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

Helen Schmitz-Steinkrüger,Catharina Lange,Ralph Buchert,Susanne Klutmann,Philipp T Meyer,Lars Frings,Sabine Hellwig,Ivayla Apostolova,Franziska L Mathies

doi:10.1007/s00259-020-05085-2

Abstract

PurposeThe 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.MethodsResearch 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.ResultsThe 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).ConclusionThese 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.

Highlights

Parkinson’s disease is characterized by the degeneration of pigmented cells in the substantia nigra pars compacta that results in loss of dopaminergic innervation of the striatum, of the putamen [1, 2]
This is the rationale for the use of SPECT with N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-123Iiodophenyl)nortropane (FP-CIT) to assess striatal dopamine transporter (DAT) availability as a marker of nigrostriatal degeneration to support the diagnostic workup of clinically uncertain parkinsonian syndromes (PS) [3,4,5,6]
The regression coefficients were negative for both age and sex, indicating age-related decline and higher specific binding ratio (SBR) in females compared to males in all samples

Summary

Introduction

Parkinson’s disease is characterized by the degeneration of pigmented cells in the substantia nigra pars compacta that results in loss of dopaminergic innervation of the striatum, of the putamen [1, 2]. This is the rationale for the use of SPECT with N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-123Iiodophenyl)nortropane (FP-CIT) to assess striatal dopamine transporter (DAT) availability as a marker of nigrostriatal degeneration to support the diagnostic workup of clinically uncertain parkinsonian syndromes (PS) [3,4,5,6]. FP-CIT SPECT studies in healthy volunteers quite consistently reported an age-related decline of the putamen SBR ranging between 2.5 and 9.6% per decade (Table 1), in good agreement with the post-mortem studies

Methods

Results

Discussion

Conclusion