Striatal and extrastriatal dysfunction in Parkinson’s disease with dementia: a 6‐[18F]fluoro‐l‐dopa PET study

Ito, Kengo; Nagano‐Saito, Atsuko; Kato, Takashi; Arahata, Yutaka; Nakamura, Akinori; Kawasumi, Yasuhiro; Hatano, Kentaro; Abe, Yuji; Yamada, Takako; Kachi, Teruhiko; Brooks, David J.

doi:10.1093/brain/awf134

Cited by 152 publications

(98 citation statements)

References 35 publications

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“…When PD patients with and without dementia were matched for age, disease duration, and disease severity, interrogation of their 18 F-dopa uptake images with statistical parametric mapping localized a reduced capacity for putamen dopamine storage in both groups. However, compared with the PD patients, the PDD patients showed additional reductions in 18 F-dopa uptake in the right caudate and bilaterally in the ventral striatum and the anterior cingulate (102). These findings support the concept that dementia in PD is associated with impaired frontal and caudate dopaminergic function.…”

Section: Dopaminergic Imagingsupporting

confidence: 68%

Imaging Approaches to Parkinson Disease

Brooks¹

2010

J Nucl Med

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192

109

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Parkinson disease (PD) is associated with nigral degeneration and striatal dopamine deficiency. Demonstrating midbrain structural abnormalities with transcranial sonography or diffusionweighted MRI or showing striatal dopamine terminal dysfunction with PET or SPECT supports the diagnosis and rationalizes the use of dopaminergic medications. In atypical PD variants, transcranial sonography can detect striatal hyperechogenicity, and diffusion-weighted imaging can detect increased putamen water diffusion, whereas 18 F-FDG PET reveals reduced lentiform nucleus glucose metabolism. PET and SPECT can detect changes in striatal dopamine levels after levodopa administration and relate these to motor responses. Loss of cortical dopaminergic and cholinergic function is present in demented PD and, on occasion, amyloid deposits can be detected. Loss of cardiac sympathetic innervation can be sensitively detected in PD with 18 F-dopamine PET or 123 I-metaiodobenzylguanidine SPECT. Finally, PET can detect widespread brain inflammation in PD. This review discusses the role of structural and functional imaging for diagnosing and managing different parkinsonian syndromes.

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Section: Dopaminergic Imagingsupporting

confidence: 68%

Imaging Approaches to Parkinson Disease

Brooks¹

2010

J Nucl Med

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192

109

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“…Our post mortem results generally support that conclusion. Ito and colleagues [47] reported that patients with PD and dementia had lower 18-fluoro-DOPA uptake in the ventral striatum and right caudate nucleus as compared to patients with PD only. Interestingly, we also have detected a more pronounced loss of TH in the ventral striatum in PDD group, although the difference was very small.…”

Section: Upregulation Of Arrestin and Grk Expression In Parkinson's Dmentioning

confidence: 99%

Arrestins and two receptor kinases are upregulated in Parkinson's disease with dementia

Bychkov

Joyce

et al. 2008

Neurobiology of Aging

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Arrestins and G proteins-coupled receptor kinases (GRKs) regulate signaling and trafficking of G protein-coupled receptors. We investigated changes in the expression of arrestins and GRKs in the striatum of patients with Parkinson's disease without (PD) or with dementia (PDD) at post mortem using Western blotting and ribonuclease protection assay. Both PD and PDD groups had similar degree of dopamine depletion in all striatal regions. Arrestin proteins and mRNAs were increased in the PDD group throughout striatum. Protein and mRNA of GRK5, the major subtype in the human striatum, and GRK3 were also upregulated, whereas GRK2 and 6 were mostly unchanged. The PD group had lower concentration of arrestins and GRKs than the PDD group. There was no statistical link between the load of Alzheimer's pathology and the expression of these signaling proteins. Upregulation of arrestins and GRK in PDD may confer resistance to the therapeutic effects of levodopa often observed in these patients. In addition, increased arrestin and GRK concentrations may lead to dementia via perturbation of multiple signaling mechanisms.

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“…When PD-MCI group was directly compared with HC and PD-NC using a post-hoc test, decreased activation of ACC and SPL was demonstrated in the PD-MCI group. The abnormal engagement of ACC in PD-MCI and PD-dementia has been related to reduced dopaminergic function (Ito et al, 2002) and higher Lewy body densities (Kövari et al, 2003) and has been held responsible for poor performance of frontal executive tasks (Fera et al, 2007;Rosenberg-Katz et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

[P3–382]: NEURAL EVIDENCE FOR DEFECTIVE TOP‐DOWN CONTROL OF VISUAL PROCESSING IN PARKINSON's AND ALZHEIMER's DISEASE

Rektorová

Elfmarková

Gajdoš

et al. 2017

Alzheimer's & Dementia

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Introduction:We used a functional MRI paradigm involving conventional vs. unconventional views of objects to assess bottom-up vs. top-down visual processing in Parkinson's disease (PD) with normal cognition, PD with mild cognitive impairment (MCI), and MCI due to Alzheimer's disease (AD) as compared to healthy controls. We particularly aimed at determining whether the task discriminated between PD with and without MCI and between two MCI groups due to distinct pathologies (AD and PD). Methods: 116 right-handed subjects (21 MCI due to AD; 16 PD with normal cognition; 24 PD with MCI; 55 healthy controls) performed a visual object-matching task in a T MR scanner. T statistic maps were computed to contrast task-based activation during unconventional vs. conventional view conditions. One-way ANOVAs and post hoc tests were performed to assess differences across and between groups. Results: Both MCI groups performed worse than controls in the unconventional views condition and showed reduced activation of right anterior cingulate cortex and right superior parietal lobule (PD with MCI), and right middle and inferior frontal gyri (MCI due to AD). Neural responses in cortical areas within the ventral and dorsal visual pathway appeared to be preserved in both MCI groups. Receiver operating characteristic analysis of MRI contrast in the right superior parietal lobule distinguished PD with and without MCI with 87.50% sensitivity and 86.98% specificity. Conclusions: Impaired recognition of objects presented in unconventional orientations in MCI due to PD and AD was associated with decreased activation of frontoparietal regions, consistent with defective top-down regulation of visual processing. Aberrant activation of superior parietal cortex may serve as an early imaging biomarker of impending cognitive impairment in PD.

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Striatal and extrastriatal dysfunction in Parkinson’s disease with dementia: a 6‐[18F]fluoro‐l‐dopa PET study

Cited by 152 publications

References 35 publications

Imaging Approaches to Parkinson Disease

Imaging Approaches to Parkinson Disease

Arrestins and two receptor kinases are upregulated in Parkinson's disease with dementia

[P3–382]: NEURAL EVIDENCE FOR DEFECTIVE TOP‐DOWN CONTROL OF VISUAL PROCESSING IN PARKINSON's AND ALZHEIMER's DISEASE

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