Association of Striatal Dopamine Depletion and Brain Metabolism Changes With Motor and Cognitive Deficits in Patients With Parkinson Disease.
Level 4 - case-series / case-control
Cross-sectional observational study with healthy controls
PubMed 39602663 · doi:10.1212/WNL.0000000000210105
What was done
In a single-center cross-sectional study, 143 patients with Parkinson disease (mean age 69.0 ± 9.0 years; 69 women) and 38 healthy controls (mean age 67.3 ± 5.9 years; 19 women) underwent 18F-FP-CIT PET (dopamine transporter availability), 18F-FDG PET (brain metabolism), MDS-UPDRS motor examination, and neuropsychological testing. General linear models and mediation analyses evaluated relationships between striatal dopamine availability, metabolic patterns, and motor subscores or cognitive domain scores.
What was found
Putaminal dopamine depletion correlated with relative hypermetabolism from paracentral lobule, pons, and limbic system to cerebellum and anterior cingulate, and hypometabolism from lateral temporal/frontal to occipital/inferior parietal cortices. Paracentral lobule hypermetabolism mediated the relationship between putaminal dopamine loss and higher rigidity subscores (standardized indirect effect β = -0.070, p = 0.025); putaminal dopamine loss directly associated with higher bradykinesia subscores (β = -0.274, p = 0.011). Caudate dopamine loss associated with higher axial subscores (β = -0.125, p = 0.004) and lower executive (β = 0.229, p = 0.004), visuospatial (β = 0.139, p = 0.006), and memory (β = 0.140, p = 0.004) domain scores via hypometabolism mediation. Tremor, language, and attention scores showed no significant associations.
Why it matters
This study maps specific regional metabolic alterations that bridge striatal dopamine depletion to distinct motor signs and multi-domain cognitive impairments in Parkinson disease.
Limits
The study is cross-sectional and single-center, precluding causal or longitudinal conclusions. Control sample size was modest (n = 38), and the abstract does not report medication status or disease duration.
Cited by
- supports Parkinson's disease motor symptoms are caused by the depletion of dopamine in the substantia nigra.