ArticlesFunctional brain activity and presynaptic dopamine uptake in patients with Parkinson's disease and mild cognitive impairment: a cross-sectional study
Introduction
Parkinson's disease is characterised by motor symptoms, but cognitive deficits are also common.1, 2, 3 Several cognitive domains are affected,1, 2, 3, 4, 5 with deficits consistently reported for measures of executive function, episodic memory, and working memory that rely on frontostriatal brain circuits5, 6, 7, 8, 9, 10 and dopaminergic neurotransmission.5, 7 Correspondingly, findings from imaging studies have shown altered functional activity in the striatum in patients with Parkinson's disease compared with that in healthy individuals during task-set shifting,6 manipulation,7 and updating.8
Between 20% and 40% of patients with Parkinson's disease have mild cognitive impairment (MCI) in the early phase of the disease.4 MCI is defined as a cognitive deficit commonly quantified as a performance level 1–2 SDs below the population mean in one or more cognitive domains.11 Patients with Parkinson's disease and MCI have an increased risk of developing dementia compared with patients without MCI.1, 5, 9 Patients with Parkinson's disease and MCI might experience more pronounced alterations in the frontostriatal circuit than those without MCI, and phasic hypoactivity has been noted in the striatum and the prefrontal cortex of patients with Parkinson's disease with impairments in executive function compared with cognitively non-impaired patients.10 However, functional brain responses have not been studied in patients with Parkinson's disease and MCI. The cognitive dysfunctions associated with Parkinson's disease are gaining clinical importance because of the relative success of therapeutic approaches in the treatment of motor symptoms, but knowledge of the neuropathology underlying cognitive impairment remains insufficient.5 We therefore examined brain responses during a working memory task and presynaptic dopamine striatal integrity during the resting state in a population-based cohort of newly diagnosed drug-naive patients with Parkinson's disease with or without MCI. We hypothesised that frontostriatal under-recruitment occurs in patients with Parkinson's disease compared with healthy individuals and in patients with Parkinson's disease with MCI compared with those without MCI.
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Participants
Participants were recruited within the newly diagnosed parkinsonism in Umeå (NYPUM) project, which is a longitudinal population-based cohort study of incident patients with idiopathic parkinsonism, including Parkinson's disease.2 Between Jan 1, 2004, and April 30, 2009, all physicians in the Umeå catchment area (about 142 000 inhabitants) were asked to refer all patients with suspected parkinsonism to the Department of Neurology at Umeå University. All referred patients underwent a standardised
Results
77 patients with Parkinson's disease were included in the study, of whom 33 (43%) were diagnosed with MCI (figure 1). Within the Parkinson's disease and MCI group, 21 participants scored below the criteria (ie, ≥1·5 SDs below the normative age-matched test data) on at least one executive function measure. The corresponding numbers of participants for the other cognitive domains were as follows: attention or working memory, 25; episodic memory, 21; language, seven; and visuospatial function,
Discussion
The main finding of this study was the pronounced working-memory-related under-recruitment of the right dorsal caudate nucleus, the bilateral anterior cingulate cortex, and, more weakly, the right dorsolateral prefrontal cortex in patients with Parkinson's disease with MCI compared with those without MCI (panel). Furthermore, patients with Parkinson's disease and MCI had lower presynaptic 123I-FP-CIT binding in the right caudate than those without MCI, and binding correlated with caudate BOLD
References (31)
- et al.
Neuropsychological and clinical heterogeneity of cognitive impairment and dementia in patients with Parkinson's disease
Lancet Neurol
(2010) Dementia associated with Parkinson's disease
Lancet Neurol
(2003)- et al.
Interpreting scan data acquired from multiple scanners: a study with Alzheimer's disease
Neuroimage
(2008) - et al.
Automated anatomical labelling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain
Neuroimage
(2002) - et al.
Relationships between striatal dopamine denervation and frontal executive tests in Parkinson's disease
Neurosci Lett
(1999) - et al.
Common regions of the human frontal lobe recruited by diverse cognitive demands
Trends Neurosci
(2000) - et al.
Brain dopamine and the syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations
J Neurol Sci
(1973) - et al.
Evolution of cognitive dysfunction in an incident Parkinson's disease cohort
Brain
(2007) - et al.
Cognitive function in early Parkinson's disease: a population-based study
Eur J Neurol
(2009) - et al.
Cognitive profile of patients with newly diagnosed Parkinson disease
Neurology
(2005)