Serum mBDNF and ProBDNF Expression Levels as Diagnosis Clue for Early Stage Parkinson's Disease

Parkinson's disease (PD) is one of the most common chronic, progressive, and neurodegenerative diseases characterized clinically by resting tremor, bradykinesia, rigidity, and postural instability. As this disease is usually detected in the later stages, the cure is often delayed, ultimately leading to disability due to the lack of early diagnostic techniques. Therefore, it is of great importance to identify reliable biomarkers with high sensitivity and specificity for the early diagnosis of PD. In this study, we aimed to investigate whether serum expressions of mature brain-derived neurotrophic factor (mBDNF) and proBDNF can serve as biomarkers for the diagnosis of PD at early stage. One hundred and fifty-six patients with limb tremor and/or bradykinesia meeting the inclusion criteria were assigned to either ex-PD group (PD cases) or ex-NPD group (non-PD cases) and then reassigned to either po-PD group (with PD) or po-NPD group (without PD) at 1-year follow-up based on the results of the rediagnoses as performed in accordance with MDS Parkinson's diagnostic criteria. To improve early diagnostic accuracy, grouping (PD group and non-PD group) at initial visit and follow-up was performed differently and independently. Serum mBDNF and proBDNF levels were measured by enzyme-linked immunosorbent assays. The results demonstrated that serum levels of mBDNF and mBDNF/proBDNF were significantly lower in the ex-PD group (19.73 ± 7.31 and 0.09 ± 0.05 ng/ml) as compared with the ex-NPD group (23.47 ± 8.21 and 0.15 ± 0.12 ng/ml) (p < 0.01 for both) and in the po-PD group (19.24 ± 7.20 and 0.09 ± 0.05 ng/ml) as compared with the po-NPD group (25.05 ± 7.67 and 0.16 ± 0.14 ng/ml) (p < 0.01 for both). However, a significantly higher serum level of proBDNF was noted in the ex-PD group (235.49 ± 60.75 ng/ml) as compared with the ex-NPD group (191.75 ± 66.12 ng/ml) (p < 0.01) and in the po-PD group (235.56 ± 60.80 ng/ml) as compared with the po-NPD group (188.42 ± 65.08 ng/ml) (p < 0.01). In conclusion, mBDNF/proBDNF can be used as biomarkers for early stage Parkinson's disease; in addition, mBDNF plus proBDNF has better diagnostic value than mBDNF alone in the diagnosis of PD.

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Retinal Morphological Changes during the Two Years of Follow-Up in Parkinson's Disease

10.21203/rs.3.rs-17217/v1 ◽

2020 ◽

Author(s):

Mahmut Atum ◽

Bekir Enes Demiryurek

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Rating Scale ◽

Early Stage ◽

Morphological Changes ◽

Fiber Layer ◽

Significant Difference ◽

Yahr Scale ◽

And Control

Abstract Background: The study aims to investigate the relationship between the progression of idiopathic Parkinson's disease (IPD) and retinal morphology. Methods: The study was carried out with 23 patients diagnosed with early-stage IPD (phases 1 and 2 of the Hoehn and Yahr scale) and 30 age-matched healthy controls. All patients were followed up at least two years, with 6-month intervals (initial, 6th month, 12th month, 18th month, and 24th month), and detailed neurological and ophthalmic examinations were performed at each follow-up. Unified Parkinson's Disease Rating Scale part III (UPDRS Part III) scores, Hoehn and Yahr (H&Y) scores, best-corrected visual acuity (BCVA), intraocular pressure (IOP) measurement, central macular thickness (CMT) and retinal nerve fiber layer (RNFL) thickness were analyzed at each visit. Results: The average age of the IPD and control groups was 43.96 ± 4.88 years, 44.53 ± 0.83 years, respectively. The mean duration of the disease in the IPD group was 7.48 ± 5.10 months at the start of the study (range 0-16). There was no statistically significant difference in BCVA and IOP values between the two groups during the two-year follow-up period (p> 0.05, p> 0.05, respectively). Average and superior quadrant RNFL thicknesses were statistically different between the two groups at 24 months and there was no significant difference between other visits (p = 0.025, p=0.034, p> 0.05, respectively). There was no statistically significant difference in CMT between the two groups during the follow-up period (p> 0.05). Conclusion: Average and superior quadrant RNFL thicknesses were significantly thinning with the progression of IPD.

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The Clinical Non-Motor Connectome in Early Parkinson’s Disease

Journal of Parkinson s Disease ◽

10.3233/jpd-202102 ◽

2020 ◽

Vol 10 (4) ◽

pp. 1797-1806

Author(s):

Nico J. Diederich ◽

Nicolas Sauvageot ◽

Vannina Pieri ◽

Géraldine Hipp ◽

Michel Vaillant

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Early Stage ◽

Correlation Coefficients ◽

P Value ◽

The Mean ◽

Disease Initiation ◽

Non Motor Symptoms ◽

Early Parkinson’S Disease

Background: Non-motor symptoms (NMS) of various anatomical origins are seen in early stage idiopathic Parkinson’s disease (IPD). Objective: To analyse when and how NMS are linked together at this stage of the disease. Methods: Prospective study recruiting 64 IPD patients with ≤3 years of disease duration and 71 age-matched healthy controls (HC). NMS were clustered in 7 non-motor domains (NMD): general cognition, executive function, visuospatial function, autonomic function, olfaction, mood, and sleep. Correlation coefficients ≥|0.3| were considered as significant. Bootstrapped correlation coefficients between the scores were generated in both groups. Fourteen IPD patients and 19 HC were available for a follow-up study two years later. Results: The mean age of both groups was similar. 58% of IPD patients and 37% of HC were male (p = 0.01). At baseline IPD patients performed less well than HC on all NMD (p value between 0.0001 and 0.02). Out of 91 possible correlations between NMD, 21 were significant in IPD patients and 14 in HC at the level of ≥|0.3|. The mean correlation level was higher in IPD patients than in HC, as evidenced by the higher box plot of correlation coefficients. Visuospatial scores at baseline were predictive of the motor deterioration at the follow-up exam. Conclusion: At early IPD stage various NMS are linked together, although not connected by anatomical networks. Such a clinical NMD connectome suggests almost synchronous disease initiation at different sites as also supported by fMRI findings. Alternatively, there may be compensation-driven interconnectivity of NMD.

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The effects of motor rehabilitation training on clinical symptoms and serum BDNF levels in Parkinson’s disease subjects

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2015-0322 ◽

2016 ◽

Vol 94 (4) ◽

pp. 455-461 ◽

Cited By ~ 24

Author(s):

Francesco Angelucci ◽

Jacopo Piermaria ◽

Francesca Gelfo ◽

Jacob Shofany ◽

Marco Tramontano ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Clinical Symptoms ◽

Serum Levels ◽

Motor Rehabilitation ◽

Walking Test ◽

Rehabilitation Training ◽

Extrapyramidal Signs ◽

Serum Bdnf

Increasing evidence suggests that motor rehabilitation may delay Parkinson’s disease (PD) progression. Moreover, parallel treatments in animals up-regulate brain-derived neurotrophic factor (BDNF). Thus, we investigated the effect of a motor rehabilitation protocol on PD symptoms and BDNF serum levels. Motor rehabilitation training consisted of a cycle of 20 days/month of physiotherapy divided in 3 daily sessions. Clinical data were collected at the beginning, at the end, and at 90 days follow-up. BDNF serum levels were detected by ELISA at 0, 7, 14, 21, 30, and 90 days. The follow-up period had a duration of 60 days (T30–T90). The results showed that at the end of the treatment (day 30), an improvement in extrapyramidal signs (UPDRS III; UPDRS III – Gait and Balance items), motor (6 Minute Walking Test), and daily living activities (UPDRS II; PDQ-39) was observed. BDNF levels were increased at day 7 as compared with baseline. After that, no changes in BDNF were observed during the treatment and in the successive follow-up. This study demonstrates that motor rehabilitation training is able to ameliorate PD symptoms and to increase temporarily BDNF serum levels. The latter effect may potentially contribute to the therapeutic action.

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Mild Gait Impairment and Its Potential Diagnostic Value in Patients with Early-Stage Parkinson’s Disease

Behavioural Neurology ◽

10.1155/2021/6696454 ◽

2021 ◽

Vol 2021 ◽

pp. 1-8

Author(s):

Zhuang Wu ◽

Xu Jiang ◽

Min Zhong ◽

Bo Shen ◽

Jun Zhu ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Early Stage ◽

Wearable Sensors ◽

Diagnostic Value ◽

Gait Pattern ◽

Heel Strike ◽

Phase Time ◽

Gait Parameters ◽

Gait Impairments

Background and Purpose. Patients with early-stage Parkinson’s disease (PD) have gait impairments, and gait parameters may act as diagnostic biomarkers. We aimed to (1) comprehensively quantify gait impairments in early-stage PD and (2) evaluate the diagnostic value of gait parameters for early-stage PD. Methods. 32 patients with early-stage PD and 30 healthy control subjects (HC) were enrolled. All participants completed the instrumented stand and walk test, and gait data was collected using wearable sensors. Results. We observed increased variability of stride length (SL) ( P < 0.001 ), stance phase time (StPT) ( P = 0.004 ), and swing phase time (SwPT) ( P = 0.011 ) in PD. There were decreased heel strike (HS) ( P = 0.001 ), range of motion of knee ( P = 0.036 ), and hip joints ( P < 0.001 ) in PD. In symmetry analysis, no difference was found in any of the assessed gait parameters between HC and PD. Only total steps ( AUC = 0.763 , P < 0.001 ), SL ( AUC = 0.701 , P = 0.007 ), SL variability ( AUC = 0.769 , P < 0.001 ), StPT variability ( AUC = 0.712 , P = 0.004 ), and SwPT variability ( AUC = 0.688 , P = 0.011 ) had potential diagnostic value. When these five gait parameters were combined, the predictive power was found to increase, with the highest AUC of 0.802 ( P < 0.001 ). Conclusions. Patients with early-stage PD presented increased variability but still symmetrical gait pattern. Some specific gait parameters can be applied to diagnose early-stage PD which may increase diagnosis accuracy. Our findings are helpful to improve patient’s quality of life.

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Is transcranial sonography useful for diagnosing Parkinson’s disease in clinical practice?

Arquivos de Neuro-Psiquiatria ◽

10.1590/0004-282x20180067 ◽

2018 ◽

Vol 76 (7) ◽

pp. 459-466 ◽

Cited By ~ 1

Author(s):

Talyta Cortez Grippe ◽

Nasser Allam ◽

Pedro Renato de Paula Brandão ◽

Danilo Assis Pereira ◽

Francisco Eduardo Costa Cardoso ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Clinical Diagnosis ◽

Positive Likelihood Ratio ◽

High Sensitivity ◽

Transcranial Sonography ◽

Substantia Nigra Hyperechogenicity ◽

Practical Usefulness ◽

Alternative Condition

ABSTRACT Transcranial sonography (TCS) is an emerging ancillary examination for diagnosing Parkinson’s disease (PD). Objective To evaluate TCS features in patients with PD and its mimics, and establish their accuracy in predicting the final clinical diagnosis after follow-up. Methods We retrospectively studied 85 patients with an initial clinical suspicion of PD, atypical parkinsonism or essential tremor, all of whom underwent TCS. Two specialists reviewed the follow-up clinical visit records and determined the final clinical diagnosis. The accuracy analysis of the TCS was determined using Bayesian statistical methods. Results The finding of substantia nigra hyperechogenicity (> 20 mm2) showed high sensitivity (93.4%) and specificity (86.6%). The positive likelihood ratio showed 6.93-fold greater odds for diagnosing PD than an alternative condition when this finding was present. Conclusions This study revealed the practical usefulness of TCS in differentiating PD from its prevalent mimics when the clinical diagnosis was initially unclear.

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Early-stage [123I]β-CIT SPECT and long-term clinical follow-up in patients with an initial diagnosis of Parkinson’s disease

European Journal of Nuclear Medicine and Molecular Imaging ◽

10.1007/s00259-004-1733-4 ◽

2005 ◽

Vol 32 (6) ◽

pp. 689-695 ◽

Cited By ~ 21

Author(s):

Diederick Stoffers ◽

Jan Booij ◽

Lisette Bosscher ◽

Ania Winogrodzka ◽

Erik C. Wolters ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Early Stage ◽

Initial Diagnosis

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Delayed orthostatic hypotension in Parkinson’s disease

npj Parkinson s Disease ◽

10.1038/s41531-021-00181-y ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Sang-Won Yoo ◽

Joong-Seok Kim ◽

Ji-Yeon Yoo ◽

Eunkyeong Yun ◽

Uicheul Yoon ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Orthostatic Hypotension ◽

Disease Severity ◽

Cortical Thickness ◽

Early Stage ◽

Brain Magnetic Resonance Imaging ◽

Clinical Scales ◽

Drug Naïve

AbstractOrthostatic hypotension (OH) is relatively common in the early stage of Parkinson’s disease (PD). It is divided into delayed OH and classical OH. Classical OH in PD has been investigated widely, however, the clinical implications of delayed OH in PD have seldom been studied. The purpose of this study is to characterize delayed OH in PD. A total of 285 patients with early drug-naïve PD were enrolled and divided into three groups according to orthostatic change: no-OH, delayed OH, and classical OH. The disease severity in terms of motor, non-motor, and cognitive functions was assessed. The cortical thickness of 82 patients was analyzed with brain magnetic resonance imaging. The differences among groups and linear tendency in the order of no-OH, delayed OH, and classical OH were investigated. Seventy-seven patients were re-evaluated. Initial and follow-up evaluations were explored to discern any temporal effects of orthostasis on disease severity. Sixty-four (22.5%) patients were defined as having delayed OH and 117 (41.1%) had classical OH. Between-group comparisons revealed that classical OH had the worst outcomes in motor, non-motor, cognitive, and cortical thickness, compared to the other groups. No-OH and delayed OH did not differ significantly. Linear trends across the pre-ordered OH subtypes found that clinical parameters worsened along with the orthostatic challenge. Clinical scales deteriorated and the linear gradient was maintained during the follow-up period. This study suggests that delayed OH is a mild form of classical OH in PD. PD with delayed OH has milder disease severity and progression.

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Osteoporosis and the Risk of Parkinson’s Disease: A Nationwide, Propensity Score–Matched, Longitudinal Follow-up Study

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa864 ◽

2020 ◽

Author(s):

Shih-Hao Feng ◽

Ya-Ping Huang ◽

Kuo-Cheng Yeh ◽

Shin-Liang Pan

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Propensity Score ◽

Propensity Scores ◽

Comparison Group ◽

Early Stage ◽

Research Database ◽

Mineral Density ◽

Increased Risk

Abstract Context Osteoporosis and Parkinson’s disease (PD) often co-occur, and even patients with early-stage PD may have reduced bone-mineral density levels. This may imply that osteoporosis is associated with a higher risk of PD. Objectives This work aimed to determine whether patients with osteoporosis are at a higher risk of subsequently developing PD. Design and Setting A retrospective cohort study was conducted using Taiwan’s National Health Insurance Research Database. Participants A total of 23 495 individuals age 50 to 80 years who had osteoporosis between 2002 and 2006 were enrolled in the osteoporosis group. The comparison group comprised 23 495 propensity score–matched patients without osteoporosis. Their propensity scores were computed using a logistic regression model that included age, sex, comorbid conditions, and socioeconomic status. Results The hazard ratio (HR) of PD for the osteoporosis group was 1.31 times larger than that of the comparison group (95% CI, 1.13-1.50, P < .001). The PD-free survival rate of the osteoporosis group was also significantly lower than that of the comparison group (P < .001). The analyses stratified by sex showed that women with osteoporosis appeared to have a higher magnitude of PD HR (HR 1.50; 95% CI, 1.27-1.77, P < .001) than their male counterparts (HR 1.23; 95% CI, 0.93-1.64, P = .15). Conclusions The present study’s results suggest that osteoporosis is related to an increased risk of PD, especially among women.

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Diagnostic accuracy of glabellar tap sign for Parkinson’s disease

Journal of Neural Transmission ◽

10.1007/s00702-021-02391-3 ◽

2021 ◽

Author(s):

Simo Nuuttila ◽

Mikael Eklund ◽

Juho Joutsa ◽

Elina Jaakkola ◽

Elina Mäkinen ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Diagnostic Value ◽

Clinical Test ◽

Diagnostic Validity ◽

Healthy Controls ◽

Validity And Reliability ◽

Dopaminergic Activity ◽

Over Time

AbstractGlabellar tap or reflex (GR) is an old bedside clinical test used in the diagnostics of Parkinson’s disease (PD), but its diagnostic value is unclear. This study examines the diagnostic validity and reliability of GR in PD in relation to brain dopaminergic activity. GR was performed on 161 patients with PD, 47 patients with essential tremor (ET) and 40 healthy controls immediately prior to dopamine transporter (DAT) [123I]FP-CIT SPECT scanning. The binding ratios were investigated with consideration of the GR result (normal/abnormal). In addition, the consistency of the GR was investigated with 89 patients after a mean follow-up of 2.2 years. PD and ET patients had higher GR scores than healthy controls (p < 0.001), but there was no difference in GR between PD and ET patients (p = 0.09). There were no differences in the ratio of abnormal to normal GRs between the PD and ET groups (73% vs. 64% abnormal, respectively, p = 0.13) or in DAT binding between PD patients with abnormal and normal GRs (p > 0.36). Over follow-up, the GR changed from abnormal to normal in 20% of PD patients despite the presence of clinically typical disease. The sensitivity and specificity of GR for differentiating PD from ET were 78.3% and 36.2%, respectively. Although GR has been used by clinicians in the diagnostics of PD, it does not separate PD from ET. It also shows considerable inconsistency over time, and abnormal GR has no relationship with dopamine loss. Its usefulness should be tested for other clinical diagnostic purposes.

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