Abstract
Identification of early changes in Dopamine-Transporter (DaT) SPECT imaging expected in the prodromal phase of Parkinson’s disease (PD), are usually overlooked. Carriers of the G2019S LRRK2 mutation are known to be at high risk for developing PD, compared to non-carriers. In this work we aimed to study early changes in Dopamine uptake in non-manifesting PD carriers (NMC) of the G2019S LRRK2 mutation using quantitative DaT-SPECT analysis and to examine the potential for early prediction of PD. Eighty Ashkenazi-Jewish subjects were included in this study: eighteen patients with PD; thirty-one NMC and thirty-one non-manifesting non-carriers (NMNC). All subjects underwent a through clinical assessment including evaluation of motor, olfactory, affective and non-motor symptoms and DaT-SPECT imaging. A population based DaT-SPECT template was created based on the NMNC cohort, and data driven volumes-of-interest (VOIs) were defined. Comparisons between groups were performed based on VOIs and voxel-wise analysis. The striatum area of all three cohorts was segmented into four VOIs, corresponding to the right/left dorsal and ventral striatum. Significant differences in clinical measures were found between patients with PD and non-manifesting subjects with no differences between NMC and NMNC. Significantly lower uptake (p<0.001) was detected in the right and left dorsal striatum in the PD group (2.2±0.3, 2.3±0.4) compared to the NMC (4.2±0.6, 4.3±0.5) and NMNC (4.5±0.6, 4.6±0.6), and significantly (p = 0.05) lower uptake in the right dorsal striatum in the NMC group compared to NMNC. Converging results were obtained using voxel-wise analysis. Two NMC participants, who later phenoconverted into PD, demonstrated reduced uptake mainly in the dorsal striatum. No significant correlations were found between the DaT-SPECT uptake in the different VOIs and clinical and behavioral assessments in the non-manifesting groups. This study shows the clinical value of quantitative assessment of DaT-SPECT imaging and the potential for predicting PD by detection of dopamine depletion, already at the pre-symptomatic stage.Clinical registration numbers: NCT01089270 and NCT01089283.
Highlights
Parkinson’s disease (PD), affects 1% of the population over 60, with incidence rates of 0.3 per 1000 person years in persons aged 55 to 65 [1, 2]
Subjects were part of a prospective observational study aimed to assess the genetic basis of PD in Ashkenazi Jews (AJ) performed at the Tel-Aviv Medical Center (TLVMC) as part of a multinational consortium funded by the Michael J Fox foundation
Patients with PD were significantly older than the non-manifesting subjects (p
Summary
Parkinson’s disease (PD), affects 1% of the population over 60, with incidence rates of 0.3 per 1000 person years in persons aged 55 to 65 [1, 2]. When the neurodegenerative process a critical point, when approximately 50–60% of the substantia nigra (SN) neurons are lost and 60–80% of the dopamine content of the striatum is depleted [3, 4], motor symptoms start to immerge and the disease is clinically diagnosed. During this long prodromal pathological process, some individuals may present with non-motor symptoms and signs but these are usually unspecific [5,6,7]. At present there are no sensitive methods to identify those likely to develop the disease
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