Early Parkinson's disease: longitudinal changes in brain activity during sequence learning.

Impairment of sequence learning is common in Parkinson's disease (PD), but the time course of this cognitive abnormality is not known. We assessed longitudinal changes in sequence learning performance and associated task-related cerebral blood flow in 13 early stage PD patients who underwent H(2)(15)O PET at baseline and again 2 years later. Ten healthy volunteer subjects served as controls. A trend toward decline in learning performance (p=0.08) was evident over the 2 years of follow-up. During this interval, significant declines in learning-related activation were detected in parietal and temporo-occipital association areas and in the right dorsolateral prefrontal cortex. Learning-related activation in these regions was normal at baseline, but declined to subnormal levels (p<0.01) at 2 years. Significant hippocampal activation (p<0.005) was present in the subjects with high learning performance over time. The findings are consistent with a decline in learning-related neural activity in cortical areas with prominent Lewy body formation.