Cognitive performance correlates with the degree of dopaminergic degeneration in the associative part of the striatum in non-demented Parkinson’s patients

Abstract

Parkinson's disease (PD) patients show cognitive deficits that are relevant in terms of prognosis and quality of life. Degeneration of striatal dopaminergic afferents proceeds from dorsal/caudal to anterior/ventral and is discussed to account for some of these symptoms. Treatment with dopamine (DA) has differential effects on cognitive dysfunctions, improving some and worsening others. We hypothesized that cognitive performance during the dopaminergic OFF state correlates with DAT availability in the associative striatum. 16 PD patients underwent motor and cognitive examination ON and OFF DA. Global cognition was measured using the Montréal Cognitive Assessment (MoCA) test and executive functioning using a Stroop test. Nigrostriatal dopaminergic innervation was characterized with [I]FP-CIT SPECT. A connectivity atlas of the striatum was used to assess DAT availability in functionally defined striatal subregions. Correlations between imaging data and behavioral data OFF medication were calculated. Correlations between DAT availability and MoCA performance in the dopaminergic OFF state was strongest in the associative part of the striatum (r = 0.674, p = 0.004). MoCA test performance did not differ between the ON and the OFF state. There was no correlation of DAT availability with Stroop performance in the OFF state but performance was significantly better during the ON state. Not only motor but also cognitive dysfunctions in PD are associated with striatal dopaminergic depletion. Cognitive decline in non-demented PD patients goes along with nigrostriatal degeneration, most pronounced in the associative subdivision of the striatum. In addition, the present findings suggest that executive dysfunctions are ameliorated by DA whereas global cognition is not improved by dopaminergic medication.

Association of Motor and Cognitive Symptoms with Health-Related Quality of Life and Caregiver Burden in a German Cohort of Advanced Parkinson’s Disease Patients

“…Executive and attentional functional deficits are well described in PD patients [33][34][35][36][37]. Nevertheless, a recent study reports that executive dysfunction might be ameliorated by dopamine, whereas global cognitive deficits were not improved [38]. Since we examined all patients in the on state, executive function might be even underestimated in our cohort.…”

Reliability of dopamine transporter PET measurements with [18F]FE-PE2I in patients with Parkinson’s disease

“…Instead, subdivision based on the connectivity between the basal ganglia and the neocortex can be used, where the striatum is divided into a limbic, associative, and sensorimotor striatum (respectively ventral striatum, caudate and ventrolateral putamen, and dorsolateral putamen) [14]. The functional regions have shown to be useful for molecular imaging studies examining correlations with behavioral and clinical outcome measures [15][16][17].…”

Striatal dopamine transporters and cognitive function in Parkinson’s disease

“…On the other hand, dopaminergic medication improves certain cognitive functions—verbal fluency, working memory, visuospatial function and executive function—in PD patients 12‐16 . FP‐CIT studies showed a correlation between striatal FP‐CIT uptake and cognitive function—primarily executive and visuospatial function—in PD patients 17‐22 …”

“…Striatal FP‐CIT binding correlated with attention/working memory, executive and visuospatial function in de novo PD patients with and without MCI 20 . Global cognitive function correlated with striatal FP‐CIT binding in non‐demented PD patients 21 . Striatal FP‐CIT binding also correlated with frontal, executive and visuospatial function in patients with advanced PD and MCI 22 .…”