James Leverenz, MDJames Leverenz, MD
There are currently has no definitive biomarkers that can be used to track disease progression or treatment effect in Lewy body dementia (LBD), and the overlap in characteristics and symptoms between LBD and Alzheimer disease can make disease differentiation especially difficult.

Utilizing imaging modalities such as MRI, amyloid scans, and dopamine scans may help further research on key biomarkers. Currently, investigators are examining the utility of cerebrospinal fluid and blood biomarkers as ways to try to distinguish LBD early on before it progresses.

In an interview with NeurologyLive, James Leverenz, MD, director of the Lou Ruvo Center for Brain Health at Cleveland Clinic, detailed the differences between the 2 diseases and what tools specialists can use to help differentiate and diagnose various dementia disorders at an early stage.

NeurologyLive: What advanced diagnostic methods are being explored right now for LBD?

James Leverenz, MD: Right now we don't have a definitive biomarker for Lewy body dementia. We do know that the clinical syndrome particularly as laid out by the DLB consortium are pretty accurate in identifying individuals who are likely to have Lewy body pathology at autopsy. What we're finding though is that a lot of people who, especially those who have Alzheimer and Lewy bodies together, frequently do not fulfill the full clinical diagnostic criteria. Because of this issue, the NIH has funded a number of studies, including one that we're a part of, the Dementia with Lewy Body Consortium based here in the US, and there are efforts in Europe and Japan as well,  to start to look at whether blood and spinal fluid imaging biomarkers can help us better identify those who truly have Lewy body dementia and those who have Alzheimer disease or some other kind of dementia disorder.

What imaging modalities are being explored for Lewy body dementia?

We know that people with dementia with Lewy bodies and Parkinson disease dementia as well, which both fit under that umbrella of Lewy body dementia, tend to see less atrophy in the brain on MRI. It's not very specific, but when you see somebody with sort of classic Lewy body dementia symptoms, such as parkinsonism, hallucinations, and not much atrophy like you would expect to see in Alzheimer, those are some of those things that clicks in my head and says maybe I should be thinking about Lewy body dementia here. The dopamine transporter scan can be helpful, although there are some patients especially in with dementia with Lewy bodies where dementia precedes the Parkinsonism, many of those individuals, maybe 15% to 20% will have a normal dopamine scan, at least initially. One of the studies were involved in is looking at whether that changes over time. Do those people become DAT scan abnormal over time?

What efforts are being put forth to differentiate Lewy body dementia from Alzheimer disease?

Well, there are a number of efforts, some of them are imaging; looking at the frequency of the dopamine scans, looking at amyloid scans, the MRIs, and volumetric measurements. Our group here is focused on also looking at blood and spinal fluid indicators, particularly spinal fluid. We do tend to see some differences that have been described by others as well, that the amyloid changes that we see in a spinal fluid look somewhat like Alzheimer disease, but we don't see that elevated phospho tau that is typically described. The alpha-synuclein measurements are not quite ready for prime time, but we are seeing that there are maybe some signals there that we can combine with the Alzheimer markers to give us a better idea.

What are the pros and cons between a cerebrospinal fluid biomarker and a blood biomarker in LBD?

The problem with blood biomarkers for Lewy body dementia is that alpha-synuclein, the protein that we typically link to Lewy bodies, is in blood products like platelets. Measuring it in blood is very difficult to do because you're getting contamination from the blood that's at a much higher concentration. Some of us have started to look at whether there are components of the blood that we could measure that are linked to the brain, although we're still at a very early stage. There have been some attempts to look at skin biopsies, to look at saliva, for example, and maybe nasal biopsies or swabs, to see if we can pick up some of the synuclein changes that we link to both Parkinson as well as dementia with Lewy bodies.

What are some of the challenges when differentiating and diagnosing LBD and Alzheimer disease?

When we talk about Lewy body dementia, we're talking about two kinds of dementia. One is Parkinson dementia and dementia with Lewy bodies, which obviously have strong overlaps. In terms of that broader group, Parkinson disease is usually pretty easy. You see somebody with classic Parkinson and they are responsive to dopaminergic agents. Maybe 2 years, maybe 10 years, maybe 15 years into the course, they start to have troubles with their cognitive function, not typically so much memory but processing speed and staying on track with organization. With that, you may see some other psychiatric symptoms classically linked to dementia with Lewy bodies such as hallucinations and false beliefs or delusions.

How can we improve awareness of these risks and the screening process?

I think it is important that physicians recognize that people with Parkinson disease are at very high risk for developing dementia that is different than Alzheimer. They're not going to come in like your Alzheimer patient, where they look to the family and say, “They brought me in because they think I have a memory problem.” More often, if you ask the patient, they will say, “Yeah, I'm struggling now with my organizational skills, I get off track more easily.” If they're still working, they may really have trouble with their job. But they're not going to have that classic memory, lack of insight stuff that you typically see with Alzheimer disease. Many times they're hallucinating and they won't tell anybody because it's not bothering them or think it's from a medication. But I ask the patient, “How's your thinking skills? Is this affecting your day to day life? Do you ever see things that other people don't see?” Many of my movement specialist friends will tell me that if you ask the patient, they will say “I think I see a shadow over there,” and I look and there's nothing there, or surprisingly, sometimes they will say “Yeah, I always see this little dog in the corner.” And even the spouse will not know that they're seeing this. The other special link to both dementia with Lewy bodies and Parkinson dementia and Parkinson disease for that matter is REM sleep disorder where people act their dreams out at night. A lot of times the spouses will see it but they don't realize that it's linked to a higher risk for these disorders.

Transcript edited for clarity.