Recently, several international Parkinson’s and Dementia with Lewy Bodies (DLB) advocacy organizations, including Cure Parkinson’s, held a roundtable to discuss the development of better tools for measuring cognitive changes in people with Parkinson’s and DLB.
It is estimated that roughly half of people with Parkinson’s will experience cognitive changes, the way we think and process information, to some extent (1). Furthermore, Parkinson’s is considered a risk factor for dementia, with this affecting an estimated 20-40% of people with Parkinson’s (2). Despite this prevalence, researchers currently do not have a means of accurately measuring cognitive changes in people with Parkinson’s specifically, making it difficult to determine the effectiveness of new therapies on cognition in clinical trials.
To help address this, a roundtable was held which brought together a diverse group of stakeholders, including researchers, clinicians, patients, and representatives from regulatory agencies. A paper discussing the outcomes of this meeting has now been published.
What is dementia and why is it relevant to Parkinson’s?
Dementia is an umbrella term for a range of conditions that involve issues with memory, thinking, and behaviour, which impair daily life. Though the exact cause can vary between conditions, a common underlying feature is an abnormal build-up of proteins in brain cells (neurons), which interfere with cell processes and lead to neuron loss. Alzheimer’s is the most common type of dementia and is driven by the accumulation of two proteins: amyloid beta and tau.
Similarly, one of the hallmarks and major drivers of Parkinson’s is the build-up of the protein alpha-synuclein, which clumps together to form Lewy bodies. Although this primarily impacts neurons in the part of the brain controlling movement, over time, it can affect other areas of the brain, leading to problems with thinking and memory. Eventually, some people with Parkinson’s may go on to develop dementia.
Dementia with Lewy bodies (DLB), like Parkinson’s, is caused by the presence of abnormal alpha-synuclein and Lewy bodies; however, this is concentrated in the parts of the brain that deal with cognition.
Diagnosing Parkinson’s dementia and DLB
People with Parkinson’s are most likely to be affected by two types of dementia: Parkinson’s dementia and Dementia with Lewy Bodies (DLB). The underlying cause of Parkinson’s dementia and DLB is the same, and they are sometimes referred together as “Lewy body dementia”. The difference between them is in the timing – if motor symptoms precede memory issues, then an individual is more likely to be diagnosed with Parkinson’s dementia. Alternatively, if memory issues present before or at the same time as motor symptoms, they are more likely to receive a DLB diagnosis.
Why is this research important?
A key message from this meeting is the need for the objectives of these tests to better align with the patients they are intended to represent. Currently, most of the tools we have for measuring cognitive changes are designed for people with Alzheimer’s; however, people with Parkinson’s, Parkinson’s dementia, and/or DLB may not experience cognitive changes in the same way. For example, early issues with memory are much more common in people with Alzheimer’s than in people with Parkinson’s dementia or DLB (3). Furthermore, these tests are often not good for measuring subtle or small changes, making them unsuitable for people with Parkinson’s who may not experience the same degree or rate of cognitive change as those with other types of dementia.
Reliance on these tests can therefore make assessments difficult, especially in clinical trials. Choosing the wrong outcome measures can affect trial results, leading to delays in the progression of promising drugs through the development pipeline and on to regulatory bodies. Some key takeaways from the roundtable address these concerns. Of particular focus was a stronger alignment between the patient population that a new treatment is being developed for with other elements of measurement such as:
- the domains of cognition that the treatment intends to target,
- the domains covered by the cognitive measure chosen,
- and the meaningfulness of the measures to patients and their loved ones.
Ultimately, people with PD and DLB cannot afford for potential new treatments to be rejected by regulators because the measurement tools were not appropriate; therefore, it is important that we continue to bring attention to and work on improving these measures.
This roundtable was led by The Michael J. Fox Foundation, Parkinson’s UK, the Critical Path Institute, Shake It Up Australia, Cure Parkinson’s, and the Lewy Body Dementia Association and supported by RAND.
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