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            I]β-CIT SPECT imaging assessment of the rate of Parkinson’s disease progression

Marek, Kenneth; Innis, Robert B.; Dyck, Christopher van; Fussell, B.; Early, Michelle; Eberly, Shirley; Oakes, David; Seibyl, John

doi:10.1212/wnl.57.11.2089

Cited by 331 publications

(236 citation statements)

References 38 publications

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“…7 Previous studies have shown a linear reduction of striatal DaT binding in early PD, with estimated annual rates of decline ranging from 4% to 10%. [8][9][10][11][12] In our study, assuming a constant decline, the estimated absolute annual rate of decline of striatal DaT binding was around 5%. It is important to highlight that we could not calculate the relative rate of decline compared to age-expected normal values at the time of the first scan, since we did not have those data.…”

Section: Discussionmentioning

confidence: 46%

Prospective clinical and DaT-SPECT imaging in premotor LRRK2 G2019S-associated Parkinson disease

et al. 2017

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Objective: To assess the value of baseline clinical and imaging biomarkers in a cohort of asymptomatic LRRK2 G2019S carriers for predicting conversion to Parkinson disease (PD) at 4 years.Methods: Thirty-two asymptomatic carriers of LRRK2 G2019S mutation underwent baseline and Results: Three carriers, asymptomatic at baseline, had converted to PD at 4-year evaluation.Twenty-three participants were fully evaluated. PD converters had lower striatal DaT binding at baseline than nonconverters (p 5 0.002). A baseline scan with a ratio of bilateral striatal uptake below 1 predicted conversion to PD within the 4-year period with high sensitivity and specificity (area under the curve 1; p 5 0.006). The slope of DaT binding decline between the 2 scans was similar in PD converters and nonconverters. Age-adjusted UPSIT score at baseline and at 4 years was similar in both groups.Conclusions: Semiquantitative DaT-SPECT could be used to predict early conversion to PD in asymptomatic carriers of the LRRK2 G2019S mutation. Rate of conversion to PD at 4 years in this cohort aged ;64 years was 12%. The slope of DaT binding decline on DaT-SPECT imaging seems to be similar across different stages of the premotor period. The G2019S mutation of the LRRK2 gene is the commonest known cause of Parkinson disease (PD). 1 Clinically and pathologically, this form of the disease is indistinguishable from idiopathic PD, and therefore it constitutes an ideal scenario in which to deepen our knowledge about the disease. The identification and follow-up of carriers of the LRRK2 G2019S mutation who still have not developed motor symptoms of PD represents a unique opportunity for studying the prodromal stage of PD. We lack information on the timing between the beginning of the neurodegenerative process and the appearance of the motor symptoms of PD and the pace of cell loss at the substantia nigra (SN) at the premotor stage. Shedding light into the prodromal stages of the disease is going to be crucial for planning drug trials aiming to modify the disease process early, before most of the damage is already done. The penetrance of the LRRK2 G2019S mutation is age-dependent and only a proportion of LRRK2 G2019S mutation carriers will develop motor symptoms of PD. 2 Besides age, no other clinical marker has been proven to be useful to predict conversion to manifest PD in asymptomatic carriers. In a previous study by our group, we characterized a cohort of 32 asymptomatic carriers of the LRRK2 G2019S mutation with brain imaging ( 123 I-ioflupane SPECT and transcranial sonography) and olfaction tests. 3

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Section: Discussionmentioning

confidence: 46%

Prospective clinical and DaT-SPECT imaging in premotor LRRK2 G2019S-associated Parkinson disease

et al. 2017

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“…DAT-SPECT has been proven to be an objective tool for monitoring PD progression. (Marek et al, 2001;Tatsch et al, 1997;Weng et al, 2004;Winogrodzka et al, 2001Winogrodzka et al, , 2003. [ 123 I]-β-CIT SPECT have been used in a group of 50 early-stage PD patients showing an average decrease of 8% in the whole striatum (8% in the putamen and 4% in the caudate) at 12-month follow-up (Winogrodzka et al, 2003).…”

Section: Dopaminergic Systemmentioning

confidence: 99%

“…[ 123 I]-β-CIT SPECT have been used in a group of 50 early-stage PD patients showing an average decrease of 8% in the whole striatum (8% in the putamen and 4% in the caudate) at 12-month follow-up (Winogrodzka et al, 2003). Sequential SPECT scans using [ 123 I]-β-CIT demonstrated a decline in striatal uptake of 11.2% per year in PD patients, compared with 0.8% per year in controls (Marek et al, 2001).…”

Section: Dopaminergic Systemmentioning

confidence: 99%

Imaging in Parkinson's Disease

Politis

Pagano

Niccolini

2017

International Review of Neurobiology

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“…Biochemical BMs used in clinical practice and clinical trials include measuring CSF oligoclonal bands to confirm the diagnosis of MS, 10 -12 and functional imaging of dopaminergic neurons in PD with dopamine transporter ligands, measures of dopamine metabolism (fluorodopa), or others. 13,14 Anatomical BMs include magnetic resonance imaging (MRI) of lesion burden or cerebral atrophy in MS 10,15-17 and confirmation of the clinical diagnosis of stroke with computed tomography (CT) or MRI. 18 In fact, in the absence of clinical signs or symptoms, these imaging methods can be used in isolation to diagnose stroke (silent stroke).…”

Section: Biomarkersmentioning

confidence: 99%

“…BMs have, however, been used extensively in clinical trials aimed at altering the progression of disease. 4,13,[41][42][43][44] Specifically, imaging measures of dopaminergic nigrostriatal integrity have been used to examine potential neuroprotective effects of drugs. In some of these studies, the BMs identified relative preservation of the dopaminergic system in subjects treated with dopamine agonists, 42,43 suggesting slowing of disease progression.…”

Section: Assessments Of Disease Severity Progression and Responses mentioning

confidence: 99%

Evidence from biomarkers and surrogate endpoints

Feigin

2004

Neurotherapeutics

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Summary:The use of physiological, anatomical, and other biological tests is commonplace in the practice of medicine. In neurology, objectively measured tests termed biomarkers (BMs) are playing an increasing role in diagnosis and management of disease, both in clinical practice and in experimental therapeutics. This article will discuss the various applications of BMs to the assessment of therapies for neurological diseases and will use examples from neurological diseases to elucidate the strengths and potential weaknesses of BMs. As the understanding of the pathophysiology of many neurological diseases has improved, new BMs have been developed, and efforts have been made to use these as proxies for clinical endpoints. A BM used in this manner is referred to as a surrogate endpoint (SE). There are many potential advantages and disadvantages of using SEs in the evaluation of new therapies, and these will be reviewed as well. Furthermore, the evidence required for the development of an SE and the nature of the evidence that can be derived from the use of BMs and SEs will be discussed.

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[ ¹²³ I]β-CIT SPECT imaging assessment of the rate of Parkinson’s disease progression

Cited by 331 publications

References 38 publications

Prospective clinical and DaT-SPECT imaging in premotor LRRK2 G2019S-associated Parkinson disease

Prospective clinical and DaT-SPECT imaging in premotor LRRK2 G2019S-associated Parkinson disease

Imaging in Parkinson's Disease

Evidence from biomarkers and surrogate endpoints

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[ 123 I]β-CIT SPECT imaging assessment of the rate of Parkinson’s disease progression

Cited by 331 publications

References 38 publications

Prospective clinical and DaT-SPECT imaging in premotor LRRK2 G2019S-associated Parkinson disease

Prospective clinical and DaT-SPECT imaging in premotor LRRK2 G2019S-associated Parkinson disease

Imaging in Parkinson's Disease

Evidence from biomarkers and surrogate endpoints

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[ ¹²³ I]β-CIT SPECT imaging assessment of the rate of Parkinson’s disease progression