PREPARED: Comparison of prolonged and immediate release ropinirole in advanced Parkinson's disease

Background: PREPARED was a randomized, parallel‐group, double‐blind, multicenter study to evaluate the efficacy of adjunctive ropinirole prolonged release (PR) versus immediate release (IR) in patients with advanced Parkinson's disease (PD). Methods: Patients received once‐daily PR (2–24 mg/d; n = 177) or three‐times‐daily IR (0.75–24 mg/d; n = 173) for 24 weeks. The primary endpoint was the proportion of patients maintaining ≥20% reduction from baseline in “off” time over two consecutive visits at Week 24 last observation carried forward (LOCF). Results: At Week 24 LOCF, PR significantly increased the proportion of patients maintaining ≥20% reduction in “off” time versus IR (adjusted odds ratio: 1.82; 95% CI: 1.16, 2.86; P = 0.009). Mean (SD) doses at Week 24 LOCF were: PR, 18.6 (6.5) mg/d; IR, 10.4 (6.4) mg/d; mean (SD) reductions from baseline in levodopa (L ‐dopa) dose were –162 (226) mg and –113 (138) mg, respectively. Adverse events (AEs) were reported by 72% of patients in the PR group and 61% in the IR group; 12% and 9% of patients, respectively, withdrew from the study due to an AE, and 6% and 5%, respectively, reported serious AEs. Conclusions: Adjunctive PR provided a significantly greater improvement in symptom control in terms of the odds of achieving ≥20% maintained reduction in time spent “off” compared with IR. Interpretation may be confounded by the higher doses of PR versus IR that were achieved, in combination with lower doses of L ‐dopa by the study end. Despite dosing differences, the PR titration regimen was generally well tolerated, with an AE profile similar to that of IR. © 2011 Movement Disorder Society     

Patient‐reported convenience of once‐daily versus three‐times‐daily dosing during long‐term studies of pramipexole in early and advanced Parkinson’s disease

Background and purpose: In chronic diseases including Parkinson’s disease (PD), complex pharmacotherapy dosing schedules are reported to reduce adherence, perhaps leading to less‐effective symptom control and, in PD, more erratic stimulation of dopamine receptors. However, blinded clinical‐trial designs preclude direct comparisons of adherence to various schedules. Methods: In two double‐blind (DB) studies of early PD and one of advanced PD, subjects received three‐times‐daily (t.i.d.) pramipexole or placebo. In open‐label (OL) extensions, subjects took extended‐release, once‐daily (q.d.) pramipexole. At 24 or 32 OL weeks, q.d. versus t.i.d. dosing preference was surveyed by questionnaire. Results: Of 590 DB‐trial completers with early PD, 511 entered the OL extension. Of 374 survey respondents, 94.4% preferred q.d. dosing (72.2% of them found it ‘very much more convenient’ and 27.8%‘more convenient’), 2.7% preferred t.i.d., and 2.9% chose ‘no difference’. Of 465 DB‐trial completers with advanced PD, 391 entered its OL extension. Of 334 survey respondents, 88.9% preferred q.d. dosing (59.9% of them found it ‘very much more convenient’ and 40.1%‘more convenient’), 5.7% preferred t.i.d., and 5.4% chose ‘no difference’. Results excluding DB‐placebo recipients were highly similar. Conclusions: In this first direct comparison of patient preference for q.d. versus t.i.d. dopamine‐agonist dosing, patients with early or advanced PD had a strong preference for q.d. rather than t.i.d. pramipexole. The high proportion of advanced‐PD patients declaring this preference indicates that it does not depend on whether a patient is taking concomitant PD medications dosed more frequently than q.d.     

Safety and tolerability of once-daily versus twice-daily memantine: a randomised, double-blind study in moderate to severe Alzheimer's disease

OBJECTIVE: To assess the safety and tolerability of three different dosing schedules of memantine in patients with moderate to severe Alzheimer's disease (AD). METHOD: This 12-week, randomised, double-blind study, investigated three dosing schedules of memantine: OD1 (20 mg once daily with a 1-step up-titration); OD3 (20 mg once daily with a 3-step up-titration); and BID3 (10 mg twice daily with a 3-step up-titration as currently recommended in the memantine labelling). The study comprised 78 patients with moderate to severe AD (DSM-IV-TR criteria; MMSE score < or = 18), 70% of whom were on stable dosing of acetylcholinesterase inhibitor (AChEI) initiated > or = 3 months prior to study start. Safety and tolerability were assessed by the number of withdrawals, adverse events (AEs) and monitoring of vital signs. RESULTS: The number of patient withdrawals was low: 3 of 27 in OD1, 1 of 25 in OD3 and 2 of 26 in BID3. One or more AEs were reported in 9 patients in OD1, 7 patients in OD3 and 12 patients in BID3. Most AEs were mild or moderate, and typical for the population studied; no clinically important differences in AEs or vital signs were observed between the different dosing schedules. There were no between-group differences in efficacy, as assessed by clinical global severity and clinical global change. These results are consistent with the good safety profile of memantine observed in larger studies. CONCLUSIONS: Although relatively small in size, the study indicates that once-daily dosing and twice-daily dosing of memantine are similar in terms of safety and tolerability.     

Pain in amyotrophic lateral sclerosis: a population-based controlled study

Background and purpose: To assess the prevalence and characteristics of pain in an epidemiological series of patients with amyotrophic lateral sclerosis (ALS) compared to population‐based controls. Methods: Of the 183 patients with ALS resident in the province of Torino, Italy, 160 accepted to be interviewed. Controls were randomly selected from the lists of general practitioners. Pain was assessed using the Brief Pain Inventory. Results: Patients with ALS reported pain more frequently than controls [91 (56.9%) vs. 53 (33.1%); P = 0.001]. Pain frequency and intensity were correlated with a worse functional score and a longer disease duration. In patients with ALS, pain was more frequently located at the extremities (P = 0.006). Pain interfered with all areas of daily function, but patients reported a greater interference than controls in the domains of enjoyment of life and relation with other people. Sixty‐four patients (70.3% of those with pain) and 24 controls (45.3% of those with pain) (P = 0.003) were treated for pain, most frequently with non‐steroidal anti‐inflammatory drugs. ALS cases were also more frequently prescribed non‐opioid analgesics and opioids than controls. Conclusions: Our study indicates that pain is frequent in all stages of ALS, but that it often goes underrecognized and undertreated. It is significantly more frequent in patients with ALS than in population‐based controls. Future studies need to clarify the mechanisms of pain in ALS and determine the most effective treatment strategy.     

Long-term effect of deep brain stimulation for essential tremor on activities of daily living and health-related quality of life

Objectives – To report long‐term effects of thalamic deep brain stimulation (DBS) on activities of daily living (ADL) and health‐related quality of life (HRQoL) in patients with essential tremor (ET). Materials and methods – Nineteen consecutive patients were evaluated at baseline, at a mean of 1 year, then at a mean of 7 years after DBS using Tremor Rating Scale, Mini Mental Test, ADL Taxonomy, Nottingham Health Profile, Life Satisfaction Checklist, Visual Analogue Scale and interview. Results – There was a decrease of DBS efficacy on tremor between 1 and 7 years post‐operatively. The marked improvement in ADL at 1 year was no longer sustained at long‐term, except for the ability to eat. Social life remained improved. Conclusion – Although there is a decrease of DBS effect on tremor at 7 years, and even though further ageing and co‐morbidities may impact on the well‐being of patients, there is still relevant benefit of DBS on few aspects of ADL and HRQoL in patients with ET.     

Therapeutic response to domperidone in gastroparesis: A prospective study using the GCSI‐daily diary

Common symptoms of gastroparesis include nausea, vomiting, early satiety, postprandial fullness, and upper abdominal pain. Domperidone is used for treatment of gastroparesis. Daily symptom scoring may help document efficacy.

Aim

To determine the effectiveness of domperidone for gastroparesis symptoms using the gastroparesis cardinal symptom index‐daily diary (GCSI‐DD) and to determine which symptoms improve and when with domperidone treatment.

Methods

Symptomatic patients with diabetic or idiopathic gastroparesis were enrolled. Gastric emptying was performed using 4 hour scintigraphy. GCSI‐DD recorded symptoms at baseline and during six weeks of treatment with domperidone 10 mg TID. GCSI‐DD records severity of nausea, early satiety, postprandial fullness, upper abdominal pain, overall gastroparesis symptoms on a scale of 0 (no symptom) to 4 (very severe) and records the number of vomiting episodes per day.

Results

Thirty‐four patients with gastroparesis (5 diabetic, 29 idiopathic) participated in this open label study. Treatment duration averaged 36.9 ± 7.6 days. Improvement in overall gastroparesis symptoms occurred on day 3 of treatment and maintained during the treatment. Early satiety, postprandial fullness, and overall symptom severity significantly improved from baseline to the final week of treatment (P < .05 for all), whereas nausea had borderline improvement (P = .055). Side effects included palpitations (5 patients), headache (5), breast tenderness (2), menstrual bleeding (2), dizziness (1), drowsiness (1), chest pain (1), swelling (1), constipation (1).

Conclusions

Domperidone improves symptoms of gastroparesis, reducing overall gastroparesis symptom severity and decreasing early satiety, postprandial fullness, and nausea. GCSI‐DD is useful to document efficacy of therapy for gastroparesis.     

Relationships between socio‐clinico‐demographic factors and global cognitive function in the oldest old living in the Tokyo Metropolitan area: Reanalysis of the Tokyo Oldest Old Survey on Total Health (TOOTH)

Background

Despite a steady increase in life expectancy, a few studies have investigated cross‐sectional correlates and longitudinal predictors of cognitive function, a core domain of the successful aging, among socio‐clinico‐demographic factors in the oldest‐old exclusively.

Objectives

The aims of this study were to examine socio‐clinico‐demographic characteristics associated with global cognition and its changes in the oldest‐old.

Methods

We reanalyzed a dataset of cognitively preserved community‐dwelling subjects aged 85 years and older in the Tokyo Oldest Old Survey on Total Health, a 6‐year longitudinal observational study. This study consisted of (1) baseline cross‐sectional analyses examining correlates of global cognition (n = 248) among socio‐clinico‐demographic factors and (2) longitudinal analyses examining baseline predictors for changes of global cognition in 3‐year follow‐up (n = 195). The Mini‐Mental State Examination was used as a screening test to assess global cognition.

Results

At baseline, higher weights were related to higher cognitive function in the oldest‐old. The baseline predictors of global cognitive decline in 3‐year follow‐up were higher global cognition, shorter education period, and lower sociocultural activities and lower instrumental activity of daily living, in this order.

Conclusions

The present study suggests that it is crucial to attain higher education during early life and avoid leanness or obesity, participate in sociocultural cognitive activities during late life, and maintain instrumental activity of daily living to preserve optimal cognitive function in the oldest‐old, which will facilitate developing prevention strategies for cognitive decline and promoting successful aging in this increasing population.     

Characterising omission errors in everyday task completion and cognitive correlates in individuals with mild cognitive impairment and dementia

Objective: Functional ability declines with age and cognitive impairment. This study investigated errors of omission made by community-dwelling older adults completing everyday tasks in a naturalistic setting.

Method: Sixty-five cognitively healthy older adults (HOA), 19 individuals with single domain mild cognitive impairment (sdMCI), 33 individuals with multi-domain MCI (mdMCI), and 13 individuals with dementia completed measures of memory, processing speed, working memory, and executive functioning, as well as eight different activities of daily living in a naturalistic environment. Task steps were divided into preparatory, action-oriented, and concluding steps.

Results: For action-oriented steps, the number of omission errors increased with level of cognitive impairment beyond sdMCI (i.e., HOA?=?sdMCI?<?mdMCI?<?dementia). In contrast, for preparatory and concluding steps, the dementia group committed more omission errors than the HOA, sdMCI, and mdMCI groups, which did not differ.

Conclusions: The results suggest that the more complex and integrative action-oriented steps may be the first type of everyday task step to be affected in the process of cognitive decline, with preparatory and concluding steps being preserved longer and only showing decline in later stages of impairment (i.e., dementia). Individuals with sdMCI may use other intact abilities to compensate for task omission errors.