Archives for July 2016

Alzheimer’s Drug LMTX Falters in Final Stage of Trials

(The New York Times) A new type of drug for Alzheimer’s disease failed to slow the rate of decline in mental ability and daily functioning in its first large clinical trial. There was a hint, though, that it might be effective for certain patients.

The drug, called LMTX, is the first one with its mode of action — trying to undo so-called tau tangles in the brain — to reach the final stage of clinical trials. So the results of the study were eagerly awaited. The initial reaction to the outcome was disappointment, with perhaps a glimmer of hopefulness.

Over all, the patients who received LMTX, which was developed by TauRx Therapeutics, did not have a slower rate of decline in mental ability or daily functioning than those in the control group.

However, the drug did seem to work for the subset of patients — about 15 percent of those in the study — who took LMTX as their only therapy. The other 85 percent of patients took an existing Alzheimer’s drug in addition to either LMTX or a placebo.

“There were highly significant, clinically meaningful, large effects in patients taking the drug as monotherapy, and no effect in patients taking it as an add-on,”

Claude Wischik, a founder and the chief executive of TauRx, said in an interview. He spoke from Toronto, where the results were being presented at the Alzheimer’s Association International Conference.

Dr. Wischik said a second clinical trial sponsored by the company, whose results will be announced later, found the same phenomenon. He said the company planned to apply for approval of LMTX to be used by itself.

But some experts not involved in the study were skeptical about drawing conclusions from a small subset of patients, especially since there was no obvious explanation why LMTX would be expected to work only in patients not getting other drugs. Regulators might also be skeptical and require the company to conduct another large study, this time only with participants not using other drugs.

“I have to say that the results that we saw here were, to me, more disappointing than not,”

Dr. David Knopman, a neurologist at the Mayo Clinic, said in moderating a news conference at the meeting in Toronto.

Dr. Rachelle Doody, director of the Alzheimer’s disease and Memory Disorders Center at Baylor College of Medicine, agreed.

“To present it to the public now as a promising approach seems unjustified,” she said.

The Alzheimer’s field is littered with unsuccessful experimental drugs. The handful of drugs that have reached the market, like Aricept and Namenda, temporarily affect symptoms but do not hit at the underlying mechanism of the disease.

Most efforts to modify the disease mechanism so far have tried to counter the buildup in the brain of beta-amyloid, a protein that forms sticky plaques.

Those drugs have not been successful. But as with TauRx, some of the companies involved say there are signs the drugs work for certain patients, particularly those in a very early stage of the disease. So studies are continuing at Eli Lilly, Biogen, Roche and other companies.

Still, the failures of the amyloid drugs so far have prompted companies, including AbbVie, Biogen and Roche, to begin looking more at tau, another protein in the brain. When it becomes abnormal, it aggregates into tangles that kill neurons and can spread through the brain. Some studies suggest that levels of tau are more closely correlated with cognitive decline than levels of amyloid.

“There is increasing evidence that tau is more proximal to the onset of disease symptoms,”

said William Jagust, professor of public health and neuroscience at the University of California, Berkeley.

The results of the LMTX trial do not necessarily spell doom for all tau drugs, because others might work differently. LMTX is

“not the be-all and end-all for tau targeting,”

said Harry M. Tracy, publisher of NeuroPerspective, a newsletter that follows companies developing neurology drugs.

Dr. Wischik has been studying tau since his days as a doctoral student at Cambridge University in the 1980s. TauRx, which is privately held, operates out of Aberdeen, Scotland, and Singapore. Investors include Genting Berhad, a Malaysian investment company, and Temasek, a government-owned investment company in Singapore.

LMTX, which is TauRx’s only drug, is a derivative of methylene blue, a dye. It is also being tested as a treatment for frontotemporal dementia, another neurodegenerative disease, with results expected next month.

TauRx’s first clinical trial in Alzheimer’s, announced in 2008, also had equivocal results. One dose slowed cognitive decline, but a higher dose had no effect. The company said there was a problem in the formulation of the higher dose. LMTX is a new formulation intended to avoid that problem.

The Phase 3 trial presented on Wednesday had 891 patients from 16 countries with mild or moderate Alzheimer’s disease. They were randomly assigned to be treated with a lower dose of LMTX, a higher dose of LMTX or a placebo. (The placebo contained a tiny amount of LMTX to turn the patients’ urine bluish green. Otherwise people would know if they were getting the drug or the placebo based on the color of their urine.)

The subset of patients taking LMTX but no other Alzheimer’s drugs had essentially no decline in cognition or daily functioning for the entire 15 months of the trial, said Dr. Serge Gauthier, director of the Alzheimer’s disease research unit at McGill University and the principal investigator of the trial. He is also chairman of TauRx’s scientific advisory board.

The difference between those patients and the total population getting the placebo, who did decline, was about six points on a measure of cognition called ADAS-cog. That difference is considered clinically meaningful.

The rate of brain atrophy, as measured by M.R.I., was also slowed in those taking LMTX without other drugs. Dr. Gauthier said it was the first time a reduction in brain atrophy had been seen in a clinical trial of an Alzheimer’s drug.

Side effects included nausea, diarrhea and urinary discomfort.

Dr. Wischik said the separate analysis of those not taking other drugs was planned in advance, not an after-the-fact “data dredging” exercise to come up with some positive sign.

He said one hypothesis why LMTX did not work with other drugs was that the other drugs set off a mechanism that cells use to expel drugs. LMTX was caught up in this and also expelled from brain cells. But this has yet to be proved.

It is possible that some other factor, not the drug, could explain why those patients did better. Such patients tended to be disproportionately from Eastern Europe and Malaysia, for example. The reported results compared the patients taking LMTX alone with the entire placebo group, not only the placebo patients getting no other Alzheimer’s drugs, which would have been a more apt comparison.

Citation

http://www.nytimes.com/2016/07/28/business/
alzheimers-drug-lmtx-trial.html?_r=1

© 2016 The New York Times Company

 

 

Alzheimer’s Is Not Normal Aging — And We Can Cure It

(TED Talks) More than 40 million people worldwide suffer from Alzheimer’s disease, and that number is expected to increase drastically in the coming years. But no real progress has been made in the fight against the disease since its classification more than 100 years ago.

St. John’s Research Fellow Samuel Cohen shares a new breakthrough in Alzheimer’s research from his lab as well as a message of hope.

“Alzheimer’s is a disease,” Cohen says, “and we can cure it.”

Transcript

0:11 In the year 1901, a woman called Auguste was taken to a medical asylum in Frankfurt. Auguste was delusional and couldn’t remember even the most basic details of her life. Her doctor was called Alois. Alois didn’t know how to help Auguste, but he watched over her until, sadly, she passed away in 1906. After she died, Alois performed an autopsy and found strange plaques and tangles in Auguste’s brain — the likes of which he’d never seen before.

0:41 Now here’s the even more striking thing. If Auguste had instead been alive today, we could offer her no more help than Alois was able to 114 years ago. Alois was Dr. Alois Alzheimer. And Auguste Deter was the first patient to be diagnosed with what we now call Alzheimer’s disease. Since 1901, medicine has advanced greatly. We’ve discovered antibiotics and vaccines to protect us from infections, many treatments for cancer, antiretrovirals for HIV, statins for heart disease and much more. But we’ve made essentially no progress at all in treating Alzheimer’s disease.

1:29 I’m part of a team of scientists who has been working to find a cure for Alzheimer’s for over a decade. So I think about this all the time. Alzheimer’s now affects 40 million people worldwide. But by 2050, it will affect 150 million people — which, by the way, will include many of you. If you’re hoping to live to be 85 or older, your chance of getting Alzheimer’s will be almost one in two. In other words, odds are you’ll spend your golden years either suffering from Alzheimer’s or helping to look after a friend or loved one with Alzheimer’s. Already in the United States alone, Alzheimer’s care costs 200 billion dollars every year. One out of every five Medicare dollars get spent on Alzheimer’s. It is today the most expensive disease, and costs are projected to increase fivefold by 2050, as the baby boomer generation ages.

2:35 It may surprise you that, put simply, Alzheimer’s is one of the biggest medical and social challenges of our generation. But we’ve done relatively little to address it. Today, of the top 10 causes of death worldwide, Alzheimer’s is the only one we cannot prevent, cure or even slow down. We understand less about the science of Alzheimer’s than other diseases because we’ve invested less time and money into researching it. The US government spends 10 times more every year on cancer research than on Alzheimer’s despite the fact that Alzheimer’s costs us more and causes a similar number of deaths each year as cancer.

3:22 The lack of resources stems from a more fundamental cause: a lack of awareness. Because here’s what few people know but everyone should: Alzheimer’s is a disease, and we can cure it. For most of the past 114 years, everyone, including scientists, mistakenly confused Alzheimer’s with aging. We thought that becoming senile was a normal and inevitable part of getting old. But we only have to look at a picture of a healthy aged brain compared to the brain of an Alzheimer’s patient to see the real physical damage caused by this disease. As well as triggering severe loss of memory and mental abilities, the damage to the brain caused by Alzheimer’s significantly reduces life expectancy and is always fatal.

4:13 Remember Dr. Alzheimer found strange plaques and tangles in Auguste’s brain a century ago. For almost a century, we didn’t know much about these. Today we know they’re made from protein molecules. You can imagine a protein molecule as a piece of paper that normally folds into an elaborate piece of origami. There are spots on the paper that are sticky. And when it folds correctly, these sticky bits end up on the inside. But sometimes things go wrong, and some sticky bits are on the outside. This causes the protein molecules to stick to each other, forming clumps that eventually become large plaques and tangles. That’s what we see in the brains of Alzheimer’s patients.

4:56 We’ve spent the past 10 years at the University of Cambridge trying to understand how this malfunction works. There are many steps, and identifying which step to try to block is complex — like defusing a bomb. Cutting one wire might do nothing. Cutting others might make the bomb explore. We have to find the right step to block, and then create a drug that does it.

5:20 Until recently, we for the most part have been cutting wires and hoping for the best. But now we’ve got together a diverse group of people — medics, biologists, geneticists, chemists, physicists, engineers and mathematicians. And together, we’ve managed to identify a critical step in the process and are now testing a new class of drugs which would specifically block this step and stop the disease.

5:43 Now let me show you some of our latest results. No one outside of our lab has seen these yet. Let’s look at some videos of what happened when we tested these new drugs in worms. So these are healthy worms, and you can see they’re moving around normally. These worms, on the other hand, have protein molecules sticking together inside them — like humans with Alzheimer’s. And you can see they’re clearly sick. But if we give our new drugs to these worms at an early stage, then we see that they’re healthy, and they live a normal lifespan. This is just an initial positive result, but research like this shows us that Alzheimer’s is a disease that we can understand and we can cure.

6:26 After 114 years of waiting, there’s finally real hope for what can be achieved in the next 10 or 20 years. But to grow that hope, to finally beat Alzheimer’s, we need help. This isn’t about scientists like me — it’s about you. We need you to raise awareness that Alzheimer’s is a disease and that if we try, we can beat it. In the case of other diseases, patients and their families have led the charge for more research and put pressure on governments, the pharmaceutical industry, scientists and regulators. That was essential for advancing treatment for HIV in the late 1980s. Today, we see that same drive to beat cancer. But Alzheimer’s patients are often unable to speak up for themselves. And their families, the hidden victims, caring for their loved ones night and day, are often too worn out to go out and advocate for change. So, it really is down to you. Alzheimer’s isn’t, for the most part, a genetic disease. Everyone with a brain is at risk. Today, there are 40 million patients like Auguste, who can’t create the change they need for themselves. Help speak up for them, and help demand a cure.

7:46 Thank you.

7:47 (Applause)


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Mild Behavioral Impairment (MBI) Checklist of Symptoms Could Support Earlier Alzheimer’s/Dementia Diagnosis

(Alzheimer’s Association International Conference) Researchers presenting at the Alzheimer’s Association International Conference 2016 (AAIC 2016) in Toronto introduced and described a new condition or patient status, known as Mild Behavioral Impairment (MBI), that may be a forerunner of neurodegeneration and progression to mild cognitive impairment (MCI) or dementia.

They also proposed new MBI checklist (MBI-C) designed to be administered by physicians that looks at five categories of behavioral symptoms, and which may eventually help clinicians capture changes in behavior that signal the beginnings of neurodegeneration. Once finalized, the proposed scale may also be made into a tool for caregivers of older adults with dementia to document the nature and extent of symptoms and measure changes over time.

According to the researchers, MBI defines a syndrome of later-life acquired neuropsychiatric symptoms (NPS) that are sustained for at least six months. Symptoms displayed as part of MBI, and included on the checklist, center on five domains: apathy/drive/motivation; mood/affect/anxiety; impulse control/agitation/reward; social appropriateness; and thoughts/perception.

The checklist was developed by an expert group participating in the NPS Professional Interest Area (PIA) under the auspices of the Alzheimer’s Association International Society to Advance Alzheimer’s Research and Treatment (ISTAART).

Note: Some common neuropsychiatric (mental/emotional disturbance related to disordered brain function) symptoms of Alzheimer’s disease/dementia: Depression, Anxiety, Wandering, “Sundowning,” Resistance to daily care, Physical aggression, Repetitious questioning, Sleep disturbance, Rummaging/hoarding, Social withdrawal from others & activities, Disruptive vocalizations, Demanding behavior/verbal aggression, Refusing to eat/drink/take medication.

Neuropsychiatric symptoms in dementia are associated with increased disability, cognitive decline, caregiver burden, institutionalization, death and neuropathology burden. NPS are present in about half of people with MCI, and are associated with faster conversion to dementia. Older people with normal cognition and NPS have a higher risk of progressing to MCI, suggesting that NPS are an early manifestation of neurodegeneration.

“Alzheimer’s is a deadly brain disease, and while memory loss is a hallmark of the disease, early symptoms such as anxiety, confusion and disorientation are often more common, troubling and obvious to family members,” said Maria C. Carrillo, PhD, chief science officer, Alzheimer’s Association.

“This proposed new checklist describes and helps identify a new clinical stage in the disease and has the potential to represent a paradigm shift in formal neurodegeneration testing – away from a sole focus on the memory to also encompass behavior. By looking beyond memory-related issues to closely evaluate the behavioral issues included in the checklist, physicians could reach a more efficient and accurate diagnosis, sooner,” said Carrillo.

Rating scales for NPS in dementia, especially the Neuropsychiatric Inventory (NPI), have been used to estimate MBI prevalence. However, MBI is by definition a pre-dementia syndrome in individuals who are functionally independent and younger than typical dementia patients.

Researchers proposed that a rating scale specifically designed for MBI is necessary to develop accurate prevalence estimates and as a later outcome measure of preventive therapies. At AAIC 2016, they unveiled the MBI-C. Questions were designed specifically to address a younger pre-dementia population and to emphasize that the emergence of NPS was a significant change from prior behavior, present for at least 6 months.

“We propose that the utility of the MBI-C – once it is refined and vetted by the Alzheimer’s community – is significant not only clinically, but also in research. In addition, we may be able to create or derive a version that can be provided to family members of older adults to determine the nature and extent of neuropsychiatric symptoms and to measure changes over time.”

“From a research perspective, the scale may prove to be usable in biomarker and neuroimaging studies in pre-dementia clinical states, in epidemiological studies of community samples, and in clinical sample observational studies to help assess the impact of NPS in older adults,” said Zahinoor Ismail, MD, from the University of Calgary.

About AAIC

The Alzheimer’s Association International Conference (AAIC) is the world’s largest gathering of researchers from around the world focused on Alzheimer’s and other dementias. As a part of the Alzheimer’s Association’s research program, AAIC serves as a catalyst for generating new knowledge about dementia and fostering a vital, collegial research community.
AAIC 2016 home page: www.alz.org/aaic/
AAIC 2016 newsroom: www.alz.org/aaic/press.asp

About the Alzheimer’s Association®

The Alzheimer’s Association is the leading voluntary health organization in Alzheimer’s care, support and research. Our mission is to eliminate Alzheimer’s disease through the advancement of research, to provide and enhance care and support for all affected, and to reduce the risk of dementia through the promotion of brain health. Our vision is a world without Alzheimer’s. Visit alz.org or call 800.272.3900.

Citation

http://www.alz.org/aaic/releases_2016/sun_445_ET.asp

Get a copy of the MBI Checklist here: MBI checklist (MBI-C)

Copyright 2016 Alzheimer’s Association

 

Smell and Eye Tests for Detection of Memory Decline and Dementia

(Alzheimer’s Association International Conference) The potential of odor identification testing and physical changes in and around the eye to detect cognitive impairment and Alzheimer’s disease at an early stage was bolstered by new evidence from four studies presented today at the Alzheimer’s Association International Conference (AAIC) 2016.

Two studies evaluated changes in odor identification as an early predictor of cognitive decline, or of the transition to dementia, and compared it to two established biological markers for cognitive decline and dementia – brain amyloid PET imaging and thickness of the brain’s cortex in areas important to memory.

Two other studies reported at AAIC 2016 found:

  • A strong association between thinning nerve layers in the retina of the eye and poor cognition, suggesting the potential of retinal imaging as part of early Alzheimer’s testing.
  • The presence of amyloid deposits in the retina of both people with Alzheimer’s and canine models of the disease by non-invasive polarization imaging; this strengthens their utility as a marker of Alzheimer’s, and a possibility for pre-symptomatic detection.

“It’s clear that the science around biological measures in the detection of Alzheimer’s continues to gather pace and validation,” said Heather Snyder, PhD, director of medical and scientific operations, Alzheimer’s Association.

“Low cost, non-invasive measures to detect dementia-related changes and evaluate the risk of future decline continue to be refined and tested; this is a positive step forward to earlier detection and intervention.”

Today, it is only possible to clinically detect Alzheimer’s relatively late in its development, when significant brain damage has already occurred. While brain positron emission tomography (PET) imaging can show the buildup of amyloid plaques in the brain years before symptoms appear, PET scans are expensive. Beta amyloid can also be detected in cerebrospinal fluid (CSF) through a lumbar puncture, and brain PET imaging of abnormal tau protein is rapidly advancing through research.

“Using other biomarkers of Alzheimer’s disease to detect the disease at an earlier stage – which have the potential to be lower-cost and non-invasive – could lead to dramatic improvements in early detection and management of the disease,” Snyder said.

About Alzheimer’s Association International Conference (AAIC)

The Alzheimer’s Association International Conference (AAIC) is the world’s largest gathering of researchers from around the world focused on Alzheimer’s and other dementias. As a part of the Alzheimer’s Association’s research program, AAIC serves as a catalyst for generating new knowledge about dementia and fostering a vital, collegial research community.

AAIC 2016 home page: www.alz.org/aaic/
AAIC 2016 newsroom: www.alz.org/aaic/press.asp

About the Alzheimer’s Association

The Alzheimer’s Association is the leading voluntary health organization in Alzheimer’s care, support and research. Our mission is to eliminate Alzheimer’s disease through the advancement of research, to provide and enhance care and support for all affected, and to reduce the risk of dementia through the promotion of brain health. Our vision is a world without Alzheimer’s. Visit alz.org or call 800.272.3900.

Citation

http://www.multivu.com/players/English/7865353-aaic-2016-smell-eye-tests/

Copyright 2016 Alzheimer’s Association

 

Researchers Successfully Decrease Use of Antipsychotics in Dementia Care

(Alzheimer’s Association International Conference) Australian researchers today presented results from an innovative project where they dramatically reduced the use of antipsychotic medicines to treat the behavioral and psychological symptoms of dementia (BPSD). Results were presented at the Alzheimer’s Association International Conference (AAIC) 2016 in Toronto.

The Halting Antipsychotic use in Long Term care (HALT) Project, based in New South Wales, Australia, successfully eliminated regular antipsychotic medication from the treatment plan in 75 percent of study participants after 6 months following initial reduction of antipsychotics (12 month follow up data to come). In this study — which involved 140 residents across 23 care facilities — deprescribing was achieved through training of long-term care facility nurses in non-pharmacological and person-centered approaches to managing BPSD.

“There is broad consensus that using antipsychotics to treat dementia symptoms should be a last resort,” said Beth Kallmyer, MSW, Alzheimer’s Association vice president of constituent services.

“These medicines must be used very carefully because they can blunt behaviors and cause sedation, and they carry serious safety concerns, such as increasing the risk of falls and death.”

“Unfortunately, we still see a systematic use of these drugs in residential care facilities in the United States and around the world. With the right type of care strategies in place, difficult-to-manage behaviors are greatly reduced and the need for the drugs is significantly decreased – as was seen in this study.”

According to the American Society of Consultant Pharmacists, more than half of nursing facility residents in the U.S. have some form of dementia, many of whom experience behavioral and psychological symptoms. These behaviors, which can pose significant challenges for both residents and nursing facility staff, are often best treated with non-pharmacologic measures such as environmental modifications.

Despite these challenges, more than 25 percent of patients in nursing facilities still receive antipsychotic medications, according to the Centers for Medicare and Medicaid Services (CMS). Evidence documenting the clinical efficacy of antipsychotics for BPSD is variable.

In 2005, the U.S. Food and Drug Administration (FDA) required manufacturers of atypical antipsychotic medications to include a boxed warning that these antipsychotics may increase the risk of death in elderly persons with psychosis related to dementia. This warning was expanded to all antipsychotic drugs in 2008.

Antipsychotic drugs have many legitimate uses, including treatment for psychotic disorders such as schizophrenia, psychotic symptoms such as delusions and hallucinations, and behavioral and psychological symptoms in certain situations.

“Results from the project presented today show there are more effective and appropriate alternatives to managing BPSD, and with well-designed programs to reduce use of antipsychotic medications, cultural barriers can be successfully overcome. We urge prescribers in the U.S. to assess results of this program and understand how they too can continue to work towards more person-centered, non-pharmacological approaches to manage these symptoms,” Kallmyer said.

Deprescribing Antipsychotics in Long-Term Care Residents with Behavioral and Psychological Symptoms of Dementia

Researchers from the University of New South Wales, based in Sydney, Australia recruited 140 residents from 23 long-term care facilities who were on regular antipsychotic medication, despite not having a primary psychotic illness and without very severe neuropsychiatric symptoms

. Concurrently, the project trained facility nurses on how to manage neuropsychiatric symptoms using person-centered, non-pharmacological approaches and performed academic detailing with the residents’ primary care physicians.

Consenting participants were assessed one month and one week prior to commencement of deprescribing. Protocols for incremental decreases in antipsychotic dose were established on an individual basis by project pharmacists with agreement from the participant’s general practitioner. Participants were reassessed 3, 6 and 12 months following initial dose reduction.

Of the 140 residents recruited, 132 commenced deprescribing and 121 have achieved antipsychotic cessation to date. Of these, 75 percent remain off the antipsychotic medication up to 6 months following initial reduction. Neuropsychiatric Inventory (NPI) and Cohen-Mansfield Agitation Inventory (CMAI) scores of the first 71 participants assessed 6 months after deprescribing remained stable from baseline to follow-up.

For participants where data were available, more than 60 percent were prescribed the current antipsychotic after admission to long-term care.

“Deprescribing of antipsychotics in long-term care residents with previous BPSD is feasible without reemergence of BPSD; however, challenges still exist regarding sustainability and culture of prescribing in aged care,” said Henry Brodaty, MD, DSc, of the Dementia Collaborative Research Centre, University of New South Wales, Sydney, Australia.

Brodaty added, “Often there can be cultural and logistical barriers to moving away from antipsychotics in aged care settings, but we hope the results of this project will serve as a positive example towards a more person-centered approach globally.”

National Partnership Aims to Reduce Antipsychotic Drug Use in U.S. Nursing Homes

The Alzheimer’s Association is participating with the Centers for Medicare & Medicaid Services (CMS) in the National Partnership to Improve Dementia Care in Nursing Homes. CMS and its partners are committed to finding new ways to enhance the quality of life for people with dementia, protect them from substandard care and promote goal-directed, person-centered care for every nursing home resident. While the initial focus was on reducing the use of antipsychotic medications, the Partnership’s larger mission is to enhance the use of non-pharmacologic approaches and person-centered dementia care practices.

Since the launch of the National Partnership, significant reductions in antipsychotic use in long-stay nursing home residents have been documented. The most recent National Partnership Antipsychotic Medication Use Trend Update reports that in 2011Q4, 23.9 percent of long-stay nursing homes residents were receiving an antipsychotic medication; that number was 17.0 percent in 2015Q4 – a decrease of 28.8 percent. (nhqualitycampaign.org/files/AP_package_20160505.pdf) Recently, CMS established new national goals for reducing the use of antipsychotic drugs in long-stay nursing home residents to 30 percent by the end of 2016.

About AAIC
The Alzheimer’s Association International Conference (AAIC) is the world’s largest gathering of researchers from around the world focused on Alzheimer’s and other dementias. As a part of the Alzheimer’s Association’s research program, AAIC serves as a catalyst for generating new knowledge about dementia and fostering a vital, collegial research community.

AAIC 2016 home page: www.alz.org/aaic/
AAIC 2016 newsroom: www.alz.org/aaic/press.asp

About the Alzheimer’s Association®
The Alzheimer’s Association is the leading voluntary health organization in Alzheimer’s care, support and research. Our mission is to eliminate Alzheimer’s disease through the advancement of research, to provide and enhance care and support for all affected, and to reduce the risk of dementia through the promotion of brain health. Our vision is a world without Alzheimer’s. Visit alz.org or call 800.272.3900.

Citation

http://www.alz.org/aaic/releases_2016/mon_415_ET.asp

Copyright 2016 Alzheimer’s Association

 

First Phase 3 Study of Tau-Targeting Drug in Alzheimer’s Disease

(Alzheimer’s Association International Conference) Important clinical trial results in Alzheimer’s disease and dementia were reported today at the 2016 Alzheimer’s Association International Conference (AAIC 2016) in Toronto, Canada – including the first completed Phase 3 trial of an anti-tau drug in Alzheimer’s.

A clinical trial of LMTM (TauRx Therapeutics, Ltd.) in people with mild to moderate Alzheimer’s failed to demonstrate a treatment benefit in the primary analysis of the full study population in both doses tested. However, in a pre-planned analysis of a small subgroup of the study population that received LMTM as a monotherapy, there was a statistically significant benefit on cognitive and functional outcomes, and slowing of brain atrophy. The study drug is thought to reduce the accumulation of the protein tau, which normally stabilizes neurons, into potentially toxic tangles.

“It is a significant event in the history of Alzheimer’s and dementia research that this Phase 3 anti-tau trial has been completed and the results reported at the Alzheimer’s Association International Conference,” said Maria C. Carrillo, PhD, Alzheimer’s Association chief science officer.

“In Alzheimer’s, the most likely scenario for successful future treatment is addressing the disease from multiple angles. Having a drug that targets tau complete a Phase 3 trial is a very hopeful sign.”

Carrillo added, “We learn a great deal from every clinical trial – for example, about how to best conduct therapy trials in older populations, how to recruit participants and properly screen them for inclusion in trials, how to measure the impact of the intervention, and the side effects of various drug therapies.”

“These all are extraordinarily important as we advance steadily toward better therapies and preventions for Alzheimer’s and other dementias; and particularly as we envision those interventions being delivered in combination.  For example, combinations of drugs that target amyloid and tau and perhaps also inflammation, and combinations of drug interventions with lifestyle changes and protective factors.”

Alzheimer’s is the most common form of dementia, a general term for memory loss and other intellectual abilities serious enough to interfere with daily life. Alzheimer’s disease accounts for 60 to 80 percent of dementia cases. According to Alzheimer’s Association’s 2016 Alzheimer’s Disease Facts and Figures, of the 5.4 million Americans with Alzheimer’s, an estimated 5.2 million people are age 65 and older, and approximately 200,000 individuals are under age 65 (younger-onset Alzheimer’s).

According to the World Alzheimer Report 2015 from Alzheimer’s Disease International, an estimated 46.8 million people worldwide are living with dementia in 2015. This number will almost double every 20 years, reaching 74.7 million in 2030 and 131.5 million in 2050.

Two abnormal structures called amyloid plaques and tau tangles are prime suspects in damaging and killing nerve cells in Alzheimer’s. Though most people develop some plaques and tangles as they age, those with Alzheimer’s tend to develop far more. Many studies have confirmed a link between the spread of tau tangles and the severity of dementia symptoms.

Click here to view the full press release.

About AAIC

The Alzheimer’s Association International Conference (AAIC) is the world’s largest gathering of researchers from around the world focused on Alzheimer’s and other dementias. As a part of the Alzheimer’s Association’s research program, AAIC serves as a catalyst for generating new knowledge about dementia and fostering a vital, collegial research community.

AAIC 2016 home page: www.alz.org/aaic/
AAIC 2016 newsroom: www.alz.org/aaic/press.asp

About the Alzheimer’s Association®

The Alzheimer’s Association is the leading voluntary health organization in Alzheimer’s care, support and research. Our mission is to eliminate Alzheimer’s disease through the advancement of research, to provide and enhance care and support for all affected, and to reduce the risk of dementia through the promotion of brain health. Our vision is a world without Alzheimer’s. Visit alz.org or call 800.272.3900.

Citation

http://www.multivu.com/players/English/7865354-aaic-alzheimers-drug-phase-3/

Copyright 2016 Alzheimer’s Association

 

Men Receive Dementia-related Misdiagnosis More Often Than Women

(Alzheimer’s Association International Conference) Among the 5.2 million Americans age 65 or older with Alzheimer’s disease, nearly two-thirds (3.3 million) are women. However, new data presented today at the Alzheimer’s Association International Conference 2016 (AAIC 2016) in Toronto, suggests a high number of men are not accurately diagnosed during their lifetime. In addition, the investigators found that there may be a relationship between sex and the age of onset of Alzheimer’s.

Researchers from the Mayo Clinic in Jacksonville, Florida, queried the State of Florida brain bank for Alzheimer’s cases and identified 1,606 individuals ranging in age from 37 to 102. Demographic and clinical data were collected, including education, family history, age of onset, disease duration, cognitive test results, and presence of known Alzheimer’s risk genes. The purpose of the study was to examine the frequency, as well as the pathologic, demographic, clinical, and genetic features of women and men with autopsy-confirmed Alzheimer’s.

Results showed that women with Alzheimer’s in the study had lower education and older age at death. Men in the study were younger at age of onset, had a shorter disease duration, and more commonly had an atypical clinical diagnosis (e.g., corticobasal degeneration, aphasia).

The study also revealed a spike in the frequency of Alzheimer’s in men in their 60s; whereas the frequency of women with AD was overrepresented in their 70s, 80s and 90s.

The study showed key sex differences in disease pathology with Alzheimer’s pathology in men in the study more often sparing the hippocampal region of their brain that coordinates memory, whereas women were more often affected in the limbic area of the brain, which includes the hippocampus.

“This study goes much deeper than just looking at the difference between the number of women and men diagnosed. It calls attention to the process of diagnosis and other lifelong factors that may influence diagnosis and timing and duration of the disease,” said Maria C. Carrillo, PhD, chief science officer, Alzheimer’s Association.

“An accurate and timely diagnosis can provide individuals and their families with more and better opportunities to receive the best possible care at the earliest time point.”

“While it is well accepted that age is the strongest risk factor for Alzheimer’s, there is an enormous need to understand additional factors that contribute to the development of the disease,” said Melissa E. Murray, PhD, Assistant Professor at the Mayo Clinic and presenting author of the new research at AAIC 2016.

“Our study demonstrates that there may be an interaction between age of onset and sex-based differences.”

“In our study population, neuropathologically diagnosed Alzheimer’s was observed at the same frequency overall in both sexes, but occurred quite differently depending on the age range being examined. Atypical clinical presentations were more common in men, suggesting that their lower reported prevalence of Alzheimer’s may be a result of the disease not being accurately recognized in life,” Murray added.

Misdiagnosis of Alzheimer’s: Inconsistencies between the clinic and neuropathology

A second study reported at AAIC 2016 – presented by a team from Keenan Research Centre for Biomedical Science, St. Michael’s Hospital, Toronto, Ontario, Canada – also focused on issues related to diagnosis and misdiagnosis of Alzheimer’s disease.

The researchers looked at inconsistencies between clinical and neuropathological diagnoses in 1,073 people from the National Alzheimer’s Coordinating Center database.

  • 841 (78.4%) had a clinical diagnosis and autopsy confirmation of Alzheimer’s using the NIA-Reagan criteria.
  • 116 (10.8%) were diagnosed with Alzheimer’s in the clinic but, on autopsy, did not have the brain changes necessary for an Alzheimer’s diagnosis (“false positives”). In other words, some disease or condition other than Alzheimer’s was causing their dementia.
  • 116 (10.8%) had Alzheimer’s changes in their brains, but were not clinically diagnosed with Alzheimer’s (“false negatives”).

The correct clinical diagnosis of Alzheimer’s disease was made in 78.4 percent of cases (83.5 percent if possible pathological diagnosis of Alzheimer’s is accepted), with equal rates of false negatives and false positives.

Of the false positives, 35 (30.2%) had primary vascular pathology, 14 (12.1%) had Lewy body pathology, 12 (10.3%) had medial temporal lobe sclerosis, 10 (8.6%) had FTD-related pathology (4-progressive supranuclear palsy, 3-frontotemporal dementia, 2-corticobasal degeneration, 1-Pick’s disease), 14 (12.1%) had another form of tauopathy (e.g. tangle-only dementia and argyrophilic grain dementia), and 17 (14.7%) had mixed pathology (two or more of the previous).

The false negative group included 51 (44.0%) diagnosed with possible Alzheimer’s, 42 (36.2%) with dementia with Lewy bodies (DLB), 12 (10.3%) with vascular dementia, and 11 (9.5%) with Parkinson’s disease dementia.

“Vascular pathology was the most common cause of a false positive clinical Alzheimer’s diagnosis while dementia with Lewy bodies was the most common cause of a false negative diagnosis. Multiple overlapping pathologies may have contributed to the discrepancy,” said Winnie Qian, BSc, Keenan Research Centre for Biomedical Science, St. Michael’s Hospital, Toronto, Canada.

“Diagnostic errors can have important implications for patient treatment and outcome. We need assessment tools with higher sensitivity and specificity to reduce diagnostic errors in Alzheimer’s,” Qian added.

The term “mixed dementia” is most commonly applied when the hallmark brain changes of Alzheimer’s disease and vascular dementia coexist, but can also describe Alzheimer’s and coexisting pathology of other forms of dementia. These pathologies may interact in important ways to increase likelihood of clinically significant cognitive decline. Mixed dementia prevalence may also become more common with increasing age.

“Recent studies suggest that the prevalence of mixed dementia is greater than previously thought,” said Carrillo, “and this study illustrates how it can complicate the process of getting a diagnosis.”

No drugs are currently approved by the FDA to treat mixed dementia. According to Carrillo, “since some of the drugs approved to treat Alzheimer’s have shown a similar benefit in treating vascular dementia, there is reason to believe they may also be of help in mixed dementia. More research is needed in this area.”

Taking Steps to Increase Diagnostic Accuracy

The Alzheimer’s Association supports research that helps improve diagnosis of Alzheimer’s disease and other dementias. For example, the Association leading the Imaging Dementia—Evidence for Amyloid Scanning (IDEAS) Study (http://www.ideas-study.org/).

The four-year study, with an estimated budget of $100 million, will determine the clinical usefulness and value in diagnosing Alzheimer’s and other dementias of a brain positron emission tomography scan that detects a core feature of Alzheimer’s disease. IDEAS is led by the Alzheimer’s Association and managed by the American College of Radiology and American College of Radiology Imaging Network.

About AAIC
The Alzheimer’s Association International Conference (AAIC) is the world’s largest gathering of researchers from around the world focused on Alzheimer’s and other dementias. As a part of the Alzheimer’s Association’s research program, AAIC serves as a catalyst for generating new knowledge about dementia and fostering a vital, collegial research community.

AAIC 2016 home page: www.alz.org/aaic/
AAIC 2016 newsroom: www.alz.org/aaic/press.asp

About the Alzheimer’s Association®
The Alzheimer’s Association is the leading voluntary health organization in Alzheimer’s care, support and research. Our mission is to eliminate Alzheimer’s disease through the advancement of research, to provide and enhance care and support for all affected, and to reduce the risk of dementia through the promotion of brain health. Our vision is a world without Alzheimer’s. Visit alz.org or call 800.272.3900.

Citation

https://www.alz.org/aaic/releases_2016/tues_245_ET.asp

Copyright 2016 Alzheimer’s Association

 

Pre-Stroke Risk Factors Influence Long-Term Future Stroke, Dementia Risk

(American Heart Association) If you had heart disease risk factors, such as high blood pressure, before your first stroke, your risk of suffering subsequent strokes and dementia up to five years later may be higher, according to new research in the American Heart Association’s journal Stroke.

“We already know that stroke patients have an increased risk of recurrent stroke and dementia. What we didn’t know was whether this increased risk persists for a long time after stroke and whether heart disease risk factors present before the first stroke influenced the risk of recurrent strokes or dementia,”

said M. Arfan Ikram, M.D., Ph.D., senior study author and associate professor, department of epidemiology, neurology and radiology, Erasmus University Medical Center in Rotterdam, the Netherlands.

“Our study found these risk factors influence future stroke and dementia and the risks persist for an extended period in some patients.”

Researchers studied a group of 1,237 stroke survivors from an existing long-term study and compared them to a stroke-free group of about 5,000 people from the same study.

They found:

  • One year after suffering a stroke, survivors retain a high risk of a recurrent stroke or dementia for at least five years.
  • After one year, first-time stroke survivors were three times more likely than those who hadn’t suffered a stroke to have a recurrent stroke.
  • Stroke survivors were nearly two times more likely to have dementia than those who had not suffered stroke.
  • Among the stroke survivors, 39 percent of recurrent strokes and 10 percent of post-stroke dementia cases were attributed to pre-stroke cardiovascular risk factors, including high blood pressure; diabetes; low levels of high-density lipoprotein (HDL – the good cholesterol); smoking; and transient ischemic attack (TIA – mini stroke).

“This study suggests that risk factors that lead to the initial stroke may also predispose patients to worsening mental and physical health after stroke. This also applies to risk of death after stroke”

“We found in a previous study that 27 percent of all deaths after stroke can be attributed to risk factors already present before stroke,” Ikram said.

Taking good care of your cardiovascular risk factors — even if you have never experienced a stroke — is not only important to prevent the first stroke, but it can go a long way to prevent a second stroke and dementia, he added.

Stroke is the fifth most common cause of death and a leading cause of disability in the United States. The American Heart Association’s Life’s Simple 7 helps people monitor and reduce cardiovascular risk factors that can lead to heart disease and stroke.

Co-authors are Marileen L.P. Portegies, M.D.; Frank J. Wolters, M.D.; Albert Hofman, M.D.; M. Kamran Ikram, M.D.; and Peter J. Koudstaal, M.D. Author disclosures are on the manuscript.

The Netherlands Heart Foundation and Erasmus MC Fellowship 2013 funded the study.

Additional Resources:

Citation

http://newsroom.heart.org/news/pre-stroke-risk-factors-influence-long-term-future-stroke-dementia-risk

Journal Reference:

Marileen L.P. Portegies, Frank J. Wolters, Albert Hofman, M. Kamran Ikram, Peter J. Koudstaal, and M. Arfan Ikram. Prestroke Vascular Pathology and the Risk of Recurrent Stroke and Poststroke Dementia. Stroke: Journal of the American Heart Association, July 2016 DOI: 10.1161/STROKEAHA.116.014094

©2016 American Heart Association, Inc. All rights reserved.