Study Rationale: Cognitive impairments cause significant disability for people with Parkinson’s disease (PD). Problems such as reduced attention or difficulty following plans can occur very early in the disease process, even before the emergence of movement symptoms. Because the earliest changes in brain function that could affect cognition occur in the striatum (a region deep inside the brain), it is likely that cognition changes may affect this area or its connections with the outer layer of the brain, the cerebral cortex. However, neither the time course nor the anatomy changes underlying these changes is known.
Hypothesis: We hypothesize that functional and anatomical disturbances of interactions between the striatum and the cerebral cortex are correlated with (and may give rise to) cognitive impairments early in the development of PD.
Study Design: We will study a group of nonhuman primates that is undergoing a pharmacologic treatment, as part of another study, that leads to the gradual development of parkinsonian signs. Before and during the treatment, we will repeatedly assess their cognitive abilities. In parallel, we will use imaging techniques to study the progressive loss of dopamine in the striatum, the chemical hallmark of PD. At three pre-determined levels of dopamine loss, some animals will undergo detailed anatomical studies of specific chemical brain systems and of the fine structure of connections linking the cortex with the striatum.
Impact on Diagnosis/Treatment of Parkinson’s disease: This study could identify new diagnostic cognitive markers that could help with the early detection of at-risk individuals. Further, the study may help us to identify new targets for pharmacologic or genetic treatments that may prevent or treat early cognitive impairments in people with PD.
Next Steps for Development: If we identify a pattern of development of cognitive impairments, the results will be verified in persons at risk of developing PD. New treatment strategies for cognition impairments, emerging from the anatomical experiments, should first be tested in animals, potentially followed by human trials.