Abstract
Objective: To explore the association between striatal dopaminergic deficits and cognitive impairment within a large cohort of early, drug-naive Parkinson’s disease patients and to test the hypothesis that executive dysfunction in Parkinson’s disease is caused by striatal dopaminergic depletion.
Background: Cognitive impairment in Parkinson’s disease is common and influences patients’ everyday functioning, but the mechanisms of early cognitive decline are not known. Understanding of these mechanisms is important for the development of methods preventing cognitive decline in Parkinson’s disease. Previous studies suggest that the dopaminergic system influences cognition in PD.
Methods: Neuropsychological and cerebral dopamine transporter SPECT imaging data of 339 Parkinson’s disease patients and 158 Healthy controls of the Parkinson’s Progression Markers Initiative study were analysed. Neuropsychological evaluation consisted of standardized tests of memory, visuospatial and executive function. SPECT imaging was performed with [123I]FP-CIT and specific binding ratios in left and right putamen and caudate nucleus were calculated. The association between specific binding ratios and cognition was performed using a cognitive composite z-score, domain z-scores and individual test scores. Multivariate general linear model regression analyses were performed including age, gender, education, and laterality as predictors and specific binding ratios as dependent variables.
Results: Uncorrected analysis showed no associations between dopamine transporter imaging and memory and visuospatial domains. A small but significant positive association between specific binding ratios and the attention/executive domain was found, which was not significant after adjusting for age. However, in a moderated mediation model, we found that cognitive executive differences between controls and patients with Parkinson’s disease were mediated by an age-moderated dopaminergic deficit in the left caudate nucleus.
Conclusions: Our findings support the hypothesis that nigrostriatal dopaminergic deficit contributes to executive impairment, but not to memory or visuospatial impairment in early Parkinson’s disease.
Background: Cognitive impairment in Parkinson’s disease is common and influences patients’ everyday functioning, but the mechanisms of early cognitive decline are not known. Understanding of these mechanisms is important for the development of methods preventing cognitive decline in Parkinson’s disease. Previous studies suggest that the dopaminergic system influences cognition in PD.
Methods: Neuropsychological and cerebral dopamine transporter SPECT imaging data of 339 Parkinson’s disease patients and 158 Healthy controls of the Parkinson’s Progression Markers Initiative study were analysed. Neuropsychological evaluation consisted of standardized tests of memory, visuospatial and executive function. SPECT imaging was performed with [123I]FP-CIT and specific binding ratios in left and right putamen and caudate nucleus were calculated. The association between specific binding ratios and cognition was performed using a cognitive composite z-score, domain z-scores and individual test scores. Multivariate general linear model regression analyses were performed including age, gender, education, and laterality as predictors and specific binding ratios as dependent variables.
Results: Uncorrected analysis showed no associations between dopamine transporter imaging and memory and visuospatial domains. A small but significant positive association between specific binding ratios and the attention/executive domain was found, which was not significant after adjusting for age. However, in a moderated mediation model, we found that cognitive executive differences between controls and patients with Parkinson’s disease were mediated by an age-moderated dopaminergic deficit in the left caudate nucleus.
Conclusions: Our findings support the hypothesis that nigrostriatal dopaminergic deficit contributes to executive impairment, but not to memory or visuospatial impairment in early Parkinson’s disease.
| Original language | English |
|---|---|
| Pages (from-to) | S363-S364 |
| Journal | Movement disorders |
| Volume | 29 |
| Issue number | S1 |
| DOIs | |
| Publication status | Published - May 2014 |
| Event | 18th International Congress of Parkinson's Disease and Movement Disorders 2014 - Stockholm, Sweden Duration: 8 Jun 2014 → 12 Jun 2014 Conference number: 18 |