Rate of progression in Parkinson's disease: A 6‐[¹⁸F]fluoro‐L‐dopa PET study

Abstract

The aim of this study was to investigate the rate of progression in Parkinson's disease (PD) with 6-[(18)F]fluoro-L-dopa (FDOPA) positron emission tomography (PET). We investigated 21 patients with PD and eight healthy controls. Ten of the patients were de novo at the time of the first PET scan and antiparkinsonian medication was started thereafter, with a favourable response. A FDOPA PET scan was carried out twice at an approximately 5-year interval. The regions of interest were drawn on individual magnetic resonance imaging (MRI) images, matched with the PET images. At the first PET scan, in PD patients the mean k(i)(occ) (x 10(-3) min(-1)) in the anterior putamen was 5.6 +/- 2.7 (mean +/- S.D.; 55% of the control mean) and in the posterior putamen 4.5 +/- 2.4 (45% of the control mean). The k(i)(occ) value for the caudate nucleus was 7.5 +/- 2.1 (x 10(-3) min(-1); 76% of the control mean). The FDOPA uptake declined by the time of the second PET scan and the annual rate of decline was 8.3 +/- 6.3% (P < 0.001) of the baseline mean in the anterior putamen and 10.3 +/- 4.8% (P < 0.001) in the posterior putamen. In the caudate nucleus, FDOPA uptake decreased by 5.9 +/- 5.1% (P < 0.001) of the baseline mean per year. The estimated preclinical period was longest for the posterior putamen being 6.5 years. For the anterior putamen the preclinical period was 4.6 years. In the caudate nucleus, the estimated FDOPA uptake was at normal level at disease onset. In healthy controls, there was no significant decline in FDOPA uptake in any striatal subregion. Our results suggest that the disease process in PD first affects posterior putamen, followed by the anterior putamen and the caudate nucleus, but once started, the absolute rate of decline is the same. In healthy controls, no significant decline in FDOPA was detected.

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

“…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.…”

Imaging in Parkinson's Disease

“…In advanced stages, dopaminergic degeneration becomes slower, and although the gradient is maintained, the degree of asymmetry diminishes (Hilker, Schweitzer, et al, 2005;Hilker, Thomas, et al, 2005;Nandhagopal et al, 2009). The mean annual decline in [ 18 F]dopa uptake ranges from 8% to 12% in the putamen and from 4% to 6% in the caudate and it is considerably more than the decline typical of aging (Nurmi et al, 2001;Pavese, Rivero-Bosch, Lewis, Whone, & Brooks, 2011). Moreover, presynaptic dopaminergic PET imaging has been used to estimate the duration of preclinical PD and it has shown 30%-55% loss of putamen dopaminergic function at the time of symptom onset (de la Fuente-Fernández et al, 2011;Hilker, Schweitzer, et al, 2005;Hilker, Thomas, et al, 2005;Lee, 2000).…”

Neuroimaging in Parkinson’s disease

“…[47][48][49] In early PD patients treated with L-dopa putamen, 18 F-dopa uptake has been reported to decline annually by around 10% of baseline (5% of the normal mean), whereas caudate uptake falls at a slower rate. Similar rates of loss of putamen dopamine transporter binding have been reported with 18 F-CFT PET 50 and with 123 I-␤-CIT, 51 123 I-FP-CIT, 52 and 123 I-IPT SPECT.…”