding has the potential to safely curb prion diseases, such as chronic wasting disease and variant Creutzfeld-Jacob disease, which are thought to be spread by oral exposure to prion.

Presentation # S3-01-04
Tau Immunotherapy Prevents Cognitive Decline in an Alzheimer's Mouse Model Einar M. Sigurdsson, PhD, Assistant Professor of Psychiatry and Pathology, NYU Langone Medical Center EMBARGOED FOR RELEASE UNTIL WEDNESDAY, JULY 30, 2008 at 3:45 p.m. CT
NYU researchers have successfully prevented the cognitive decline of mice by employing a vaccine that targets tangles of tau, a type of protein associated with Alzheimer's disease. Tests confirmed that the immunotherapy helped preserve cognition as well as reduced tau protein tangles in the brain. The findings support the possibility of an immunotherapy that treats Alzheimer's disease by directly targeting toxic forms of the tau protein.

Presentation # O4-04-04
Enzyme inhibition modulates Alzheimer's pathology in mice Jose Morales-Corraliza, Ph.D, NYU Langone Medical Center and Research Scientist, Nathan S. Kline Institute EMBARGOED FOR RELEASE UNTIL SUNDAY, JULY 27, 2008 at 12:30 p.m. CT
Researchers at NYU Langone Medical Center and the Nathan Kline Institute found that the inhibition of the calpain enzyme, which is involved in various cellular processes, led to a robust decrease in amyloid deposition in mice that develop plaque pathology commonly seen in Alzheimer's disease. Modulation of neuronal calpain activity presents a potential therapeutic approach to Alzheimer's, they report. Presentation #P1-079
Partial gene-deletion improves memory dysfunction in Alzheimer's mice Masuo Ohno, Ph.D., NYU Langone Medical Center and head of the Laboratory of Molecular and Cellular Cognition, Center for Dementia Research at the Nathan Kline Institute EMBARGOED FOR RELEASE UNTIL SUNDAY, JULY 27, 2008 at 12:30 p.m. CT
An animal study by NYU researchers reveals that partially inhibiting an enzyme that initiates the release of amyloid beta led to an improvement in neuronal and cognitive deficits in mice that produced excessive amounts of the plaque forming protein. The approach poses a possibility to rescue Alzheimer's-related deficits, the researchers report.

Presentation #P1-092
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About NYU Langone Medical Center
One of the world's premier academic medical institutions for more than 167 years, NYU Langone Medical Center continues to be a leader in patient care, physician education and scientific research. NYU Langone Medical Center is internationally renowned for excellence in areas such as cardiovascular disease, pediatrics, skin care, neurosurgery, urology, cancer care, rehabilitation, plastic surgery, minimally invasive surgery, transplant surgery, infertility, women's health and day surgery.

Medivation Alzheimer's drug helps -- if used early

By Julie Steenhuysen
31 july 2008--A drug for Alzheimer's disease made by Medivation Inc kept symptoms at bay for 18 months, U.S. researchers said on Wednesday, but people who got the drug after first taking a placebo fared less well, suggesting early treatment is best.
The latest results, being presented at the Alzheimer's Association's international meeting in Chicago, found Dimebon was safe and continued to benefit people who took it for a year and a half.
"The most important thing from my point of view is there were no new safety issues that emerged with longer exposure of the patients," said Dr. Jeffrey Cummings of UCLA, who helped with the study.
The results from the 183-patient study conducted in Russia found people continued to improve, with benefits seen in cognition, memory, activities of daily living and behavior.
The study also found that people who were treated with a placebo for a year and then took Dimebon stabilized across five measures of thinking ability, but were unable to catch up to the group who had taken it for the full 18 months.
"People initially treated with the placebo and then crossed over to Dimebon did not show the same level of benefit as those people who took Dimebon for the full 18 months," Cummings said in a statement.
"This emphasizes the benefit of earlier treatment and suggests the possibility that Dimebon may slow the progress of Alzheimer's," he said.
Medivation has provided frequent updates of patients in the study in Russia, where patients in the study took few if any drugs other than Dimebon.
Such a study would not be possible in Western countries, where most Alzheimer's patients take a variety of other drugs.
Some doctors think the true test of whether Dimebon represents an advance over current therapies will come from studies done in the West, where patients have ready access to other drugs that can slow progression of the disease.
These include Eisai Co Ltd's and Pfizer Inc's Aricept, Forest Laboratories Inc's Namenda, Novartis AG's Exelon and Johnson & Johnson's Razadyne.
All affect message-carrying chemicals in the brain called neurotransmitters, but lose their effect over time.
"The one issue with this trial is that no other treatments were allowed," Dr. Scott Turner, incoming director of the Memory Disorders Program at Georgetown University Medical Center in Washington, said in a telephone interview.
"Here it will be tested as an add-on, and the question is will it have any other benefit (when taken) with the current therapies," he said. "I think that is a big if."
Cummings thinks the drug has a shot.
"I think we will continue to see an effect because the signal was strong; but under the circumstances of a global trial, it will likely be not as clearly seen as it was in the Russian trial," he said in a telephone interview.

New study finds healthy children of Alzheimer patients show early brain changes

30 july 2008--Medical College of Wisconsin researchers in Milwaukee have reported that children of Alzheimer's patients who are carriers of a genetic risk factor for Alzheimer's disease have neurological changes that are detectable long before clinical symptoms may appear.
Functional MRI brain imaging revealed that these symptomless carriers of the APOE-4 gene demonstrated significantly reduced functional brain connectivity between the hippocampus and the posterior cingulated cortex, two important brain structures for memory processing. These structures are relevant for information acquisition, filtering and sorting.
The study, conducted at Froedtert Hospital, was led by Shi Jiang Li, Ph.D., professor of biophysics, and was presented at the Alzheimer's Association International Conference on Alzheimer's disease in Chicago, July 29th
"Just as if cancer could be detected when there were only a few cells, decades before it was evident, the advantage of identifying those at great risk for having Alzheimer's would be of tremendous value in development of interventional therapies," says Dr. Li.
The researchers studied 28 neurologically-normal subjects, between ages 45 and 65. Twelve carried the APOE-4 gene and 16 did not. The two groups showed no significant difference in age, educational level, or neuropsychological performances. All subjects received fMRI scans. For each subject, functional connectivity between the two brain structures was measured in a resting state.
Results showed that functional connectivity in the non APOE-4 carriers was approximately 65 percent better than that of the carriers.
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Other members of the research team were Piero Antuono, M.D., professor of neurology, and Zhilin Wu, Ph.D., Chunming Xie, Ph.D., and Jennifer L. Jones, M.S., research associates in the departments of biophysics and neurology.

Study: 'Pre-dementia' is rising, especially in men

By MARILYNN MARCHIONE ,

29 july 2008--A milder type of mental decline that often precedes Alzheimer's disease is alarmingly more common than has been believed, and in men more than women, doctors reported Monday.
Nearly a million older Americans slide from normal memory into mild impairment each year, researchers estimate, based on a Mayo Clinic study of Minnesota residents.
That's on top of the half million Americans who develop full-blown Alzheimer's or other forms of dementia — a problem sure to grow as baby boomers age. The oldest boomers turn 62 this year.
"We're seeing that in fact there's a much larger burgeoning problem out there" of people at risk of developing dementia, said Dr. Ronald Petersen, the Mayo scientist who led the study.
Dr. Ralph Nixon, a New York University psychiatrist and scientific adviser to the Alzheimer's Association, was blunt.
"We're facing a crisis," he said.
There are no treatments now to prevent this mental slide or reverse it once it starts.
But that may be changing. Researchers on Monday reported early, somewhat encouraging results from an experimental nose spray that seemed to improve certain memory measures in a study of mildly impaired people.
The drug, for now just called AL-108, needs testing in a longer, larger study. It is being developed by Allon Therapeutics Inc., based in Vancouver, B.C.
Doctors said it shows the potential for new types of medicines that target the protein tangles that kill nerve cells, instead of targeting the sticky brain deposits that have gotten most of the attention up to now.
The studies were reported at the International Conference on Alzheimer's Disease in Chicago.
Petersen is the scientist who defined mild cognitive impairment, or MCI, as a transition phase between healthy aging and dementia. It is more than "senior moments" like forgetting where you parked the car, but not as severe as having dementia, where you forget what a car is for.
People with it have impaired memory but not other problems like confusion, inattention or trouble putting thoughts into words.
The Alzheimer's Association says more than 5 million Americans have Alzheimer's, but no estimate for this "pre-dementia" has been available until now.
Petersen's federally funded study involved roughly 1,600 people, ages 70 through 89, living in Olmstead County, which surrounds the Mayo Clinic in Rochester, Minn. All tested normal when they were enrolled in the study, but more than 5 percent had developed mild impairment when evaluated a year later.
Men were nearly twice as likely as women to develop it. That's a surprise, because some studies have found more women with Alzheimer's than men. But there may be a simple explanation:
Even though more men may be impaired, women outlive them and therefore have more time to develop full-blown dementia.
"This is a very large and important issue for our country and for the world," said Duke University psychologist Brenda Plassman. A smaller study she published earlier this year backs up the Mayo study's findings.
The mild impairment rate is two to three times larger than many researchers had expected, Petersen said.
"It's the iceberg under the tip," agreed Dr. R. Scott Turner, incoming director of the memory disorders program at Georgetown University Medical Center. A prime goal is finding drugs to treat the mild impairment before Alzheimer's develops.
The AL-108 study tried to do that. Scientists gave 144 people with mild impairment either a low or high dose of the drug or a dummy drug for 12 weeks. The study missed its main goal — a composite of various memory scores — and the low dose showed no effect. But those on the higher dose improved on some memory tasks after one month and benefits lasted a month after they stopped treatment, said the study's leader, Dr. Donald Schmechel of Duke University.
The study was sponsored by the drug maker.
In another study presented at the conference on Sunday and published on the Internet by the British medical journal The Lancet, researchers reported that dementia rates in developing countries may be considerably higher than official estimates and closer to rates in wealthy countries.
Scientists used a more liberal definition of dementia more suitable to poorer, less educated populations, where respect for family often means relatives don't regard dementia as a burden so much and may be less likely to report problems.
The study involved nearly 15,000 people in 11 sites from China, India, Cuba, Mexico and other nations. Dementia rates ranged from nearly 6 percent in rural China to nearly 12 percent in the Dominican Republic, said co-author Martin Prince of King's College in London.
The World Health Organization and the Alzheimer's Association were among the study's sponsors.
On the Net:
National Institute on Aging: http://www.nia.nih.gov
Alzheimer's Association: http://www.alz.org

Hypnosis shown to reduce symptoms of dementia

29 july 2008--A scientist at the University of Liverpool has found that hypnosis can slow down the impacts of dementia and improve quality of life for those living with the condition.
Forensic psychologist, Dr Simon Duff, investigated the effects of hypnosis on people living with dementia and compared the treatment to mainstream health-care methods. He also looked at how hypnosis compared to a type of group therapy in which participants were encouraged to discuss news and current affairs.
They found that people living with dementia who had received hypnosis therapy showed an improvement in concentration, memory and socialisation compared to the other two treatment groups. Relaxation, motivation and daily living activities also improved with the use of hypnosis.
Dr Duff said: "Over a nine month period of weekly sessions, it became clear that the participants attending the discussion group remained the same throughout. The group who received 'treatment as usual' showed a small decline over the assessment period, yet those having regular hypnosis sessions showed real improvement across all of the areas that we looked at.
"Participants who are aware of the onset of dementia may become depressed and anxious at their gradual loss of cognitive ability and so hypnosis – which is a tool for relaxation – can really help the mind concentrate on positive activity like socialisation."
Further research will now take place to establish whether hypnosis maintains its effects on dementia as the illness progresses, over longer periods of time.
Dr Dan Nightingale, co-author of the research and leading dementia consultant at the Abacus Clinic in Newark, added: "Evidence to date has shown that we can enhance the quality of life for people living with dementia through the correct use of hypnosis. We have now developed a course for clinicians who wish to incorporate hypnosis into health care plans."

Angiotensin receptor blockers are lower incidence, progression of Alzheimer's disease

Boston, MA, 28 july 2008—Researchers at Boston University School of Medicine (BUSM) have, for the first time, found that angiotensin receptor blockers (ARBs)—a particular class of anti-hypertensive medicines—are associated with a striking decrease in the occurrence and progression of dementia. Data from this study will be presented this weekend (July 27) at the 2008 International Conference on Alzheimer's disease in Chicago.
Using data from the Decision Support System Database of the U.S. Department of Health System Veterans Affairs (with information on more than 5 million people), researchers looked at records from patients using ARBs, and compared them with subjects who had a similar health status, but were taking different medications. They found patients taking ARBs had about a 35-40 percent lower chance of getting Alzheimer's disease or dementia.
The researchers also examined patients who were already suffering from Alzheimer's disease or dementia, and found those subjects had up to a 45 percent lower chance of developing delirium, being admitted to nursing homes or dying. Patients who appeared to benefit particularly well from use of ARBs were those who had experienced strokes before or during the course of their illness.
According to the researchers these results suggest that ARBs might protect against developing Alzheimer's disease and dementia. "For those who already have dementia, use of ARBs might delay deterioration of brain function and help keep patients out of nursing homes," said lead presenter Benjamin Wolozin, MD, PhD, a professor of pharmacology at BUSM. "The study is particularly interesting because we compared the effects of ARBs to other medications used for treating blood pressure or cardiovascular disease. This suggests that ARBs are more effective than other blood pressure and cardiovascular medications for preventing Alzheimer's disease or dementia," he added.
Although the researchers are unsure why ARBs might be so beneficial, they believe one possibility suggested by prior studies on animal models is that ARBs help prevent nerve cell injury from blood vessel damage or help promote nerve cell recovery after blood vessel damage. Damage to blood vessels is thought to reduce brain capacity and promote dementia, so reducing this damage might prevent the occurrence or progression of dementia.
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This study was funded by the Retirement Research Foundation and from the Casten Foundation.

MRIs show promise for early Alzheimer's diagnosis

By Julie Steenhuysen
28 july 2008--Researchers have used magnetic resonance imaging scans to locate Alzheimer's-like plaques in rabbits, bringing researchers a step closer to being able to diagnose the disease using ordinary MRI equipment.
"Although some of the technology used to generate these images was designed specifically for rabbits, this preliminary discovery hints at the promise of using clinical MRI scanners to visualize plaques in people with Alzheimer's," John Ronald of Ontario's Robarts Research Institute said in a statement.
The study, unveiled at the International Conference on Alzheimer's Disease in Chicago on Sunday, was one of several showing how widely available MRI scans could be used for early diagnosis of the brain-wasting disease.
The study marks the first time researchers have been able to "see" brain plaques using conventional MRI scanners. Currently, high-powered MRI scanners have been able to spot them in animals, and PET scanners using special marker chemicals have worked as well.
Currently, an autopsy is the only sure way to confirm Alzheimer's disease, by identifying the brain lesions such as amyloid plaques that characterize the disease. Doctors typically rely on a series of tests to give them a good idea of whether someone has Alzheimer's.
Researchers in the Canadian study fed rabbits a high-cholesterol diet for two years, which caused them to form amyloid plaques in their brains. Scans of these rabbits revealed void areas or black spots in several areas including the hippocampus, an important memory center in the brain.
Autopsies found small clusters of amyloid plaques in these void areas, not found in rabbits fed a normal diet.
"This may be used for animal imaging, but potentially down the road it may be used for human imaging," Ronald told a media briefing.
Dr. Jeffrey Kaye of the Oregon Health & Science University in Portland, who moderated the briefing, said the study has promise but the jump between rabbits and humans may not be effortless. He said researchers using special high-field MRI magnets can already see amyloid plaques in mice, but so far have not been able to see them in human brains.
"I have to believe it will be solved," Kaye added.
In a separate study, researchers at the Mayo Clinic in Rochester, Minnesota, said they were able to use a computer program to analyze information on MRI scans that could distinguish between normal and Alzheimer's brains with 90 percent accuracy.
The program, known as STAND, measures the degree of atrophy in a person's brain.
The researchers compared data gathered from 101 people who had an MRI within four years of their death to data gathered after they died by a test known as Braak staging, which measures the severity of fibrous tangles in the brain.
"This study shows that information extracted from MRI scans can accurately capture the severity of Alzheimer's tangle pathology," Prashanthi Vemuri, who presented the results, said in a statement.
A third group from the University of Pennsylvania in Philadelphia, using a new computer-based image analysis technique, was able to find Alzheimer-like activity in the brains of elderly people who had normal cognitive capabilities, and in a group with mild cognitive impairment.
While more study is needed to understand the findings, they hope the tools will help in the search for early brain changes that signal the start of Alzheimer's.
"These MRI studies show that researchers are moving closer to accurate early detection of the disease, and that we may soon be able to use this technology to determine who is at greater risk," William Thies of the Alzheimer's Association said in a statement.

A new century of Alzheimer's disease research
Mayo Clinic scientists aim to improve risk prediction, diagnosis and treatment

JACKSONVILLE, Fla. -- Imagine the day when a routine visit to the family doctor includes a simple blood test to predict the risk for developing Alzheimer’s disease (AD). If the test returns a worrisome result -- too many sticky brain proteins that might begin to gum up memory and thought in 10 to 15 years -- a person could be offered an aspirin-like pill to keep those proteins in check.
That is the future a visionary team of researchers at Mayo Clinic’s campus in Jacksonville aims to reach.
“It will be very straightforward, like today’s blood cholesterol test to gauge risk of developing heart disease,” says Steve Younkin, M.D., Ph.D., a Mayo Clinic neuroscientist. “If your cholesterol profile is out of whack, treatment with a simple statin drug can reduce that risk. Our goal is to develop a similar kind of testing and treatment to keep the brain in balance.”
Researchers and physicians at Mayo Clinic’s sites in Florida, Minnesota and Arizona are studying various aspects of Alzheimer’s. When combined, the elements provide a comprehensive approach to unraveling the mystery of the disease: from understanding why it develops, to how it can be diagnosed early, treated effectively and, ultimately, prevented.
Much of the basic lab, animal research and drug discovery occurs in Jacksonville. Mayo researchers in Jacksonville, Rochester, Minn., and Scottsdale, Ariz., are studying aging’s effects in thousands of elderly individuals. Researchers want to know how aging changes brain structure, thought processes and blood chemistry, so they can model and predict progression to Alzheimer’s disease.
“Whether it is working with people or doing lab science, we have really tried to focus our research on ways in which we can make a difference in the lives of our patients, both today and tomorrow,” says Todd Golde, M.D., an Alzheimer’s disease researcher who chairs the Department of Neurosciences at Mayo Clinic Jacksonville.
And, by all accounts, that focus will likely begin to pay off in this second century of Alzheimer’s research. Until 1986, some 80 years after German physician Alois Alzheimer discovered the brain abnormalities associated with the disease, physicians understood little about Alzheimer’s disease. But several decades ago, the pace of discovery began to accelerate, says Ronald Petersen, M.D., Ph.D., a Mayo physician in Rochester who directs the Mayo Clinic Alzheimer’s Disease Research Center (ADRC), encompassing the research programs in Jacksonville and Rochester.
“We have moved a great distance forward in understanding what might be the key, or, in the least, an important aspect of this disease,” Dr. Petersen says. “And we are at the threshold of developing therapies that we hope will eventually impact Alzheimer’s disease.”
“We are not slogging through a fog anymore,” says Dr. Younkin, who has helped define the direction that Alzheimer’s research has taken in many of the world’s research labs. “We can see the top of the hill for the first time, and while we probably won’t get where we want to be for many years, it is really exciting.” Dr. Younkin helped discover that a single brain protein, known as amyloid-beta 42 (AB42), appears to be the central player in the disorder. And much of Alzheimer’s drug research is focused on different ways to attack Aâ42, believed to be the most vulnerable target -- the Achilles’ heel -- of Alzheimer’s disease.
“We know AB42 is always on the scene and is clearly important,” says Richard Caselli, M.D., who heads Alzheimer’s disease research at Mayo Clinic in Arizona. “So the prevailing model is that AB42 is it, and if you can somehow control AB42, you can control Alzheimer’s disease.”

Heart Disease a Risk Factor for Alzheimer's

By Carolyn ColwellHealthDay ReporterMon Jun 11, 7:02 PM ET
SUNDAY, June 10 (HealthDay News) -- There's more evidence that cardiovascular problems help drive Alzheimer's disease, scientists say, and that treating the heart might help protect the brain.
The findings "represent hope that interventions with well-known drugs can interfere with the disease's progression," said lead investigator Yan Deschaintre, a neurologist and research fellow at the University Regional Hospital Center in Lille, France.
In fact, cognitive impairment, as measured by a standard test, stayed in the low end of the mild range over 36 months for Alzheimer's patients who got treatments for both the neurological disease and their cardiovascular problems, the researchers reported.
In contrast, Alzheimer's patients with vascular trouble who did not receive these medications experienced declines in cognition that approached the severe level, Deschaintre's team found.
They were slated to present the findings Sunday at the Alzheimer Association's International Conference on Prevention of Dementia, in Washington, D.C.
According to the National Institute on Aging, about 4.5 million Americans have Alzheimer's disease. Rates rise steadily with age, and experts estimate that "nearly half of those 85 and older may have the disease." One recent study from the World Health Organization, released this week, warned that Alzheimer's -- which currently has no cure -- could affect 100 million people worldwide by 2050.
The new study was based on chart reviews of 891 French patients diagnosed with either Alzheimer's disease, cardiovascular disease plus Alzheimer's disease, or vascular dementia. The cognitive risk factors included in the study were high blood pressure, diabetes, high cholesterol, atherosclerotic disease and tobacco smoking.
Treatment was defined as receiving an antihypertensive drug, insulin or drugs to lower blood sugar, a cholesterol-lowering statin, or anti-clotting medications. The patients with Alzheimer's disease typically received medications aimed at temporarily curbing their symptomsthat included Aricept, Exelon or Reminyl.
Deschaintre's findings represent "pretty exciting work," because cardiovascular risk factors are "something we can do something about," said Dr. Sam Gandy, director of Emory University's Center for Neurodegenerative Diseases. Gandy also is chairman of the Alzheimer's Association's National Medical and Scientific Advisory Council.
The work done by Deschaintre's team is consistent "with what we've been hearing over the past three to five years" about vascular risk factors increasing the risk for Alzheimer's, Gandy said. The new study, "really nails that down by looking at the other side of the coin by establishing that treating vascular risk factors slows the progression of cognitive decline," he added.
He suggested that physicians begin to take vascular risk factors seriously as they treat patients with Alzheimer's. The vascular risk factors for early Alzheimer's patients "certainly should be treated" because it "seems to slow progression," Gandy said.
Another expert agreed.
The Lille results "reinforce the treatment guidelines for these vascular conditions, such as hypertension and diabetes, and emphasize that Alzheimer's and demented patients should be treated, too," said Hugh C. Hendrie, a professor of psychiatry at the Indiana University Medical School and a scientist at its Center for Aging Research.
However, Deschaintre and Hendrie both noted that physicians at times may not treat vascular risk factors in Alzheimer's patients, for a variety of reasons. For example, Alzheimer's disease often leaves patients apathetic, so they may neglect to tell their physicians about vascular symptoms, Hendrie said.
And Deschaintre noted that, in the clinic where the research was done, patients with Alzheimer's were less likely than other patients to be treated for vascular risk factors. The reverse was true, as well -- patients with vascular dementia were more likely to be treated for heart risk factors, but not for Alzheimer's.
But, "since the majority of patients have both Alzheimer's disease and cerebrovascular disease, and since patients with pure Alzheimer's do seem to benefit from treatment of vascular risk factors, the message is to treat both conditions rather than to focus only on one," he said.
Hendrie remained cautious about the scientific impact of Deschaintre's study, however. He said results from a clinical epidemiological study, such as the Lille research, aren't as conclusive or compelling as those from randomized, controlled clinical trials.
Two other studies scheduled for release at the Alzheimer's conference on Sunday also emphasized the role of the brain-body connection in cognitive impairment and dementia.
Weight loss may signal the onset of Alzheimer's, and the rate of weight loss could be early warning of dementia severity, according to a new review of data from what's known as the Nun's Study. That effort followed health outcomes for a group of 537 non-demented Catholic sisters, aged 75 to 102, for 10 years.
In the study, a team led by Dr. James Mortimer, a professor of epidemiology and biostatistics at the University of South Florida, Tampa, found that unexplained weight loss late in life was often linked to Alzheimer's neuropathology in the brain and not to any change in eating habits linked to Alzheimer's.
Mortimer explained that, "early weight loss appears to result from the Alzheimer's disease process itself before that process leads to dementia. That's why it is a marker of impending dementia."
In a third study, a team from the Mayo Clinic in Rochester, Minn., found an increased risk of mild cognitive impairment (MCI) or dementia among 70- to 89-year-olds who have had a carotid endarterectomy (surgical clearance of the carotid artery, which brings blood to the brain) or a stroke or "mini-stroke," also known as a transient ischemic attack (TIA).
In the study, the team compared the medical histories of 295 people with MCI and 590 age and sex-matched controls. "Elderly subjects who have had a carotid endarterectomy or stroke or TIA are about two times more likely to have MCI," lead researcher Dr. Rosebud O. Roberts, a Mayo epidemiologist, said in a prepared statement.
More information
For more on Alzheimer's disease, visit the Alzheimer's Association.

Wandering Is Health Risk For 1 In 5 Cognitively Impaired Nursing Home Patients

In a study involving over 15,000 cognitively impaired VA nursing home patients, researchers from the International Research Consortium on Wandering found that one in five were prone to aimless wandering through nursing home facilities, putting themselves at increased health risk and creating additional strain on nursing staff. This presents a challenging behavior problem and safety issue. Adverse outcomes associated with wandering include an increased incidence of weight loss, fatigue, sleep disturbance, getting lost, injuries as a result of falling and untimely death. Wandering can also lead to increased caregiver stress, stress among other residents due to intrusions into their rooms and safety concerns that challenge care providers responsible for managing behavior problems.