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.

scholarly journals Sex Differences in Cognitive Changes in De Novo Parkinson’s Disease

2019 ◽  
Vol 26 (2) ◽  
pp. 241-249 ◽  
Author(s):  
Ece Bayram ◽  
Sarah J. Banks ◽  
Guogen Shan ◽  
Nikki Kaplan ◽  
Jessica Z.K. Caldwell
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Sex Differences ◽  
Verbal Memory ◽  
Healthy Aging ◽  
De Novo ◽  
Cognitive Changes ◽  
Progression Markers ◽  
Cognitively Intact

AbstractObjective:To evaluate the sex differences in cognitive course over 4 years in Parkinson’s disease (PD) patients with and without mild cognitive impairment (MCI) compared to controls.Methods:Four-year longitudinal cognitive scores of 257 cognitively intact PD, 167 PD-MCI, and 140 controls from the Parkinson’s Progression Markers Initiative were included. Longitudinal scores of men and women, and PD with and without MCI were compared.Results:Women had better verbal memory, men had better visuospatial function. There was no interaction between sex, diagnostic group, and/or time (4-year follow-up period).Conclusions:Sex differences in cognitive course in de novo PD are similar to healthy aging. Cognitive decline rates in PD with and without MCI are similar for the first 4 years of PD.

scholarly journals Predicting the onset of freezing of gait in de novo Parkinson’s disease

2021 ◽  
Author(s):  
Fengting Wang ◽  
Yixin Pan ◽  
Miao Zhang ◽  
Kejia Hu
Keyword(s):  
Risk Factors ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
De Novo ◽  
Freezing Of Gait ◽  
Poor Quality ◽  
Csf Biomarkers ◽  
Genetic Characteristics ◽  
Progression Markers ◽  
Independent Risk Factors

AbstractFreezing of gait (FoG) is a debilitating symptom of Parkinson’s disease (PD) related to higher risks of falls and poor quality of life. In this study, we predicted the onset of FoG in PD patients using a battery of risk factors from patients enrolled in the Parkinson’s Progression Markers Initiative (PPMI) cohort. The endpoint was the presence of FoG, which was assessed every year during the five-year follow-up visit. Overall, 212 PD patients were included in analysis. Seventy patients (33.0%) developed FoG during the visit (pre-FoG group). Age, bradykinesia, TD/PIGD classification, fatigue, cognitive impairment, impaired autonomic functions and sleep disorder were found to be significantly different in patients from pre-FoG and non-FoG groups at baseline. The logistic regression model showed that motor factors such as TD/PIGD classification (OR = 2.67, 95% CI = 1.41-5.09), MDS-UPDRS part III score (OR = 1.05, 95% CI = 1.01-1.09) were associated with FoG occurrence. Several indicators representing non-motor symptoms such as SDMT total score (OR = 0.95, 95% CI = 0.91-0.98), HVLT immediate/Total recall (OR = 0.91, 95% CI = 0.86-0.97), MOCA (OR = 0.87, 95% CI = 0.76-0.99), Epworth Sleepiness Scale (OR = 1.13, 95% CI = 1.03-1.24), fatigue(OR = 1.98, 95% CI = 1.32-3.06), SCOPA-AUT gastrointestinal score (OR = 1.27, 95% CI = 1.09-1.49) and SCOPA-AUT urinary score (OR = 1.18, 95% CI = 1.06-1.32) were found to have the predictive value. PD patients that developed FoG showed a significant reduction of DAT uptake in the striatum. However, no difference at baseline was observed in genetic characteristics and CSF biomarkers between the two patient sets. Our model indicated that TD/PIGD classification, MDS-UPDRS total score, and Symbol Digit Modalities score were independent risk factors for the onset of FoG in PD patients. In conclusion, the combination of motor and non-motor features including the akinetic subtype and poor cognitive functions should be considered in identifying PD patients with high risks of FoG onset.

scholarly journals P.015 Long-term progression and prognosis in different subtypes of Parkinson’s disease: validation of a new multi-domain subtyping method

2019 ◽  
Vol 46 (s1) ◽  
pp. S17
Author(s):  
S Fereshtehnejad ◽  
Y Zeighami ◽  
A Dagher ◽  
RB Postuma
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
De Novo ◽  
Early Stage ◽  
Real Life ◽  
Clinical Manifestations ◽  
Personalized Care ◽  
Autonomic Disturbance ◽  
Progression Markers

Background: Parkinson’s disease (PD) varies in clinical manifestations and course of progression from person to person. Identification of distinct PD subtypes is of great priority to develop personalized care approaches. We aimed to compare long-term progression and prognosis between different PD subtypes. Methods: Data on 421 individuals with de novo early-onset PD was retrieved from Parkinson’s Progression Markers Initiative (PPMI). Using a newly developed multi-domain subtyping method (based on motor phenotype, RBD, autonomic disturbance, early cognitive deficit), we divided PD population into three subtypes at baseline: “mild motor-predominant”, “Diffuse malignant” and “Intermediate”. Rate of global progression (mixed motor and non-motor features) and developing dementia were compared between the subtypes. Results: Patients with “diffuse malignant” PD experienced 0.5 z-score further worsening of global composite outcome (p=0.017) and 2.2 further decline in MOCA score (p=0.001) after 6-years of follow-up. Hazard for MCI/dementia was significantly higher in “diffuse malignant” (HR=3.2, p<0.001) and “intermediate” (HR=1.8, p<0.001) subtypes. Individuals with “diffuse malignant” PD had the lowest level of CSF amyloid-beta (p=0.006) and SPECT striatal binding ratio (p=0.001). Conclusions: This multi-domain subtyping is a valid method to predict subgroups of PD with distinct patterns of long-term progression at drug-naïve early-stage with potential application in real-life clinical practice.

scholarly journals High diagnostic performance of independent alpha-synuclein seed amplification assays for detection of early Parkinson’s disease

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Marco J. Russo ◽  
Christina D. Orru ◽  
Luis Concha-Marambio ◽  
Simone Giaisi ◽  
Bradley R. Groveman ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Diagnosis ◽  
Diagnostic Performance ◽  
De Novo ◽  
Alpha Synuclein ◽  
Diagnostic Tools ◽  
Dat Spect ◽  
Progression Markers ◽  
Early Parkinson’S Disease

AbstractAlpha-synuclein seed amplification assays (αSyn-SAAs) are promising diagnostic tools for Parkinson’s disease (PD) and related synucleinopathies. They enable detection of seeding-competent alpha-synuclein aggregates in living patients and have shown high diagnostic accuracy in several PD and other synucleinopathy patient cohorts. However, there has been confusion about αSyn-SAAs for their methodology, nomenclature, and relative accuracies when performed by various laboratories. We compared αSyn-SAA results obtained from three independent laboratories to evaluate reproducibility across methodological variations. We utilized the Parkinson’s Progression Markers Initiative (PPMI) cohort, with DATSCAN data available for comparison, since clinical diagnosis of early de novo PD is critical for neuroprotective trials, which often use dopamine transporter imaging to enrich their cohorts. Blinded cerebrospinal fluid (CSF) samples for a randomly selected subset of PPMI subjects (30 PD, 30 HC, and 20 SWEDD), from both baseline and year 3 collections for the PD and HC groups (140 total CSF samples) were analyzed in parallel by each lab according to their own established and optimized αSyn-SAA protocols. The αSyn-SAA results were remarkably similar across laboratories, displaying high diagnostic performance (sensitivity ranging from 86 to 96% and specificity from 93 to 100%). The assays were also concordant for samples with results that differed from clinical diagnosis, including 2 PD patients determined to be clinically inconsistent with PD at later time points. All three assays also detected 2 SWEDD subjects as αSyn-SAA positive who later developed PD with abnormal DAT-SPECT. These multi-laboratory results confirm the reproducibility and value of αSyn-SAA as diagnostic tools, illustrate reproducibility of the assay in expert hands, and suggest that αSyn-SAA has potential to provide earlier diagnosis with comparable or superior accuracy to existing methods.

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 Sex-Related Longitudinal Change of Motor, Non-Motor, and Biological Features in Early Parkinson’s Disease

2021 ◽  
pp. 1-16
Author(s):  
Marina Picillo ◽  
David-Erick LaFontant ◽  
Susan Bressman ◽  
Chelsea Caspell-Garcia ◽  
Christopher Coffey ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
De Novo ◽  
Longitudinal Change ◽  
Csf Biomarkers ◽  
Longitudinal Changes ◽  
Multiplicative Factor ◽  
Progression Markers ◽  
And Biological Markers ◽  
Updrs Part

Background: Investigation of sex-related motor and non-motor differences and biological markers in Parkinson’s disease (PD) may improve precision medicine approach. Objective: To examine sex-related longitudinal changes in motor and non-motor features and biologic biomarkers in early PD. Methods: We compared 5-year longitudinal changes in de novo, untreated PD men and women (at baseline N = 423; 65.5%male) of the Parkinson’s Progression Markers Initiative (PPMI), assessing motor and non-motor manifestations of disease; and biologic measures in cerebrospinal fluid (CSF) and dopamine transporter deficit on DaTscanTM uptake. Results: Men experienced greater longitudinal decline in self-reported motor (p <  0.001) and non-motor (p = 0.009) aspects of experiences of daily living, such that men had a yearly increase in MDS-UPDRS part II by a multiplicative factor of 1.27 compared to women at 0.7, while men had a yearly increase in MDS-UPDRS part I by a multiplicative factor of 0.98, compared to women at 0.67. Compared to women, men had more longitudinal progression in clinician-assessed motor features in the ON medication state (p = 0.010) and required higher dopaminergic medication dosages over time (p = 0.014). Time to reach specific disease milestones and longitudinal changes in CSF biomarkers and DaTscanTM uptake were not different by sex. Conclusion: Men showed higher self-assessed motor and non-motor burden of disease, with possible contributions from suboptimal dopaminergic therapeutic response in men. However, motor features of disease evaluated with clinician-based scales in the OFF medication state, as well as biological biomarkers do not show specific sex-related progression patterns.

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.

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