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Marco Onofrj

Publications and source records attributed to Marco Onofrj.

13 recordsLinked to original sources
PubMed2006

Long-term benefits of rivastigmine in dementia associated with Parkinson's disease: an active treatment extension study.

In patients with dementia associated with Parkinson's disease (PD), the efficacy and safety of rivastigmine, an inhibitor of acetylcholinesterase and butyrylcholinesterase, were previously demonstrated in a 24-week double-blind placebo-controlled trial. Our objective was to determine whether benefits were sustained over the long term. Following the double-blind trial, all patients were permitted to enter an active treatment extension study, during which they received rivastigmine 3-12 mg/day. Standard safety assessments were performed. Efficacy assessments included the Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog) and other measures of cognition, daily function, neuropsychiatric symptoms, and executive function. Of 433 patients who completed the double-blind trial, 334 entered and 273 completed the active treatment extension. At 48 weeks, the mean ADAS-cog score for the whole group improved by 2 points above baseline. Placebo patients switching to rivastigmine for the active treatment extension experienced a mean cognitive improvement similar to that of the original rivastigmine group during the double-blind trial. The adverse event profile was comparable to that seen in the double-blind trial. Long-term rivastigmine treatment appeared well tolerated and may provide sustained benefits in dementia associated with PD patients who remain on treatment for up to 48 weeks.

Activities of Daily Living↗
PubMed2006

End-of-dose deterioration in non ergolinic dopamine agonist monotherapy of Parkinson's disease.

The study was designed to investigate the possible occurrence of "wearing-off" (WO) during dopamine agonist (DA) monotherapy. Sixty patients with "de novo" idiopathic PD were randomised into one of two DA monotherapy branches to receive oral ropinirole at 15 mg per day, or pramipexole at 2.1 mg per day. DA doses could be increased in the following two years but levodopa could not be added until the study ended. WO was assessed by self-evaluation charts confirmed by a blinded observation of a 30% or greater deterioration in the Unified Parkinson's Disease Rating Scale (UPDRS) motor score. Proc Mixed and Kaplan-Meier curves evaluated treatment variables as a function of time. T-tests were used to compare post-hoc variables reclassified according to WO occurrence. Thirty patients received ropinirole, and 30 pramipexole monotherapy. Eighteen patients (30%) experienced "wearing-off" 15-21 months after beginning monotherapy. No differences were observed between treatments. WO phenomena was observed 3.4+/-0.3 hours after intake of the morning or afternoon dose and consisted of UPDRS score worsening by 11.1+/-2.1 points (69-111% more than "on" score). Statistical evaluation gave evidence of differences between patients who experienced WO and those who did not: UPDRS motor scores obtained at admission to the study were higher (by 3.4+/-0.2 points, p=0.01 t-test) and DA doses at 6-12 months were higher in fluctuating patients. UPDRS motor scores deteriorated, however. similarly and there were no differences, in UPDRS scores recorded in ON conditions, between fluctuating and non-fluctuating patients at the end of the study. Our findings provide evidence of WO phenomena in patients with early PD receiving non-ergolinic DA monotherapy.

Benzothiazoles↗
PubMed2006

Comprehensive analysis of the LRRK2 gene in sixty families with Parkinson's disease.

Mutations in the gene leucine-rich repeat kinase 2 (LRRK2) have been recently identified in families with Parkinson's disease (PD). However, the prevalence and nature of LRRK2 mutations, the polymorphism content of the gene, and the associated phenotypes remain poorly understood. We performed a comprehensive study of this gene in a large sample of families with Parkinson's disease compatible with autosomal dominant inheritance (ADPD). The full-length open reading frame and splice sites of the LRRK2 gene (51 exons) were studied by genomic sequencing in 60 probands with ADPD (83% Italian). Pathogenic mutations were identified in six probands (10%): the heterozygous p.G2019S mutation in four (6.6%), and the heterozygous p.R1441C mutation in two (3.4%) probands. A further proband carried the heterozygous p.I1371 V mutation, for which a pathogenic role could not be established with certainty. In total, 13 novel disease-unrelated variants and three intronic changes of uncertain significance were also characterized. The phenotype associated with LRRK2 pathogenic mutations is the one of typical PD, but with a broad range of onset ages (mean 55.2, range 38-68 years) and, in some cases, slow disease progression. On the basis of the comprehensive study in a large sample, we conclude that pathogenic LRRK2 mutations are frequent in ADPD, and they cluster in the C-terminal half of the encoded protein. These data have implications both for understanding the molecular mechanisms of PD, and for directing the genetic screening in clinical practice.

Adult↗
PubMed2005

Acute akinesia in Parkinson disease.

OBJECTIVE: To assess acute akinesia in patients with Parkinson disease (PD) ("acute akinesia" defined as a sudden deterioration in motor performance that persists for > or =48 hours despite treatment). METHODS: The study population was a cohort of 675 patients followed regularly for 12 years in the authors' outpatient clinic. All patients were studied when acute akinesia led to hospitalization. Unified Parkinson's Disease Rating Scale (UPDRS) scores were rated during the akinetic state and compared with ratings obtained 1.6 +/- 0.9 months before the onset or after recovery. RESULTS: Twenty-six patients developed acute akinesia; in 17 of the 26 patients, new akinetic symptoms first manifested at the onset of an infectious disease or after surgery and appeared unrelated to changes in treatment or altered levodopa kinetics. In nine patients, acute akinesia developed concurrently with gastrointestinal diseases or drug manipulations showed features of neuroleptic malignant syndrome. Acute akinesia severe enough to increase the UPDRS Motor Subscale score by 31.4 +/- 12.8 appeared within 2 to 3 days and persisted for 11.2 +/- 6.2 days despite attempts to increase the dopaminergic drug dose or administer continuous subcutaneous apomorphine infusion. Symptomatic recovery began 4 to 26 days after the onset of acute akinesia and appeared incomplete in 10 patients. Four patients of 26 died despite treatment. Levodopa kinetics were normal in all patients without gastrointestinal disease and in one patient with gastric stasis. CONCLUSIONS: Acute akinesia is a life-threatening complication of Parkinson disease (PD). It is unlike the "wearing-off" phenomenon that occurs when dopaminergic drug levels decline and responds to dopaminergic rescue drugs. Acute akinesia may be a clinical entity distinct from the previously described PD motor fluctuations.

Acute Disease↗
PubMed2003

HLA typing does not predict REM sleep behaviour disorder and hallucinations in Parkinson's disease.

HLA-DR2 haplotype and DQ1 DNA alleles, characterizing 90 to 100% of all narcoleptic patients, were found to be equally distributed in 20 Parkinson's disease (PD) patients with early hallucinations, rapid eye movement (REM) sleep-related behaviour disturbances (RBD), and sleep onset in REM (SOREM), and in 20 PD patients without hallucinations, despite 10 to 15 years of treatment, and no RBD or SOREM.

Aged↗
PubMed2003

Dual dopamine agonist treatment in Parkinson's disease.

We studied the effectiveness of cabergoline as an adjunct in patients with early Parkinson's disease receiving another dopamine agonist (pramipexole or ropinirole), at the maximal permitted dose. The study enrolled 47 patients: 35 had motor fluctuations and were receiving a dopamine agonist with levodopa; and 12, without motor fluctuations, were receiving a dopamine agonist without levodopa. These medications had in all cases failed to achieve adequate symptom control. In the 35 patients with motor fluctuations, when cabergoline was added to therapy, the time spent in the OFF period decreased by 65.6% (from 3.14+/-1.11 to 1.08+/-1.07 hours p<0.0001); and the Unified Parkinson's Disease Rating Scale (UPDRS) motor score decreased by 19.24% (from 41.68+/-12.6 to 33.66+/-10.22; (p<0.0001) during the OFF condition, and by 7.11% (from 17.01+/-6.63 to 15.8+/-7.22; p<0.001) during the ON condition. Nocturnal akinesia improved in all the patients except one. In the 12 patients without motor fluctuations, when cabergoline was added, the UPDRS score improved by 34.4% (from 23.5+/-5.3 to 15.5+/-4.7). This open study shows that dual dopamine agonist therapy can be useful in the symptomatic treatment of patients with early or more advanced Parkinson's disease receiving therapy with or without levodopa.

Adult↗
PubMedDate not supplied

Donepezil versus vitamin E in Alzheimer's disease: Part 2: mild versus moderate-severe Alzheimer's disease.

SUMMARY: Early studies showed that the latency of P300 (P3) event related potential increases or diminishes when anticholinergic or cholinergic drugs are administered. We tested the hypothesis that new cholinesterase inhibitors like Donepezil (DPZ) may have an effect on the often abnormal P300 of patients with Alzheimer's Disease (AD), and therefore, that P300 recordings might simplify the evaluation of responses to cholinesterase inhibitor in patients with mild and moderate-severe AD. We evaluated 60 patients with AD: 30 patients with "mild" (Mini Mental State Examination 26-19) and 30 patients with "moderate-severe" (Mini Mental State Examination 18-10), according to the National Institute of Neurological and Communicative Disorders and Alzheimer's Disease and Related Disorders Association criteria in comparison with 40 age-matched controls. All subjects underwent P300 recordings and neuropsychologic examinations (Alzheimer's Disease Assessment Scale-Cognition and Wechsler Adult Intelligence Scale) during the 6-month follow-up. Patients were divided into four groups of 15 patients each: Group I DPZ (10 mg/day) and Group I Vitamin E (2000 IU/day) with "mild" AD; Group II DPZ and Group II Vitamin E with "moderate-severe" AD and same drug dosages. In patients treated with Vitamin E, we observed P3 latency increments (delta) by 11.8 +/- 1.8 ms in Group I and by 12.8 +/- 2.8 ms in Group II at 6 months; neuropsychologic test scores significantly worsened at 6 months (p < 0.001) in Group II patients. Donepezil induced significant P3 latency reductions (11.2 +/- 2.4 ms) in nine patients of Group I and all patients of Group II (16.1 +/- 4.0 ms), reaching a maximum at 3 months (23.2 +/- 2.7 ms). Alzheimer's Disease Assessment Scale-Cognition and Wechsler Adult Intelligence Scale scores improved during the same period, and the difference between Vitamin E and DPZ treated patients was highly significant for P3 (analysis of variance) and for P3-Alzheimer's Diseases Assessment Scale-Cognition (analysis of covariance) with p < 0.001 for pooled groups of patients with AD and Group II (DPZ) versus Group II (Vitamin E). Combined P3 event related potentials measurements, neuropsychologic test comparison evidences significant effects of DPZ in mild and in moderate-severe AD.

Aged↗
PubMedDate not supplied

The effects of a cholinesterase inhibitor are prominent in patients with fluctuating cognition: a part 3 study of the main mechanism of cholinesterase inhibitors in dementia.

Fluctuating cognition is evidenced in different forms of dementia and is accompanied by electroencephalographic (EEG) abnormalities. The authors hypothesize that cholinesterase inhibitors are effective mostly in patients with fluctuating cognition. Twenty-three patients affected by mild dementia with similar scores on Mini-Mental State Examination (MMSE), Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-cog), and Unified Parkinson's Disease Rating Scale evaluation were classified in a group with fluctuating cognition (n = 11) and a group of nonfluctuators (n = 12). All patients were assigned randomly to the branches of a double-blind crossover study of donepezil (DPZ), a 5 to 10-mg dose, versus vitamin E, a 2000 IU dose, for 30 days. MMSE, ADAS-cog, University of California at Los Angeles Neuropsychiatric Inventory (NPI), quantitative EEG, P3 event-related potentials, choice reaction time variability (CRTV) were assessed at baseline and at the end of treatments. At the end of the crossover study all patients received DPZ for 6 months. The dominant EEG frequency variability, low EEG frequencies amplitude, the P3 latency and jitter, CRTV, and NPI was significantly different in the fluctuating cognition group than the nonfluctuating group at baseline (P < 0.001). Short-term DPZ administration induced a significant increase in MMSE scores, reduction of ADAS-cog and of NPI scores (P < 0.003-0.001), increase of EEG alpha activity and reductions of P3 latency and jitter, dominant frequency variability and CRTV (P < 0.009-0.001) in the fluctuating cognition group, and significant increases of MMSE scores (P = 0.03) and a decrease of P3 jitter and dominant frequency variability (P < 0.034-0.041) in the nonfluctuating group. Short-term DPZ effects differed significantly between fluctuating cognition and nonfluctuating patients (0.001). Significant effects of the 6-month observation were observed only in fluctuating cognition patients. Logistic analysis showed that P3 latency predicts the effect of DPZ (P = 0.04, P < 0.01) in the crossover study, and CRTV predicts the effect at the 6-month follow-up.

Aged↗