Association of striatal dopaminergic neuronal integrity with cognitive dysfunction and cerebral cortical metabolism in Parkinson's disease with mild cognitive impairment.

Objective: Cognitive impairment is a common non-motor feature of Parkinson's disease (PD). However, the underlying pathophysiology of cognitive decline is unclear. We investigated the association of striatal dopamine transporter (DAT) loss with cognitive function and cerebral cortical metabolism in PD.

Methods: Twenty-eight patients (63.1 ± 7.1 yrs, M:F = 15:13) with advanced stage of PD were enrolled, including 15 (53.6%) diagnosed with mild cognitive impairment (MCI). All patients underwent FP-CIT PET/CT, neuropsychological tests, and FDG PET/CT within a 2-week interval. We calculated the specific to non-specific binding ratio on FP-CIT PET images in 12 striatal subregional VOIs, using one occipital VOI template as a reference. Age-adjusted normalized specific to non-specific binding ratios (%BRs) of striatal subregions were compared in two groups: PD with MCI versus PD (without cognitive impairment).

Results: There were no statistical differences in age, age at onset, disease duration, motor symptoms, or level of education between the two groups. The PD with MCI had lower %BRs in all striatal subregions (P < 0.05) except the posterior putamen, compared with the PD. Striatal DAT availability correlated with frontal/executive function (r = 0.567, P = 0.003) and visuospatial function (r = 0.614, P = 0.001) but not with memory function. Dopamine transporter binding of striatal subregions also correlated with posterior cortical metabolism.

Conclusions: This study suggest that DAT loss in the striatum, except in the posterior putamen, is associated with cognitive dysfunction, specifically frontal/executive function and visuospatial function in PD subjects.