The Tangled Neuron

Can Lifting Weights Improve Your Attention and Thinking?

Summary:  Lifting weights as little as once per week may improve your attention and thinking.

     Teresa Liu-Ambrose, Ph.D., PT

Several studies have shown that exercise might reduce your risk of memory loss, or even improve your memory and thinking.  Most of these studies have focused on aerobic exercise such as walking or aerobics classes.  

What about lifting weights?  Research by Teresa Liu-Ambrose, Assistant Professor at the University of British Columbia, and her colleagues suggests lifting weights once or twice per week can improve attention and thinking in older women.  

Lifting weights might not have an immediate effect.  In this clinical trial, the women who lifted weights were split into two groups:  those who trained once per week and those who trained twice per week.  Both groups were compared to a group of women participating in a twice weekly balance and toning program.  At the six month point, Dr. Liu-Ambrose and her colleagues found no significant differences between those lifting weights and those in the balance and toning program.  At the one year point, however, the once per week group had improved performance by 12.6% and the twice per week group by 10.9%.  The performance of the balance and toning group worsened slightly.

In a follow-up study one year after the formal training sessions ended, the once per week group still showed a 15% improvement on tests of attention and thinking over the balance and toning group.

Alzheimer's Drugs in Trial, Part 2

Summary:  There is a new emphasis on cooperative efforts to speed the development and approval of Alzheimer’s drugs.  The difficulties in bringing new Alzheimer’s drugs to market, along with doubts about a cure, highlight the continued need for research on (and funding for) care.

I wrote in Part 1 of this post about the difficulties of getting new Alzheimer’s drugs to market.   This problem is not entirely specific to Alzheimer’s – overall, new drug approvals are at a 25 year low.   

For patients and families waiting for more effective treatments, it may seem like nothing is happening.  But in reality, there are a lot of efforts underway to address this problem.  Given tight funding, the difficulties of drug development, and the recent failure of several drugs in trial, there is a new emphasis on collaboration to bring Alzheimer’s treatments to market.

Alzheimer's Drugs in Trial, Part 1

One of my friends diagnosed with Alzheimer’s recently talked with his counselor about how depressing his cognitive problems are.  He is losing hope that new Alzheimer’s drugs will be available in time to help him.  Based on media reports, his counselor said she thought he was too pessimistic, and that new treatments were around the corner. 

Should patients and families really expect new drugs to be available soon?

Nondrug Treatments for Alzheimer's: A New Systematic Review

Summary:  A systematic review of clinical trials of nondrug treatments for Alzheimer’s disease found good evidence that a program of caregiver education and support lengthens the time a person with dementia can be cared for at home, rather than in an institution.  The same review found evidence (although not from large, well-designed trials) that some nondrug treatments for people with dementia and their caregivers may improve patients’ memory, mood, behavior and functionality as well as improve caregivers’ mood, psychological well-being and quality of life.  More research is needed to investigate the costs and benefits of nondrug treatments.

Research on drugs to treat memory loss dominates the headlines, but some researchers think nondrug treatments may be just as effective.  Sometimes called “nonpharmacological therapies” or “psychosocial interventions,” these nondrug treatments include physical exercise, caregiver education, cognitive stimulation, counseling, music therapy, reminiscence therapy and training on completing “activities of daily living” (ADLs).   Unlike drug-based treatments, these treatments are often for caregivers, as well as for people with memory loss.

The Trouble With Expectations

You’ve probably seen recent media reports on the proposed changes to the guidelines for diagnosing Alzheimer’s, along with an article claiming that “a spinal fluid test can be 100 percent accurate in identifying patients with significant memory loss who are on their way to developing Alzheimer’s disease.”   Today’s headlines include a story about a blood test for predicting whether you’ll develop Alzheimer’s.

Although most professionals are careful to say the proposed guidelines and tests aren’t ready for widespread use, public expectations seem very high.   On a flight last month, I sat next to a man in his 20s whose stepfather is showing signs of memory loss.  My seatmate wasn’t terribly concerned about his stepfather, he said, because he had seen the recent reports of progress in Alzheimer’s research and believed that a cure is around the corner. 

Expecting Improved Diagnosis and Treatment

        Mary Kay Baum

Two of my friends diagnosed with young onset dementia also have high expectations.  They sent me their thoughts supporting the proposed guidelines for diagnosis, particularly the guidelines for a diagnosis of “preclinical Alzheimer’s.”  Their strong support is based on the long and difficult process each went through to get diagnosis and treatment, and the relative success of treatments in stabilizing their conditions.   It’s also based on their assumption that they would have been diagnosed with some form of Alzheimer’s if the proposed guidelines were used when they first sought answers about their symptoms.

“Consider me,” wrote Mary Kay Baum, who has a strong family history of dementia.   “I am a 63 year-old woman who was a lawyer and pastor with two graduate degrees, thirty years of public service, and ten years of cognitive challenges. The old Alzheimer’s disease criteria ignored me. It did not have a vocabulary for my issues. Doctors did not know what to do with me! The criteria from 25 years ago did not advise practitioners to help me prevent the dementia we had seen in my mother and my aunt while in their mid-fifties. Most research excluded me…. Many in my situation fear we won’t be treated until we are really demented.”

From The Financial Industry, A Gloomy View of Alzheimer's Research

There’s been a lot of optimistic headlines about diagnosing, treating and curing Alzheimer’s lately.  It seems some financial and industry analysts are not so optimistic. 

MarketWatch reports that the September issue of Neuroinvestment contains an extremely gloomy assessment of prospects for new Alzheimer’s drugs, and suggests that all research efforts need a “reset.”

Aspirin, Brain Bleeding and Memory Loss

I’ve written before about how bleeding in the brain is more common than previously thought, especially for people diagnosed with Alzheimer’s.  Bleeding in the brain (which can be detected by a type of MRI) may be a sign of the cerebral amyloid angiopathy my father had, and is linked to memory loss. 

A new study suggests that if you’ve already had bleeding in your brain, aspirin may increase the risk of further bleeding.  This adds to the evidence that you should check with your doctor before taking aspirin on an ongoing basis.

Eli Lilly StopsTrial of Alzheimer's Drug

Eli Lilly has stopped its Phase III trial of semagacestat, a potential Alzheimer's treatment.  Memory and thinking in trial participants receiving treatment declined faster than those receiving placebo, and semagacestat was associated with an increased risk of skin cancer.

Another failure of a treatment targeting beta amyloid is sure to further intensify the controversy about whether that protein causes Alzheimer's.

Fish Oil and Omega-3 Fatty Acids for Alzheimer's or Memory Loss?

Population studies have shown that people who report eating more Omega-3 fatty acids (in the form of fatty fish) seem to have a lower risk of developing dementia.   Because of this, scientists have hypothesized that fish oil supplements (or supplements containing DHA, an Omega-3 fatty acid found in fish oil and algae) could be used to treat Alzheimer’s.  So far, evidence from clinical trials doesn’t support that hypothesis, at least not much.

Update on Axona

Summary:   Results of a clinical trial of Axona show the medical food may be an effective treatment for people with mild to moderate Alzheimer’s, at least for those who don’t have the APOE4 genetic variation.   Accera is planning a larger trial to confirm these results.

The company is also planning an imaging study to try to prove that treatment with Axona changes the metabolism of certain areas of the brain, and that those changes are linked with improvements in cognition.    If successful, Accera could be among the first to show that changes to a “biomarker” reflect real changes in memory and thinking.

I’ve written before about Accera’s Axona, a medical food available by prescription for people diagnosed with mild to moderate Alzheimer’s.  The theory behind Axona is that if brain cells aren’t getting or using enough glucose, you can substitute ketone bodies for glucose.  A ketone body is a substance created when fats are broken down in the body.  Axona increases the level of ketone bodies in the blood, and in theory, provides an alternate fuel for brain cells.

Last week, I talked with Steve Orndorff, President and CEO of Accera, to get an update on his company’s product.  Data from an initial trial of Axona have now been published, and the results are encouraging enough for Accera to plan a larger clinical trial, he says.

Bapineuzumab May Reduce Plaques, But Does it Treat Alzheimer’s?

Elan reported last week that its Phase II study of bapineuzumab in 28 Alzheimer’s patients showed that the potential drug reduced a type of beta amyloid (the protein that makes up Alzheimer’s plaques) in the brains of the patients receiving treatment.  This reduction was seen with PET scans using the PiB compound. 

The study is interesting because PiB imaging is a non-invasive way for researchers to measure the amount of amyloid in the brain, and it did show that the treatment reduced amyloid.

But it’s hard to say whether this means bapineuzumab might actually treat dementia.  A previous Phase II clinical trial of the potential drug in 234 patients did not show a difference between those receiving treatment and those receiving a placebo, perhaps because of issues with trial design.  We’ll have to wait a couple of years for the results of the Phase III trial to see whether bapineuzumab can improve memory and thinking.

If the drug reduces amyloid in the brain, but doesn’t affect symptoms, we’re bound to hear a lot of questions about the strategy of reducing amyloid to prevent or treat dementia. 

Note:  Elan has sold the rights to bapineuzumab to Janssen Alzheimer Immunotherapy, but now owns part of that company.

Dimebon Fails in Clinical Trials

Pfizer and its partner Medivation have announced the failure of Dimebon in Phase 3 clinical trials.  This news, just the latest of several failures, will give more weight to the idea of pushing the reset button for Alzheimer's research.

MCI Symposium: Memory Loss and Exercise

Nicola Lautenschlager, MD, FRANZCP

I recently started running again, five years after a knee injury slowed me down.  It isn't pretty, but it might be good for my brain.

At last year’s MCI Symposium, Nicola Lautenschlager, Professor of Psychiatry of Old Age at the University of Western Australia, presented the results of a clinical trial of exercise to prevent cognitive decline. Those who took part in an exercise program actually improved their scores on tests of memory and thinking.

     Yonas Geda, MD

Since then, results of several studies on exercise to prevent memory loss or improve memory and thinking have been published, including a population-based study led by Yonas Geda at Mayo Clinic and a small trial led by Laura Baker at the University of Washington.

Laura Baker, Ph.D.

The results of these studies are being published so fast I can hardly keep up.  You can read what I've found out so far in my latest report on the MCI Symposium.

Johnson & Johnson Risperdal Kickback Allegations

Last week, the New York Times published an article about a U.S. government complaint that Johnson & Johnson paid kickbacks to the biggest nursing home pharmacy in the U.S. to increase prescriptions of the antipsychotic Risperdal and other drugs.  On her blog ElderCareTalk, Laura Bramly has posted a great analysis of what this means for people whose family members are in memory care units.

Ginkgo Fails Again

Late last year, initial results from GEMS, the Ginkgo Evaluation of Memory Study, showed that ginkgo did not prevent older people from developing Alzheimer’s or other dementias during a six year follow up period.

But did it help prevent smaller changes in memory and thinking in study participants?  What about the milder memory loss considered normal with aging?  In an analysis of GEMS data published this week, ginkgo failed to slow these smaller declines in memory as well.

Alzheimer's Clinical Trial Setbacks

A clinical trial of an Alzheimer’s treatment has failed, and another has been modified due to serious side effects.

German Institute Cites Lack of Evidence for Alzheimer's Treatments

The Institute for Quality and Efficiency in Healthcare has issued a new report on Alzheimer's treatments.  Comissioned by the German government, the report concludes:

• there is not enough proof that memantine (sold as Namenda in the U.S.) is effective in treating Alzheimer's
• cholinesterase inhibitors can "slightly delay" a decline in memory and thinking
• the evidence on ginkgo is mixed
• there's not enough proof that non-drug treatments are effective.

Access to Potential Alzheimer's Treatments Outside of Clinical Trials

Summary:  The FDA’s “Expanded Access to Investigational Drugs for Treatment Use” rule provides a way for patients who can’t participate in clinical trials to gain access to potential treatments not yet approved by the FDA.  Despite optimistic headlines about Alzheimer’s cures and breakthroughs, many drugs currently in trial seem to have only incremental benefits.  This may keep demand for expanded access to potential Alzheimer’s treatments low.

Over the past few months, I’ve received several emails from people diagnosed with Alzheimer’s or their caregivers asking how they can get access to Alzheimer’s drugs still in clinical trials.  Most of these inquiries were about Dimebon, Rember or potential “Alzheimer’s vaccines” such as Bapineuzumab.

In each case, someone saw an optimistic media report about the promise of a drug in clinical trials (an “investigational drug”), and wanted access to it before trials were completed and it could be approved for the U.S. market. 

Axona: A Different Approach to Alzheimer's

Summary:  Axona is Accera’s new product for people with mild to moderate Alzheimer’s.  Available in the U.S. by prescription only, Axona is marketed as a medical food.  This means it was not subject to FDA pre-market review and approval.  Results of the company’s trials of Axona sound promising, but we’ll have to wait for more data to be published to get a better idea how effective the product is.

Suddenly, Axona is everywhere.  I heard people talking about it at a local Alzheimer’s educational event last week.  There’s an advertisement for it on the back cover of the latest edition of the Alzheimer’s Foundation of America’s magazine, care ADvantage.   Accera, the company that developed Axona, is also a silver sponsor of the Alzheimer’s Association’s upcoming ICAD conference.  

Axona is designed to address the “hypometabolism,” or reduced use of glucose, seen in some areas of the brains of people with Alzheimer’s.   Glucose is the brain’s source of energy.  Axona is formulated as a powder, and is mixed with water to make a once-a-day drink. 

The product is unique in its approach to Alzheimer’s and in Accera's choice to market it as a “medical food.”  I talked last week with Steve Orndorff, Ph.D., founder and CEO of Accera, to get more details.

Expert Consensus on Brain Health

Expert Consensus on Brain Health, a statement issued by researchers from the Stanford Center on Longevity and  the Max Planck Institute for Human Development, gives a great summary of the science (or lack thereof) behind supplements and programs marketed for brain health.  More than 30 experts from Stanford, the Max Planck Institute and other institutions signed the statement.

While there are things that can be done to improve brain health and mental fitness, they say, there's not enough evidence to support the claims of many supplements and programs.  Physical exercise and maintaining overall health are important for cognitive fitness.  More research is needed to see if various products promoted for brain health are effective.