Understanding Cognitive Challenges in Parkinson’s Disease: PDD vs. DLB
Cognitive challenges are a very common non-motor symptom of Parkinson’s disease (PD). When the cognitive challenges are severe enough to interfere with daily activity, they are known as Parkinson’s disease dementia (PDD). You may have heard of another condition called Dementia with Lewy Bodies (DLB). Although they are two different diagnoses, there is a fair amount of similarity between these two conditions. There may even be confusion or conflicting opinions among the neurologists you have seen as to whether you or your loved one has PDD or DLB. This understandably can cause great confusion and frustration. In this article, we will explain these conditions and try to provide some clarity.
Useful Definitions
Contributing to the confusion between these different conditions and terminology is that you may find that different sources give different definitions!
To help you as we go through our explanation below, we’ve compiled a short glossary you can refer to as you read this post:
- Dementia – a loss of cognitive function significant enough to interfere with daily activities.
- Alpha-synuclein – a protein normally found in the brain that forms abnormal clumps in Parkinson’s disease and other related disorders.
- Lewy body – an abnormal aggregation or clumping of alpha-synuclein, which can be present in the brain in a range of neurologic diseases including Parkinson’s disease and other related disorders.
- Parkinson’s disease (PD) – a degenerative neurologic disease marked by a constellation of movement and non-movement symptoms and associated with the presence of Lewy bodies in the brain. This term does not address specifically whether dementia is among the symptoms.
- Parkinson’s disease dementia (PDD) – dementia that has developed in someone with established PD. Dementia develops later in the course of the disease.
- Dementia with Lewy Bodies (DLB)– a degenerative neurologic disease marked by a constellation of movement and non-movement symptoms, including dementia, and associated with the presence of Lewy bodies in the brain. In this disease, dementia develops early in the course of the disease.
- Lewy Body Dementia (LBD) – an umbrella term which encompasses DLB and PDD.
“Location, location, location”
Because different parts of the brain control different functions, the same lesion in one part of the brain will cause one set of symptoms, and in another part of the brain, it will cause a different set of symptoms.
Alpha-synuclein Buildup
In PD, PDD, and DLB, the protein alpha-synuclein abnormally accumulates in the brain in aggregates, or clumps, called Lewy bodies.
The location of those clumps makes a difference:
- When Lewy bodies are present in the brainstem, body functions that are controlled by the brainstem will be affected, causing symptoms such as constipation, depression and sleep disorders. Other important symptoms of Lewy body disorders include wide fluctuations in blood pressure, poor temperature control and bowel and bladder dysfunction.
- When Lewy bodies affect the substantia nigra, located in the midbrain portion of the brainstem, hallmark motor symptoms will emerge including resting tremor, slowness and stiffness.
- Lewy bodies can also affect areas beyond the brainstem, including the cortex or the ‘thinking part’ of the brain. When this occurs, cognitive symptoms become apparent. Patients may experience difficulty with executive function (planning, ordering, multi-tasking), visuo-spatial function (navigating, constructing) and memory. A variety of other symptoms can be prominent including visual hallucinations, fluctuating levels of alertness, apathy, agitation, anxiety, and delusions (believing something that isn’t true – e.g. that someone is stealing from the patient or that the patient is being watched by the CIA).
Symptoms of Parkinson’s Disease Dementia and Dementia with Lewy Bodies
In both PDD and DLB, symptoms caused by Lewy bodies in the lower brainstem (e.g. constipation, depression, sleep disorders), midbrain (e.g. resting tremor, slowness, stiffness) and cortex (e.g. cognitive difficulties, hallucinations,) can all occur.
Differences between Parkinson’s Disease Dementia and Dementia with Lewy Bodies?
Technically, the difference between these two conditions lies in how quickly the cognitive difficulties and hallucinations develop in relation to the movement issues. In DLB, the cognitive difficulties and hallucinations develop much sooner in the disease course than in PDD, sometimes even prior to the movement difficulties.
It is important to note that there are other common types of dementia that are caused by the abnormal accumulations of other proteins. Alzheimer’s disease (AD) for example, does not show Lewy bodies but rather beta-amyloid plaques and tau tangles. APDA had an important conversation with the Alzheimer’s Association about some key features of Alzheimer’s disease and how AD and PD are related.
Is there a biomarker that can distinguish between PDD and DLB?
A biomarker is a measurable characteristic in the body which indicates that disease is present. The biomarker can be a lab test, an imaging test or a clinical test.
There has been a lot of talk recently about biomarkers for Parkinson’s disease and related disorders and these are:
- The DaTscan is an imaging test which measures the loss of dopamine nerve endings in a part of the brain called the striatum.
- The Syn-One test detects the phosphorylated form of alpha-synuclein in a set of skin biopsies that are taken from the neck, thigh, and back of the legs as a way of diagnosing disease.
- The Syn-Tap test detects abnormal alpha-synuclein in cerebral spinal fluid.
However, because both DLB and PDD are characterized by abnormal accumulations of alpha-synuclein and loss of dopamine nerve endings, each of these biomarkers are abnormal in both PDD and DLB and current tests are not able to distinguish between the two.
Treatments for Parkinson’s Disease Dementia and Dementia with Lewy Bodies
Treatments for DLB are similar to those for PDD and are aimed at symptom control. The motor symptoms of slowness, stiffness and walking difficulties can be treated with levodopa. However, levodopa can cause or exacerbate hallucinations, making it difficult to use it as a treatment for patients who have or are at risk of hallucinating. Sometimes, clinicians will need to treat the hallucinations more aggressively for a patient to tolerate levodopa given to help the motor symptoms. On the flipside, anti-psychotic medications to control hallucinations can worsen motor symptoms, so treating all the symptoms of PDD or DLB simultaneously can be a tricky balancing act.
Anti-psychotics
Most of the available anti-psychotics are always avoided in both the DLB and PDD population because they block dopamine receptors and can cause significant motor dysfunction. However, two anti-psychotic medications, quetiapine and clozapine, are sometimes used in PDD and DLB patients as they have less of an ability to worsen motor symptoms. However, data for the use of quetiapine in these disorders is limited and clozapine requires the patient to undergo frequent blood draws to monitor blood counts. A newer medication, pimavanserin, has a different mechanism of action, and does not block the dopamine system but rather the serotonin system, and therefore does not increase motor symptoms. It was approved by the FDA to treat PD psychosis, although the overlap between PDD and DLB may make it reasonable to try pimavanserin in DLB as well.
Medications for cognition
Cognitive symptoms in DLB can be treated with the same medications developed for other dementias. These include medications such as donepezil and rivastigmine. Memantine is sometimes used as well.
DLB gained more visibility in the press when Robin Williams, the beloved comedian, died in 2014 with this condition. At APDA, we strive to further our understanding of Lewy body disorders through our research funding. Check out the research being done by Dr. Laura Volpicelli who is studying Lewy body formation in the amygdala and changes which may contribute to the cognitive and behavioral dysfunction in PD, and Dr. William Zieger, who is studying how alpha-synuclein causes problems with thinking and memory by using advanced microscopes to directly measure activity in the thinking areas of the brain.
Tips & Takeaways
- Differentiating between the different cognitive conditions associated with PD can be challenging.
- Focus less on the label that has been attached to your condition and seek to maximize both your physical and mental health.
- This means consulting with your physician to improve your medication regimen to treat all aspects of your disease – including motor symptoms, cognitive symptoms, and hallucinations.
- Always be open and honest with your doctor about all of the symptoms you may be experiencing so they can create the best treatment plan for you.
- This also means that you must increase your level of physical, mental, and social activities to keep your brain and body functioning at their best.