First Author: Lothar Burghaus
All Authors: Burghaus L, Sch├╝tz U, Krempel U, Lindstrom J, Schr├Âder H
Journal Title: Parkinsonism & related disorders
Abstract: Cerebral cortical cholinergic deficits, represented by a decrease in choline acetyltransferase activity, severe losses of nicotinic binding sites as well as cell degeneration in the basal forebrain can be observed in neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. The potential role of nicotinic acetylcholine receptor subunits as pharmacological targets for the treatment of cognitive deficits raises the question as to what extent these subunits are affected in neurodegenerative diseases. We here report on a significant decrease of the alpha4 and the alpha7 nicotinic acetylcholine receptor subunit in cortices of Parkinson patients which turns out to be similar to recent findings in Alzheimer patients.
The Role of Brain-Derived Neurotrophic Factor in the Pathophysiology of Psychiatric and Neurological Disorders
Authors: Jessop RT, Horowicz C, Dibble LE
Abstract: To investigate the effects of practice on performance and retention of a balance task in persons with Parkinson disease (PD).Ten persons with PD and 10 age and gender-matched healthy control subjects were tested on an anticipatory, static base of support, limits of stability (LOS) balance task on a force plate. The motor learning paradigm utilized for all subjects included an acquisition phase and retention tests at 24 h and 1 week after acquisition. A force plate was used for testing and to collect outcome measures including movement velocity (MVL), endpoint excursion (EPE), and directional control. Data were analyzed for differences between groups and change over time.Persons with PD demonstrated performance deficits relative to controls for MVL at all testing periods (P < 0.05), and initially for EPE (P < 0.05), but were able to maintain significant improvements through retention testing relative to baseline (P < 0.05).Persons with PD demonstrated unimpaired capacity for motor learning in a LOS balance task for MVL and EPE, although performance deficits remained for MVL. The results concur with previous motor learning research of upper extremity tasks by suggesting that individuals with mild to moderate PD exhibit a preserved ability to benefit from practice as a means of improving balance task performance.
Authors: Baumgartner CA, Sapir S, Ramig TO
Abstract: Perceptual ratings of hoarseness and breathiness were used to assess the efficacy of two intensive methods for treating dysarthrophonia in individuals with idiopathic Parkinson disease. One method emphasized phonatory-respiratory effort (the Lee Silverman Voice Treatment, LSVT) and the other emphasized respiratory effort alone (RET). Perceptual ratings were performed by two expert listeners based on random order presentation of the patients' pretreatment and posttreatment recordings of the "Rainbow Passage." The listeners were blinded to the patients and their treatment group. Statistically significant pretreatment to posttreatment improvement in hoarseness and breathiness was observed in the LSVT group but not in the RET group. The present findings are consistent with acoustic and physiologic findings reported previously, providing further evidence for the efficacy of the LSVT.
Authors: Soˇs J, Engelhardt JI, Siklˇs L, Havas L, MajtÚnyi K
Abstract: Immunohistochemical techniques revealed a significant increase of poly(ADP-ribose) polymerase (PARP)-containing nuclei in the dopaminergic neurons of the substantia nigra (SN) in Parkinson disease and in diffuse Lewy body disease as compared with a group of patients with other neurodegenerative diseases and normal controls. The nuclear translocation of nuclear factor kappa B (NF-kappa B) was also noted in the same cells. The over-activation of PARP and the transcriptional activation of NF-kappa B can contribute to the pathomechanism of the disease specific lesion of the neurons in the SN. However, in another subgroup of dopaminergic cells of the SN an increased parvalbumin content was detected reflecting a natural protective mechanism against the putative increase of intracellular calcium caused by excitotoxic injury and oxidative stress.
Authors: Santos JG, Chien HF, Barbosa ER
Abstract: (1) To evaluate whether the Nine Items Questionnaire (WOQ-9) for the detection of wearing-off (WO) in Parkinson Disease (PD), by means of its screening ability, is a helpful tool to assist neurologists in diagnosing WO; (2) To determine the sensitivity and the specificity of a free Brazilian Portuguese translation of WOQ-9.A sample obtained by convenience included 60 patients. The WOQ-9 was answered by the patients themselves before their routine consultations. The detection of the WO by the WOQ-9 was compared with the neurologist assessment. Statistical significance was 5%.The WOQ-9 showed sensitivity of 100%, specificity of 10.3%, positive and negative predictive values of 54.4% and 100% respectively. The identification of WO by the WOQ-9 was congruent in 54.5% of cases with neurological evaluation.The WOQ-9 is a convenient screening tool to aid physicians to detect WO in PD patients, and it is a quick and easy self-administered questionnaire.
Authors: Gordon PH, Zhao H, Bartley D, Sims LJ, Begay MG, Pirio Richardson S, Lewis J, Rowland AS
Abstract: The prevalence of Parkinson disease (PD) varies by geographic location and ethnicity, but has never been studied among the Navajo.Period prevalence was calculated using the number of people diagnosed with PD in the Shiprock Service Unit Indian Health Service database during 1995-1999, 2000-2004, and 2005-2009 as the numerator, and the number seen for any reason as the denominator. Age-standardized rates were calculated using the 2000 US population.During 2005-2009, 126 people were seen with PD (crude prevalence = 203.7/100,000 population). The age-adjusted rate was 335.9 (95% C. I. 277.8-394.0) overall, 438.5 (95% C.I. 336.5-540.5) in men and 259.7 (95% C.I. 192.8-326.7; p = 0.004) in women. The adjusted rate increased with age: 788.8 (95% C.I. 652.0-925.7) for age 40 and above to 1964.9 (95% C.I. 1613.7-2316.1) for age 60 and above. Adjusted rates were 246.6 (95% C.I. 187.2-306.0) in 1995-1999 and 284.7 (95% C.I. 227.0-342.4) in 2000-2004.Parkinson disease appears common among the Navajo. Estimates increased with age and time, and were higher in men. In-person interviews are needed to confirm these estimates, and to determine incidence, quality of care, and risk factors for PD among the Navajo.
Authors: Parashos SA, Elm J, Boyd JT, Chou KL, Dai L, Mari Z, Morgan JC, Sudarsky L, Wielinski CL
Abstract: A construct calculated as the sum of items 13-15, 29, 30 of the Unified Parkinson's Disease Rating Scale (UPDRS) has been used as an "Ambulatory Capacity Measure" (ACM) in Parkinson disease (PD). Its construct validity has never been examined. A similar construct, consisting of the mean value of the same UPDRS items has been used under the acronym PIGD as a measure of postural instability and gait disorder in PD.To examine the construct validity of the ACM and PIGD in PD.We analyzed data in an existing database of 340 PD patients, Hoehn and Yahr stages (HYS) 1-5 who participated in a study of falls. Number of falls (NOF) was recorded over 4 weeks, and UPDRS (mental, ADL, and motor subscales), HYS, Activities Based Confidence Scale (ABC), Freezing of Gait Questionnaire (FOG), Five Times Sit-to-Stand (FTSS), Timed Up-and Go (TUG), Gait Velocity (GV), and Berg Balance Scale (BBS) evaluations were performed. Internal consistency was assessed by Cronbach's alpha. Construct validity was assessed through correlations of the ACM and PIGD to these measures and to their summed-ranks. A coefficient of determination was calculated through linear regression.Mean age was 71.4, mean age at diagnosis 61.4 years; 46% were women; mean UPDRS subscale scores were: Mental 3.7; ADL 15.7; motor: 27.1; mean ACM was 6.51, and mean PIGD 1.30. Cronbach's alpha was 0.78 for both ACM and PIGD. Spearman correlation coefficients between the ACM/PIGD and ABC, FOG, TUG, GV and BBS were 0.69, 0.72, 0.67, 0.58, and 0.70 respectively. Correlation between the ACM/PIGD and summed-ranks of HYS, NOF, ABC, FOG, FTSS, TUG, GV and BBS was high (Spearman r = 0.823, p < 0.0001); 68% of the variability in the summed-ranks was explained by ACM/PIGD.The ACM and the PIGD are valid global measures and accurately reflect the combined effects of the various components of ambulatory capacity in PD patients with HY stages 1-4.
Authors: Alcalay RN, Mejia-Santana H, Tang MX, Rosado L, Verbitsky M, Kisselev S, Ross BM, Louis ED, Comella CL, Colcher A, Jennings D, Nance MA, Bressman S, Scott WK, Tanner C, Mickel SF, Andrews HF, Waters CH, Fahn S, Cote LJ, Frucht SJ, Ford B, Rezak M, Novak K, Friedman JH, Pfeiffer R, Marsh L, Hiner B, Siderowf A, Caccappolo E, Ottman R, Clark LN, Marder KS
Abstract: To determine the motor phenotype of LRRK2 G2019S mutation carriers. LRRK2 mutation carriers were previously reported to manifest the tremor dominant motor phenotype, which has been associated with slower motor progression and less cognitive impairment compared with the postural instability and gait difficulty (PIGD) phenotype.Cross-sectional observational study.Thirteen movement disorders centers.Nine hundred twenty-five early-onset Parkinson disease cases defined as age at onset younger than 51 years.LRRK2 mutation status and Parkinson disease motor phenotype: tremor dominant or PIGD. Demographic information, family history of Parkinson disease, and the Unified Parkinson's Disease Rating Scale score were collected on all participants. DNA samples were genotyped for LRRK2 mutations (G2019S, I2020T, R1441C, and Y1699C). Logistic regression was used to examine associations of G2019S mutation status with motor phenotype adjusting for disease duration, Ashkenazi Jewish ancestry, levodopa dose, and family history of Parkinson disease.Thirty-four cases (3.7%) (14 previously reported) were G2019S carriers. No other mutations were found. Carriers were more likely to be Ashkenazi Jewish (55.9% vs 11.9%; P < .001) but did not significantly differ in any other demographic or disease characteristics. Carriers had a lower tremor score (P = .03) and were more likely to have a PIGD phenotype (92.3% vs 58.9%; P = .003). The association of the G2019S mutation with PIGD phenotype remained after controlling for disease duration and Ashkenazi Jewish ancestry (odds ratio, 17.7; P < .001).Early-onset Parkinson disease G2019S LRRK2 carriers are more likely to manifest the PIGD phenotype, which may have implications for disease course.
Authors: Lin SC, Lin KJ, Hsiao IT, Hsieh CJ, Lin WY, Lu CS, Wey SP, Yen TC, Kung MP, Weng YH
Abstract: PET with (18)F-9-fluoropropyl-(+)-dihydrotetrabenzazine ((18)F-DTBZ), a novel radiotracer targeting vesicular monoamine transporter type 2 (VMAT2), has been proven as a useful imaging marker to measure dopaminergic integrity.The aim of this study was to evaluate the capability of (18)F-DTBZ PET in detecting the monoaminergic degeneration in early Parkinson disease (PD) in vivo. Seventeen age-matched healthy subjects and 30 PD patients at early stage of disease (duration of disease ? 5 y) with mild and unilateral motor symptoms underwent (18)F-DTBZ PET scans. The severity of disease, including Unified Parkinson Disease Rating Scale and modified Hoehn and Yahr Stage (mHY), were recorded at off-medication states. The standardized volumes of interest were applied to the spatial normalized image for quantification analysis. The specific uptake ratios (SURs) were calculated according to the formula (specific volumes-of-interest counts/occipital cortex counts) - 1. SUR measurements were summarized for each brain region.The mean duration of disease in the PD group was 3.2 ▒ 2.1 y (range, 0.5-5 y). The mean mHY was 1.0 ▒ 0.1 (range, 1-1.5). The SURs of bilateral caudate, anterior putamen, posterior putamen, substantia nigra, and nucleus accumbens were significantly lower in PD patients than those of healthy subjects. The reduction of SURs was most severe in the contralateral (the brain regions that are located opposite to the symptomatic side) posterior putamen (-81%), followed by the ipsilateral posterior putamen (-67%). Receiver-operating-characteristic curve analysis showed that the SURs of the bilateral posterior putamen and contralateral anterior putamen had a sensitivity of 100% and specificity of 100% in differentiating PD patients from healthy subjects.(18)F-DTBZ PET was as an excellent tool for the early diagnosis of PD. The obvious decline of (18)F-DTBZ uptake in the ipsilateral (asymptomatic) striatum suggested that (18)F-DTBZ PET might serve as an in vivo biomarker to detect the monoaminergic degeneration in the premotor phase of PD.
Authors: Lauretani F, Ticinesi A, Meschi T, Teresi G, Ceda GP, Maggio M
Abstract: The continuous increase in elderly and oldest-old population, and subsequent rise in prevalence of chronic neurological diseases like Alzheimer's disease (AD) and Parkinson's disease (PD), are a major challenge for healthcare systems. These two conditions are the most prevalent neurodegenerative diseases in older persons and physicians should engage treatment for these patients. In this field, Randomized Clinical Trials (RCTs) specifically focused on elderly populations are still lacking. The aim of this study was to identify RCTs conducted among AD and PD and to examine the difference between mean age of enrollment and incidence of these two neurodegenerative diseases. We found that the scenario is different between PD and AD. In particular, the enrollment for PD trials seems to include younger persons than AD, although the incidence of both diseases is similar and highest after 80 years old. The consequence of these results could influence conclusive guidelines of treatment in older parkinsonian patients.
Authors: Niccoli Asabella A, Ruggeri M, Rubini D, Polimeno L, Spinelli C, Polito M, Pennelli M, Altini C, De Caro MS, Defazio G, Rubini G
Abstract: Cognitive impairment is frequent in patients with Parkinson's disease (PD), and can range from mild deterioration to dementia. Recently a contribution of Alzheimer's disease for the cognitive dysfunction in PD has been proposed, whereas the presence of tau protein and amyloid was recognized. Clusterin/ApoJ is a protein involved in the deposition of beta-amyloid and in its neurotoxicity. In this study we aimed to investigate the clusterin/ApoJ's plasma levels in patients with PD to assess its potential role in fisiopathogenetic cognitive impairment.