Objective: To investigate the relationship between the sub-regional pattern of striatal dopamine depletion and cognitive impairment in early-stage Parkinson’s disease (PD), and determine the effect of striatal dopamine density on cognitive prognosis.

Background: Although the neurobiology underlying early cognitive changes in PD is still under investigation, dysregulation in neurotransmitter systems has long been described as an important contributor. In particular, the loss of dopamine, the main neurochemical disturbance in PD, occurs prior to changes in the other neurotransmitters, and executive dysfunction secondary to dopamine deficiency in fronto-striatal circuits is the earliest cognitive impairment in PD.

Methods: Patients with drug-naïve non-demented PD were divided into mild cognitive impairment (PD-MCI; n = 129) and cognitively normal (PD-CogN; n = 182) groups. Using quantification of the DAT availability in each striatal sub-region with 18F-FP-CIT PET scans, we performed inter-group comparative analysis of DAT availability and multivariate linear regression analysis to assess the association between DAT availability and cognitive performance. Additionally, the effect of baseline DAT availability on the cognitive decline across time as well as on changes in the cognitive status was estimated.

Results: The PD-MCI group exhibited more severely decreased DAT availability in all the striatal sub-regions compared to the PD-CogN group, although there was no significant difference in PD duration. The DAT availability in the caudate, anterior putamen, and ventral striatum was directly associated with attention/working memory, frontal/executive, and visuospatial functions, while the DAT availability of the posterior putamen was not. However, the baseline DAT availability of the striatal sub-regions did not influence the cognitive decline or cognitive status in the longitudinal cognitive assessment.

Conclusions: Our results suggest that striatal DAT availability may determine MCI in patients with de novo PD. Dopamine loss in the associative and limbic striatum is closely linked to cognitive deficits in early-stage PD, although it does not affect cognitive prognosis.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/effect-of-striatal-dopamine-depletion-on-cognition-in-de-novo-parkinsons-disease/