A novel type of PET scan of the brain can detect changes associated with cognitive difficulties in Parkinson’s disease (PD), according to research published in the July 12 online edition of Neurology. The finding suggests a new potential target for drugs to treat mild cognitive impairment in PD.
Most people living with PD will experience some degree of cognitive change in their journey with PD. Difficulty with spatial working memory – the kind of memory involved in matching cards in game of concentration – is particularly common and can be an early sign of mild cognitive impairment (MCI).
Scientists are trying to better understand how cognitive changes in PD affect the brain, and find new therapies to treat them. Earlier animal studies suggested that decreases in an enzyme called PDE4 (phosphodiesterase 4) may be involved. The enzyme is found throughout the brain, and its activity can be measured with a type of positron emission tomography (PET) brain scan.
In new research, scientists led by Marios Politis, M.D., Ph.D. at King’s College London – a Parkinson’s Foundation Center of Excellence – compared the PET scans of 12 people with PD and 12 healthy individuals to assess their PDE4 levels. The study participants with PD all took levodopa for their PD, and none had a diagnosis of mild cognitive impairment or dementia. The researchers evaluated all study participants with a battery of neurological and cognitive tests.
- People with PD, as compared to healthy individuals, performed worse on tests of reaction time; memory associated with events or experiences (episodic memory); memory involved in solving a puzzle (spatial working memory); and ability to plan and to focus attention (executive function).
- The brain scans of participants with PD showed decreases in PDE4 of up to 32 percent in an area of the brain called the striato-thalamo-cortical circuit, which is different from the area involved in movement and is involved in spatial working memory.
- Lower PDE4 levels were not associated with older age and did not appear to be affected by PD duration or medications.
What Does It Mean?
The mechanism underlying cognitive changes in PD is not yet fully understood, and need for treatments to ease their effects is urgent. This is the first study to investigate PDE4 in Parkinson’s, and the number of study participants was small. In it, researchers found that low levels of PDE4 in certain areas of the brain were associated with changes in working memory, suggesting the possibility that reduction in PDE4 may lead to cognitive decline in PD. The study authors suggest that new drugs to increase PDE4 may have the potential to improve cognitive symptoms in PD if the link between PDE4 and cognition holds true in further research. More research is needed to explore this possibility, and these findings should be followed up in larger longitudinal studies.
References: Niccolini F, Wilson H, Pagano G, et al. (2017). Loss of Phosphodiesterase 4 in Parkinson Disease: Relevance to Cognitive Deficits. Neurology 89:1-8, DOI 10.1212/WNL.0000000000004201.
Jacova C, Factor S. (2017). Phosphodiesterase 4: Rethinking Cognition in Parkinson Disease. Neurology 89:1-2, DOI 10.1212/WNL.0000000000004221.