Objective: To investigate if a less prominent dopaminergic dysfunction on 123I-ioflupane SPECT imaging (DaTSCAN) despite a more severe motor phenotype in Late Onset Parkinson’s Disease (LOPD) than in Early-Onset PD (EOPD) reflects the failure of presynaptic compensatory mechanisms in LOPD subjects.

Background: There are convincing data showing differences regarding clinical, genetic, and drug response between Early Onset Parkinson’s Disease (EOPD) and Late-Onset PD (LOPD). Younger PD subjects may have more efficient compensatory mechanisms. Down-regulation of presynaptic dopamine reuptake system is reportedly a possible compensatory mechanism in surviving nigral neurons. However, molecular imaging studies comparing Dopamine Transporter (DAT) density between EOPD and LOPD found controversial results since ageing is related to a physiological decline of DAT.

Method: To test whether the level of denervation in the striatum is different between EOPD (55 years or less) and LOPD (more than 70 years), we compared 76 de novo PD patients matched for disease duration (within 24 months at scanning time) with 92 healthy controls (HC). In particular, we compared LOPD and EOPD pts with their age-matched HC and specific z-scores of putamen and caudate uptake in each PD subgroup was calculated. Our primary null hypothesis was that EOPD have a more pronounced DAT decrement than LOPD with respect to HC age-matched.

Results: As expected because of aging, LOPD had a greater dopaminergic dysfunction than EOPD. However by using z-scores, EOPD showed greater (p <0.0001) DAT reduction in the putamen with respect to LOPD. In contrast, the severity of motor impairment (UPDRS III) was greater in the LOPD subjects, although not significantly different between the two groups.

Conclusion: Our study show higher 123-FP-CIT putaminal binding in LOPD than in EOPD patients when compared to the mean of the age-matched HC suggesting that the compensatory mechanisms in the dopaminergic system might be less effective in LOPD. Interestingly, the failure of such adaptive changes could account, at least in part, for the greater severity of parkinsonian symptoms in LOPD, in contrast with higher DAT density in EOPD patients which in turn could be responsible for a greater risk of motor complications.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/age-related-failure-in-compensatory-mechanisms-and-its-relation-to-the-parkinson-phenotype-evidence-from-a-spect-study-in-early-and-late-onset-pd/