scholarly journals Sex effects on brain structure in de novo Parkinson’s disease: a multimodal neuroimaging study

Brain ◽  
2020 ◽  
Vol 143 (10) ◽  
pp. 3052-3066
Author(s):  
Christina Tremblay ◽  
Nooshin Abbasi ◽  
Yashar Zeighami ◽  
Yvonne Yau ◽  
Mahsa Dadar ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
De Novo ◽  
Parietal Lobe ◽  
Age Of Onset ◽  
Occipital Cortex ◽  
Clinical Severity ◽  
Tissue Loss ◽  
Left Frontal Lobe ◽  
Cortical Regions

Abstract Parkinson’s disease varies in severity and age of onset. One source of this variability is sex. Males are twice as likely as females to develop Parkinson’s disease, and tend to have more severe symptoms and greater speed of progression. However, to date, there is little information in large cohorts on sex differences in the patterns of neurodegeneration. Here we used MRI and clinical information from the Parkinson Progression Markers Initiative to measure structural brain differences between sexes in Parkinson’s disease after regressing out the expected effect of age and sex. We derived atrophy maps from deformation-based morphometry of T1-weighted MRI and connectivity from diffusion-weighted MRI in de novo Parkinson’s disease patients (149 males: 83 females) with comparable clinical severity, and healthy control participants (78 males: 39 females). Overall, even though the two patient groups were matched for disease duration and severity, males demonstrated generally greater brain atrophy and disrupted connectivity. Males with Parkinson’s disease had significantly greater tissue loss than females in 11 cortical regions including bilateral frontal and left insular lobe, right postcentral gyrus, left inferior temporal and cingulate gyrus and left thalamus, while females had greater atrophy in six cortical regions, including regions in the left frontal lobe, right parietal lobe, left insular gyrus and right occipital cortex. Local efficiency of white matter connectivity showed greater disruption in males in multiple regions such as basal ganglia, hippocampus, amygdala and thalamus. These findings support the idea that development of Parkinson’s disease may involve different pathological mechanisms and yield distinct prognosis in males and females, which may have implications for research into neuroprotection, and stratification for clinical trials.

scholarly journals Network structure of brain atrophy in de novo Parkinson's disease

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Yashar Zeighami ◽  
Miguel Ulla ◽  
Yasser Iturria-Medina ◽  
Mahsa Dadar ◽  
Yu Zhang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Medial Temporal Lobe ◽  
Healthy Aging ◽  
De Novo ◽  
Progression Markers ◽  
Magnetic Resonance Imaging Mri ◽  
Cortical Regions ◽  
Clinical Measures ◽  
Deformation Based Morphometry

We mapped the distribution of atrophy in Parkinson's disease (PD) using magnetic resonance imaging (MRI) and clinical data from 232 PD patients and 117 controls from the Parkinson's Progression Markers Initiative. Deformation-based morphometry and independent component analysis identified PD-specific atrophy in the midbrain, basal ganglia, basal forebrain, medial temporal lobe, and discrete cortical regions. The degree of atrophy reflected clinical measures of disease severity. The spatial pattern of atrophy demonstrated overlap with intrinsic networks present in healthy brain, as derived from functional MRI. Moreover, the degree of atrophy in each brain region reflected its functional and anatomical proximity to a presumed disease epicenter in the substantia nigra, compatible with a trans-neuronal spread of the disease. These results support a network-spread mechanism in PD. Finally, the atrophy pattern in PD was also seen in healthy aging, where it also correlated with the loss of striatal dopaminergic innervation.

Parkinson’s Disease

2008 ◽  
Author(s):  
Laura Marsh
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Age Of Onset ◽  
Lewy Bodies ◽  
Biological Marker ◽  
Prevalence Rates ◽  
Parkinsonian Disorders ◽  
Clinical Diagnoses ◽  
Cortical Regions

Parkinson’s disease (PD), the second most common neurodegenerative disorder after Alzheimer’s disease (AD), causes a progressive neurologic syndrome characterized by bradykinesia, tremor, rigidity, and, in its later stages, postural instability. The motor signs of PD correspond to loss of dopaminergic neurons in the substantia nigra pars compacta within the ventral midbrain. Neuronal inclusions, called Lewy bodies, are also present in the same region, but they can also be present in limbic and cortical regions and, along with other neurotransmitter deficits, are associated with nonmotor aspects of the disease. PD is to be distinguished from parkinsonism, a general term that refers to clinical conditions with the same motor phenomena, but without reference to a specific etiology. Prevalence rates of PD vary. Epidemiologic studies show ageadjusted prevalence rates (per 100,000 individuals) range from 104.7 in Japan, 114.6 in the United States, 168.8 in Taiwan, and 258.8 in Sicily (Korell and Tanner, 2005). The disease affects about 1 million individuals in North America—approximately 0.5% to 1% of the population older than age 65 years of age. The average age of onset is about 60 years, but 5% to 10% of patients have young-onset PD, beginning before age 40 (Tanner and Ben-Shlomo, 1999). The disease affects all races, and there is a slightly higher prevalence of PD among men. The diagnosis of PD relies on the clinical history and motor examination, which usually distinguish it from other parkinsonian disorders. However, because there is no biological marker that verifies the diagnosis of PD, neuropathologic findings remain the gold standard for confirmation of the clinical diagnosis. Even at specialized movement disorder centers, autopsy studies reveal that 10% to 20% of patients with clinical diagnoses of PD have other neuropathologic diagnoses (Hughes, Daniel, and Lees, 2001). Two of the three cardinal motor signs (tremor, akinesia/bradykinesia, and rigidity) are required to establish the diagnosis of PD, but these motor features overlap with other parkinsonian disorders. However, in patients without an overt tremor, early signs of PD such as decreased arm swing, limb stiffness, and diminished facial expression can be subtle, and the diagnosis of PD maybe delayed for several years.

Serum hs-CRP Levels are Increased in de Novo Parkinson's Disease Independently from Age of Onset

2014 ◽  
Vol 72 (5-6) ◽  
pp. 285-289 ◽  
Author(s):  
In-Uk Song ◽  
Hyun-Ji Cho ◽  
Jung-Seok Kim ◽  
In-Seok Park ◽  
Kwang-Soo Lee
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
De Novo ◽  
Age Of Onset ◽  
Hs Crp

The Neuropsychology of de Novo Patients with Idiopathic Parkinson's Disease: The Effects of Age of Onset

1989 ◽  
Vol 48 (3-4) ◽  
pp. 205-217 ◽  
Author(s):  
W. G. J. Reid ◽  
G. A. Broe ◽  
M. A. Hely ◽  
J. G. L. Morris ◽  
P. M. Williamson ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
De Novo ◽  
Age Of Onset ◽  
Idiopathic Parkinson’S Disease ◽  
Idiopathic Parkinson's Disease

Association of the Non-Motor Burden with Patterns of Striatal Dopamine Loss in de novo Parkinson’s Disease

2020 ◽  
Vol 10 (4) ◽  
pp. 1541-1549
Author(s):  
Seok Jong Chung ◽  
Sangwon Lee ◽  
Han Soo Yoo ◽  
Yang Hyun Lee ◽  
Hye Sun Lee ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
De Novo ◽  
Early Stage ◽  
Striatal Dopamine ◽  
Motor Deficits ◽  
Dopamine Depletion ◽  
Severe Motor ◽  
Severe Group ◽  
Striatal Dopamine Depletion

Background: Striatal dopamine deficits play a key role in the pathogenesis of Parkinson’s disease (PD), and several non-motor symptoms (NMSs) have a dopaminergic component. Objective: To investigate the association between early NMS burden and the patterns of striatal dopamine depletion in patients with de novo PD. Methods: We consecutively recruited 255 patients with drug-naïve early-stage PD who underwent 18F-FP-CIT PET scans. The NMS burden of each patient was assessed using the NMS Questionnaire (NMSQuest), and patients were divided into the mild NMS burden (PDNMS-mild) (NMSQuest score <6; n = 91) and severe NMS burden groups (PDNMS-severe) (NMSQuest score >9; n = 90). We compared the striatal dopamine transporter (DAT) activity between the groups. Results: Patients in the PDNMS-severe group had more severe parkinsonian motor signs than those in the PDNMS-mild group, despite comparable DAT activity in the posterior putamen. DAT activity was more severely depleted in the PDNMS-severe group in the caudate and anterior putamen compared to that in the PDMNS-mild group. The inter-sub-regional ratio of the associative/limbic striatum to the sensorimotor striatum was lower in the PDNMS-severe group, although this value itself lacked fair accuracy for distinguishing between the patients with different NMS burdens. Conclusion: This study demonstrated that PD patients with severe NMS burden exhibited severe motor deficits and relatively diffuse dopamine depletion throughout the striatum. These findings suggest that the level of NMS burden could be associated with distinct patterns of striatal dopamine depletion, which could possibly indicate the overall pathological burden in PD.

The Superior Colliculus in De Novo Parkinson's Disease: A Prodromal Dysfunction?

2018 ◽  
Author(s):  
Elena Moro ◽  
Emmanuelle Bellot ◽  
Sara Meoni ◽  
Pierre Pelissier ◽  
Ruxandra Hera ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Superior Colliculus ◽  
De Novo

Recent Advances in Drug Repurposing for Parkinson’s Disease

2019 ◽  
Vol 26 (28) ◽  
pp. 5340-5362 ◽  
Author(s):  
Xin Chen ◽  
Giuseppe Gumina ◽  
Kristopher G. Virga
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Drug Discovery ◽  
De Novo ◽  
Drug Repositioning ◽  
Drug Repurposing ◽  
Cost Effective ◽  
New Drugs ◽  
Recent Advances ◽  
Clinical Drugs

:As a long-term degenerative disorder of the central nervous system that mostly affects older people, Parkinson’s disease is a growing health threat to our ever-aging population. Despite remarkable advances in our understanding of this disease, all therapeutics currently available only act to improve symptoms but cannot stop the disease progression. Therefore, it is essential that more effective drug discovery methods and approaches are developed, validated, and used for the discovery of disease-modifying treatments for Parkinson’s disease. Drug repurposing, also known as drug repositioning, or the process of finding new uses for existing or abandoned pharmaceuticals, has been recognized as a cost-effective and timeefficient way to develop new drugs, being equally promising as de novo drug discovery in the field of neurodegeneration and, more specifically for Parkinson’s disease. The availability of several established libraries of clinical drugs and fast evolvement in disease biology, genomics and bioinformatics has stimulated the momentums of both in silico and activity-based drug repurposing. With the successful clinical introduction of several repurposed drugs for Parkinson’s disease, drug repurposing has now become a robust alternative approach to the discovery and development of novel drugs for this disease. In this review, recent advances in drug repurposing for Parkinson’s disease will be discussed.

Asymmetric Dopaminergic Dysfunction in Brain-First versus Body-First Parkinson’s Disease Subtypes

2021 ◽  
pp. 1-11
Author(s):  
Karoline Knudsen ◽  
Tatyana D. Fedorova ◽  
Jacob Horsager ◽  
Katrine B. Andersen ◽  
Casper Skjærbæk ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
De Novo ◽  
Specific Binding ◽  
Asymmetry Index ◽  
The Body ◽  
Specific Binding Ratio ◽  
Dat Spect ◽  
Vagal Innervation ◽  
Nigrostriatal Degeneration

Background: We have hypothesized that Parkinson’s disease (PD) comprises two subtypes. Brain-first, where pathogenic α-synuclein initially forms unilaterally in one hemisphere leading to asymmetric nigrostriatal degeneration, and body-first with initial enteric pathology, which spreads through overlapping vagal innervation leading to more symmetric brainstem involvement and hence more symmetric nigrostriatal degeneration. Isolated REM sleep behaviour disorder has been identified as a strong marker of the body-first type. Objective: To analyse striatal asymmetry in [18F]FDOPA PET and [123I]FP-CIT DaT SPECT data from iRBD patients, de novo PD patients with RBD (PD +RBD) and de novo PD patients without RBD (PD - RBD). These groups were defined as prodromal body-first, de novo body-first, and de novo brain-first, respectively. Methods: We included [18F]FDOPA PET scans from 21 iRBD patients, 11 de novo PD +RBD, 22 de novo PD - RBD, and 18 controls subjects. Also, [123I]FP-CIT DaT SPECT data from iRBD and de novo PD patients with unknown RBD status from the PPPMI dataset was analysed. Lowest putamen specific binding ratio and putamen asymmetry index (AI) was defined. Results: Nigrostriatal degeneration was significantly more symmetric in patients with RBD versus patients without RBD or with unknown RBD status in both FDOPA (p = 0.001) and DaT SPECT (p = 0.001) datasets. Conclusion: iRBD subjects and de novo PD +RBD patients present with significantly more symmetric nigrostriatal dopaminergic degeneration compared to de novo PD - RBD patients. The results support the hypothesis that body-first PD is characterized by more symmetric distribution most likely due to more symmetric propagation of pathogenic α-synuclein compared to brain-first PD.

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