Salience network and parahippocampal dopamine dysfunction in memory‐impaired Parkinson disease

Christopher, Leigh; Duff‐Canning, Sarah; Koshimori, Yuko; Segura, Bàrbara; Boileau, Isabelle; Chen, Robert; Lang, Anthony E.; Houle, Sylvain; Rusjan, Pablo; Strafella, Antonio P.

doi:10.1002/ana.24323

Cited by 99 publications

(102 citation statements)

References 70 publications

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“…Although the decline of ALFFs was more significant in the R-putamen, the selective lateral effect must be regarded cautiously due to the small sample size. However, previous studies did report neural disruptions can be more pronounced on the right side in AD-associated neurodegeneration [35, 36]. Further study is needed to clarify laterality issues.…”

Section: Discussionmentioning

confidence: 86%

Longitudinal Alteration of Intrinsic Brain Activity in the Striatum in Mild Cognitive Impairment

Ren

Chapman

et al. 2016

JAD

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The striatum is a critical functional hub in understanding neurological disorders. However, the Alzheimer’s disease (AD)-associated striatal change is unclear, nor the relationship between striatal change and AD pathology. Three-year resting-state fMRI data from 15 healthy control (HC) and 20 mild cognitive impairment (MCI) participants were obtained. We analyzed the amplitude of low-frequency fluctuations (ALFF) (0.01–0.08 Hz) and two subdivided bands (slow-4: 0.027–0.073 Hz; slow-5: 0.01–0.027 Hz). We calculated Aβ/pTau ratio using baseline cerebrospinal fluid pTau and beta-amyloid1–42 to represent AD pathology. Compared to HC, MCI participants showed greater decline in right putaminal ALFF, including the slow-4 band. Greater decline of ALFF in the right putamen was significantly related to the memory decline over time and lower baseline Aβ/pTau ratio regardless of age or group. The slow-4 band, relative to slow-5 band, showed a stronger correlation between Aβ/pTau ratio and decline of ALFF in the right putamen. The results suggest that the putaminal function declines early in the AD-associated neurodegeneration. The continuous decline in putaminal ALFF, especially slow-4 band, may be a sensitive marker of AD pathology such as Aβ/pTau ratio regardless of clinical diagnosis.

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Section: Discussionmentioning

confidence: 86%

Longitudinal Alteration of Intrinsic Brain Activity in the Striatum in Mild Cognitive Impairment

Ren

Chapman

et al. 2016

JAD

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“…Graph theoretical analyses have revealed a decreased hub role in the left dorsal anterior insula in PD patients compared to healthy controls (HCs) (Tinaz et al, 2016). Furthermore, recent data from our group have demonstrated that D2 receptor availability in the anterior insula was associated with executive and memory dysfunction in PD patients with mild cognitive impairment (Christopher et al, 2014b, 2015). Thus, the anterior insula, in particular, seems to be a critical “hub” for cognitive impairment in Parkinsonian patients (Christopher et al, 2014a; Criaud et al, 2016).…”

Section: Introductionmentioning

confidence: 91%

Disrupted Nodal and Hub Organization Account for Brain Network Abnormalities in Parkinson’s Disease

Koshimori

Cho

Criaud

et al. 2016

Front. Aging Neurosci.

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The recent application of graph theory to brain networks promises to shed light on complex diseases such as Parkinson’s disease (PD). This study aimed to investigate functional changes in sensorimotor and cognitive networks in Parkinsonian patients, with a focus on inter- and intra-connectivity organization in the disease-associated nodal and hub regions using the graph theoretical analyses. Resting-state functional MRI data of a total of 65 participants, including 23 healthy controls (HCs) and 42 patients, were investigated in 120 nodes for local efficiency, betweenness centrality, and degree. Hub regions were identified in the HC and patient groups. We found nodal and hub changes in patients compared with HCs, including the right pre-supplementary motor area (SMA), left anterior insula, bilateral mid-insula, bilateral dorsolateral prefrontal cortex (DLPFC), and right caudate nucleus. In general, nodal regions within the sensorimotor network (i.e., right pre-SMA and right mid-insula) displayed weakened connectivity, with the former node associated with more severe bradykinesia, and impaired integration with default mode network regions. The left mid-insula also lost its hub properties in patients. Within the executive networks, the left anterior insular cortex lost its hub properties in patients, while a new hub region was identified in the right caudate nucleus, paralleled by an increased level of inter- and intra-connectivity in the bilateral DLPFC possibly representing compensatory mechanisms. These findings highlight the diffuse changes in nodal organization and regional hub disruption accounting for the distributed abnormalities across brain networks and the clinical manifestations of PD.

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“…Specifically, the DRD2 system is linked to transient memory updating processes 31, 32. A reduction in D2 receptors has been found in PD13 and in imaging studies, memory deficits in PD are correlated with reduced extrastriatal D2 receptor binding in the medial temporal lobe, including the insula, in parts of the so‐called salience network 14. The present findings of poorer performances in attention and episodic memory and an increased risk of dementia in DRD2 957 T/T carriers with PD could, potentially, relate to reduced function or increased vulnerability in D2‐dependent “salience networks” of the brain (eg, in medial, temporal structures).…”

Section: Discussionmentioning

confidence: 99%

“…The 957 C/C genotype correlates with higher D2 receptor densities in extrastriatal, thalamic and neocortical areas,11 and better episodic memory in healthy elders 12. Hypofunction of extrastriatal dopamine receptor D2 subsystems, including in the insula, was recently found to contribute to cognitive decline in PD 13, 14…”

Section: Introductionmentioning

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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Salience network and parahippocampal dopamine dysfunction in memory‐impaired Parkinson disease

Abstract: Dopaminergic differences in the salience network and the medial temporal lobe contribute to memory impairment in PD. Furthermore, these findings indicate the vulnerability of the salience network in PD and its potential role in memory and executive dysfunction.

Cited by 99 publications

References 70 publications

Longitudinal Alteration of Intrinsic Brain Activity in the Striatum in Mild Cognitive Impairment

Longitudinal Alteration of Intrinsic Brain Activity in the Striatum in Mild Cognitive Impairment

Disrupted Nodal and Hub Organization Account for Brain Network Abnormalities in Parkinson’s Disease

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

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