Role of Dopamine and Metabolism in Parkinson’s Symptoms and Deficits

The following is a summary of “Association of Striatal Dopamine Depletion and Brain Metabolism Changes With Motor and Cognitive Deficits in Patients With Parkinson Disease,” published in the November 2024 issue of Neurology by Yoo et al.  

Parkinson’s disease (PD), characterized by degeneration of dopaminergic neurons in the substantia nigra, is associated with distinct changes in brain metabolism that impact motor and cognitive function.  

Researchers conducted a retrospective study examining the relationship between dopamine depletion, brain metabolism, and motor and cognitive challenges in individuals with PD.  

They enrolled individuals with PD (n = 143, mean age 69.0 ± 9.0 years; 69 women) who underwent N-(3-[₁₈F]fluoropropyl)-2β-carbomethoxy-3β-(4-iodophenyl) nortropane positron emission tomography (₁₈F-FP-CIT PET), ₁₈F-fluorodeoxyglucose positron emission tomography (₁₈F-FDG PET), the Movement Disorder Society–sponsored Unified PD Rating Scale and neuropsychological testing. Healthy individuals without PD (n = 38, mean age 67.3 ± 5.9 years; 19 women) also underwent PET scans. General linear models and mediation analyses were used to explore these relationships.  

The results showed that individuals living with PD exhibited relative brain hypermetabolism and hypometabolism that correlated with reduced striatal dopamine transporter availability. Increased dopamine loss in the putamen was associated with relative hypermetabolism in the paracentral lobule (standardized indirect effect, β = −0.070, P=0.025) and directly linked to higher bradykinesia subscores (β = −0.274, P=0.011). Dopamine loss in the caudate correlated with greater axial symptom severity (β = −0.125, P=0.004) and lower executive (β = 0.229, P=0.004), visuospatial (β = 0.139, P=0.006), and memory scores (β = 0.140, P=0.004). Tremor and language/attention scores showed no significant associations with dopamine levels or brain metabolism.  

They concluded that striatal dopamine depletion and spatially distinct changes in brain metabolism were closely related and differentially affect motor and cognitive challenges in individuals with PD.  

Source: neurology.org/doi/10.1212/WNL.0000000000210105

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