Alzheimer's disease drugs linked to reduced risk of heart attacks

Drugs that are used for treating Alzheimer's disease in its early stages are linked to a reduced risk of heart attacks and death, according to a large study of over 7,000 people with Alzheimer's disease in Sweden.

5 jun 2013--The research, which is published online today (Wednesday) in the European Heart Journal [1], looked at cholinesterase inhibitors (ChEIs), such as donepezil, rivastigmine and galantamine, which are used for treating mild to moderate Alzheimer's disease [2]. Side-effects of ChEIs include a beneficial effect on the vagus nerve, which controls the rate at which the heart beats, and some experimental studies have suggested that ChEIs could also have anti-inflammatory properties.

Professor Peter Nordström, of Umeå University, Umeå, Sweden, and colleagues followed 7073 people with Alzheimer's disease, who were on the Swedish Dementia Registry from May 2007 to December 2010. They found that those who were on ChEIs had a 36% reduced risk of death from any cause, a 38% reduced risk of a myocardial infarction (heart attack) and a 26% reduced risk of death from cardiovascular causes such as stroke compared to people not taking ChEIs. These results included adjustments for various confounding factors such as age, sex, whether the diagnosis was for Alzheimer's dementia or Alzheimer's mixed dementia (where more than one type of dementia occur simultaneously), level of care, and medical history including medications for other conditions.

Prof Nordström said: "If you translate these reductions in risk into absolute figures, it means that for every 100,000 people with Alzheimer's disease, there would be 180 fewer heart attacks – 295 as opposed to 475 – and 1125 fewer deaths from all causes – 2000 versus 3125 – every year among those taking ChEIs compared to those not using them."

Patients taking the highest recommended doses of ChEIs had the lowest risk of heart attack or death: 65% and 46% lower respectively compared with those who had never used ChEIs.

The researchers also checked whether the reduction in risk applied only to the use of ChEIs or was seen in other drug treatments for dementia. Memantine is a drug indicated for use in moderate to advanced Alzheimer's disease and works in a different way to ChEIs [3]. The researchers found it made no difference to the risk of heart attack or death from any cause.

Prof Nordström said: "As far as we know, this is the first time that the use of ChEIs has been linked to a reduced risk of heart attacks and deaths from cardiovascular disease in general or from any cause. As this is an observational study, we cannot say that ChEI use is causing the reduction in risk, only that it is associated with a reduction. However, the strengths of the associations make them very interesting from the clinical point of view, although no clinical recommendations should be made on the basis of the results from our study. It would be of great value if a meta-analysis of previous, randomised controlled trials could be performed, as this might produce answers on which clinical recommendations could be based."

As the study was based on a nationwide group of patients, Prof Nordström said it should be possible to extrapolate the findings to other countries.

More information: [1] "The use of cholinesterase inhibitors and the risk of myocardial infarction and death: a nationwide cohort study in subjects with Alzheimer's disease", by Peter Nordström, Dorota Religa, Anders Wimo, Bengt Winblad, and Maria Eriksdotter. European Heart Journal. doi:10.1093/eurheartj/eht182

[2] Donepezil, rivastigmine and galantamine are also known by the trade names Aricept, Exelon and Reminyl respectively.

[3] Memantine is known by the trade name Ebixa.

Provided by European Society of Cardiology

Drug offers hope on Alzheimer's

A new drug which shows promise as a treatment for Alzheimer's disease has been developed by UK scientists.

23 april 2009--The Proceedings of the National Academy of Sciences reports the drug, CPHPC, removes a protein thought to play a key role in Alzheimer's from the blood.

Tests at the University College London found the protein also disappeared from the brains of five Alzheimer's patients given the drug for three months.

Longer and larger scale clinical studies are now being planned.

“ New treatments for Alzheimer's disease are desperately needed ”
Rebecca Wood Alzheimer's Research Trust

The protein - serum amyloid P component (SAP) is always present in both the sticky clumps (plaques) and the tangles of nerve fibres that are found in the brains of people with Alzheimer's disease, and are thought to damage healthy cells.

It appears to prevent both structures from breaking up, and has also been shown - in lab experiments at least - to promote formation of the amyloid protein which forms the damaging plaques.

There is also some evidence that SAP itself can damage brain cells directly.

Two of the big potential advantages CPHPC are that it is not broken down once inside the body, and it has a very specific action, not interacting with cells at all, thus reducing the risk of side effects.

Molecular process

The researchers expected a depletion of SAP in the five patients' blood - but were taken aback at the drug's apparent effect on the brain.

By using laboratory tests they were also able to reveal both the molecular process underpinning the effect of the drug, and the way in which SAP accumulates in the brain in Alzheimer's disease.

The study also confirmed that use of the drug - and the removal of SAP from the brain - had no side effects on the patients.

CPHPC has already been given to patients with other diseases without any any adverse effects.

Although the three-month treatment period was too short to show any clinical benefit there was no obvious deterioration.

Longer and larger scale clinical studies are being planned to confirm safety and seek evidence of benefit to the patients.

Lead researcher Professor Mark Pepys said: "The complete disappearance of SAP from the brain during treatment with CPHPC could not have been confidently predicted, and the drug, also to our surprise, entered the brain.

"Coupled with the absence of any side effects, these new findings strongly support further clinical studies to see whether longer term treatment with CPHPC protects against the inexorable mental decline in patients with Alzheimer's disease."

Dr Susanne Sorensen, head of research at the Alzheimer's Society, said: "A key characteristic of Alzheimer's disease is the clumping together of proteins in the brain.

"It's very exciting that this drug could potentially interfere with this process, but it's too early to say how much it will benefit people with the disease."

Rebecca Wood, of the Alzheimer's Research Trust, said the study was small, but the results were cause for "cautious optimism".

"New treatments for Alzheimer's disease are desperately needed, and it's possible that this small molecule could be a future candidate."

Newer Antipsychotics May Boost Weight in Alzheimer's Patients

16 april 2009--Newer antipsychotic drugs promote weight gain and lower levels of HDL ("good") cholesterol in Alzheimer's patients, according to a new study of more than 400 elderly patients.

The drugs, olanzapine and quetiapine, were both associated with significant weight gain. In addition, patients who took olanzapine experienced increases in waist circumference and declines in HDL cholesterol.

The longer patients took the drugs, the more likely they were to experience significant weight gain. However, the weight gain occurred in women but not in men. Another drug, risperidone, wasn't associated with harmful metabolic changes, according to findings from the Clinical Antipsychotic Trials of Intervention Effectiveness -- Alzheimer's Disease (CATIE-AD) study, funded by the U.S. National Institute of Mental Health.

The study was to be published online April 15 in the American Journal of Psychiatry.

"These findings are especially troubling, because antipsychotics are associated with a higher risk of death and cerebrovascular adverse events in patients with dementia. They're often used to minimize disruptive symptoms (such as psychosis or agitation), but patients should be monitored more closely," principal investigator Dr. Lon S. Schneider said in an American Psychiatric Association news release.

These kinds of metabolic side effects have been noted in schizophrenia patients who take second-generation antipsychotic drugs, experts said.

Results from Largest Statin Study of Patients with Alzheimer’s Disease Show Lipitor Has No Significant Impact on Disease


NEW YORK, 20 april 2008--In a study in patients with mild-to-moderate Alzheimer’s disease (AD), the addition of Lipitor (atorvastatin calcium tablets) 80 mg to Aricept® (donepezil HCl) 10 mg showed no significant differences in cognition or global function (key measures of Alzheimer’s progression) compared to placebo plus Aricept 10 mg. Furthermore, no statistically significant differences were seen on various cognitive, behavioral and functional secondary endpoints. However, the Lipitor arm was not associated with greater cognitive decline than the placebo arm in this trial. The results were presented today at the annual American Academy of Neurology meeting in Chicago.
The 18-month study, called Lipitor’s Effect on Alzheimer’s Dementia (LEADe), included 640 patients and is the largest statin study in Alzheimer’s disease.
While rates of decline in cognition and global function were similar for both the Lipitor and placebo groups, there were some interesting findings from the trial:
In a sub set of 64 patients for whom MRI scans were available, patients in the Lipitor arm had significantly less decline in hippocampal volume in the brain compared to the placebo arm. While the clinical significance of this result is not yet fully understood, less decline in hippocampal volume may be beneficial since declines have been associated with the progression of Alzheimer’s disease. This finding requires further investigation and analysis.
In a sub-analysis completed after the trial, men in the Lipitor arm had a significantly slower rate of decline in cognition compared to men in the placebo arm. There was no difference in the rate of decline in cognition in women in the Lipitor arm compared to women in the placebo arm. However, no definitive conclusions can be drawn from this post-hoc analysis.
“The results of our investigation of Lipitor on the symptoms of Alzheimer’s disease have been long awaited,” said Professor Howard Feldman, chair of the LEADe Steering Committee and professor and head of the division of neurology, University of British Columbia Hospital in Canada. “While the LEADe study did not demonstrate significant benefits on the symptoms of mild to moderate Alzheimer’s disease, there are some noteworthy findings that require further analysis and should inform further research to determine the potential for statin use in this population.”
Lipitor 80 mg was shown to be well tolerated and the incidence of liver and muscle adverse events in patients was low.
Aricept was selected as the background therapy since it is proven effective for treating the symptoms of Alzheimer’s and is the most widely used cholinesterase inhibitor. The effect of Aricept on Alzheimer’s was not investigated in this study.
“Over the past 15 years, Pfizer has been committed to researching the potential benefit of Lipitor in patients at various levels of cardiovascular risk as well as in non cardiovascular diseases such as Alzheimer’s disease,” said Dr. Rochelle Chaiken, vice president of the cardiovascular/metabolic team in Pfizer global medical. “While we are not planning additional studies with Lipitor in patients with Alzheimer’s disease at this time, LEADe provides the medical community with important data. In addition, Pfizer is committed to advancing research and treatment in Alzheimer’s disease.”
About Alzheimer’s Disease
Alzheimer’s disease is a progressive degenerative brain disorder that gradually destroys a person’s memory and ability to learn, reason, make judgments, communicate, and carry out daily activities. As the disease progresses, patient may experience changes in personality and behavior, such as anxiety, suspiciousness or agitation, as well as delusions or hallucinations.
About Lipitor
Lipitor is the most prescribed cholesterol-lowering therapy in the world, with nearly 144 million patient-years of experience. Lipitor is supported by an extensive clinical trial program involving more than 400 ongoing and completed trials with more than 80,000 patients.
Important U.S. Prescribing Information for Lipitor
Lipitor is a prescription medication. It is used in patients with multiple risk factors for heart disease such as family history, high blood pressure, age, low HDL (“good” cholesterol) or smoking to reduce the risk of a heart attack, stroke, certain types of heart surgery and chest pain.
Lipitor is also used in patients with type 2 diabetes and at least one other risk factor for heart disease such as high blood pressure, smoking or complications of diabetes, including eye disease and protein in urine, to reduce the risk of heart attack and stroke.
Lipitor is used in patients with existing coronary heart disease to reduce the risk of heart attack, stroke, certain kinds of heart surgery, hospitalization for heart failure, and chest pain.
When diet and exercise alone are not enough, Lipitor is used along with a low-fat diet and exercise to lower cholesterol.
Lipitor is not for everyone. It is not for those with liver problems. And it is not for women who are nursing, pregnant or may become pregnant.
Patients taking Lipitor should tell their doctors if they feel any new muscle pain or weakness. This could be a sign of rare but serious muscle side effects. Patients should tell their doctors about all medications they take. This may help avoid serious drug interactions. Doctors should do blood tests to check liver function before and during treatment and may adjust the dose. The most common side effects are gas, constipation, stomach pain and heartburn. They tend to be mild and often go away.

UK must change Alzheimer's drug advice

By JILL LAWLESS, Associated Press WriterFri Aug 10, 6:02 PM ET
A judge ruled Friday that Britain's state-run health service must change the way it advises doctors on supplying some Alzheimer's patients with drugs to treat the brain-destroying disease.
However, the judge upheld an argument by the government medicines monitor that the drugs are only cost-effective for patients in later stages of the illness — defeating an attempt to force authorities to prescribe the medicines to those with early-stage Alzheimer's.
The case is the latest in a series of legal challenges to Britain's National Health Service, which offers free health care and low-cost medicines to all Britons, but is regularly accused of rationing access to treatment. The dispute does not concern patients who choose — and can afford — private treatment.
Pharmaceutical companies and Alzheimer's advocates had asked the High Court to overturn a decision by the National Institute for Health and Clinical Excellence, which declined to approve a group of drugs known as acetyl cholinesterase inhibitors for patients in early stages of the disease.
Judge Linda Dobbs said NICE's recommendation that doctors use language-based tests to assess the severity of the disease — and thus whether a patient was eligible for the drugs — "creates confusion and the potential for discrimination" against people with learning disabilities and those whose first language is not English. She ordered NICE to change its guidance.
NICE, which regulates use of prescription drugs, recommended last year that three drugs — donepezil, rivastigmine and galantamine — not be prescribed for patients with early stage Alzheimer's.
It said the treatment was not particularly effective for people with mild Alzheimer's and at about $5 per patient per day was not cost effective. It recommended the drugs for patients with moderate-stage Alzheimer's.
Drug companies Eisai Co. Ltd. and Pfizer Inc., along with the Alzheimer's Society, challenged NICE's decision.
In a statement, Eisai and Pfizer said the court ruling was "a major victory for the many critics of the process by which NICE reaches its often seemingly clinically perverse decisions."
But NICE claimed victory, saying the judge had dismissed five of the six arguments in the case against it.
"Our guidance stands and the drugs continue to be recommended only for people with moderate Alzheimer's disease, but the court has asked us to clarify our guidance when it is used for certain groups," said chief executive Andrew Dillon.

Hopes rise for Alzheimer's drug from Elan & Wyeth

Ireland's Elan Corp and U.S. partner Wyeth plan to start final-stage clinical tests of a new antibody drug to fight Alzheimer's disease, offering new hope to patients and boosting shares in Elan.
Bapineuzumab, also known as AAB-001, will begin Phase III trials in treating patients with mild to moderate Alzheimer's in the second half of this year, once clinical trial design is finalized with regulatory agencies, the firms said on Monday.
The development is encouraging, since Alzheimer's research has been a graveyard of failed drugs, but the project remains high risk.
The decision to push ahead with Phase III tests was reached taking into account the seriousness of the disease and a review of interim data from Phase II studies, Elan and Wyeth said.
"No conclusion about the Phase II study can be drawn until the study is completed and the final data are analyzed and released in 2008," they added.
Despite the companies' caution, industry analysts said the decision to push ahead with late-stage testing suggested Elan and Wyeth had a promising new technology to tackle one of the world's most intractable diseases.
"This is a very positive development for both Elan and Wyeth, given that the acceleration of the drug into a Phase III study was only going to be considered if the interim data showed a significant improvement in patient progress," Ian Hunter of Goodbody Stockbrokers said in a note.
Shares in Elan were 13.7 percent higher at a 10-month high of 13.3 euros by 1015 GMT.
Orla Hartford of NCB Stockbrokers said there was a possibility the new drug could be submitted for regulatory approval based on Phase II data alone, if the results were good enough.
A filing based on Phase II would increase the chance of the product's success to 60 percent from 25 percent and add around 50 percent to the stock's valuation, she added.
"AAB-001 has the potential to transform Elan's investment case," Hartford said.
TOUGH DISEASE
Alzheimer's, which destroys memory and eventually leads to death, has been a focus of research for years but it is a very tough disease to fight and there are so far no very effective treatments.
Drugs approved since the 1990s, including Pfizer Inc. and Eisai Co. Ltd's market-leading Aricept, provide only modest symptomatic relief.
Elan and Wyeth's new drug could be the first disease-modifying treatment, making it a potential multibillion-dollar product -- if it works.
Bapineuzumab is a humanized monoclonal antibody designed to attack the A-beta peptide, which is one component of amyloid plaque that builds up in the brain and is thought to be responsible for damaging brain cells.
Elan and Wyeth are also working on a vaccine called ACC-001 designed to coax the body to make its own antibodies against A-beta peptide, which is in early-stage human trials.
An earlier experimental Alzheimer's vaccine from the two partners was abandoned in 2002 after it caused dangerous brain inflammation in some patients, although later research suggested it did help clear some brain-destroying plaques.