The Combination of DAT-SPECT, Structural and Diffusion MRI Predicts Clinical Progression in Parkinson’s Disease

OBJECTIVES/SPECIFIC AIMS: Identify objective neurological substrates of cognitive fatigue in Parkinson’s disease and in aging. METHODS/STUDY POPULATION: Structural and diffusion MRI. Behavioral assessments for aged adults and Parkinson’s disease. RESULTS/ANTICIPATED RESULTS: Gray and white matter deficits that correlate with deficits in the basal ganglia for fatigued Parkinson’s disease patients Versus anterior cingulate cortex in healthy aged adults with fatigue. DISCUSSION/SIGNIFICANCE OF IMPACT: Over 50% of patients with Parkison’s disease and 38% of healthy older adults suffer from cognitive fatigue. However, diagnostics are limited to subjective surveys and there are no treatments for either population. Therefore, objective measures are greatly needed for better diagnosis and development of treatment targets.

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Imaging Parkinson's disease using functional and diffusion MRI

Parkinsonism & Related Disorders ◽

10.1016/j.parkreldis.2019.06.006 ◽

2019 ◽

Vol 62 ◽

pp. 1-2 ◽

Cited By ~ 2

Author(s):

Irena Rektorova

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Diffusion Mri ◽

And Diffusion

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

Journal of Parkinson s Disease ◽

10.3233/jpd-212761 ◽

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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Using Artificial Neural Network to Discriminate Parkinson’s Disease from Other Parkinsonisms by Focusing on Putamen of Dopamine Transporter SPECT Images

Biomedicines ◽

10.3390/biomedicines9010012 ◽

2020 ◽

Vol 9 (1) ◽

pp. 12

Author(s):

Chung-Yao Chien ◽

Szu-Wei Hsu ◽

Tsung-Lin Lee ◽

Pi-Shan Sung ◽

Chou-Ching Lin

Keyword(s):

Neural Network ◽

Parkinson’S Disease ◽

Artificial Neural Network ◽

Support Vector Machine ◽

Parkinson's Disease ◽

Dopamine Transporter ◽

Support Vector ◽

Dat Spect ◽

Ann Classifier ◽

Spect Images

Background: The challenge of differentiating, at an early stage, Parkinson’s disease from parkinsonism caused by other disorders remains unsolved. We proposed using an artificial neural network (ANN) to process images of dopamine transporter single-photon emission computed tomography (DAT-SPECT). Methods: Abnormal DAT-SPECT images of subjects with Parkinson’s disease and parkinsonism caused by other disorders were divided into training and test sets. Striatal regions of the images were segmented by using an active contour model and were used as the data to perform transfer learning on a pre-trained ANN to discriminate Parkinson’s disease from parkinsonism caused by other disorders. A support vector machine trained using parameters of semi-quantitative measurements including specific binding ratio and asymmetry index was used for comparison. Results: The predictive accuracy of the ANN classifier (86%) was higher than that of the support vector machine classifier (68%). The sensitivity and specificity of the ANN classifier in predicting Parkinson’s disease were 81.8% and 88.6%, respectively. Conclusions: The ANN classifier outperformed classical biomarkers in differentiating Parkinson’s disease from parkinsonism caused by other disorders. This classifier can be readily included into standalone computer software for clinical application.

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Transcranial sonography of the substantia nigra and its correlation with DAT-SPECT in the diagnosis of Parkinson’s disease

Journal of the Neurological Sciences ◽

10.1016/j.jns.2015.08.835 ◽

2015 ◽

Vol 357 ◽

pp. e238

Author(s):

S. Chen

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Substantia Nigra ◽

Transcranial Sonography ◽

Dat Spect

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Parkinson’s Disease Progression and Statins: Hydrophobicity Matters

Journal of Parkinson s Disease ◽

10.3233/jpd-212819 ◽

2021 ◽

pp. 1-10

Author(s):

Mechelle M. Lewis ◽

Richard M. Albertson ◽

Guangwei Du ◽

Lan Kong ◽

Andrew Foy ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Rating Scales ◽

Motor Symptoms ◽

Clinical Progression ◽

Mixed Effect ◽

Lipophilic Statin ◽

Hydrophilic Statin ◽

Non Motor Symptoms ◽

Statin Use

Background: Recent randomized clinical trials using hydrophobic statins reported no influence on Parkinson’s disease (PD) clinical progression. Hydrophobicity is a key determinant for blood-brain barrier penetrance. Objective: Investigate a potential effect of statins on PD progression. Methods: Statin use was determined at baseline and subtyped according to hydrophobicity in 125 PD patients participated PD Biomarker Program (PDBP, 2012–2015) at our site. Clinical (N = 125) and susceptibility MRI (N = 86) data were obtained at baseline and 18-months. Movement Disorders Society-Unified PD Rating Scales were used to track progression of non-motor (MDS-UPDRS-I) and motor (MDS-UPDRS-II) symptoms, and rater-based scores (MDS-UPDRS-III) of patients in the “on” drug state. R2 * values were used to capture pathological progression in the substantia nigra. Associations between statin use, its subtypes, and PD progression were evaluated with linear mixed effect regressions. Results: Compared to statin non-users, overall statin or lipophilic statin use did not significantly influence PD clinical or imaging progression. Hydrophilic statin users, however, demonstrated faster clinical progression of non-motor symptoms [MDS-UPDRS-I (β= 4.8, p = 0.010)] and nigral R2 * (β= 3.7, p = 0.043). A similar trend was found for MDS-UPDRS-II (β= 3.9, p = 0.10), but an opposite trend was observed for rater-based MDS-UPDRS-III (β= –7.3, p = 0.10). Compared to lipophilic statin users, hydrophilic statin users also showed significantly faster clinical progression of non-motor symptoms [MDS-UPDRS-I (β= 5.0, p = 0.020)], but R2 * did not reach statistical significance (β= 2.5, p = 0.24). Conclusion: This study suggests that hydrophilic, but not lipophilic, statins may be associated with faster PD progression. Future studies may have clinical and scientific implications.

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Dermal fibroblasts from patients with Parkinson’s disease have normal GCase activity and autophagy compared to patients with PD and GBA mutations

F1000Research ◽

10.12688/f1000research.12090.1 ◽

2017 ◽

Vol 6 ◽

pp. 1751 ◽

Cited By ~ 3

Author(s):

Lucy M Collins ◽

Janelle Drouin-Ouellet ◽

Wei-Li Kuan ◽

Timothy Cox ◽

Roger A Barker

Keyword(s):

Risk Factors ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Genetic Risk ◽

Gaucher Disease ◽

Dermal Fibroblasts ◽

Skin Fibroblasts ◽

Autophagic Flux ◽

Clinical Progression ◽

Gba Mutations

Background: Recently, the development of Parkinson’s disease (PD) has been linked to a number of genetic risk factors, of which the most common is glucocerebrosidase (GBA) mutations. Methods: We investigated PD and Gaucher Disease (GD) patient derived skin fibroblasts using biochemistry assays. Results: PD patient derived skin fibroblasts have normal glucocerebrosidase (GCase) activity, whilst patients with PD and GBA mutations have a selective deficit in GCase enzyme activity and impaired autophagic flux. Conclusions: This data suggests that only PD patients with a GBA mutation have altered GCase activity and autophagy, which may explain their more rapid clinical progression.

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Chronic coffee consumption and striatal DAT-SPECT findings in Parkinson’s disease

Neurological Sciences ◽

10.1007/s10072-018-3253-1 ◽

2018 ◽

Vol 39 (3) ◽

pp. 551-555 ◽

Cited By ~ 2

Author(s):

Angelo Fabio Gigante ◽

Artor Niccoli Asabella ◽

Giovanni Iliceto ◽

Tommaso Martino ◽

Cristina Ferrari ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Coffee Consumption ◽

Dat Spect

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Levodopa-Responsive Primary Slow Orthostatic Tremor: A Premotor Sign of Parkinson’s Disease?

Case Reports in Neurology ◽

10.1159/000504798 ◽

2020 ◽

Vol 12 (1) ◽

pp. 1-6

Author(s):

Fumihito Yoshii ◽

Wakoh Takahashi ◽

Koji Aono

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Surface Electromyography ◽

Specific Binding ◽

Low Frequency ◽

Orthostatic Tremor ◽

Specific Binding Ratio ◽

Dopaminergic Medication ◽

Neurological Signs ◽

Dat Spect

We present a case of primary orthostatic tremor (OT) responsive to dopaminergic medication. The patient was a 62-year-old woman, who had leg tremor on standing for 2 years. No parkinsonian or other neurological signs were observed. Surface electromyography of the quadriceps muscles showed regular 5–6 Hz muscle discharges. [123I]-FP-CIT DAT-SPECT imaging revealed decreased specific binding ratio values in the striatum compared with age-matched controls. Her leg tremor almost completely disappeared following administration of levodopa 200 mg and pramipexole 0.75 mg. Since her OT with low-frequency discharge was responsive to dopaminergic medication, we speculate that it may be a premotor sign of Parkinson’s disease.

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