Neuroimaging biomarkers for <scp>P</scp>arkinson disease: Facts and fantasy

Perlmutter, Joel S.; Norris, Scott A.

doi:10.1002/ana.24291

Cited by 43 publications

(52 citation statements)

References 78 publications

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“…First, there are discrepancies in the current literature that await further investigation and understanding. Perlmutter & Norris’ (2014) review of neuroimaging biomarkers in PD provided several examples of discrepancies. Additional examples of discrepancies were described in this review.…”

Section: Overall Summary and Future Directionsmentioning

confidence: 99%

“…Fourth, development of the clinical value of neuroimaging will continue to be an important area of endeavor as the clinical value of neuroimaging has been limited (Perlmutter & Norris, 2014; Politis, 2014). So far the additive value of neuroimaging over a good history and physical exam has not been very useful for clinical purposes (e.g.…”

Section: Overall Summary and Future Directionsmentioning

confidence: 99%

“…Hellwig et al, 2013). For example, although many neuroimaging studies of PD cited in this review refer to one or more of their neuroimaging findings as a biomarker or potential biomarker, currently there are no established neuroimaging biomarkers for clinical use in PD (Duncan et al, 2013; Miller & O’Callaghan, 2015; Perlmutter & Norris, 2014; Schapira, 2013; Sharma et al, 2013). Further, it is possible that any single measure, neuroimaging or otherwise, may not be sufficiently useful as a clinical biomarker of PD (Schapira, 2013).…”

Section: Overall Summary and Future Directionsmentioning

confidence: 99%

“…The ability to image α-synuclein would be of particular importance as α-synuclein deposits in Lewy bodies and neurites are the neuropathological signature of PD. Efforts to image α-synuclein are underway (Perlmutter & Norris, 2014; Vernon et al, 2010). A better understanding of the biochemical and cellular pathways that lead to neurodegeneration may also open up new imaging targets to facilitate early detection and disease staging (e.g.…”

Section: Overall Summary and Future Directionsmentioning

confidence: 99%

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Neuroimaging of Parkinson's disease: Expanding views

Weingarten

Sundman

Hickey

et al. 2015

Neuroscience & Biobehavioral Reviews

139

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Advances in molecular and structural and functional neuroimaging are rapidly expanding the complexity of neurobiological understanding of Parkinson’s disease (PD). This review article begins with an introduction to PD neurobiology as a foundation for interpreting neuroimaging findings that may further lead to more integrated and comprehensive understanding of PD. Diverse areas of PD neuroimaging are then reviewed and summarized, including positron emission tomography, single photon emission computed tomography, magnetic resonance spectroscopy and imaging, transcranial sonography, magnetoencephalography, and multimodal imaging, with focus on human studies published over the last five years. These included studies on differential diagnosis, co-morbidity, genetic and prodromal PD, and treatments from L-DOPA to brain stimulation approaches, transplantation and gene therapies. Overall, neuroimaging has shown that PD is a neurodegenerative disorder involving many neurotransmitters, brain regions, structural and functional connections, and neurocognitive systems. A broad neurobiological understanding of PD will be essential for translational efforts to develop better treatments and preventive strategies. Many questions remain and we conclude with some suggestions for future directions of neuroimaging of PD.

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Section: Overall Summary and Future Directionsmentioning

confidence: 99%

Section: Overall Summary and Future Directionsmentioning

confidence: 99%

Section: Overall Summary and Future Directionsmentioning

confidence: 99%

Section: Overall Summary and Future Directionsmentioning

confidence: 99%

See 2 more Smart Citations

Neuroimaging of Parkinson's disease: Expanding views

Weingarten

Sundman

Hickey

et al. 2015

Neuroscience & Biobehavioral Reviews

139

View full text Add to dashboard Cite

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“…PD L was defined as PD participants having at least 5 years of disease duration for several reasons. For example, nigrostriatal terminal labeling has been suggested to reach a floor after approximately 5 years, 1 although some data suggest that nigral cell death continues, 34 and dopamine levels certainly decline throughout disease progression. 35 Clinically, dyskinesias, cognitive decline, and dopamine-nonresponsive symptoms tend to be more prominent after the first 5 years (honeymoon phase).…”

mentioning

confidence: 99%

Stage-dependent loss of cortical gyrification as Parkinson disease “unfolds”

et al. 2016

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Objective: Nigrostriatal terminal losses are known to progress most rapidly in early-stage Parkinson disease (PD) and then plateau, whereas cortical pathology continues and may provide a better marker of PD progression in later stages. We investigated cortical gyrification indices in patients with different durations of PD, since cortical folding may capture complex processes involving transverse forces of neuronal sheets or underlying axonal connectivity.Methods: Longitudinal cohort structural MRI were obtained at baseline, 18 months, and 36 months from 70 patients with PD without dementia and 70 control participants. Cortical local gyrification index (LGI) was compared between controls and PD subgroups based upon duration of illness (DOI, ,1 year [PD E , n 5 17], 1-5 years [PD M , n 5 19], .5 years [PD L , n 5 24]) and adjusted using false discovery rate. Associations between LGI and clinical measurements were assessed using multiple linear regression. Areas having significantly reduced LGI also were analyzed using baseline data from a newly established cohort (PD n 5 87, control n 5 66) to validate our findings.Results: In the longitudinal cohort, PD L had significantly reduced overall gyrification, and bilaterally in the inferior parietal, postcentral, precentral, superior frontal, and supramarginal areas, compared to controls (p , 0.05). Longitudinally, loss of gyrification was accelerated in PD M participants, compared to controls.LGI showed robust correlations with DOI and also was correlated with PD-related clinical measurements. Similar results were obtained in the validation sample.Conclusions: Loss of cortical gyrification may be accelerated within the first few years after PD diagnosis, and become particularly prominent in later stages. Thus, it may provide a metric for monitoring progression in vivo. In Parkinson disease (PD), degeneration of dopamine terminals is thought to progress rapidly within the first few years after diagnosis and then plateau.1 Thus, in more advanced stages of disease, non-nigrostriatal brain changes may serve as better markers of PD progression. Evidence suggests that widespread pathologic changes occur in the cortex, including apoptotic signaling, Lewy pathology, reduction in other neurotransmitters, and interneuron loss. [2][3][4] It is unclear, however, how cell death relates to the pattern of cortical Lewy pathology, and whether cortical changes can be used to gauge PD progression. 5 Lewy pathology has been documented in specific cortical layers (i.e., preferentially in deep layers of high-order sensory association areas). 5,6 Some previous imaging studies have demonstrated decreased cortical thickness in PD, 7,8 but reported results have been inconsistent and have not shown robust associations with disease progression in the absence of dementia. These

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Emerging Neuroimaging Biomarkers Across Disease Stage in Parkinson Disease

et al. 2021

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Imaging biomarkers in Parkinson disease (PD) are increasingly important for monitoring progression in clinical trials and also have the potential to improve clinical care and management. This Review addresses a critical need to make clear the temporal relevance for diagnostic and progression imaging biomarkers to be used by clinicians and researchers over the clinical course of PD. Magnetic resonance imaging (diffusion imaging, neuromelanin-sensitive imaging, iron-sensitive imaging, T1-weighted imaging), positron emission tomography/single-photon emission computed tomography dopaminergic, serotonergic, and cholinergic imaging as well as metabolic and cerebral blood flow network neuroimaging biomarkers in the preclinical, prodromal, early, and moderate to late stages are characterized.OBSERVATIONS If a clinical trial is being carried out in the preclinical and prodromal stages, potentially useful disease-state biomarkers include dopaminergic imaging of the striatum; metabolic imaging; free-water, neuromelanin-sensitive, and iron-sensitive imaging in the substantia nigra; and T1-weighted structural magnetic resonance imaging. Disease-state biomarkers that can distinguish atypical parkinsonisms are metabolic imaging, free-water imaging, and T1-weighted imaging; dopaminergic imaging and other molecular imaging track progression in prodromal patients, whereas other established progression biomarkers need to be evaluated in prodromal cohorts. Progression in early-stage PD can be monitored using dopaminergic imaging in the striatum, metabolic imaging, and free-water and neuromelanin-sensitive imaging in the posterior substantia nigra. Progression in patients with moderate to late-stage PD can be monitored using free-water imaging in the anterior substantia nigra, R2* of substantia nigra, and metabolic imaging. Cortical thickness and gyrification might also be useful markers or predictors of progression. Dopaminergic imaging and free-water imaging detect progression over 1 year, whereas other modalities detect progression over 18 months or longer. The reliability of progression biomarkers varies with disease stage, whereas disease-state biomarkers are relatively consistent in individuals with preclinical, prodromal, early, and moderate to late-stage PD.CONCLUSIONS AND RELEVANCE Imaging biomarkers for various stages of PD are readily available to be used as outcome measures in clinical trials and are potentially useful in multimodal combination with routine clinical assessment. This Review provides a critically important template for considering disease stage when implementing diagnostic and progression biomarkers in both clinical trials and clinical care settings.

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Neuroimaging biomarkers for Parkinson disease: Facts and fantasy

Cited by 43 publications

References 78 publications

Neuroimaging of Parkinson's disease: Expanding views

Neuroimaging of Parkinson's disease: Expanding views

Stage-dependent loss of cortical gyrification as Parkinson disease “unfolds”

Emerging Neuroimaging Biomarkers Across Disease Stage in Parkinson Disease

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