Exercise may ward off Alzheimer's and Parkinson's

When US scientists gave non-exercising mice a protein produced by exercising mice, they found it switched on genes that help preserve brain health and boost growth of new nerves in regions important for learning and memory.

They suggest their findings could pave the way to a drug that improves treatments against cognitive decline in older people and help slow progression of brain-wasting diseases like Alzheimer's and Parkinson's.

Dr. Bruce Spiegelman, from Dana-Farber Cancer Institute and Harvard Medical School in Boston reports the discovery in the latest online issue of the journal Cell Metabolism.

Endurance exercise has previously been shown to improve brain function, particularly in older people. But until this study the underlying molecular mechanisms were not understood.

In an earlier study, Dr. Spiegelman's team had already discovered that the protein, called FNDC5, is released into the bloodstream as a variant called irisin as a result of muscular exertion.

In this latest work, the researchers monitored the effect of endurance exercise on mice (they voluntarily ran on an exercise wheel for 30 days).

Boosting production of FNDC5

They found endurance exercise increased the effect of a regulatory metabolic compound, PGC-1alpha in the muscles of mice, which boosted production of FNDC5. This had the knock-on effect of switching on genes that increased the expression of a brain-protective protein, BDNF, in the hippocampus, a part of the brain involved in learning and memory.

Researchers found that a protein produced during exercise switches on genes that preserve brain health.

The hippocampus is only one of two areas in the adult brain that can grow new nerve cells. Exercise increases the effect of BDNF in the hippocampus, where it preserves brain cells and promotes the growth of new nerves and synapses or junctions between nerve cells, thereby aiding learning and memory.

But until now it was not clear what linked exercise to BDNF at the molecular level, which is what you need to know in order to develop drugs that have the same effect.

This study is the first to suggest that the molecular pathway that links exercise to raised BDNF activity goes via PGC-1alpha and FNDC5.

However, the authors suggest there may also be other pathways, waiting to be discovered.

In a second stage of the study, the researchers showed artificially increasing FNDC5 without the help of exercise had the same effect.

Dr. Spiegelman says:

"What is exciting is that a natural substance can be given in the bloodstream that can mimic some of the effects of endurance exercise on the brain."

However, he cautions that more studies are now needed to find out whether giving mice FNDC5 actually leads to improved brain function.

Also, the researchers did not establish whether it was FNDC5 itself that ended up in the brains of the mice, or its variant, irisin.

If drug developers choose to start with irisin, they will first have to make a more stable form of the protein, says Dr. Spiegelman.

Funds from the JPB Foundation and National Institutes of Health helped finance the study.

Earlier this year, researchers from Princeton University reported in the Journal of Neuroscience that physicalexercise helps the brain withstand stress.

Written by Catharine Paddock PhD

About Alzheimer's / Dementia

About Alzheimer's / Dementia

• What is Dementia?

  

  The word dementia comes from the Latin de meaning "apart" and mens from the genitive mentis meaning "mind". Dementia is the progressive deterioration in cognitive function - the ability to process thought (intelligence).
• What Is Alzheimer's Disease?

  

  Alzheimer's disease is a progressive neurologic disease of the brain leading to the irreversible loss of neurons and the loss of intellectual abilities, including memory and reasoning.

The Peanut butter helps to diagnose Alzheimer's disease

A dollop of peanut butter and a ruler can be used to confirm a diagnosis of early stage Alzheimer's disease, University of Florida Health researchers have found.

Jennifer Stamps, a graduate student in the University of Florida (UF) McKnight Brain Institute Center for Smell and Taste, and her colleagues reported the findings of a small pilot study in the Journal of the Neurological Sciences.

Stamps came up with the idea of using peanut butter to test for smell sensitivity while she was working with Dr. Kenneth Heilman, one of the world's best known behavioral neurologists, from the UF College of Medicine's department of neurology.

While shadowing doctors in Heilman's clinic, she noticed that patients were not tested for their sense of smell. The ability to smell is associated with the first cranial nerve and is often one of the first things to be affected in cognitive decline.

"Dr. Heilman said, 'If you can come up with something quick and inexpensive, we can do it,'" Stamps says.

She thought of peanut butter because, she said, it is a "pure odorant" that is only detected by the olfactory nerve and is easy to access.

Widespread problem

According to the Alzheimer's Association, Alzheimer's disease affects 5.2 million people in the US and will cost the nation $203 billion in this year alone.

Researchers found that by placing a dollop of peanut butter on a ruler, they could identify early stages of Alzheimer's disease, based on patients' ability to detect the odor at certain distances.

The Association estimates that one American develops Alzheimer's every 68 seconds, and they expect to see this figure rise to one American every 33 seconds by 2050.

In the study, patients who were coming to the clinic for testing also sat down with a clinician, who was armed with 14 grams of peanut butter - which equals about 1 tablespoon - and a metric ruler. The patient closed his or her eyes and mouth and blocked one nostril.

The clinician opened the peanut butter container and held the ruler next to the open nostril while the patient breathed normally. By moving the peanut butter up the ruler 1 cm at a time during the patient's exhalation, they were able to measure the distance at which the patient could detect the odor.

The distance was recorded and the procedure repeated on the other nostril after a 90-second delay.

The clinicians running the test did not know the patients' diagnoses, which were not usually confirmed until weeks after the initial clinical testing.

Sense of smell loss

The scientists found that patients in the early stages of Alzheimer's disease had a dramatic difference in detecting odor between the left and right nostril - the left nostril was impaired and did not detect the smell until it was an average of 10 cm closer to the nose than the right nostril had made the detection in patients with Alzheimer's disease.

This was not the case in patients with other kinds of dementia; instead, these patients had either no differences in odor detection between nostrils or the right nostril was worse at detecting odor than the left one.

Of the 24 patients tested who had mild cognitive impairment, which sometimes signals Alzheimer's disease and sometimes turns out to be something else, about 10 patients showed a left nostril impairment and 14 patients did not.

The researchers said more studies must be conducted to fully understand the implications.

Stamps explains:

"At the moment, we can use this test to confirm diagnosis. But we plan to study patients with mild cognitive impairment to see if this test might be used to predict which patients are going to get Alzheimer's disease."

Stamps and Dr. Heilman point out that this test could be used by clinics that do not have access to the personnel or equipment to run other, more elaborate tests required for a specific diagnosis, which can lead to targeted treatment.

At UF Health, the peanut butter test will be one more tool to add to a full suite of clinical tests for neurological function in patients with memory disorders.

Non-invasive, early stage test

One of the first places in the brain to degenerate in people with Alzheimer's disease is the front part of the temporal lobe that evolved from the smell system, and this portion of the brain is involved in forming new memories.

"We see people with all kinds of memory disorders," Heilman said. Many tests to confirm a diagnosis of Alzheimer's disease or other dementias can be time-consuming, costly or invasive. "This can become an important part of the evaluation process."

The UF study could help by detecting a person's likelihood of developing the disease at a much earlier stage, with a non-invasive test.

The Alzheimer's Association acknowledge that at the moment, there is no cure for the disease, nor can current Alzheimer's treatments stop Alzheimer's from progressing. They can, however, temporarily slow the worsening of dementia symptoms. This improves the quality of life for both sufferers and their caregivers.

As Stamps says:

"If we can catch it at that early stage, we can start treatment more aggressively at the early stage and you can possibly prevent a lot of the progression."

Medical News Today reported in July this year that taking certain lifestyle measures, including taking regular exercise and eating a balanced diet, could reduce your risk of developing Alzheimer's.

Written by Belinda Weber