Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Feb 17;10(4):539-546.
doi: 10.1002/mdc3.13687. eCollection 2023 Apr.

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

Nicholas Heng  1 , Naveed Malek  2 , Michael A Lawton  3 , Anahita Nodehi  3 , Vanessa Pitz  1 , Katherine A Grosset  1 , Yoav Ben-Shlomo  3 , Donald G Grosset  1
Affiliations
Review

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

Nicholas Heng et al. Mov Disord Clin Pract. .

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.

PubMed Disclaimer

Figures

FIG. 1
FIG. 1
PRISMA diagram of paper selection for the systematic review.
FIG. 2
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
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
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
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.
See this image and copyright information in PMC

References

    1. Bernheimer H, Birkmayer W, Hornykiewicz O, Jellinger K, Seitelberger F. Brain dopamine and the syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations. J Neurol Sci 1973;20(4):415–455. - PubMed
    1. Fearnley JM, Lees AJ. Ageing and Parkinson's disease: Substantia nigra regional selectivity. Brain 1991;114:2283–2301. - PubMed
    1. Riederer P, Wuketich S. Time course of nigrostriatal degeneration in Parkinson's disease. A detailed study of influential factors in human brain amine analysis. J Neural Transm 1976;38(3–4):277–301. - PubMed
    1. Cheng HC, Ulane CM, Burke RE. Clinical progression in Parkinson's disease and the neurobiology of axons. Ann Neurol 2010;67(6):715–725. - PMC - PubMed
    1. DerSimonian R, Kacker R. Random‐effects model for meta‐analysis of clinical trials: An update. Contemp Clin Trials 2007;28:105–114. 10.1016/j.cct.2006.04.004. - DOI - PubMed

LinkOut - more resources