Striatal dopamine synthesis capacity in Parkinson's disease: Effects of age, sex, and body mass index in a large fluorodopa PET cohort

Abstract

BACKGROUNDIn Parkinsons disease (PD), the degeneration of nigrostriatal dopaminergic neurons leads to motor symptoms. Positron emission tomography (PET) using radioligand [18F]fluorodopa detects reduced striatal dopamine synthesis capacity in PD patients. Demographic factors such as sex and BMI are also associated with dopamine synthesis capacity. The combined contribution of demographic and clinical effects however remains elusive. It also remains unresolved how the dopamine synthesis capacity is correlated between striatal subregions and how the dopamine synthesis capacity and dopamine receptor function across striatal regions are associated with each other in PD patients and healthy controls. MATERIAL, AIMS, AND METHODSFor this retrospective register-based study, we used baseline [18F]fluorodopa PET data acquired at the Turku PET Centre between the years 1988-2016 with three different scanners (Ecat 931, GE Advance, HRRT). The data included scans of 350 adult human subjects, including 132 healthy controls (65 males and 67 females), and 218 PD patients (134 males and 84 females). The primary aim was to simultaneously investigate the effects of PD, age, sex and BMI on regional dopamine synthesis capacity (influx rate constant Kiref quantified with Patlak) using Bayesian linear regression. Secondary aims were to assess interregional correlations of dopamine synthesis capacity, and the association between regional presynaptic dopamine synthesis and postsynaptic dopamine type 2 receptor (D2R) availability in subjects who also had a proximal [11C]raclopride PET scan. RESULTSWe found modest support for age-dependent decline in dopamine synthesis capacity, increased capacity for higher BMIs, and for higher capacity in females versus males. These effects were smaller than the effect of PD status. Dopamine synthesis capacity across regions was correlated in both patients and controls. Support for positive correlation between the synthesis capacity and the D2R was observed in caudate nucleus. CONCLUSIONSPD and demographic effects are independently associated with the striatal dopamine synthesis capacity. The capacity is reduced by PD, decreased through age (particularly after the age of around 50), higher in females versus males, and weakly increased in higher BMIs. Synthesis capacity is correlated between the striatal and thalamic regions in both PD patients and controls. The dopamine synthesis capacity was positively correlated with the D2R availability in caudate. Scanner affects the estimates of dopamine synthesis capacity measured with [18F]fluorodopa PET, and it is preferrable to adjust for such variation in the data.