Direct correlation between cardiac and striatal F-18-DOPA uptake in de novo Parkinson's disease

Aim: Subtle cognitive impairment may be found in Parkinson’s disease (PD) already at the time of diagnosis. The pathogenesis of this impairment is still matter of debate and could be heterogeneous, including changes in several neurotransmitter systems. The present study aims to unveil cognitive‐dopaminergic correlations in PD by assessing cognitive and dopaminergic functions at the time of diagnosis and cognitive function 1 and 3 years later, during chronic dopaminergic treatment. We report here the preliminary data concerning the correlation between dopaminergic and cognitive functions at baseline. Methods: Fifteen consecutive, drug‐naïve, de novo PD patients (mean age 69.0±5.0) underwent an extended neuropsychological test battery and brain 18F‐FluoroDOPA (Fluoro‐DOPA) PET/CT as a biomarker of dopaminergic activity. Sixteen neuropsychological variables were grouped into 5 factors by means of factor analysis, i.e., executive (NPS‐EX), visuo‐constructive (NPS‐VS), verbal memory (NPS‐VM), verbal fluency (NPS‐VF) and abstract reasoning (NPS‐AB) factors. PET images were flipped in order to have the less affected hemisphere (LAH), defined clinically, on the same side. A fully MRI‐based normalization was applied and images were smoothed (8 mm Gaussian filter). Normalized scans were then submitted to multiple regression analysis in SPM8 for voxel‐wise evaluation of the correlation between cognitive factors and dopaminergic activity (age and education as nuisance). p<0.005 at peak level and p<0.05 False Discovery Rate corrected at cluster level were accepted as significant. Results: NPS‐AB showed correlation with Fluoro‐DOPA uptake in the striatum, insula and inferior frontal gyrus (BA47) of the LAH while NPS‐EX correlated with Fluoro‐DOPA uptake in the striatum and insula of the more affected hemisphere (MAH). NPS‐VF and NPS‐VS correlated with Fluoro‐DOPA in bilateral striatum and BA47, in the insula of the LAH, and (NPS‐VS only) in the temporal lobe of the LAH. No correlation was found for NPS‐VM. Conclusion: The consistent correlation of almost all neuropsychological factors (but verbal memory) with striatal Fluoro‐DOPA uptake confirms that even at the earliest stages the cognitive function is correlated with the biological severity of the disease. Moreover, these results point to the insula and the inferior frontal gyrus (BA47) as key nodes in the dopaminergic extrastriatal pathways involved in cognitive function in early PD.