Most people think of Alzheimer’s disease as an illness of aging. But in fact, the brain changes that characterize it begin much earlier – sometime around the third decade of life.

In the earliest of these changes, a tangled version of a protein called tau starts building up in a tiny region deep in the brain involved in sleep, attention and alertness, called the locus 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 a canary in the coal mine for 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.

Emerging research from my lab and others is investigating the idea that a therapy called vagus 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 a pigment called neuromelanin that its cells produce.

The locus coeruleus plays a crucial role in multiple aspects of basic human functioning. It makes virtually all of the brain’s norepinephrine, a chemical critical for sleep, alertness, focus, learning and even immune 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 explores this brain region’s structure, how nerve cells pass messages within it and how it connects 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 get damaged by tau buildup, and that damage may correlate with declines in memory. Tau buildup, cell death and loss of function in the locus coeruleus precedes and predicts Alzheimer’s diagnosis and symptoms.

This has led researchers to hypothesize that keeping the locus coeruleus healthy could 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 sending rest and digest messages throughout the brain and body, stimulating digestion and promoting cellular repair.

In the 1980s and 1990s, researchers discovered that stimulating the vagus nerve can help ease epilepsy. They also found that doing so often also had other benefits, such as improving mood and thinking.

Today, vagus nerve stimulation is approved by the Food and Drug Administration not just for treating epilepsy, but also for migraine and depression, as well as to aid with stroke rehabilitation.

Vagus nerve stimulation for 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 have too 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 helps regulate the activity of nerve cells in 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 some symptoms of post-traumatic stress disorder. Conversely, too little could cause depression or memory problems.

Some forms of vagus nerve stimulation neither turn up nor turn down locus coeruleus activity. Instead, they seem to affect the timing and pace of firing in its neurons. Other forms of vagus nerve stimulation seem to increase norepinephrine in the brains of rats, and researchers hypothesize that this may also be how vagus nerve stimulation treats 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 can prevent memory from worsening, or even improve it, in people with mild cognitive impairment or 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 cognition after getting vagus nerve stimulation for an hour per day, five days a week for about six months.

Research in healthy adults around age 60 – and in healthy 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.

Elizabeth Riley receives funding from the National Institute on Aging.