by Elizabeth Riley,The Conversation

Credit: Pixabay/CC0 Public Domain

Most people think of Alzheimer's disease as an illness of aging. But in fact, thebrain changes that characterize itbegin much earlier—sometime around the third decade of life.

In the earliest of these changes, a tangled version of aprotein called taustarts building upin a tiny region deep in the brain involved in sleep, attention, and alertness, called thelocus coeruleus. Tau later spreads to the rest of the brain.

Developing tau tangles doesn't mean a person has Alzheimer's disease—in fact, it happens to nearly everyone to varying degrees. But because these changes start in the locus coeruleus, some brain researchers—myself included—see this area as acanary in the coal minefor developing Alzheimer's disease.

We are exploring whether stopping or slowing down tau tangles in this brain region, or otherwise maintaining its health, may be a way to interrupt how the disease ultimately unfolds and to prevent other aspects of cognitive aging.

Emergingresearch from my laband others is investigating the idea that a therapy calledvagus nerve stimulation, which is already widely used for other health conditions, could be one way of keeping the locus coeruleus functioning properly.

The locus coeruleus and Alzheimer's disease

The locus coeruleus sits in the brain stem, the lowest part of the brain. Its name, "blue spot," comes from apigment called neuromelaninthat its cells produce.

Thelocus coeruleusplays a crucial role in multiple aspects ofbasic human functioning. It makes virtually all of the brain's norepinephrine, a chemical critical forsleep,alertness,focus,learning, and evenimmune function. And it receives inputs from nerves originating throughout the brain and body—including from the vagus nerve, which carries information to and from the heart, lungs, and other organs.

My research exploresthis brain region's structure, hownerve cells pass messages within it, and how itconnects with other brain regions. I also investigate how those features change throughout life and affect thinking and memory.

Studies suggest that starting in middle age, nerve cells in the locus coeruleus may getdamaged by tau buildup, and that damage may correlate withdeclines in memory.Tau buildup, cell death, and loss of function in thelocus coeruleus precedesandpredicts Alzheimer's diagnosis and symptoms.

This has led researchers to hypothesize thatkeeping the locus coeruleus healthycould be a way to protect the rest of the brain, too.

Vagus nerve stimulation and brain health

The vagus nerve carries information between the brain and organs in the chest and abdomen, such as the heart and intestines, helping the brain monitor and regulate many of the body's essential organs. It is responsible for sendingrest and digestmessages throughout the brain and body, stimulating digestion and promoting cellular repair.

In the 1980s and 1990s, researchers discovered that stimulating the vagus nerve canhelp ease epilepsy. They also found that doing so often alsohad other benefits, such asimproving mood and thinking.

Today,vagus nerve stimulationis approved by the Food and Drug Administration not just fortreating epilepsy, but also formigraineanddepression, as well as to aid withstroke rehabilitation.

Vagus nerve stimulationfor epilepsy and depression generally involves implanting an electrical stimulator in the left side of a patient's chest, where the vagus nerve passes. Noninvasive devices for treating headaches deliver gentle pulses of electricity to certain places on the neck or ear where the vagus nerve is very close to the surface of the skin.

Even before the discovery of locus coeruleus's link to Alzheimer's disease, researchers hypothesized that vagus nerve stimulation might help mood and thinking in people with the condition. That's because vagus nerve stimulation might work in part by raising brain levels of norepinephrine—and people with Alzheimer's havetoo little norepinephrine in their brains.

Keeping the pace

Neuroscientists still don't know exactly how or why vagus nerve stimulation might be beneficial for the brain, but one leading theory is that it helpsregulate the activity of nerve cellsin the locus coeruleus, enabling it to function properly.

Too much locus coeruleus activity could potentially make people too alert, causing them to feel stressed or even panicked. In fact, a hyperactive locus coeruleus fuels somesymptoms of post-traumatic stress disorder. Conversely, too littlecould cause depressionor memory problems.

Some forms of vagus nerve stimulationneither turn up nor turn downlocus coeruleus activity. Instead, they seem to affect thetiming and pace of firing in its neurons. Other forms of vagus nerve stimulation seem toincrease norepinephrine in the brains of rats, and researchers hypothesize that this may also be how vagus nerve stimulationtreats epilepsy.

These different findings have led researchers to suggest that vagus nerve stimulation could act as an effective regulator for the locus coeruleus, enabling it to establish just the right level of activity for optimal functioning.

Can vagus nerve stimulation counter memory loss?

Intriguing hints are emerging that vagus nerve stimulation may help the aging brain.

A handful of studies have found that vagus nerve stimulation canprevent memory from worsening, or even improve it, in people withmild cognitive impairmentor in the early stages of Alzheimer's disease. One trial of 52 people ages 55 to 75 who were diagnosed with mild cognitive impairment reported meaningful improvements in memory and overall cognitionafter getting vagus nerve stimulationfor an hour per day, five days a week for about six months.

Research inhealthy adults around age 60—and inhealthy adults age 18 to 25—has even reported improvements in different aspects of memory after just one session of vagus nerve stimulation.

This work is still very preliminary, but it offers hope for a new way of keeping some of the distressing symptoms of Alzheimer's disease and aging at bay.

This article is republished fromThe Conversationunder a Creative Commons license. Read theoriginal article.

Key medical concepts Alzheimer's Disease Vagus Nerve Stimulation Locus Coeruleus tau Proteins Mild Cognitive Impairment