Brainstem and cerebellar radiological findings in progressive supranuclear palsy DOI Creative Commons

Chloe Spiegel,

Cassandra Marotta, Kelly Bertram

и другие.

Brain Communications, Год журнала: 2024, Номер 7(1)

Опубликована: Дек. 24, 2024

Abstract Progressive supranuclear palsy is a sporadic neurodegenerative 4-repeat tauopathy associated with significant morbidity. Heterogeneity of symptom expression among this group increasingly recognized, reflecting variable tau spread and neurodegeneration. Clinical manifestations consist debilitating rapidly progressive motor, oculomotor, speech, cognitive affective impairments. Core pathological changes are noted predominance in the midbrain basal ganglia; however, to more caudal brainstem cerebellar regions reported at various stages. Accordingly, whilst atrophy best recognized supportive imaging finding, quantitative neuroimaging studies using MRI PET approaches have revealed wider profile brain abnormalities cohorts individuals palsy. This expanded neurobiological scope disease may account for individual heterogeneity highlight additional biological markers that relevant diagnosing tracking illness. Additionally, there increasing understanding diverse cognitive, speech functions cerebellum, which be implicated beyond current recognition. In review, we undertake systematic literature search summary vivo structural functional findings cerebellum date. Novel multimodal techniques emerged over recent years, reveal several infratentorial alterations Most saliently, evidence volume loss microstructural damage pons, middle peduncles cortex deep nuclei, alongside superior peduncle changes. Whilst supporting presence these features not unanimous, base compelling, including correlations progression, severity or variant differences. A smaller number report on measures iron deposition, neuromelanin, viscoelasticity glymphatic system involving regions. Molecular also shown increased uptake tracer dentate nucleus, although concern remains regarding possible off-target binding. Imaging other molecular targets has been sparse, but reports neurotransmitter, inflammatory synaptic density available. Taken together, an established highlights often accompanied by people Further research examining contribution clinical morbidity inter-individual variability warranted.

Язык: Английский

The noradrenergic subtype of Parkinson disease: from animal models to clinical practice DOI
К. Ray Chaudhuri, Valentina Leta, Kirsty Bannister

и другие.

Nature Reviews Neurology, Год журнала: 2023, Номер 19(6), С. 333 - 345

Опубликована: Май 4, 2023

Язык: Английский

Процитировано

44
Noradrenergic and cholinergic systems take centre stage in neuropsychiatric diseases of ageing DOI Creative Commons
Isabella F. Orlando, James M. Shine, Trevor W. Robbins

и другие.

Neuroscience & Biobehavioral Reviews, Год журнала: 2023, Номер 149, С. 105167 - 105167

Опубликована: Апрель 11, 2023

Noradrenergic and cholinergic systems are among the most vulnerable brain in neuropsychiatric diseases of ageing, including Alzheimer's disease, Parkinson's Lewy body dementia, progressive supranuclear palsy. As these fail, they contribute directly to many characteristic cognitive psychiatric symptoms. However, their contribution symptoms is not sufficiently understood, pharmacological interventions targeting noradrenergic have met with mixed success. Part challenge complex neurobiology systems, operating across multiple timescales, non-linear changes adult lifespan disease course. We address challenges a detailed review outlining roles cognition behaviour, how influence disease. By bridging levels analysis, we highlight opportunities for improving drug therapies pursuing personalised medicine strategies.

Язык: Английский

Процитировано

33
Age-dependent dysregulation of locus coeruleus firing in a transgenic rat model of Alzheimer's disease DOI Creative Commons
Michael A. Kelberman, Jacki M. Rorabaugh,

Claire R. Anderson

и другие.

Neurobiology of Aging, Год журнала: 2023, Номер 125, С. 98 - 108

Опубликована: Фев. 1, 2023

Язык: Английский

Процитировано

27
Apathy in Parkinson’s Disease: Clinical Patterns and Neurobiological Basis DOI Creative Commons
Matthieu Béreau, Vincent Van Waes, Mathieu Servant

и другие.

Cells, Год журнала: 2023, Номер 12(12), С. 1599 - 1599

Опубликована: Июнь 10, 2023

Apathy is commonly defined as a loss of motivation leading to reduction in goal-directed behaviors. This multidimensional syndrome, which includes cognitive, emotional and behavioral components, one the most prevalent neuropsychiatric features Parkinson’s disease (PD). It has been established that prevalence apathy increases PD progresses. However, pathophysiology anatomic substrate this syndrome remain unclear. seems be underpinned by impaired anatomical structures link prefrontal cortex with limbic system. can encountered prodromal stage fluctuating patients receiving bilateral chronic subthalamic nucleus stimulation. In these stages, may considered disorder embodies amotivational combined dopaminergic serotonergic denervation dopa-responsive. contrast, advanced patients, cognitive announces decline dementia, diffuse neurotransmitter system dysfunction Lewy pathology spreading no longer review, we discuss clinical patterns their treatment, neurobiological basis apathy, potential role involved pathways motivational apathy.

Язык: Английский

Процитировано

26
Neuroimaging and fluid biomarkers in Parkinson’s disease in an era of targeted interventions DOI Creative Commons
Angeliki Zarkali, George E. Thomas, Henrik Zetterberg

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Июль 5, 2024

Abstract A major challenge in Parkinson’s disease is the variability symptoms and rates of progression, underpinned by heterogeneity pathological processes. Biomarkers are urgently needed for accurate diagnosis, patient stratification, monitoring progression precise treatment. These were previously lacking, but recently, novel imaging fluid biomarkers have been developed. Here, we consider new approaches showing sensitivity to brain tissue composition, examine specificity processes, including seed amplification assays extracellular vesicles. We reflect on these context biological staging systems, emerging techniques currently development.

Язык: Английский

Процитировано

17
Diagnostic utility of 7T neuromelanin imaging of the substantia nigra in Parkinson’s disease DOI Creative Commons
Dhairya A. Lakhani, Xiangzhi Zhou, Shengzhen Tao

и другие.

npj Parkinson s Disease, Год журнала: 2024, Номер 10(1)

Опубликована: Янв. 8, 2024

Abstract Parkinson’s disease (PD) is a prevalent neurodegenerative disorder that presents diagnostic challenge due to symptom overlap with other disorders. Neuromelanin (NM) imaging promising biomarker for PD, but adoption has been limited, in part subpar performance at standard MRI field strengths. We aimed evaluate the utility of ultra-high 7T NM-sensitive diagnosis PD versus controls and essential tremor (ET), as well NM differences among subtypes. A retrospective case-control study was conducted including patients, ET controls. 3D-GRE acquired, substantia nigra pars compacta (SNpc) volumes, contrast ratios, asymmetry indices were calculated. Statistical analyses, general linear models ROC curves, employed. Twenty-one 13 18 assessed. patients exhibited significantly lower SNpc volumes compared non-PD subjects. total volume showed 100% sensitivity 96.8% specificity (AUC = 0.998) differentiating from 95.2% 0.996) ET. Contrast ratio not different between groups ( p 0.07). There also higher index cohorts < 0.001). signal loss predominantly involved inferior, posterior, lateral aspects SNpc. Akinetic-rigid subtype more significant dominant demonstrates potential tool distinction subtypes, allowing improved understanding progression subtype-related characteristics.

Язык: Английский

Процитировано

10
Morphological basis of Parkinson disease-associated cognitive impairment: an update DOI
K. A. Jellinger

Journal of Neural Transmission, Год журнала: 2022, Номер 129(8), С. 977 - 999

Опубликована: Июнь 20, 2022

Язык: Английский

Процитировано

30
Impaired value-based decision-making in Parkinson’s disease apathy DOI Creative Commons

William Gilmour,

Graeme Mackenzie,

Mathias Feile

и другие.

Brain, Год журнала: 2024, Номер 147(4), С. 1362 - 1376

Опубликована: Фев. 2, 2024

Abstract Apathy is a common and disabling complication of Parkinson’s disease characterized by reduced goal-directed behaviour. Several studies have reported dysfunction within prefrontal cortical regions projections from brainstem nuclei whose neuromodulators include dopamine, serotonin noradrenaline. Work in animal human neuroscience confirmed contributions these on aspects motivated decision-making. Specifically, overlapping to encoding the value decisions, influence whether explore alternative courses action or persist an existing strategy achieve rewarding goal. Building upon this work, we hypothesized that apathy should be associated with impairment value-based learning. Using four-armed restless bandit reinforcement learning task, studied decision-making 75 volunteers; 53 patients disease, without clinical apathy, 22 age-matched healthy control subjects. Patients exhibited impaired ability choose highest bandit. Task performance predicted individual patient’s severity measured using Lille Rating Scale (R = −0.46, P &lt; 0.001). Computational modelling choices group made decisions were indifferent learnt options, consistent previous reports reward insensitivity. Further analysis demonstrated shift away exploiting option reduction perseveration, which also correlated scores −0.5, We went acquire functional MRI 59 19 20 controls performing Restless Bandit Task. Analysis signal at point feedback diminished ventromedial cortex was more marked but not predictive their severity. model-based categorization choice type, lower bandits activated similar degree controls. In contrast, significantly increased activation across distributed thalamo-cortical network. Enhanced activity thalamus both patient groups connectivity dorsal anterior cingulate insula. Given task no different subjects, interpret recruitment network as possible compensatory mechanism, compensates against symptomatic manifestation disease.

Язык: Английский

Процитировано

9
Pathomechanisms of neuropsychiatric disturbances in atypical parkinsonian disorders: a current view DOI
K. A. Jellinger

Journal of Neural Transmission, Год журнала: 2025, Номер unknown

Опубликована: Фев. 15, 2025

Язык: Английский

Процитировано

1
Application of Neuromelanin MR Imaging in Parkinson Disease DOI Creative Commons
Naying He, Yongsheng Chen, Peter A. LeWitt

и другие.

Journal of Magnetic Resonance Imaging, Год журнала: 2022, Номер 57(2), С. 337 - 352

Опубликована: Авг. 26, 2022

MRI has been used to develop biomarkers for movement disorders such as Parkinson disease (PD) and other neurodegenerative with parkinsonism progressive supranuclear palsy multiple system atrophy. One of these imaging is neuromelanin (NM), whose integrity can be assessed from its contrast volume. NM found mainly in certain brain stem structures, namely, the substantia nigra pars compacta (SNpc), ventral tegmental area, locus coeruleus. Another major biomarker iron, which often increases concert degeneration. These have potential improve diagnostic certainty differentiating between PD similar PD, well provide a better understanding pathophysiology. Mapping vivo clinical importance gauging premotor phase when there greater than 50% loss dopaminergic SNpc melanized neurons. As metal ion chelator, absorb iron. When released neurons, it deposits iron into intracellular tissues SNpc; result that imaged measured using quantitative susceptibility mapping. An increase also leads disappearance nigrosome‐1 sign, another neuroimage PD. Therefore, mapping changes are practical means improving early diagnosis monitoring progression. In this review, we discuss functions location NM, how NM‐MRI performed, automatic content, NM‐related enhance differentiate disorders, advances methods. With currently evolving rapid artificial intelligence, likely increasingly important roles enhancing capabilities Evidence Level 1 Technical Efficacy Stage 2

Язык: Английский

Процитировано

27