2019 ILBDC: What Are Biomarkers?

This presentation at the 2019 International Lewy Body Dementia Conference by Dr. David Irwin of the University of Pennsylvania offered a thorough overview of biomarkers. He started out with this "pre-test."

A biomarker is:

a) Paper and pencil cognitive test

b) Survey/questionnaire

c) Blood test

d) Spinal fluid test

d) Physical exam finding

e) Neuroimaging

f) Sleep study- Electrophysiology

g) ALL OF THE ABOVE

Yes, the answer is "All of the above." In the past, I had thought biomarkers were mainly those expensive and involved imaging tests that physicians use improve their diagnosis things like dementia. And they are that. But it turns out that many of the things we've experienced in doctor's offices and hospitals for years can be defined as "biomarkers."

According to the National Institute of Health, a biomarker is "a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes or a pharmacologic response to a therapeutic intervention."

More simply, a biomarker is anything that can be used to objectively measure an aspect of one's health or a response to treatment.

Biomarkers are used in two ways. The first is to assist in diagnosis (measure an aspect of one's health) The second is to track the progress of (a response to) an illness or its treatment.

Blood pressure is a biomarker we've used for centuries measure and track the health of our heart and circulatory system. Doctors can also use it to track the body's response to various drugs, such as those for high blood pressure. In the same way, the blood tests used to diagnose certain cancers can be used to track the body's response to treatment later.

With DLB, the type of LBD that starts before motor symptoms are evident, biomarkers are used diagnostically and as trackers.  Diagnostically, they can facilitate an earlier diagnosis. The hope is that eventually, we will be able to use biomarkers to find Lewy bodies so early that they can be eliminated before they spread. They also help the diagnosing doctor differentiate DLB from the different dementias. Biomarkers can even firm up a choice of DLB vs. Parkinson's with dementia, the "other" LBD. As trackers, they help the doctor track progression and decide upon the best treatment.

The three most used DLB biomarkers are DAT (dopamine transport) imaging, I-MIBG scanning of the heart, and sleep studies. DAT measures the movement of a protein used to move dopamine in and out of a cell. Less activity means that DLB is more likely. I-MIBG is a radio-active tracer used to measure damage to the nerves that control automatic heart function. This damage can signal the presence of LBD. Sleep studies are used to identify the presence of REM sleep behavior disorder, or active dreams.

Another biomarker that you might come into contact is a short questionnaire that a primary doctor--or even care partners!--may use to identify the presence of enough LBD symptoms that a referral to a specialist is appropriate. This may or may not include the "clock test," where a hand drawn clock is used to judge concept and hand-eye coordination.

Naturally, biomarkers are also used with Alzheimer's disease (AD). There is more and more effort on identifying AD prior to symptoms. This will likely happen before it does with LBD, but many of the same techniques can be used for other neuro-diseases such as LBD, once they have succeeded with AD.

We aren't through talking about what happened at the LBD Conference yet! Next week, we will tell you about the LBDA's Research Centers of Excellence and what they can do for you.

For more information about Lewy body disorders, read our books:
A Caregivers’ Guide to Lewy Body Dementia
Managing Cognitive Issues in Parkinson's and Lewy Body Dementia
Responsive Dementia Care: Fewer Behaviors Fewer Drugs
Riding A Roller Coaster with Lewy Body Dementia: A Manual for Staff

Helen and James Whitworth are not doctors, lawyers or social workers. As informed caregivers, they share the information here for educational purposes only. It should never be used instead of a professional's advice.

Decoding the DLB Diagnostic Criteria: #4, More Biomarkers

The 2017 diagnostic criteria for dementia with Lewy bodies (DLB) is important for care partners to know but this part of it especially is written in scientific language that is difficult for even a well-educated person to understand. This series of blogs attempts some decoding.

Last week introduced a two-part biomarker section and the three indicative biomarkers. This week's blog presents the three suggestive biomarkers. If you haven't read the previous blogs in this series, please go back and read them now so that you will better understand this one.

Supportive biomarkers are signs indicating the presence and intensity of DLB that cannot stand alone but can support a diagnosis based on other symptoms and biomarkers.

Supportive Biomarker 1. Relative preservation of medial temporal lobe structures on CT/MRI scan.

• relative preservation: maintenance of function in relation to the norm
• medial temporal lobe: The part of the brain responsible for memory of facts and events.
• CT/MRI scans: Two types of 2-D scans of organ tissues.

What are they testing for? The amount of shrinkage in a part of the brain involved with memory.

Why? Shrinkage of this area is significantly related to Alzheimer's, but not to DLB.

In plain English: Little shrinkage of the area of the brain involved with memory of facts and events supports a DLB diagnosis.

Supportive Biomarker 2.  Generalized low uptake on SPECT/PET profusion/metabolism scan with reduced occipital activity +/- the cingulate island sign on FDG-PET imaging.

Let's divide this one into two parts:

Supportive Biomarker 2a. Generalized low uptake on SPECT/PET profusion/metabolism scan with reduced occipital activity

location of  the posterier
cingulate cortex

• Generalized low uptake: All-around low activity
• SPECT/PET scans: 3D scans using radio-active tracers.
• Profusion/metabolism scan: scan for brain activity
• Occipital (lobe): an area at the back of the brain.

What are they looking for? Low levels of activity in the occipital lobe.

Why? This area of the brain controls visual functions related to DLB symptoms, including the core symptom of visual hallucinations. It is usually less damaged by Alzheimer's.

Supportive Biomarker 2b. The cingulate island sign on FDG-PET imaging may or may not accompany 2a.

• FDG: A radio-active tracer used with PET scanning.
• Cingulate island sign: a finding of preserved metabolism in the posterior cingulate cortex
• Preserved metabolism: normal activity
• Posterior cingulate cortex: An area deep in the back of the brain.

What are they looking for? Fairly normal levels of activity in an area of the brain ordinarily damaged by Alzheimer's.

Why? Brain damage in this area is common with Alzheimer's. The more normal brain activity called "cingulate island sign" is usually present with DLB.

2a and 2b together in plain English: A scan that shows decreased brain activity in the occipital cortex supports a DLB vs. a Alzheimer's diagnosis, as does the presence of the cingulate island sign.

Supportive Biomarker 3. Prominent posterior slow wave activity on EEG with periodic fluctuations in the pre-alpha/theta range.

• EEG: (Electroencephalogram): measures electrical waves of brain activity through the scalp.
• posterior slow-wave activity: Slower than normal brain wave activity.
• periodic fluctuations: periods of changes in wave activity.
• the pre-alpha/theta range: Alpha waves occur when a person is awake and alert. Theta waves occur during relaxation and light sleep. (I could not find a definition for "pre-alpha/theta range." Help invited!)

What are they looking for? Slow brain activity with periodic episodes of higher functioning.

Why? Cognitive fluctuations are common with DLB but not with Alzheimer's.

In plain English: An EEG that shows slow cognitive activity with periods of an increased level of functioning is supportive of a diagnosis of DLB vs. Alzheimer's.

Next week: The "clinical features" or symptoms.

LBD is an umbrella term for all Lewy body diseases and starts with an L for Lewy.
DLB is for Dementia with Lewy bodies and starts with a D for the way the disease starts.
PDD is for Parkinson's disease with dementia and starts with a P for the way that disease starts.
Biomarker: Something measurable that can indicate the presence and severity of whatever you are testing for.
Indicative: A strong sign.
Supportive: A weaker sign that can still be helpful.
Radio-active imaging: An imaging process that uses a radio-active tracer.
Radio-active tracer: biomarker that can enter the tissues or cells of the body.
Uptake: The process of absorbing a substance so that it can be released on the other side of the cell.

For more information about Lewy body disorders, read our books:
A Caregivers’ Guide to Lewy Body Dementia
Managing Cognitive Issues in Parkinson's and Lewy Body Dementia
Responsive Dementia Care: Fewer Behaviors Fewer Drugs
Riding A Roller Coaster with Lewy Body Dementia: A Manual for Staff

Helen and James Whitworth are not doctors, lawyers or social workers. As informed caregivers, they share the information here for educational purposes only. It should never be used instead of a professional's advice.

Decoding the DLB Diagnostic Criteria, #3: Biomarkers

This series of blogs will attempt to decode the scientific language used to write the latest DLB diagnostic criteria and come up with a plainer version. If you haven't read the previous blogs, please go back and read them before you read more.

A biomarker is a fancy word used to describe a something measurable that can indicate the presence and severity of whatever you are testing for. We are all familiar with blood, urine and saliva tests. These are all used to test for biomarkers for a variety of conditions from pregnancy to strep throat to HIV and much more.

Presently, biomarkers are mainly used for confirming a diagnosis. However, they are the hope of the future. They can reach inside cells to fine minute, early signs of a disease well before there are symptoms, and before it grows too big to eliminate. Many people are now living healthy lives after being treated for a cancer that was found while it was still small enough to treat successfully. Until recently, that was not possible with neurological diseases like DLB. One had to wait for the symptoms to show up to know it was present--and by then the disease is so entrenched that one can do little but treat the symptoms. However, researchers can now focus on finding ways to stop it from growing.

But that is for tomorrow. Today, biomarkers help to diagnose DLB by signaling the presence of Lewy bodies in a tested item and providing a measurement of how plentiful they are--or of the damage they have done.

The criteria divides the biomarkers into "Indicative" (strong) and "Supportive" (helpful). Today's blog will discuss the three Indicative Biomarkers. Next week's blog will go on to discuss the Supportive ones.

The first two indicative biomarkers involve radio-active imaging. To go deep into the body tissues, they use a tiny amount of a radio-active tracer substance that goes to a targeted area and then normally exits the body within 48 hours.

1. Reduced dopamine transporter (DaT) uptake in basal ganglia demonstrated by SPECT or PET scans.

• dopamine (DA): A brain chemical that is involved in the control of many tasks, including voluntary movement.
• dopamine transporter (DaT): A protein that the body uses to move dopamine in and out of a cell.
• uptake: the process of absorbing the dopamine so that it can be released on the other side of the cell.
• basal ganglia: Area of the brain where movement, speech, posture and much more is regulated.
• SPECT and PET scans: 3-D imaging technologies that measure the presence and progress of specific radio-active tracer substances inside body cells. See this article for a discussion about these two imaging processes.

What are they looking for? Signs of an inadequate amount of dopamine inside the cells.

Why? Lewy bodies are known to target and damage dopamine in these cells, which require the chemical to function properly.

In plain English: Lewy bodies are probably present if the scan shows signs of inadequate amounts of a dopamine in cells that control functions related to several LBD symptoms.

2.  Abnormal (low uptake) ¹²³iodineMIBG myocardial scintigraphy

• Abnormal (low uptake): unusually low activity
• ¹²³iodineMIBG: a radio-active tracer substance
• myocardial: of the heart muscle. From myo (muscle) and cardia (heart)
• scintigraphy: 2-D imaging that measure the presence and progress of specific radio-active tracer substances inside body organs. (More about MIBG imaging)

What are they looking for? Damage to nerves that control autonomic heart function.

Why? Lewy bodies are known to damage the nerves that control autonomic functions such as heart beat and blood pressure. (More about LBD's autonomic symptoms.)

In plain English: DLB is probable if an image of lower than normal tracer activity shows the type of heart muscle nerve damage connected with several DLB symptoms.

3. Polysomographic confirmation of REM sleep without atonia (muscle relaxation).

• poly (many) somno (sleep) graph (test): Sleep study that measures brain waves, blood oxygen level, heart rate, breathing, eye movements and leg movements.
• Rapid Eye Movement (REM) sleep: The part of the sleep cycle when a person dreams.
• atonia: Muscle relaxation. 

What they are looking for? Evidence of muscle activity during dreams.

Why? During REM sleep a person's muscles are normally so relaxed that they can't physically act out their dreams.

In plain English: DLB is probably present if a sleep study confirms the presence of muscle activity during dream sequences.

Or: DLB is probably present if a sleep study confirms the presence of REM sleep behavior disorder (RBD), a core DLB symptom. (more about RBD, also called Active Dreams)

The above biomarkers provide objective tests for inadequate dopamine, a body chemical necessary for good cognition, heart nerve damage known to cause certain DLB-related autonomic dysfunctions, and Active Dreams, a core DLB symptom. None of the tests are considered 100% reliable alone but used with the more subjective clinical symptoms, they make a diagnosis about as accurate as it gets.

Next week: Exploring the Supportive Biomarkers.

LBD is an umbrella term for all Lewy body diseases and starts with an L for Lewy.
DLB is for Dementia with Lewy bodies and starts with a D for the way the disease starts.
PDD is for Parkinson's disease with dementia and starts with a P for the way that disease starts.
Biomarker: Something measurable that can indicate the presence and severity of whatever you are testing for.
Indicative: A strong sign.
Supportive: A weaker sign that can still be helpful.
Probable Diagnosis: almost--but not quite!-100% accurate.
Possible diagnosis: Likely, but unproven without further evidence.
Radio-active imaging: An imaging process that uses a radio-active tracer.
Radio-active tracer: biomarker that can enter the tissues or cells of the body.
Uptake: The process of absorbing a substance so that it can be released on the other side of the cell.

For more information about Lewy body disorders, read our books:
A Caregivers’ Guide to Lewy Body Dementia
Managing Cognitive Issues in Parkinson's and Lewy Body Dementia
Responsive Dementia Care: Fewer Behaviors Fewer Drugs
Riding A Roller Coaster with Lewy Body Dementia: A Manual for Staff

Helen and James Whitworth are not doctors, lawyers or social workers. As informed caregivers, they share the information here for educational purposes only. It should never be used instead of a professional's advice.