Imaging, Cognition, and Parkinson’s Disease—An Overview

Imaging, Cognition, and Parkinson’s Disease—An Overview

Eidelberg David, Mattis Paul

US Neurology, 2010;5(2):26-9

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Abstract
Although the clinical diagnosis of Parkinson’s disease (PD) is defined by motor symptoms, cognitive dysfunction is a common manifestation of this disease and an important contributor to functional disability. Functional brain imaging tools have proved valuable in the study of cognitive impairment in PD. Recent advances in imaging methodology and analysis have provided novel insights into the pathophysiology of cognitive decline in these patients. This review summarizes how positron emission tomographic (PET) imaging of metabolic activity in the rest state has enhanced understanding of cognitive dysfunction in PD. This tool has also created the basis for an objective biomarker for use in clinical trials of new therapeutic agents for this disease manifestation. Moreover, insights gained from the use of specific radiotracers targeting the dopaminergic and cholinergic neurotransmitter systems will be discussed, as well as findings from in vivo detection of amyloid-beta.

Keywords
Brain networks, positron emission tomography, Parkinson’s disease, metabolism, cognition, dopaminergic system, cholinergic system, protein aggregation

Disclosure: The authors have no conflicts of interest to declare.
Received: November 14, 2008 Accepted: May 11, 2009
Correspondence: David Eidelberg, MD, Center for Neurosciences, The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System,350 Community Drive, Manhasset, NY 11030. E: david1@nshs.edu

Parkinson’s disease (PD) is characterized by motor symptoms including resting tremor, rigidity, and bradykinesia. However, cognitive and behavioral problems in PD are common1 and can have a significant effect on quality of life.2,3 The prevalence of dementia in patients with PD has conservatively been estimated to range between 24 and 31%.4 The cognitive profile observed in PD patients with dementia (PDD) is substantially different from that of the primarily cortical dementia of Alzheimer’s disease (AD). Patients with PDD typically exhibit difficulties with executive functions, the retrieval aspects of memory, and visuospatial skills.4 They do not exhibit clear aphasia, apraxia, or agnosia, which are common features of AD. The onset of dementia in PD is insidious, typically occurring years after the onset of motor symptoms. However, cognitive difficulties have been observed even in early PD.5 Although debated, the pattern of early cognitive dysfunction in PD is believed to be generally similar to that of PDD.6,7

The pathophysiology of cognitive symptoms in PD is believed to be different from that of the motor symptoms.8–10 Several theories exist regarding the origins of this particular clinical manifestation. It is possible that cognitive dysfunction in PD is related to the depletion of striatal dopamine and its effect on non-motor cortico–striato–pallidal– thalamocortical (CSPTC) circuits.6 Nevertheless, other dopaminergic systems may mediate these cognitive changes, including mesocortical dopamine projections to the prefrontal cortex.11,12 Other pathological processes, such as regional cortical Lewy body formation, are also likely to contribute to PD cognitive decline,13 as well as abnormalities of other neurotransmitter systems.14

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Keywords:
Brain networks, positron emission tomography, Parkinson’s disease, metabolism, cognition, dopaminergic system, cholinergic system, protein aggregation, protein aggregation disease, protein misfolding aggreation, protein aggregation neurodegenerative disease, protein folding, Parkinson’s disease tremor, Parkinson’s disease deep brain stimulation, Parkinson’s disease levodopa, Parkinson’s disease dopamine agnonists,

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