Background and purpose
The clinical differentiation between parkinsonism in idiopathic normal pressure hydrocephalus (iNPH) and Parkinson's disease (PD) remains challenging in the initial phase. ...Whether an early cognitive profiling might support the differential diagnosis of early iNPH and PD was addressed.
Methods
Neuropsychological tests of 40 iNPH subjects with early symptoms resembling parkinsonism were retrospectively evaluated together with 47 de novoPD patients (dnPD). Only neuropsychological tests performed within 1 year from the first motor symptom were included. The cognitive spectrum of iNPH and dnPD was also compared with a sample of 70 normal controls.
Results
A clear difference in the cognitive profile of iNPH, dnPD patients and normal controls was shown. 65% of iNPH subjects showed a diffuse cognitive impairment, including memory, visuospatial abilities, fronto‐executive functioning and attention, whereas only 25.5% of the dnPD patients presented an executive dysfunction. 35% of iNPH and 74.5% of PD patients performed within the normal range (P < 0.05).
Conclusion
Subjects with iNPH showed an early and diffuse alteration of cognition with respect to dnPD patients. Performing a prompt and accurate neuropsychological evaluation might support the differential diagnosis of these two conditions of parkinsonism.
Gender is an important factor influencing epidemiological and clinical features of Parkinson’s disease (PD). We aimed to evaluate gender differences in the expression of a panel of miRNAs ...(miR-34a-5p, miR-146a, miR-155, miR-29a, miR-106a) possibly involved in the pathophysiology or progression of disease. Serum samples were obtained from 104 PD patients (58 men and 46 women) never treated with levodopa. We measured levels of miRNAs using quantitative PCR. Correlations between miRNA expression and clinical data were assessed using the Spearman’s correlation test. We used STRING to evaluate co-expression relationship among target genes. MiR-34a-5p was significantly upregulated in PD male patients compared to PD female patients (fc: 1.62;
p
< 0.0001). No correlation was found with age, BMI, and disease severity, assessed by UPDRS III scale, in male and female patients. MiR-146a-5p was significantly upregulated in female as compared to male patients (fc: 3.44;
p
< 0.0001) and a significant correlation was also observed between disease duration and mir-146a-5p. No differences were found in the expression of miR-29a, miR-106a-5p and miR-155 between genders. Predicted target genes for miR-34a-5p and miR-146-5p and protein interactions in biological processes were reported. Our study supports the hypothesis that there are gender-specific differences in serum miRNAs expression in PD patients. Follow-up of this cohort is needed to understand if these differences may affect disease progression and response to treatment.
A significant percentage of patients with Parkinson's disease (PD) continue to experience motor fluctuations and dyskinesias despite the association of dopamine agonists and levodopa with COMT or ...MAO-B inhibitors. The use of apomorphine infusion is limited by compliance while deep brain stimulation is feasible only for a small number of patients mostly because of age constraints.
To assess prospectively the effectiveness of duodenal levodopa infusion on quality of life as well as motor features in patients with advanced PD. In all but 1 case levodopa infusion was stopped at nighttime.
We report the outcome of 22 PD patients, followed for up to 2 years, who were on continuous duodenal levodopa/carbidopa infusion through percutaneous endoscopic gastrostomy.
We found a significant reduction in 'off' period duration as well as dyskinesia severity (Unified Parkinson's Disease Rating Scale part IV, items 33 and 39). There was significant improvement in the 39-item Parkinson's Disease Quality of Life Questionnaire as well as in the Unified Parkinson's Disease Rating Scale part II up to the 2-year follow-up. Five patients withdrew: 2 for poor compliance and 3 for adverse events (1 was related to percutaneous endoscopic gastrostomy).
These results demonstrate significant clinical improvements in quality of life and activities of daily living consistent with the occurrence of a satisfactory therapeutic response and a reduction in dyskinesia severity.
Abstract Background Nocturnal stridor and respiratory abnormalities are important features of multiple system atrophy (MSA) with relevance to patient survival, and they are detected and evaluated ...mainly through video-polysomnography (video-PSG). Diurnal laryngoscopy seems to yield abnormal findings only in the presence of significant vocal cord (VC) dysfunction. Aim To assess whether specific electrophysiological patterns of diurnal EMG of VC muscles may indicate nocturnal stridor or respiratory dysfunctions in MSA patients. Materials and methods Seventeen patients with probable MSA were examined. A full-night video-PSG to collect standard breathing parameters (apnea/hypopnea index, mean HbSAO2 , oxygen desaturation index, total sleep time with HbSaO2 below 90%) was performed in all the patients. Laryngoscopy and EMG investigation of adductor (thyroarytenoid-TA) and abductor (posterior cricoarytenoid-PCA) muscles of the VCs were also performed. Results Both the laryngeal EMG abnormalities (based on MUAP analysis and kinesiologic EMG investigation of VC muscles) and the laryngoscopic alterations correlated with video-PSG respiratory abnormalities. Specific patterns of EMG findings were consistently found in MSA subjects with nocturnal stridor detected at PSG. In particular, the following EMG findings were related to the severity of breathing abnormalities and the presence of stridor on video-PSG: neurogenic pattern on MUAP analysis of the PCA, paradoxical activation of the TA during inspiration and tonic EMG activity of the TA during quiet breathing. Conclusions Electromyographic/kinesiologic investigation of VC muscles during wakefulness provides additional information on the pathophysiology of the respiratory abnormalities in MSA patients that could be useful for guiding the choice of the best appropriate treatment and care.
Background and purpose: A possible association between Parkinson’s disease (PD) and the polymorphism of Brain Derived Neurotrophic Factor (BDNF) G196A (Val66Met) has been suggested by different ...studies that nevertheless yielded‐contrasting result. The purpose of this study was to analyze such possible association in a cohort of Italian PD patients.
Methods: The BDNF polymorphisms were analyzed in 294 Italian patients with PD; results were compared to those obtained in 233 age‐ and sex‐matched healthy controls (HC) enrolled from two tertiary centres in Italy. Polymorphisms were determined by Restriction Fragment Length Polymorphism (RFLP) analysis; correlations between BDNF G196A polymorphism, and cognitive function were established by sub analyzing the results upon dividing PD patients based on their Mini Mental State Examination (MMSE) score.
Results: Univariate analysis showed a highly significant correlation between the BDNF(AA) genotype and a MMSE score ≤24. Hence, the distribution of this genotype in PD individuals with a MMSE score ≤24 was significantly increased compared to PD patients with an MMSE score >24 and HC (P < 0.001 in both cases). Multivariate analyses showed that BDNF (AA) genotype was associated to a sixfold risk of cognitive impairment.
Conclusions: The BDNF(AA) homozygote genotype is over‐represented in PD patients compared with normal individuals; this genotype was significantly correlated to cognitive impairment, age and disease severity. These results, although preliminary, could be important in establishing novel diagnostic and therapeutic approaches to PD.
Abstract Alteration of key regulatory kinases may cause aberrant protein phosphorylation and aggregation in Alzheimer's disease (AD) and Parkinson's disease (PD). In this study, we investigated ...expression and phosphorylation status of glycogen synthase kinase 3 (GSK-3), protein kinase B (Akt) and tau protein in peripheral blood lymphocytes of 20 AD, 25 PD patients and 20 healthy controls. GSK-3 was increased in AD and PD patients. In these latter, GSK-3 levels were positively correlated with daily l -Dopa intake. Phosphorylated Akt expression was augmented in both groups; total Akt levels were increased only in AD patients and were positively correlated with disease duration and severity. Total and phosphorylated tau were increased only in AD, with phospho-tau levels being positively correlated with levels of total tau, Akt, and disease duration. No correlations between protein levels and clinical variables were found in PD patients. Investigation of peripheral changes in the expression of specific kinases may, therefore, lead to the development of innovative biomarkers of neurodegeneration, particularly for AD.
Defects of the ubiquitin-proteasome (UP) system, a multicatalytic complex degrading polyubiquitinated proteins, may intervene in the pathogenesis of neurodegenerative disorders characterized by ...intracellular formation of protein aggregates such as Parkinson disease (PD) and Alzheimer disease (AD) by inducing proapoptotic conditions.
The authors measured the activity of proteolytic UP core, proteasome 20S, and of proapoptotic caspase-3 and -9 in peripheral blood lymphocytes (PBLs) of PD and AD patients to establish whether changes in these systems are detectable peripherally.
Proteasome 20S activity was reduced in PBLs of treated PD patients vs healthy controls (mean +/- SEM: 1.0 +/- 0.1 vs 2.3 +/- 0.2 nmol 7-amino-4-methylcoumarin (AMC)/10(6) cells, p < 0.001), whereas marked increases in caspase-3 activity (1370 +/- 153 vs 586 +/- 104 pmol AMC/10(6) cells, p < 0.001) and caspase-9 activity (873 +/- 86 vs 304 +/- 27 U/10(6) cells, p < 0.001) were found. Increased caspase-9 activity was also detected in PBLs of untreated PD patients (900 +/- 193 U/10(6) cells). PD duration and severity (Unified Parkinson's Disease Rating Scale score) were inversely correlated with proteasome 20S activity and directly correlated with caspase-3 activity. An inverse correlation was also observed in PD patients between caspase-3 activity and proteasome 20S activity. No significant changes in proteasome 20S or caspase activity or correlations between biochemical and clinical variables were found in patients with AD.
A decrease in proteasome activity, possibly related to caspase activation, is detectable in peripheral blood lymphocytes of patients with Parkinson disease but not patients with Alzheimer disease, suggesting that these variables may be considered for the development of peripheral biomarkers of Parkinson disease.
Abstract Homocysteine, a sulphur-containing amino acid formed by demethylation of methionine, is involved in numerous processes of methyl group transfer, all playing pivotal roles in the biochemistry ...of the human body. Increased levels of plasma homocysteine (hyperhomocysteinemia) – which may result from a deficiency of folate, vitamin B6 or B12 or mutations in enzymes regulating the catabolism of homocysteine – are associated with a wide range of clinical manifestations, mostly affecting the central nervous system ( e.g. , mental retardation, cerebral atrophy and epileptic seizures). Recent evidence suggests that changes in the metabolic fate of homocysteine, leading to hyperhomocysteinemia, may also play a role in the pathophysiology of neurodegenerative disorders, particularly Parkinson's disease (PD). The nervous system might be particularly sensitive to homocysteine, due to the excitotoxic-like properties of the amino acid. However, experimental findings have shown that homocysteine does not seem to posses direct, cytotoxic activity, while the amino acid has proven able to synergize with more specific neurotoxic insults. Hyperhomocysteinemia has been repeatedly reported in PD patients; the increase, however, seems mostly related to the methylated catabolism of l -Dopa, the main pharmacological treatment of PD. Therefore, hyperhomocysteinemia may not be specific to movement disorders or other neurological diseases, the condition being, in fact, rather the result of the combinations of different factors, mainly metabolic, but also genetic and pharmacological, intervening in the neurodegenerative process.
