Dementia with Lewy Bodies Has Its Own Genetic Signature

About 15 years ago, I became acquainted with Lewy body disease the hard way when my father was diagnosed. In the meantime, I learned that nobody really knew that much about the disease or how to effectively treat it. Unlike other diseases that had been pulled apart hundreds of ways to find the best ways to treat them, this second leading cause of dementia has remained a scientific ghost. That is, perhaps until now, as researchers are zeroing in on its genetics.

My Introduction to Lewy Body Dementia

My father began to exhibit the first signs of what everyone thought was Parkinson’s disease about 20 years ago. The problem was that while the slow and limited movements of Parkinson’s can be easily treated with medications, my dad wasn’t responding in the same way. His local physicians didn’t know why, so I had a local expert neuropsychologist see him, and to her it was clear—he had Lewy body dementia.

Like to many people, this diagnosis didn’t resonate. While I had learned a little about this issue in medical school, the more I researched the disease the more questions I unearthed. Turned out nobody really knew much about it, why it happened, or how to treat it. All they knew was that these patients had the worst parts of Parkinson’s disease and Alzheimer’s disease with some hallucinations thrown in for good measure. They also knew that on postmortem exams they had these small inclusions in the brain that are called Lewy bodies.

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What in the World Are Lewy Bodies?

Lewy bodies are formed when proteins (called alpha-synuclein) that live in the nerve cells in the brain begin to clump together, creating deposits. Deposits of these Lewy bodies deplete biochemicals in the brain and disrupt the function of the nerve cells, and eventually, the cells will die. This can lead to Lewy body dementia, causing symptoms such as memory loss, problems sleeping, cognitive decline, alterations in mood and behavior, problems with movement, and even hallucinations.

What Is Dementia with Lewy Bodies?

Lewy body dementia (DLB) is often associated with Alzheimer’s or Parkinson’s. Indeed, it can occur in conjunction with and worsen these diseases. In the case of Parkinson’s, for example, Lewy body deposits are found in the brain stem. However, as today’s feature study will show, DLB is also, in fact, its own neurodegenerative condition with its own genetic makeup.

In DLB, Lewy bodies can be found in many areas of the brain, such as the cerebral cortex, hippocampus, and midbrain. Dementia with Lewy bodies accounts for 10–15% of dementia cases, making it second on the list of the most common progressive dementias, with Alzheimer’s dementia being, by far, the most common. Lewy body dementia, like Alzheimer’s, is an incurable progressive dementia, which means it will continue to worsen over time and until death. My dad died about five or so years after the diagnosis, and his last years were not great.

Before we dig into today’s study, let’s review what else we’ve learned about dementia.

What We’ve Learned in Recent Years About Dementia

While there are many theories out there as to what causes dementia with Lewy bodies (genetics, environmental toxins, lifestyle, etc.), we aren’t really certain what all plays into the etiologies of this debilitating disease. The new study suggests there is certainly a strong genetic link (with up to 36% inherited). While we already knew this link existed in other progressive dementias, according to the researchers, this cause hadn’t yet been studied in DLB. A few other things we’ve learned about dementia in recent years follow:

What can you do now to possibly lower your risk? Seek nonsurgical options whenever possible. Address your pain early, before it becomes chronic, and without nonsteroidal inflammatory drugs (NSAIDs), which have also been shown to increase dementia risk. Stay away from artificial sweeteners. And, if possible, try to live in areas away from highways and high traffic, especially if you are genetically already at a high risk for dementia.

Dementia with Lewy Bodies and Its Unique Genetic Signature

The new study consisted of over 1,700 subjects from ten different countries with dementia with Lewy bodies as well as nearly 4,500 control subjects. Gene samples were collected from the subjects (in over 1,300 of the dementia subjects, these samples were collected after death). Certain genetic markers (APOE and GBA) found in Alzheimer’s and Parkinson’s were associated in the same way in dementia with Lewy bodies. However, a different part of another marker (SNCA) was associated only with dementia with Lewy bodies. Researchers concluded that dementia with Lewy bodies does indeed have its own unique genetic signature, making it its own distinct neurodegenerative disorder, not just part of Alzheimer’s or Parkinson’s disease.

The upshot? The first step in finding a cure or an effective treatment for DLB is to understand why it happens. Now that the genes responsible have been found, perhaps scientists can figure this one out. While it’s too late for my dad, this is an awful disease, and millions of patients and their families deserve a way to have some control over the long, progressive slide into disability that this disease represents.

 

Chris Centeno, MD is a specialist in regenerative medicine and the new field of Interventional Orthopedics. Centeno pioneered orthopedic stem cell procedures in 2005 and is responsible for a large amount of the published research on stem cell use for orthopedic applications. View Profile

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