Impact of age and sex correction on the diagnostic performance of dopamine transporter SPECT

Abstract

Purpose The specific binding ratio (SBR) of 123I-FP-CIT (FP-CIT) in the putamen decreases with age by about 5% per decade and most likely is about 10% higher in females. However, the clinical utility of age and sex correction of the SBR is still a matter of debate. This study tested the impact of age and sex correction on the diagnostic performance of the putamen SBR in three independent patient samples. Methods Research sample: 207 healthy controls (HC) and 438 Parkinson’s disease (PD) patients. Clinical sample A: 183 patients with neurodegenerative parkinsonian syndrome (PS) and 183 patients with non-neurodegenerative PS from one site. Clinical sample B: 84 patients with neurodegenerative PS and 38 patients with non-neurodegenerative PS from another site. Correction for age and sex of the putamen SBR was based on linear regression in the HC or non-neurodegenerative PS, separately in each sample. The area under the ROC curve (AUC) was used as performance measure. Results The putamen SBR was higher in females compared to males (PPMI: 14%, p < 0.0005; clinical sample A: 7%, p < 0.0005; clinical sample B: 6%, p = 0.361). Age-related decline of the putamen SBR ranged between 3.3 and 10.4% (p ≤ 0.019). In subjects ≥ 50 years, age and sex explained < 10% of SBR between-subjects variance. Correction of the putamen SBR for age and sex resulted in slightly decreased AUC in the PPMI sample (0.9955 versus 0.9969, p = 0.025) and in clinical sample A (0.9448 versus 0.9519, p = 0.057). There was a small, non-significant AUC increase in clinical sample B (0.9828 versus 0.9743, p = 0.232). Conclusion These findings do not support age and sex correction of the putaminal FP-CIT SBR in the diagnostic workup of parkinsonian syndromes. This most likely is explained by the fact that the proportion of between-subjects variance caused by age and sex is considerably below the symptom threshold of about 50% reduction in neurodegenerative PS.

Decreased thalamic monoamine availability in drug-induced parkinsonism

“…Second, we could not match the sex ratio among groups. A recent study conducted age and sex correlation of dopamine transporter imaging, which showed putaminal dopamine availability was about 10% higher in female than male 18 . However, sex effect was weaker than age effect, and sex effect was most prominent at young age 18 .…”

“…A recent study conducted age and sex correlation of dopamine transporter imaging, which showed putaminal dopamine availability was about 10% higher in female than male 18 . However, sex effect was weaker than age effect, and sex effect was most prominent at young age 18 . In this study of subjects, most subjects were aged over 60 years old, and therefore we can suppose sex effect of striatal monoamine availability might be minimized.…”

Molecular Imaging in Parkinsonian Disorders—What’s New and Hot?

“…Decision algorithm and practical issues have been previously reviewed [ 1 , 3 , 59 , 60 ]. Importantly, recent technical advances improved the reliability of semi-quantitative analysis of striatal binding, thanks to the better atlas-based delineation of the striatum and normative databases for age standardization [ 61 , 62 ].…”

The human dopaminergic system: cerebral SPECT

“…4 These transporters influence the neural signals the striatum receives. [4][5] Disturbances that affect these transporters may cause Parkinson's disease, a condition intimately linked with the dopaminergic system. [6][7][8][9] It is believed that in Parkinson's disease, more than 70% of the dopamine-producing neurons have died.…”

“…[10][11] Dopamine transporters can be used as a biomarker for evaluating striatal neuronal function. 5,7 When 99mTc is labeled on the tropane analog TRODAT-1, 99mTc-TRODAT-1 is formed. 8 99mTc-labeled Trodat scintigraphy is an exam that the tracer selectively binds to presynaptic dopamine receptors in the substantia nigra of the midbrain.…”