Functional brain activity and presynaptic dopamine uptake in patients with Parkinson's disease and mild cognitive impairment: a cross-sectional study

Ekman, Urban; Eriksson, Johan; Forsgren, Lars; Mo, Susanna Jakobson; Riklund, Katrine; Nyberg, Lars

doi:10.1016/s1474-4422(12)70138-2

Cited by 141 publications

(130 citation statements)

References 29 publications

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“…When paired with performance, however, increased activity appears to be associated with preserved task performance [Gerrits et al, 2015; Trujillo et al, 2015], while decreased activity is present when task performance is already significantly impaired [Ekman et al, 2012; Lewis et al, 2003]. This suggests that hyperactivation is a compensatory mechanism associated with intact behavioural performance, which was not present in our sample of PD patients, even at baseline.…”

Section: Discussionmentioning

confidence: 67%

“…In tasks of visuospatial working memory [Trujillo et al, 2015] and set‐shifting [Gerrits et al, 2015], for example, PD patients perform the tasks with similar accuracy to that of healthy controls, but show hyperactivation of task‐related regions relative to controls . Conversely, behavioural deficits are apparent during verbal working memory tasks that were accompanied by decreased task‐related activity [Ekman et al, 2012; Lewis et al, 2003]. These results suggest that in early PD, impaired performance is accompanied by decreased task‐related activity, whereas intact behavioural performance is associated with compensatory increased activity.…”

Section: Introductionmentioning

confidence: 99%

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Impaired planning in Parkinson's disease is reflected by reduced brain activation and connectivity

Trujillo

Gerrits

Vriend

et al. 2015

Human Brain Mapping

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ObjectiveParkinson's disease (PD) often entails impairments of executive functions, such as planning. Although widely held that these impairments arise from dopaminergic denervation of the striatum, not all executive functions are affected early on, and the underlying neural dynamics are not fully understood. In a combined longitudinal and cross‐sectional study, we investigated how planning deficits progress over time in the early stages of PD compared to matched healthy controls. We used functional magnetic resonance imaging (fMRI) to identify accompanying neural dynamics.MethodsSeventeen PD patients and 20 healthy controls performed a parametric Tower of London task at two time points separated by ∼3 years (baseline and follow‐up). We assessed task performance longitudinally in both groups; at follow‐up, a subset of participants (14 patients, 19 controls) performed a parallel version of the task during fMRI. We performed meta‐analyses to localize regions‐of‐interest (ROIs), that is, the bilateral dorsolateral prefrontal cortex (DLPFC), inferior parietal cortex, and caudate nucleus, and performed group‐by‐task analyses and within‐group regression analyses of planning‐related neural activation. We studied task‐related functional connectivity of seeds in the DLPFC and caudate nucleus.ResultsPD patients, compared with controls, showed impaired task performance at both time‐points, while both groups showed similar performance reductions from baseline to follow‐up. Compared to controls, patients showed lower planning‐related brain activation together with decreased functional connectivity.ConclusionThese findings support the notion that planning is affected early in the PD disease course, and that this impairment in planning is accompanied by decreases in both task‐related brain activity and connectivity. Hum Brain Mapp 36:3703–3715, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 67%

Section: Introductionmentioning

confidence: 99%

Impaired planning in Parkinson's disease is reflected by reduced brain activation and connectivity

Trujillo

Gerrits

Vriend

et al. 2015

Human Brain Mapping

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“…Dysfunctional dopamine neurotransmission may, at least in part, account for workingmemory deficits in aging (Karlsson et al 2009;Fischer et al 2010;Nyberg et al 2014;see Bäck-man et al 2010) and in Parkinson's disease (Marklund et al 2009;Ekman et al 2012). Dopamine has also been implicated as a source of working-memory difficulties in schizophrenia (Cohen and Servan-Schreiber 1992;GoldmanRakic 1999;Castner et al 2000;Abi-Dargham et al 2002), attention-deficit/hyperactivity disorder (Castellanos and Tannock 2002;Martinussen et al 2005;Sagvolden et al 2005), and other psychiatric and neurological conditions (see Maia and Frank 2011).…”

Section: Working Memory In Actionmentioning

confidence: 99%

Working Memory: Maintenance, Updating, and the Realization of Intentions

Nyberg

Eriksson

2015

Cold Spring Harb Perspect Biol

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Correspondence: lars.nyberg@umu.se "Working memory" refers to a vast set of mnemonic processes and associated brain networks, relates to basic intellectual abilities, and underlies many real-world functions. Workingmemory maintenance involves frontoparietal regions and distributed representational areas, and can be based on persistent activity in reentrant loops, synchronous oscillations, or changes in synaptic strength. Manipulation of content of working memory depends on the dorsofrontal cortex, and updating is realized by a frontostriatal '"gating" function. Goals and intentions are represented as cognitive and motivational contexts in the rostrofrontal cortex. Different working-memory networks are linked via associative reinforcement-learning mechanisms into a self-organizing system. Normal capacity variation, as well as workingmemory deficits, can largely be accounted for by the effectiveness and integrity of the basal ganglia and dopaminergic neurotransmission.

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“…Patients with early PD underrecruit an extensive frontostriatal brain network as a consequence of dopaminergic hypofunction,23 contributing to cognitive impairments. In later disease phases, accumulating cortical Lewy bodies, Alzheimer disease‐type brain pathology and hypofunction in non‐dopaminergic (ie, acetylcholinergic) transmitter systems contribute to PD dementia (PDD) 24.…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms in dopamine-associated genes and cognitive decline in Parkinson's disease

et al. 2017

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ObjectivesCognitive decline is common in Parkinson's disease (PD), but the underlying mechanisms for this complication are incompletely understood. Genotypes affecting dopamine transmission may be of importance. This study investigates whether genotypes associated with reduced prefrontal dopaminergic tone and/or reduced dopamine D2‐receptor availability (Catechol‐O‐methyltransferase [COMT] Val158Met genotype and DRD2 C957T genotype) affect the development of cognitive deficits in PD.Materials and methodsOne hundred and 34 patients with idiopathic PD, participating in a regional, population‐based study of incident parkinsonism, underwent genotyping. After extensive baseline investigations (including imaging and biomarker analyses), the patients were followed prospectively during 6‐10 years with neuropsychological evaluations, covering six cognitive domains. Cognitive decline (defined as the incidence of either Parkinson's disease mild cognitive impairment [PD‐MCI] or dementia [PDD], diagnosed according to published criteria and blinded to genotype) was studied as the primary outcome.ResultsBoth genotypes affected cognition, as shown by Cox proportional hazards models. While the COMT 158Val/Val genotype conferred an increased risk of mild cognitive impairment in patients with normal cognition at baseline (hazard ratio: 2.13, P = .023), the DRD2 957T/T genotype conferred an overall increased risk of PD dementia (hazard ratio: 3.22, P < .001). The poorer cognitive performance in DRD2 957T/T carriers with PD occurred mainly in episodic memory and attention.ConclusionsThe results favor the hypothesis that dopamine deficiency in PD not only relate to mild cognitive deficits in frontostriatal functions, but also to a decline in memory and attention. This could indicate that dopamine deficiency impairs a wide network of brain areas.

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Functional brain activity and presynaptic dopamine uptake in patients with Parkinson's disease and mild cognitive impairment: a cross-sectional study

Cited by 141 publications

References 29 publications

Impaired planning in Parkinson's disease is reflected by reduced brain activation and connectivity

Impaired planning in Parkinson's disease is reflected by reduced brain activation and connectivity

Working Memory: Maintenance, Updating, and the Realization of Intentions

Polymorphisms in dopamine-associated genes and cognitive decline in Parkinson's disease

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