Journal of Parkinson's Disease - Volume 6, issue 2

Authors: van Uem, Janet M.T. | Isaacs, Tom | Lewin, Alan | Bresolin, Eros | Salkovic, Dina | Espay, Alberto J. | Matthews, Helen | Maetzler, Walter

Article Type: Review Article

Abstract: In this viewpoint, we discuss how several aspects of Parkinson’s disease (PD) – known to be correlated with wellbeing and health-related quality of life–could be measured using wearable devices (‘wearables’). Moreover, three people with PD (PwP) having exhaustive experience with using such devices write about their personal understanding of wellbeing and health-related quality of life, building a bridge between the true needs defined by PwP and the available methods of data collection. Rapidly evolving new technologies develop wearables that probe function and behaviour in domestic environments of people with chronic conditions such as PD and have the potential to serve …their needs. Gathered data can serve to inform patient-driven management changes, enabling greater control by PwP and enhancing likelihood of improvements in wellbeing and health-related quality of life. Data can also be used to quantify wellbeing and health-related quality of life. Additionally these techniques can uncover novel more sensitive and more ecologically valid disease-related endpoints. Active involvement of PwP in data collection and interpretation stands to provide personally and clinically meaningful endpoints and milestones to inform advances in research and relevance of translational efforts in PD. Show more

Keywords: Body fixed sensors, health-related quality of life, Parkinson’s disease, wearable devices, wellbeing

DOI: 10.3233/JPD-150740

Citation: Journal of Parkinson's Disease, vol. 6, no. 2, pp. 279-287, 2016

Authors: Swallow, Diane M.A. | Lawton, Michael A. | Grosset, Katherine A. | Malek, Naveed | Smith, Callum R. | Bajaj, Nin P. | Barker, Roger A. | Ben-Shlomo, Yoav | Burn, David J. | Foltynie, Thomas | Hardy, John | Morris, Huw R. | Williams, Nigel | Wood, Nicholas W. | Grosset, Donald G. | on behalf of PRoBaND Clinical Consortium

Article Type: Review Article

Abstract: Background: The detection of prodromal Parkinson’s disease (PD) is desirable to test drugs with neuroprotective potential, but will be affected by known disease variations. Objective: To assess the prevalence of four key non-motor prodromal PD markers, and evaluate the sensitivity of case detection when non-motor screening tools for prodromal PD are implemented in an early clinical PD cohort. Methods: Hyposmia (University of Pennsylvania smell identification test ≤15th centile or Sniffin’ Sticks at or ≤10th centile corrected for age and sex), rapid-eye movement sleep behaviour disorder (RBD questionnaire >4), constipation (<1 daily spontaneous bowel motion) and …depression (Leeds >6) were recorded in recent onset PD cases, and proposed non-motor screening criteria applied. Results: In 1,719 PD cases, mean age 68.6 years (SD 8.1), 65.5% male, mean disease duration 1.3 years (SD 0.9), 72.2% were hyposmic, 43.3% had RBD, 22.1% depression, and 21.5% constipation. 11.6% of cases had no key non-motor features, 38.8% one, 32.1% two, 15.5% three, and 2.0% all four. Increasing numbers of non-motor features were associated with younger age (p  = 0.019), higher motor scores (p  < 0.001), more postural instability gait difficulty (PIGD) (p  < 0.001), greater cognitive impairment (p  < 0.001) and higher total non-motor burden (p  < 0.001). Cases with hyposmia alone were younger (p  < 0.001), had less severe cognitive (p = 0.006) and other non-motor features (p  < 0.001). All screening criteria selected younger patients (p = 0.001, p  < 0.001), three of four greater overall non-motor burden (p = 0.005, p  < 0.001), and inclusion of RBD more cognitive impairment (p = 0.003, p = 0.001) and PIGD (p = 0.004, p = 0.001). Conclusions: Varying sensitivity levels, and age and phenotype selectivity, are found when different non-motor screening methods to detect prodromal PD are applied to an early clinical PD cohort. Show more

Keywords: Parkinson disease, anosmia, rapid eye movement sleep behavior disorder, depression, constipation

DOI: 10.3233/JPD-150741

Citation: Journal of Parkinson's Disease, vol. 6, no. 2, pp. 289-300, 2016

Authors: Paul, Serene S. | Ellis, Terry D. | Dibble, Leland E. | Earhart, Gammon M. | Ford, Matthew P. | Foreman, K. Bo | Cavanaugh, James T.

Article Type: Short Communication

Abstract: We determined the number of days required, and whether to include weekdays and/or weekends, to obtain reliable measures of ambulatory physical activity in people with Parkinson’s disease (PD). Ninety-two persons with PD wore a step activity monitor for seven days. The number of days required to obtain a reliable estimate of daily activity was determined from the mean intraclass correlation (ICC2,1 ) for all possible combinations of 1–6 consecutive days of monitoring. Two days of monitoring were sufficient to obtain reliable daily activity estimates (ICC2,1  > 0.9). Amount (p  = 0.03) but not intensity (p  = 0.13) of ambulatory activity was greater on …weekdays than weekends. Activity prescription based on amount rather than intensity may be more appropriate for people with PD. Show more

Keywords: Exercise, physical fitness, Parkinson disease, reproducibility of results

DOI: 10.3233/JPD-160791

Citation: Journal of Parkinson's Disease, vol. 6, no. 2, pp. 301-305, 2016

Authors: Boman, Andrea | Svensson, Samuel | Boxer, Adam | Rojas, Julio C. | Seeley, William W. | Karydas, Anna | Miller, Bruce | Kågedal, Katarina | Svenningsson, Per

Article Type: Research Article

Abstract: Background: Clinical diagnosis of parkinsonian syndromes like Parkinson’s disease (PD), corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) is hampered by overlapping symptomatology and lack of diagnostic biomarkers, and definitive diagnosis is only possible post-mortem. Objective: Since impaired protein degradation plays an important role in many neurodegenerative disorders, we hypothesized that profiles of select lysosomal network proteins in cerebrospinal fluid could be differentially expressed in these parkinsonian syndromes. Methods: Cerebrospinal fluid samples were collected from PD patients (n  = 18), clinically diagnosed 4-repeat tauopathy patients; corticobasal syndrome (CBS) (n  = 3) and PSP (n  = 8); and pathologically …diagnosed PSP (n  = 8) and CBD patients (n  = 7). Each patient set was compared to its appropriate control group consisting of age and gender matched individuals. Select lysosomal network protein levels were detected via Western blotting. Factor analysis was used to test the diagnostic sensitivity, specificity and accuracy of the select lysosomal network protein expression profiles. Results: PD, CBD and PSP were markedly different in their cerebrospinal fluid lysosomal network protein profiles. Lysosomal-associated membrane proteins 1 and 2 were significantly decreased in PD; early endosomal antigen 1 was decreased and lysozyme increased in PSP; and lysosomal-associated membrane proteins 1 and 2, microtubule-associated protein 1 light chain 3 and lysozyme were increased in CBD. A panel of lysosomal-associated membrane protein 2, lysozyme and microtubule-associated protein 1 light chain discriminated between controls, PD and 4-repeat tauopathies. Conclusions: This study offers proof of concept that select lysosomal network proteins are differentially expressed in cerebrospinal fluid of Parkinson’s disease, corticobasal syndrome and progressive supranuclear palsy. Lysosomal network protein analysis could be further developed as a diagnostic fluid biomarker in parkinsonian syndromes. Show more

Keywords: Biomarkers, CSF, parkinson’s disease (PD), corticobasal degeneration (CBD), progressive supranuclear palsy (PSP)

DOI: 10.3233/JPD-150759

Citation: Journal of Parkinson's Disease, vol. 6, no. 2, pp. 307-315, 2016

Authors: Wang, Zhi-Yong | Lian, Hui | Zhou, Li | Zhang, Yi-Min | Cai, Qing-Qing | Zheng, Li-Fei | Zhu, Jin-Xia

Article Type: Research Article

Abstract: Background: Parkinson’s disease (PD) is characterized by dopaminergic neuron degeneration in the substantia nigra (SN) accompanied by pathology of the dorsal motor nucleus of the vagus (DMV). Gastroparesis is a common non-motor system symptom of PD in patients and in animal models. However, the underlying mechanism of this symptom is not clear. We previously reported on the expression of enhanced tyrosine hydroxylase (TH) and decreased choline acetyltransferase (ChAT) in the DMV of a PD animal model and colocalization of TH and ChAT with the dopamine receptors D1 and D2 . We hypothesize that these receptors might contribute to …the delayed gastric emptying observed in PD. Objective: To investigate the distribution of D1 and D2 in gastric-projecting DMV neurons and alteration of their distribution in a PD rat model. Methods: Retrograde tracing, double-labeling immunofluorescence techniques and western blotting were used. Results: After injection of the retrograde tracer fluoro-gold (FG) into the gastric wall, FG-labeled gastric-projecting motoneurons were observed in the caudal and rostral parts of the DMV, and neurons with D1 -, D2 - and ChAT- immunoreactivity (IR) were widely colocalized in the DMV. Many TH-IR fibers were observed around the D1 - and D2 -IR neurons. Moreover, decreased D1 and enhanced D2 expression in the DMV was observed in 6-hydroxydopamine (6-OHDA) rats that were treated with a bilateral microinjection of 6-OHDA in the SN. Conclusions: The results indicate that dopamine receptors might affect the activity of gastric-projecting neurons in the DMV, their altered expression may contribute to the gastroparesis observed in PD. Show more

Keywords: Dopamine receptor, dorsal motor nucleus of vagus, retrograde tracer, gastroparesis, Parkinson’s disease

DOI: 10.3233/JPD-160817

Citation: Journal of Parkinson's Disease, vol. 6, no. 2, pp. 317-323, 2016

Authors: Hatsuta, Hiroyuki | Takao, Masaki | Nakano, Yuta | Nogami, Akane | Uchino, Akiko | Sumikura, Hiroyuki | Kanemaru, Kazutomi | Arai, Tomio | Itoh, Yoshiaki | Murayama, Shigeo

Article Type: Research Article

Abstract: Background and objective: Loss of intermediolateral nucleus (IML) neurons is considered to play a major role in orthostatic hypotension (OH) of multiple system atrophy (MSA). In Parkinson disease (PD) and dementia with Lewy bodies (DLB), autonomic phenomena such as OH are common and attributed to dysfunction of sympathetic, parasympathetic, and visceral autonomic neurons. However, apart from MSA, few reports have focused on the neuropathologic aspects in PD and DLB. Here we assessed IML degeneration as well as the fine myelinated fibers (FFs; maximum diameter less than 3 μm) considered to be preganglionic sympathetic nerve fibers derived from IML neurons …in PD, DLB, MSA, and age-matched normal controls (NC). Methods: We counted IML neurons and measured the diameter and number of myelinated fibers of the ventral root at the level of the 12th thoracic segment. Results: Compared to NC, number of IML neurons and density of FF were significantly reduced in PD (53% and 67%), DLB (47% and 71%) and MSA (27% and 42%). Compared to combined group of PD and DLB without OH (OH–), IML neurons in combined group of PD and DLB with OH (OH+) were significantly reduced (77%). Compared to NC, FF densities in OH–, OH+ were significantly reduced (74% and 59%). The mean ratio of small to large myelinated fibers in OH+ (1.18), but not that in OH–(1.58), was significantly lower than that in NC (3.17). Conclusions: We present neuropathological evidence that IML neurons and FFs in the ventral root are reduced in PD and DLB and that the reduction was more severe in the combined group of OH+ than in OH–. Show more

Keywords: Dementia with Lewy bodies (DLB), intermediolateral nucleus (IML), orthostatic hypotension (OH), Parkinson disease (PD), small myelinated fibers, B fibers

DOI: 10.3233/JPD-150773

Citation: Journal of Parkinson's Disease, vol. 6, no. 2, pp. 325-334, 2016

Authors: Hariz, Gun-Marie | Limousin, Patricia | Hamberg, Katarina

Article Type: Research Article

Keywords: Parkinson disease, deep brain stimulation, qualitative research, grounded theory, adverse effects, patient satisfaction, activities of daily living

DOI: 10.3233/JPD-160799

Citation: Journal of Parkinson's Disease, vol. 6, no. 2, pp. 335-347, 2016

Authors: Paul, Kimberly C. | Rausch, Rebecca | Creek, Michelle M. | Sinsheimer, Janet S. | Bronstein, Jeff M. | Bordelon, Yvette | Ritz, Beate

Article Type: Research Article

Abstract: Background: Cognitive decline is well recognized in Parkinson’s disease (PD) and a major concern for patients and caregivers. Apolipoprotein E (APOE ), catechol-O-methyl transferase (COMT ), and microtubule-associated protein tau (MAPT ) are of interest related to their contributions to cognitive decline or dementia in PD. Objective: Here, we investigate whether APOE , COMT , or MAPT influence the rate of cognitive decline in PD patients. Methods: We relied on 634 PD patients and 879 controls to examine gene-PD susceptibility associations, and nested longitudinal cohort of 246 patients from the case-control study, which followed …patients on average 5 years and 7.5 years into disease. We repeatedly assessed cognitive symptom progression with the MMSE and conducted a full neuropsychological battery on a subset of 183 cognitively normal patients. We used repeated-measures regression analyses to assess longitudinal associations between genotypes and cognitive progression scores. Results: The MAPT H1 haplotype was associated with PD susceptibility. APOE 4 carriers (ɛ 4+) (p  = 0.03) and possibly COMT Met/Met (p  = 0.06) carriers exhibited faster annual decline on the MMSE. Additionally, APOE ɛ 4+ carriers showed faster decline in many of the neuropsychological test scores. No such differences in neuropsychological outcomes were seen for the COMT genotypes. Conclusion: This work supports a growing set of research identifying overlapping etiology and pathology between synucleinopathies, such as PD, Alzheimer’s disease, and tauopathies, especially in the context of cognitive dysfunction in PD. We provide support for the argument that APOE ɛ 4+ and COMT Met/Met genotypes can be used as predictors of faster cognitive decline in PD. Show more

Keywords: APOE, COMT, MAPT, Parkinson’s disease, cognition, cognitive decline

DOI: 10.3233/JPD-150762

Citation: Journal of Parkinson's Disease, vol. 6, no. 2, pp. 349-359, 2016

Authors: Sidtis, John J. | Alken, Amy G. | Tagliati, Michele | Alterman, Ron | Van Lancker Sidtis, Diana

Article Type: Research Article

Abstract: Background: Stimulation of the subthalamic nuclei (STN) is an effective treatment for Parkinson’s disease, but complaints of speech difficulties after surgery have been difficult to quantify. Speech measures do not convincingly account for such reports. Objective: This study examined STN stimulation effects on vowel production, in order to probe whether DBS affects articulatory posturing. The objective was to compare positioning during the initiation phase with the steady prolongation phase by measuring vowel spaces for three “corner” vowels at these two time frames. Methods: Vowel space was measured over the initial 0.25 sec of sustained productions of …high front (/i/), high back (/u/) and low vowels (/a/), and again during a 2 sec segment at the midpoint. Eight right-handed male subjects with bilateral STN stimulation and seven age-matched male controls were studied based on their participation in a larger study that included functional imaging. Mean values: age = 57±4.6 yrs; PD duration = 12.3±2.7 yrs; duration of DBS = 25.6±21.2 mos, and UPDRS III speech score = 1.6±0.7. STN subjects were studied off medication at their therapeutic DBS settings and again with their stimulators off, counter-balanced order. Results: Vowel space was larger in the initiation phase compared to the midpoint for both the control and the STN subjects off stimulation. With stimulation on, however, the initial vowel space was significantly reduced to the area measured at the mid-point. For the three vowels, the acoustics were differentially affected, in accordance with expected effects of front versus back position in the vocal tract. Conclusions: STN stimulation appears to constrain initial articulatory gestures for vowel production, raising the possibility that articulatory positions normally used in speech are similarly constrained. Show more

Keywords: Deep brain stimulation, Parkinson’s disease, speech, subthalamic nucleus, vowels

DOI: 10.3233/JPD-150739

Citation: Journal of Parkinson's Disease, vol. 6, no. 2, pp. 361-370, 2016

Authors: Lee, Will | Evans, Andrew | Williams, David R.

Article Type: Research Article

Abstract: Background: Measurement of motor function is critical to the assessment and management of Parkinson’s disease. Ambulatory motor assessment has the potential to provide a glimpse of the patient’s clinical state beyond the consultation. We custom-designed a smartphone application that quantitatively measures hand dexterity and hypothesized that this can give an indication of a patient’s overall motor function. Objective: The aims of this study were to (i) validate this smartphone application against MDS-UPDRS motor assessment (MDS-UPDRS-III) and the two-target tapping test; (ii) generate a prediction model for MDS-UPDRS-III; (iii) assess repeatability of our smartphone application and (iv) examine …compliance and user-satisfaction of this application. Methods: 103 patients with Parkinson’s disease were recruited from two movement disorders clinics. After initial assessment, a group of patients underwent repeat assessment within two weeks. Patients were invited to use the smartphone application at home over three days, followed by a survey to assess their experience. Results: Significant correlation between key smartphone application test parameters and MDS-UPDRS-III (r  = 0.281–0.608, p  < 0.0001) was demonstrated. A prediction model based on these parameters accounted for 52.3% of variation in MDS-UPDRS-III (R2  = 0.523, F(4,93) = 25.48, p  < 0.0001). Forty-eight patients underwent repeat assessment under identical clinical conditions. Repeatability of key smartphone application tests parameters and predicted MDS-UPDRS-III was moderate to strong (intraclass correlation coefficient 0.584–0.763, p  < 0.0001). The follow-up survey identified that our patients were very comfortable with the smartphone application and mobile technology. Conclusions: Our smartphone application demonstrated satisfactory repeatability and validity when measured against MDS-UPDRS-III. Its performance is acceptable considering our smartphone application measures hand dexterity only. Show more

Keywords: Parkinson’s disease, bradykinesia, measurement, motor, validation

DOI: 10.3233/JPD-150708

Citation: Journal of Parkinson's Disease, vol. 6, no. 2, pp. 371-382, 2016

Authors: Fleisher, Jori E. | Dahodwala, Nabila A. | Xie, Sharon X. | Mayo, Mark | Weintraub, Daniel | Chodosh, Joshua | Shea, Judy A.

Article Type: Research Article

Abstract: Background: Medication non-adherence is common in Parkinson’s disease (PD) and is associated with increased disability and healthcare costs. Individuals’ beliefs regarding their medical conditions and treatments impact medication adherence. While instruments exist to measure patients’ beliefs about medications in general, no such tool exists for PD. Objectives: Create an instrument eliciting medication beliefs of persons with PD; identify demographic and clinical characteristics associated with beliefs; and examine whether beliefs are associated with dopaminergic therapy adherence. Methods: We developed the Parkinson’s Disease Medication Beliefs Scale (PD-Rx) in four phases: focus groups of patients and caregivers to …generate items, scale development, expert and patient revision of items, and a cross-sectional validation sample (n  = 75). Adherence was calculated using two approaches incorporating self-reported medication lists. Results: The PD-Rx consists of 11 items covering benefits and risks of PD pharmacotherapies. The scale covers motor improvement, current adverse effects, and future concerns. Higher scores indicate more positive beliefs. Internal consistency was acceptable (Cronbach’s alpha = 0.67). Test-retest reliability was 0.47. Quality of life was associated with PD-Rx scores, and lower scores were associated with non-adherence. Conclusions: Negative beliefs about PD treatments are associated with lower quality of life and may be related to medication non-adherence. Further study of any causal relationship between beliefs and medication non-adherence in PD will inform the design of future patient-centered interventions to improve adherence. Show more

Keywords: Patient beliefs, psychometric, adherence, health belief model, Parkinson’s disease

DOI: 10.3233/JPD-150765

Citation: Journal of Parkinson's Disease, vol. 6, no. 2, pp. 383-392, 2016

Authors: Bouwyn, Jean-Paul | Derrey, Stéphane | Lefaucheur, Romain | Fetter, Damien | Rouille, Audrey | Le Goff, Floriane | Maltête, David

Article Type: Research Article

Abstract: Background: Clinical pre-operative predictive factors of optimal STN-DBS motor outcome in Parkinson’s disease (PD) have been previously reported. However, available data involving elderly patients are conflicting. Objective: To compare early post-operative outcomes in parkinsonian patients younger than 65 years old (group 1) vs patients 65 years old or older (group 2) at the time of surgery. Methods: The cognitive and motor effects of DBS were evaluated by comparison of different scores obtained before (baseline) and 6 months after surgery using a repeated measures analysis of variance. Results: Post-operative motor improvement (UPDRS part III and UPDRS …part IV scores) and drug reduction were not statistically different between groups 1 and 2 (P  > 0.05). Axial motor score which was significantly worse in group 2 in the on -drug condition before surgery was also significantly worse both in off -drug/on -stimulation and on -drug/on -stimulation conditions (P  < 0.05). Similarly, cognitive performances (Wisconsin Card Sorting Test, Stroop interference test, Free and Cued Selective Reminding Test with Immediate Recall, Verbal Fluency) significantly worsened post-operatively ingroup 2. Conclusions: Although effective and safe, STN-DBS has a more negative impact on cognitive functions in elderly patient, requiring a careful preoperative selection. Show more

Keywords: Subthalamic nucleus, deep brain stimulation, Parkinson’s disease, elderly

DOI: 10.3233/JPD-150742

Citation: Journal of Parkinson's Disease, vol. 6, no. 2, pp. 393-400, 2016

Authors: Giladi, Nir | Asgharnejad, Mahnaz | Bauer, Lars | Grieger, Frank | Boroojerdi, Babak

Article Type: Research Article

Abstract: Background: Monoamine oxidase B (MAO-B) inhibitors and dopamine receptor agonists are common first-line treatment options in early Parkinson’s disease (PD). Objective: To evaluate the efficacy and safety of rotigotine transdermal patch as an add-on therapy to an MAO-B inhibitor in patients with early-PD. Methods: In two Phase III, randomized, double-blind, placebo-controlled studies in early-PD (SP512, SP513), patients were randomized to rotigotine (titrated to optimal dose ≤8 mg/24 h) or placebo, and maintained for 24 (SP512) or 33 (SP513) weeks. Post hoc analyses were performed on pooled data for patients receiving an MAO-B inhibitor (selegiline) at a …stable dose at randomization and throughout the studies, with groups defined as “Selegiline+Rotigotine” and “Selegiline+Placebo”. Outcome measures included change from baseline in Unified Parkinson’s Disease Rating Scale (UPDRS) II (activities of daily living), III (motor), UPDRS II+III and responders (patients achieving ≥20%, ≥25% or ≥30% decrease in UPDRS II+III). As post hoc analyses, p -values are exploratory. Results: 130 patients were evaluable for efficacy analyses (“Selegiline+Rotigotine”: 84, “Selegiline+Placebo”: 46). Combined treatment with rotigotine and selegiline improved UPDRS III and UPDRS II+III scores versus selegiline alone (LS-mean [95% CI] treatment difference for UPDRS III: –4.89 [–7.87 to –1.91], p  = 0.0015; for UPDRS II+III: –5.76 [–9.71 to –1.82], p  = 0.0045). Higher proportion of patients in the “Selegiline+Rotigotine” group were classified as ≥20%, ≥25% or ≥30% responders (all p  < 0.001). Combined treatment appeared more effective in patients aged ≤65 years versus > 65 years (although patient numbers in the subgroups were low). Adverse event profile was consistent with the known safety profile of rotigotine. Conclusions: In these post hoc analyses, adjunctive treatment with rotigotine in patients already receiving an MAO-B inhibitor improved UPDRS II+III score; this appeared to be largely driven by improvements in the motor aspects of PD. Show more

Keywords: Dopamine receptor agonist, monoamine oxidase inhibitors, Parkinson’s disease, clinical trial

DOI: 10.3233/JPD-150758

Citation: Journal of Parkinson's Disease, vol. 6, no. 2, pp. 401-411, 2016

Authors: Hessen, Erik | Stav, Ane Løvli | Auning, Eirik | Selnes, Per | Blomsø, Linn | Holmeide, Cathrine Emilie | Johansen, Krisztina Kunszt | Eliassen, Carl Fredrik | Reinvang, Ivar | Fladby, Tormod | Aarsland, Dag

Article Type: Research Article

Abstract: Background: Neuropsychological comparisons between patients with mild cognitive impairment due to Parkinson’s disease (MCI-PD) and Alzheimer’s disease (MCI-AD) is mostly based on indirect comparison of patients with these disorders and normal controls (NC). Objective: The focus of this study was to make a direct comparison between patients with these diseases. Methods: The study compared 13 patients with MCI-PD and 19 patients with MCI-AD with similar age, education and gender. The participants were recruited and assessed at the same university clinic with equal methods. Results: The main finding was that on group level, MCI-AD …scored significantly poorer on learning and memory tests than MCI-PD, whereas MCI-PD were impaired on 1 of 3 measures of executive functioning. Conclusion: MCI-AD performed poorer learning and memory tests, whereas MCI-PD only scored below the employed cut-off on one single executive test. In general, MCI-PD was noticeably less cognitively impaired than MCI-AD. Show more

Keywords: Mild cognitive impairment, Parkinson’s disease, Alzheimer’s disease, neuropsychology, cerebrospinal fluid biomarkers

DOI: 10.3233/JPD-150761

Citation: Journal of Parkinson's Disease, vol. 6, no. 2, pp. 413-421, 2016

Authors: Hirayama, Masaaki | Tsunoda, Makoto | Yamamoto, Mitsutoshi | Tsuda, Takao | Ohno, Kinji

Article Type: Research Article

Abstract: Background: Noninvasive biomarkers for Parkinson’s disease (PD) are currently unavailable. Objective: To search for a biomarker unique to PD in sweat and serum. Methods: Sweat samples in 42 PD patients and 16 controls were analyzed using liquid chromatography/mass spectrometry (LC/MS). The principal component analysis (PCA) and the orthogonal projections to latent structures (OPLS) analysis were employed. Serum Phe and Tyr levels were determined using the HPLC-fluorescence detection system in 28 de novo PD patients, 52 L-Dopa-treated PD patients, and 27 controls. Results: PCA and OPLS analyses of LC/MS of sweat samples revealed …that Tyr, Phe, Leu (Ile), and Asp have high effect sizes to differentiate PD and controls. As Phe and Tyr are precursors of dopamine, we quantified the serum Phe and Tyr levels in de novo and treated PD patients, as well as in controls. Phe was high in de novo patients, but not in treated patients. In contrast, Tyr tended to be low in treated patients, but not in de novo patients. Tyr/Phe ratios were lower in both de novo and treated patients than in controls. The Tyr/Phe ratios were all higher than 0.82 in controls, whereas 49% of the de novo and treated patients had Tyr/Phe ratios less than 0.82. The low Tyr/Phe ratios were associated with male patients and low doses of entacapone. However, Tyr/Phe ratios were not different between male and female patients, and between patients with and without entacapone. Conclusions: The low serum Tyr/Phe ratio differentiates PD from controls with sensitivity = 0.49, specificity = 1.00, positive predictive value = 1.00, and negative predictive value = 0.40. Show more

Keywords: Parkinson’s disease, biomarker, phenylalanine, tyrosine

DOI: 10.3233/JPD-150736

Citation: Journal of Parkinson's Disease, vol. 6, no. 2, pp. 423-431, 2016

Authors: Criaud, Marion | Poisson, Alice | Thobois, Stéphane | Metereau, Elise | Redouté, Jérôme | Ibarrola, Danièle | Baraduc, Pierre | Broussolle, Emmanuel | Strafella, Antonio P. | Ballanger, Bénédicte | Boulinguez, Philippe

Article Type: Research Article

Abstract: Background: Impairment in initiating movements in PD might be related to executive dysfunction associated with abnormal proactive inhibitory control, a pivotal mechanism consisting in gating movement initiation in uncertain contexts. Objective: Testing this hypothesis on the basis of direct neural-based evidence. Methods: Twelve PD patients on antiparkinsonian medication and fifteen matched healthy controls performed a simple reaction time task during event-related functional MRI scanning. Results: For all subjects, the level of activation of SMA was found to predict RT on a trial-by-trial basis. The increase in movement initiation latency observed in PD patients …with regard to controls was associated with pre-stimulus BOLD increases within several nodes of the proactive inhibitory network (caudate nucleus, precuneus, thalamus). Conclusions: These results provide physiological data consistent with impaired control of proactive inhibition over motor initiation in PD. Patients would be locked into a mode of control maintaining anticipated inhibition over willed movements even when the situation does not require action restraint. The functional and neurochemical bases of brain activity associated with executive settings need to be addressed thoroughly in future studies to better understand disabling symptoms that have few therapeutic options like akinesia. Show more

Keywords: Response inhibition, fMRI, proactive control, reaction time, Parkinson’s disease

DOI: 10.3233/JPD-150750

Citation: Journal of Parkinson's Disease, vol. 6, no. 2, pp. 433-440, 2016

Authors: Herb, Joshua N. | Rane, Swati | Isaacs, David A. | Van Wouwe, Nelleke | Roman, Olivia C. | Landman, Bennett A. | Dawant, Benoit M. | Hedera, Peter | Zald, David H. | Neimat, Joseph S. | Wylie, Scott A. | Donahue, Manus J. | Claassen, Daniel O.

Article Type: Research Article

Abstract: Background: Parkinson’s Disease patients with predominant gait dysfunction appear to have reduced cortical thickness compared to other motor phenotypes. The extent to which advancing age or disease duration impact the pattern of these distinctions is unclear. Objective: We examine if PD patients with predominant signs of postural instability and gait dysfunction are distinguished by distinct patterns of cerebral atrophy, and how these differences are influenced by age and disease duration. Methods: The Unified Parkinson’s Disease Rating Score (UPDRS) was administered to 196 PD patients (age = 61.4±8.9yrs) in the Off and On dopamine state. All …completed a structural T1-weighted brain MRI. We defined 3 motor phenotypes: tremor dominant, akinetic-rigid, and postural instability with gait disorder. General linear modeling quantified cortical thickness in relation to disease duration, and motor improvement after dopaminergic therapy. Cortical thickness and subcortical volumes were compared between the three motor subtypes, after controlling for disease duration and age. Results: We identified 177/196 patients who met criteria for a motor subtype. When corrected for disease duration, postural-instability patients had marked cortical thinning of the bilateral frontal-temporal and posterior cortical regions (cuneus/precuneus). After regressing for age, reduced frontal thickness was evident in patients with gait dysfunction. Widespread cortical thinning was associated with increasing disease duration and reduced motor improvement to dopaminergic therapy. Conclusions: Results emphasize that the profile of motor signs, especially prominent gait manifestations, relate to cortical thinning in distinct regions. Unique patterns of atrophy appear to be driven by advancing pathology related to age and disease duration. Show more

Keywords: Parkinson’s disease, MRI, gait disorders, PIGD, tremor dominant, motor phenotypes

DOI: 10.3233/JPD-150753

Citation: Journal of Parkinson's Disease, vol. 6, no. 2, pp. 441-451, 2016