Cognitive dysfunction is common in untreated patients in early PD, affecting attention, psychomotor function, episodic memory, executive function and category fluency. Education level was an independent predictor of severe cognitive dysfunction.
Recent studies have reported cognitive decline to be common in the early phase of Parkinson's disease. Imaging data connect working memory and executive functioning to the dopamine system. It has also been suggested that bradykinesia is the clinical manifestation most closely related to the nigrostriatal lesion. Exploring the relationship between motor dysfunction and cognition can help us find shared or overlapping systems serving different functions. This relationship has been sparsely investigated in population-based studies of untreated Parkinson's disease. The aim of the present study was to investigate the association between motor signs and cognitive performance in the early stages of Parkinson's disease before the intake of dopaminergic medication. Patients were identified in a population-based study of incident cases with idiopathic parkinsonism. Patients with the postural instability and gait disturbances phenotype were compared with patients with the tremor-dominant phenotype on demographics and cognitive measures. Associations between cognitive and motor scores were investigated, with age, education, and sex controlled for. Bradykinesia was associated with working memory and mental flexibility, whereas axial signs were associated with episodic memory and visuospatial functioning. No significant differences in the neuropsychological variables were found between the postural instability and gait disturbances phenotype and the tremor phenotype. Our results indicate a shared system for slow movement and inflexible thinking that may be controlled by a dopaminergic network different from dopaminergic networks involved in tremor and/or rigidity. The association between axial signs and memory and visuospatial function may point to overlapping systems or pathologies related to these abilities.
The new PD-MCI guidelines are useful to detect patients at risk for developing PDD. The PIGD phenotype at diagnosis was not a predictor of PDD within 5 years, but the study supports a temporal association between postural/gait disturbances and PDD. Older patients with PD-MCI at baseline with decline in episodic memory, semantic fluency, and mental flexibility need to be carefully monitored regarding cognition and likely also for fall risk.
Using hybrid-blocked/event-related fMRI and the 2-back task we aimed to decompose tonic and phasic temporal dynamics of basal ganglia response abnormalities in working memory associated with early untreated Parkinson's disease. In view of the tonic/phasic dopamine hypothesis, which posits a functional division between phasic D(2)-dependent striatal updating processes and tonic D(1)-dependent prefrontal context-maintenance processes, we predicted that newly diagnosed, drug-naïve Parkinson's disease patients, with selective striatal dopamine deprivation, would demonstrate transient rather than sustained activation changes in the basal ganglia during 2-back performance. Task-related activation patterns within discrete basal ganglia structures were directly compared between patients and healthy elderly controls. The obtained results yielded uniquely transient underactivation foci in caudate nuclei, putamen and globus pallidus in Parkinson's disease patients, which indicates suboptimal phasic implementation of striatal D(2)-dependent gating mechanisms during updating. Sustained underactivation was only seen in the anterior putamen, which may reflect initial signs of tonic control impairment. No significant changes were exhibited in prefrontal cortex. The present findings resonate well with the tonic/phasic dopamine account and suggest that basal ganglia under-recruitment associated with executive dysfunction in early Parkinson's disease might predominantly stem from deficiencies in phasic executive components subserved by striatum.
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