Dataset Information

Multimodal Evaluation of Neurovascular Functionality in Early Parkinson's Disease.

ABSTRACT: Parkinson's disease (PD) is a multisystem neurological condition affecting different neurotransmitter pathways characterized by aberrant functional connectivity (FC) and perfusion alteration. Since the FC, measuring neuronal activity, and cerebral blood flow (CBF) are closely related through the neurovascular coupling (NVC) mechanism, we aim to assess whether FC changes found in PD mirror perfusion ones. A multimodal MRI study was implemented by acquiring resting state functional MRI (rsfMRI) and arterial spin labeling (ASL) datasets on a group of 26 early PD (66.8 ± 8 years, 22 males, median [interquartile range] Hoehn and Yahr = 1.5 [1]) and 18 age- and sex-matched healthy controls (HCs). In addition, a T1-weighted MPRAGE was also acquired in the same scan session. After a standard preprocessing, resting state networks (RSNs) and CBF maps were extracted from rsfMRI and ASL dataset, respectively. Then, by means of a dual regression algorithm performed on RSNs, a cluster of FC differences between groups was obtained and used to mask CBF maps in the subsequent voxel-wise group comparison. Furthermore, a gray matter (GM) volumetric assessment was performed within the FC cluster in order to exclude tissue atrophy as a source of functional changes. Reduced FC for a PD patient with respect to HC group was found within a sensory-motor network (SMN, pFWE = 0.01) and visual networks (VNs, primary pFWE = 0.022 and lateral pFWE = 0.01). The latter was accompanied by a decreased CBF (primary pFWE = 0.037, lateral pFWE = 0.014 VNs), while no GM atrophy was detected instead. The FC alteration found in the SMN of PD might be likely due to a dopaminergic denervation of the striatal pathways causing a functional disconnection. On the other hand, the changes in connectivity depicted in VNs might be related to an altered non-dopaminergic system, since perfusion was also reduced, revealing a compromised NVC. Finally, the absence of GM volume loss might imply that functional changes may potentially anticipate neurodegeneration. In this framework, FC and CBF might be proposed as early functional biomarkers providing meaningful insights in evaluating both disease progression and therapeutic/rehabilitation treatment outcome.

SUBMITTER: Lagana MM

PROVIDER: S-EPMC7479303 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Multimodal Evaluation of Neurovascular Functionality in Early Parkinson's Disease.

Laganà Maria Marcella MM Pirastru Alice A Pelizzari Laura L Rossetto Federica F Di Tella Sonia S Bergsland Niels N Nemni Raffaello R Meloni Mario M Baglio Francesca F

Frontiers in neurology 20200826

Parkinson's disease (PD) is a multisystem neurological condition affecting different neurotransmitter pathways characterized by aberrant functional connectivity (FC) and perfusion alteration. Since the FC, measuring neuronal activity, and cerebral blood flow (CBF) are closely related through the neurovascular coupling (NVC) mechanism, we aim to assess whether FC changes found in PD mirror perfusion ones. A multimodal MRI study was implemented by acquiring resting state functional MRI (rsfMRI) an ...[more]

PMID: 32982906

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Project description:Background: Cognitive deficits are prominent non-motor symptoms in Parkinson's disease (PD) and have been shown to involve the neurovascular unit (NVU). However, there is a lack of sufficient neuroimaging research on the associated modulating mechanisms. The objective of this study was to identify the contribution of neurovascular decoupling to the pathogenesis of cognitive decline in PD. Methods: Regional homogeneity (ReHo), a measure of neuronal activity, and cerebral blood flow (CBF), a measure of vascular responses, were obtained from patients with PD with mild cognitive impairment (MCI) and normal cognition (NC) as well as matched healthy controls (HCs). Imaging metrics of neurovascular coupling (global and regional CBF-ReHo correlation coefficients and CBF-ReHo ratios) were compared among the groups. Results: Neurovascular coupling was impaired in patients with PD-MCI with a decreased global CBF-ReHo correlation coefficient relative to HC subjects (P < 0.05). Regional dysregulation was specific to the PD-MCI group and localized to the right middle frontal gyrus, right middle cingulate cortex, right middle occipital gyrus, right inferior parietal gyrus, right supramarginal gyrus, and right angular gyrus (P < 0.05). Compared with HC subjects, patients with PD-MCI showed higher CBF-ReHo ratios in the bilateral lingual gyri (LG), bilateral putamen, and left postcentral gyrus and lower CBF-ReHo ratios in the right superior temporal gyrus, bilateral middle temporal gyri, bilateral parahippocampal gyri, and right inferior frontal gyrus. Relative to the HC and PD-NC groups, the PD-MCI group showed an increased CBF-ReHo ratio in the left LG, which was correlated with poor visual-spatial performance (r = -0.36 and P = 0.014). Conclusion: The involvement of neurovascular decoupling in cognitive impairment in PD is regionally specific and most prominent in the visual-spatial cortices, which could potentially provide a complementary understanding of the pathophysiological mechanisms underlying cognitive deficits in PD.

Project description:The heterogenous aetiology of Parkinson's disease is increasingly recognized; both mitochondrial and lysosomal dysfunction have been implicated. Powerful, clinically applicable tools are required to enable mechanistic stratification for future precision medicine approaches. The aim of this study was to characterize bioenergetic dysfunction in Parkinson's disease by applying a multimodal approach, combining standardized clinical assessment with midbrain and putaminal 31-phosphorus magnetic resonance spectroscopy (31P-MRS) and deep phenotyping of mitochondrial and lysosomal function in peripheral tissue in patients with recent-onset Parkinson's disease and control subjects. Sixty participants (35 patients with Parkinson's disease and 25 healthy controls) underwent 31P-MRS for quantification of energy-rich metabolites [ATP, inorganic phosphate (Pi) and phosphocreatine] in putamen and midbrain. In parallel, skin biopsies were obtained from all research participants to establish fibroblast cell lines for subsequent quantification of total intracellular ATP and mitochondrial membrane potential (MMP) as well as mitochondrial and lysosomal morphology, using high content live cell imaging. Lower MMP correlated with higher intracellular ATP (r = -0.55, P = 0.0016), higher mitochondrial counts (r = -0.72, P < 0.0001) and higher lysosomal counts (r = -0.62, P = 0.0002) in Parkinson's disease patient-derived fibroblasts only, consistent with impaired mitophagy and mitochondrial uncoupling. 31P-MRS-derived posterior putaminal Pi/ATP ratio variance was considerably greater in Parkinson's disease than in healthy controls (F-tests, P = 0.0036). Furthermore, elevated 31P-MRS-derived putaminal, but not midbrain Pi/ATP ratios (indicative of impaired oxidative phosphorylation) correlated with both greater mitochondrial (r = 0.37, P = 0.0319) and lysosomal counts (r = 0.48, P = 0.0044) as well as lower MMP in both short (r = -0.52, P = 0.0016) and long (r = -0.47, P = 0.0052) mitochondria in Parkinson's disease. Higher 31P-MRS midbrain phosphocreatine correlated with greater risk of rapid disease progression (r = 0.47, P = 0.0384). Our data suggest that impaired oxidative phosphorylation in the striatal dopaminergic nerve terminals exceeds mitochondrial dysfunction in the midbrain of patients with early Parkinson's disease. Our data further support the hypothesis of a prominent link between impaired mitophagy and impaired striatal energy homeostasis as a key event in early Parkinson's disease.

Project description:PurposeClinical practice guidelines establish that occupational therapy (OT) services are indicated for people with early Parkinson's disease (PD). However, OT is uncommon compared to other rehabilitation services. This study describes the development and evaluation of a proactive, consultative OT program for people with early PD as a part of an integrated care approach.Materials and methodsThe program was developed by an occupational therapist adapting practice guidelines for people with early PD. Retrospective program evaluation occurred at an outpatient rehabilitation clinic. The consultative OT program for early PD includes a 90-minute evaluation with instruction in self-management techniques, individually tailored exercises, and follow-up recommendations. The program was evaluated with the RE-AIM framework. Postprogram semistructured interviews provided patient-reported program effectiveness and satisfaction.ResultsIn 2018, 23 individuals used OT out of 77 people with early PD who attended the proactive rehabilitation program. Most individuals (n = 16, 69.6%) were within Hoehn and Yahr stages 1-2 and were seen within 3 years of PD diagnosis. Participants presented with deficits in hand strength (60.0 ± 23.4 pounds) and dexterity (right hand 30.0 ± 8.0 seconds) and reported complaints about basic and/or instrumental activities of daily living (n = 15, 65.2%). Semistructured interviews (n = 16) revealed that most individuals (75%) reported high satisfaction. Of the 10 who recalled a home exercise program, 60% reported continued adherence. Consultative OT was delivered with fidelity in 22/23 individuals (96%). After one year, only two occupational therapists at one clinic had adopted the program, and the program is maintained in the organization.ConclusionOccupational therapists reached people in the early stages of PD when a specific program was tailored to evaluate and target their specific needs. Motor activity deficits noted in individuals with early PD support future scaling and sustainability efforts of OT within this population. Quality improvement suggestions are discussed for future implementation and clinical trials.

Dataset Information

Multimodal Evaluation of Neurovascular Functionality in Early Parkinson's Disease.

Publications

Multimodal Evaluation of Neurovascular Functionality in Early Parkinson's Disease.

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