Neurodegenerative Disease Parkinson’s Disease
Advances in the Role of Neuroimaging to Monitor Disease Progression in Parkinson’s Disease
Pankaj A Agarwal, MD, DNB, DM1 and A Jon Stoessl, CM, MD, FRCPC, FAAN, FCAHS2 1. Postdoctoral Fellow; 2. Director, Pacific Parkinson’s Research Centre, University of British Columbia and Vancouver Coastal Health
Abstract
Since structural imaging has generally failed to demonstrate consistent abnormalities in Parkinson’s disease (PD), from an imaging perspective, the diagnosis has typically been based upon the demonstration of impaired striatal dopamine (DA) function. Radiotracer imaging techniques such as positron emission tomography (PET) and single photon emission computerized tomography (SPECT) allow the in vivo assessment of nigrostriatal DA function as well as regional cerebral blood flow, glucose metabolism, and functional connectivity, and changes in these measures have been used to infer disease progression. Pre-synaptic radiotracer imaging (RTI) has shown that striatal dopaminergic hypofunction follows a negative exponential pattern with the fastest rate of decline in early disease. Moreover, while striatal subregions remain differentially affected throughout the course of disease, with the posterior putamen affected more than anterior structures, the rate of deterioration is similar in all subregions. However, although functional imaging is undoubtedly a very useful tool in the assessment of PD progression, various studies have shown discordance between clinical progression of PD and nigrostriatal degeneration estimated by PET or SPECT. Therefore, considerable caution is warranted in the interpretation of imaging findings. While a potentially invaluable complement in assessing the severity of dopaminergic dysfunction, functional imaging is not a substitute for clinical assessment and other objective measures of PD severity, and cannot be currently considered a biomarker for progression of PD.
Keywords Neuroimaging, positron emission tomography, progression, Parkinson’s disease
Disclosure: Pankaj A Agarwal, MD, DNB, DM, has no conflicts of interest to declare. A Jon Stoessl, CM, MD, FRCPC, FAAN, FCAHS, has received research, team or operating grants from the Canada Research Chair, Canadian Institutes of Health Research, Pacific Alzheimer Research Foundation, Michael Smith Foundation for Health Research, and Michael J Fox Foundation, whereby money was paid to his institution, and he has received payment for lectures and served on speakers bureaus for Novartis and Teva (payment less than $5,000 over three years). Received: May 10, 2011 Accepted: May 24, 2011 Citation: US Neurology, 2011;7(1):27–32 Correspondence: A Jon Stoessl, CM, MD, FRCPC, FAAN, FCAHS, 2221 Wesbrook Mall, Vancouver BC, Canada, V6T 2B5. E:
jstoessl@interchange.ubc.ca
Parkinson’s disease (PD) is the second most common neurodegenerative disorder and affects more than one in 100 people over the age of 65.1
The
cardinal clinical features of PD are bradykinesia, resting tremor, rigidity, and postural instability.2
degeneration of the dopaminergic neurons of the substantia nigra leading to striatal dopamine (DA) deficiency.3
when 80 % of striatal DA, or 50 % of nigral cells, are lost.4,5
Symptoms of PD appear While there
has been a recent emphasis on non-dopaminergic aspects of PD,6 DA replacement therapies, including levodopa and DA agonists, are very effective in treating the cardinal features of the disease. With the possible exception of recent evolving techniques, structural imaging has generally failed to demonstrate consistent abnormalities in PD. Thus, from an imaging perspective, the diagnosis has typically been based upon the demonstration of impaired striatal DA function and changes in these measures have been used to infer disease progression. Radiotracer imaging (RTI) techniques such as positron emission tomography (PET) and single photon emission computerized tomography (SPECT) allow the in vivo assessment of nigrostriatal DA function, as
© TOUCH BRIEFINGS 2011 The pathophysiologic hallmark of PD is
well as regional cerebral blood flow, glucose metabolism and functional connectivity. Molecular imaging techniques may also provide insights into pathophysiologic mechanisms such as neuroinflammation or abnormal protein deposition. However, considerable caution is required in the interpretation of the findings and while a potentially invaluable complement in assessing the presence and severity of dopaminergic dysfunction, these techniques are not a substitute for careful clinical assessment and other objective measures of PD severity.
Neuroimaging of the Nigrostriatal System Dopamine Synthesis, Storage and Re-uptake DA is synthesized by the hydroxylation of tyrosine to L-3,4- dihydroxyphenylalanine (L-dopa), which is in turn decarboxylated to DA by L-aromatic amino acid decarboxylase (AADC). Exogenously administered L-dopa crosses the blood–brain barrier via the large neutral amino acid transporter. The vesicular monoamine transporter type 2 (VMAT2) pumps both newly synthesized and recycled DA into presynaptic vesicles. Vesicular storage helps to maintain the molecular
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