Striatal Dopamine Loss in Early Parkinson's Disease: Systematic Review and Novel Analysis of Dopamine Transporter Imaging

Abstract

Background: Neuropathological studies, based on small samples, suggest that symptoms of Parkinson's disease (PD) emerge when dopamine/nigrostriatal loss is around 50-80%. Functional neuroimaging can be applied in larger numbers during life, which allows analysis of the extent of dopamine loss more directly.

Objective: To quantify dopamine transporter (DaT) activity by neuroimaging in early PD.

Methods: Systematic review and novel analysis of DaT imaging studies in early PD.

Results: In our systematic review, in 423 unique cases from 27 studies with disease duration of less than 6 years, mean age 58.0 (SD 11.5) years, and mean disease duration 1.8 (SD 1.2) years, striatal loss was 43.5% (95% CI 41.6, 45.4) contralaterally, and 36.0% (95% CI 33.6, 38.3) ipsilaterally. For unilateral PD, in 436 unique cases, mean age 57.5 (SD 10.2) years, and mean disease duration 1.8 (SD 1.4) years, striatal loss was 40.6% (95% CI 38.8, 42.4) contralaterally, and 31.6% (95% CI 29.4, 33.8) ipsilaterally. In our novel analysis of the Parkinson's Progressive Marker Initiative study, 413 cases had 1436 scans performed. For a disease duration of less than 1 year, age was 61.8 (SD 9.8) years, and striatal loss was 51.2% (95% CI 49.1, 53.3) contralaterally and 39.5% (36.9, 42.1) ipsilaterally, giving an overall striatal loss of 45.3% (43.0, 47.6).

Conclusions: Loss of striatal DaT activity in early PD is less at 35-45%, rather than the 50-80% striatal dopamine loss estimated to be present at the time of symptom onset, based on backwards extrapolation from autopsy studies.

Keywords: Parkinson's disease; dopamine transporter.; neuroimaging.

FIG. 1

PRISMA diagram of paper selection for the systematic review.

FIG. 2

Striatal dopaminergic activity during the first six years after a diagnosis of PD. Individual and pooled analysis of studies reporting striatal values are shown. There was significant heterogeneity between studies. The overall difference between sides was 7–8%.

FIG. 3

Striatal dopaminergic activity in early unilateral PD. There was significant heterogeneity between studies. There was a loss of around 32% in the clinically unaffected striatum, and the overall difference between sides was 8–9%.

FIG. 4

Striatal dopaminergic activity in early PD expressed as a percentage of mean values in matched controls. Striatal dopaminergic loss increased gradually, from 46.4% within 1 year of diagnosis, to 62.3% after more than 5 years. Data are mean and SD.

FIG. 5

Striatal dopaminergic activity in relation to severity grade, expressed as a percentage of mean values in matched controls. For striatum, losses increased from 43.2% at Grade 1% to 62.2% at Grade 3 and higher. Data are mean and SD.