Why are we more susceptible to developing dementia after brain injury?

BY: SOPHIA VOUMVAKIS

A post on this blog by Alison discussed research which suggests that those of us who have sustained a Traumatic Brain Injury (TBI) have a higher risk of developing dementia, including Alzheimer’s, one of the causes of dementia.

Alison also provided some great advice on maintaining a healthy lifestyle and how participating in key activities can help reduce the risk of dementia from Alzheimer’s.

I’ve also read that those who have sustained a TBI are at higher risk of developing dementia. To clarify, dementia is a set of symptoms that consistently occur together. It is not a specific disease. Dementia is caused by damage to the brain cells, Alzheimer’s disease is the most common cause of dementia. Other causes are Parkinson’s disease, Multiple Sclerosis, Huntington’s Disease and stroke.

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I recently came across some interesting new research which sheds light on the possible cause of increased risk of Alzheimer’s in people who have sustained a TBI, and a couple of more suggestions we can employ to reduce the risk of dementia caused by Alzheimer’s.

The Glymphatic Network – A New Discovery

The research is out of the University of Helsinki in Finland, and its findings were published in the Washington Post on May 21, 2017. Like many breakthrough discoveries in science, this finding was accidental.

Kari Alitalo, a scientist at the University of Helsinki had studied the lymphatic network for two decades. The lymphatic network carries immune cells throughout our body and removes waste and toxins. For over three hundred years it was believed that the lymphatic network stopped at the brain. It was accepted wisdom.

Three years ago, Alitalo wanted to develop a more precise map of the lymphatic network. To do this, he used genetically modified mice, whose lymphatic vessels glowed when illuminated by a specific wavelength of light.

When viewing the modified mice under the light, a medical student in Alitalo’s lab noticed that the heads of the mice also glowed. This went against the common wisdom that the lymphatic network did not extend to the brain. At first the scientists suspected that there was something wrong with their equipment, and when they repeated the experiment, they got the same result – the lymphatic network does indeed include the brain.

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Working independently, several scientists, including Maiken Nedergaard at the University of Rochester and Jonathan Kipnis of the University of Virginia School of Medicine, have also shown that the lymphatic vessels extend into the brain.

This discovery has major implications for a variety of brain diseases, such as Alzheimer’s, Multiple Sclerosis, and stroke which cause dementia. It also provides an explanation of why those of us who have sustained a TBI may be more susceptible to developing Alzheimer’s.

Researchers have identified two networks: the vessels that lead into and surround the brain, and those in the brain itself. The first network is the lymphatic system for the brain, and the second is called the glymphatic system – the addition of the “g” is for the glia neuron, that makes up the lymphatic vessels in the brain.

The glymphatic vessels carry cerebrospinal fluid and immune cells into the brain and remove cellular trash from it. The analogy that Nedergaard employs to describe this system is a dishwasher for the brain. When the lymphatic and glymphatic systems do not function properly, the brain can become clogged with toxins and suffused with inflammatory immune cells. Over decades, this process may play a key role in Alzheimer’s disease, Huntington’s disease, Parkinson’s disease and other neurodegenerative diseases.

Nedergaard told the Washington Post, “This is a revolutionary finding. This system plays a huge role in the health of the brain.”

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Malfunctioning of the Lymphatic and Glymphatic Systems and the link to Alzheimer’s Nedergaard and Helene Benveniste, a scientist at Yale University, have found evidence that links the malfunctioning of the lymphatic and glymphatic systems to the development of Alzheimer’s. In a study of mice, they found that glymphatic dysfunction contributes to the buildup of amyloid beta, a protein that plays a key role in the disease.

In 2016, Jeff Iliff, a neuroscientist at Oregon Health & Science University, along with several colleagues examined post mortem tissue from 79 human brains. They zeroed in on aquaporin – a key protein in glymphatic vessels. In the brains of those with Altzhiemer’s, this protein was jumbled – in those without the disease, the protein was well organized. This suggests that glymphatic breakdown plays a key role in the disease.

The link to TBI

How does all this relate to TBI and an increased risk of Alzheimer’s? The scientists have shown that in mice, a TBI can produce lasting damage to the glymphatic vessels, which are quite fragile. Mice are a good model, Nedergaard explains, because their glymphatic systems are very similar to humans. She has found that months after a TBI, the brains of these animals were not clearing waste efficiently, leading to a buildup of toxic compounds, including amyloid beta. Returning to the dishwasher analogy, Nedergaard likens it to using only a third of the water required, you’re not going to get clean dishes!

Strategies to improve the functioning of our Glymphatic System Sleep

Important to the healthy functioning of the glymphatic system is sleep. Nedergaard has demonstrated, at least in mice, that the system processes twice as much fluid during sleep than it does during wakefulness. She suggests, that over time, sleep dysfunction may contribute to Alzheimer’s and other brain diseases. We clean our brain when we are sleeping – this is probably an important reason we sleep.

Man sleeping on his side

Nedergaard and Benveniste have also found that sleep position is crucial. In an upright position – sitting in a chair – waste is removed less efficiently. Sleeping on your stomach is not very effective; sleeping on your back is somewhat better, while sleeping on your side proves to be the most effective, although why this is the case isn’t known.

Other ways to improve glymphatic flow

Other ways to improve glymphatic flow are also being studied. In January, Chinese researchers reported that in mice, omega-3 fatty acids improved glymphatic functioning. I relate this to other advice about staving off the risk of dementia I’ve come across – following a “Mediterranean” diet, which is high in omega-3 fatty acids.

Benveniste is also examining the anesthetic dexmedetomidine’s ability to improve glymphatic flow, while in a separate, small human study, researchers have found that deep breathing significantly increases the glymphatic transport of cerebrospinal fluid into the brain.

Alitalo is experimenting with growth factors – these are compounds that can foster regrow the of vessels around the brain. He is currently using this to repair lymphatic vessels in pigs, and is now testing this approach in the brain’s of mice who have a version of Alzheimer’s.

Currently, there are no clinical therapies in treating Alzheimer’s and other brain diseases, however this particular mechanism of brain disease has only just been discovered and as Alitalo says “give it a little time.”

In the meantime follow Alison’s advice on strategies to prevent, slow down, and possibly even reverse cognitive decline and remember to include good sleep hygiene and a diet rich in omega 3 fats, and take some deep breaths.

Source: Washington Post


Since her TBI in 2011, Sophia has educated herself about TBI. She is interested in making research into TBI accessible to other survivors.

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