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F Sherriff

Publications and source records attributed to F Sherriff.

6 recordsLinked to original sources
PubMed2005

Memantine for dementia.

BACKGROUND: Memantine, a low affinity antagonist to glutamate NMDA receptors, may prevent excitatory neurotoxicity in dementia. OBJECTIVES: To determine efficacy and safety of memantine for people with Alzheimer's disease (AD), vascular (VD) and mixed dementia. SEARCH STRATEGY: The Specialized Register of the Cochrane Dementia and Cognitive Improvement Group was searched on 20 May 2005. This register contains references from all major healthcare databases and many ongoing trial databases and is updated regularly. In addition the search engines Copernic and Google were used to identify unpublished trials through inspection of the websites of licensing bodies like the FDA , EMEA and NICE and of companies' websites (Lundbeck, Merz, Forest, Suntori etc) and clinical trials registries. SELECTION CRITERIA: Double-blind, parallel group, placebo-controlled, randomized trials of memantine in people with dementia. DATA COLLECTION AND ANALYSIS: Data were pooled where possible. Intention-to-treat (ITT) and observed case (OC) analyses are reported. MAIN RESULTS: 1. Moderate to severe AD. Two out of three six month studies show a small beneficial effect of memantine. Pooled data indicate a beneficial effect at six months on cognition (4.12 points on the 100 point SIB , 95% CI 2.14 to 5.74, P < 0.00001), activities of daily living (1.27 points on the 54 point ADCS-ADLsev, 95% CI 0.44 to 2.09, P = 0.003) and behaviour (2.76 points on the 144 NPI, 95% CI 0.88 to 4.63, P = 0.004), supported by clinical impression of change (0.28 points on the 7 point CIBIC+, 95% CI 0.15 to 0.41, P < 0.0001).2. Mild to moderate AD. In a single six month trial, memantine had a beneficial effect on ITT analysis of cognition, (1.9 ADAS-Cog points, 95% CI 0.35 to 3.45, P = 0.02) and behaviour (3.50 NPI points 95% CI 0.15 to 6.85, P = 0.04) supported by clinical global impression of change (0.30 CIBIC+ points, 95% CI 0.09 to 0.51, P = 0.005), but no effect on activities of daily living or OC analysis of cognition. The statistical significance of these benefits could be overturned by data from two unpublished studies which are known to show no significant effect. 3. Mild to moderate vascular dementia. In two six month studies, memantine improved cognition (1.85 ADAS-Cog points, 95% CI 0.88 to 2.83, P = 0.0002), and behaviour (0.84 95% CI 0.06 to 0.91, P = 0.03) but this was not supported by clinical global measures.4. Patients taking memantine appeared to be less likely to develop agitation (93/1167 [8%] versus 134/1141 [12%] (Peto odds ratio (OR): 0.65, 95% CI 0.49 to 0.86, P = 0.002). This was consistently seen in moderate to severe dementia. There were no data which suggested an effect on agitation which is already present.5. Memantine is well tolerated. AUTHORS' CONCLUSIONS: Published data suggest a small beneficial effect of memantine at six months in moderate to severe AD. The beneficial effect on cognition in patients with mild to moderate vascular dementia was not detectable on global assessment at six months. Whether memantine has any effect in mild to moderate AD is unknown.

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PubMed2005

Memantine for dementia.

BACKGROUND: Memantine, a low affinity antagonist to glutamate NMDA receptors, may prevent excitatory neurotoxicity in dementia. OBJECTIVES: To determine efficacy and safety of memantine for people with Alzheimer's disease (AD), vascular (VD) and mixed dementia. SEARCH STRATEGY: The Specialized Register of the Cochrane Dementia and Cognitive Improvement Group was searched on 28 October 2004. This register contains references from all major healthcare databases and many ongoing trial databases and is updated regularly. In addition the search engines Copernic and Google were used to identify unpublished trials through inspection of the websites of licensing bodies like the FDA , EMEA an Nice and of companies' websites (Lundbeck, Merz, Forest, Suntori etc). SELECTION CRITERIA: Double-blind, parallel group, placebo-controlled, randomized trials of memantine in people with dementia. DATA COLLECTION AND ANALYSIS: Data were pooled where possible. Intention-to-treat (ITT) and observed case (OC) analyses are reported. MAIN RESULTS: 1. Moderate to severe AD. A major study (MD-01) is unpublished. Published data from two six month studies show a small beneficial effect of memantine at six months on cognition (4.12 SIB points, 95% Confidence Interval (CI) 2.14 to 5.74, P < 0.00001), activities of daily living (1.70 ADCS-ADLsev19 points, 95% CI 0.63 to 2.76, p = 0.002) and behaviour (3.64 NPI points, 95% CI 1.38 to 5.90, p = 0.002), supported by clinical impression of change (0.27 CIBIC+ points, 95% CI 0.10 to 0.43, p = 0.002). The unpublished study would need to have found a detrimental effect of memantine to overturn the statistical significance of the benefits apparent in the two published studies. 2. Mild to moderate AD. In a single six month trial, memantine had a beneficial effect on ITT analysis of cognition, (1.9 ADAS-Cog points, 95% CI 0.35 to 3.43, p = 0.02) and behaviour (3.50 NPI points 95% CI 0.15 to 6.85, p = 0.04) supported by clinical global impression of change (0.30 CIBIC+ points, 95% CI 0.09 to 0.51, p = 0.005), but no effect on activities of daily living or OC analysis of cognition. The statistical significance of these benefits could be overturned by data from two unpublished studies which are known to show no significant effect. 3. Mild to moderate vascular dementia. In two six month studies, memantine improved cognition (1.85 ADAS-Cog points, 95% CI 0.88 to 2.83, p = 0.0002), and behaviour (Weighted Mean Difference (WMD) 0.84 95% CI 0.06 to 0.91, p = 0.03) but this was not supported by clinical global measures.4. Patients taking memantine were less likely to develop agitation (Odds Ratio (OR): 0.65, 95% CI 0.48 to 0.89, p = 0.007). The effect on agitation which is already present is unknown.5. Memantine is well tolerated. AUTHORS' CONCLUSIONS: Published data suggest a small beneficial effect of memantine at six months in moderate to severe AD. The beneficial effect on cognition in patients with mild to moderate vascular dementia was not clinically discernible at six months. Whether memantine has any effect in mild to moderate AD is unknown.

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PubMed2004

Memantine for dementia.

BACKGROUND: Alzheimer's disease, vascular and mixed dementia are the three commonest forms of dementia affecting older people. There is evidence that the excitatory activity of L-glutamate plays a role in the pathogenesis of Alzheimer's disease and in the damage from an ischaemic stroke. A low affinity antagonist to N-Methyl-D-aspartate (NMDA) type receptors, such as memantine, may prevent excitatory amino acid neurotoxicity without interfering with the physiological actions of glutamate required for memory and learning. OBJECTIVES: To determine the clinical efficacy and safety of memantine for people with Alzheimer's disease, or vascular or mixed dementia. SEARCH STRATEGY: Trials were identified from a search of the Trial-based Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 7 April 2004 using the terms: memantin*, namenda*, ebixa*, axura*, D-145, DMAA, DRG-0267. All major health care databases and many ongoing trial databases are searched regularly to keep this Register up to date. SELECTION CRITERIA: Double-blind, parallel group, placebo-controlled, randomised and unconfounded trials in which memantine was administered to people with dementia. DATA COLLECTION AND ANALYSIS: Data were extracted, pooled where possible, and weighted mean differences, standardized mean differences or odds ratios were estimated. Intention-to-treat (ITT) and observed cases (OC) analyses are reported, where data were available. MAIN RESULTS: The evidence suggests that memantine has a positive effect on cognition, mood and behaviour and the ability to perform activities of daily living in patients with moderate to severe Alzheimer's disease. The results in patients with mild to moderate vascular dementia, suggest a beneficial effect of 20mg/day of memantine on cognitive function measured at 28 weeks. However, these results are neither supported by an effect on ability to perform activities of daily living nor by an effect on the clinical impression of change. This suggests that, in patients with mild to moderate vascular dementia, the effect on cognitive function is not translated into clinically detectable changes. REVIEWERS' CONCLUSIONS: :Memantine 20 mg/day caused a clinically noticeable reduction in deterioration over 28 weeks in patients with moderate to severe Alzheimer disease. This was supported by less functional and cognitive deterioration. Patients taking memantine were less likely to become agitated. The effect in mild to moderate AD is unknown. Patients with mild to moderate vascular dementia receiving memantine 20 mg/day had less cognitive deterioration at 28 weeks but the effects were not clinically discernible. There is an early beneficial effect on cognition, mood, behaviour and clinical impression for memantine at 6 weeks. The drug is well tolerated in general and the incidence of adverse effects is low.

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PubMed2003

Memantine for dementia.

BACKGROUND: Alzheimer's disease, vascular and mixed dementia are the commonest forms of dementia in older people. There is evidence that the excitatory activity of L-glutamate plays a role in the pathogenesis of Alzheimer's disease and in the damage from an ischaemic stroke. A low affinity antagonist to N-Methyl-D-aspartate (NMDA) type receptors, such as memantine, may prevent excitatory amino acid neurotoxicity without interfering with the physiological actions of glutamate required for memory and learning. OBJECTIVES: To determine the clinical efficacy and safety of memantine for people with Alzheimer's disease, vascular, or mixed dementia. SEARCH STRATEGY: Trials were identified from a search of the Trial-based Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 9 October 2002 using the terms: memantin*, D-145, DMAA, DRG-0267. All major health care databases and trial databases within the scope of the group are searched regularly to keep this Register up to date. SELECTION CRITERIA: Double-blind, parallel group, placebo-controlled, randomized and unconfounded trials in which memantine was administered to people with dementia. DATA COLLECTION AND ANALYSIS: Data were extracted, pooled where possible, and weighted mean differences, standardized mean differences or odds ratios were estimated. Intention-to-treat (ITT) and observed cases (OC) analyses are reported, where data were available. MAIN RESULTS: There were a total of seven trials that met inclusion criteria, of which five had sufficient data for analysis. The analysis of change from baseline for cognition gave statistically significant results in favour of memantine (20 mg/day) (MD: -2,83 95% CI -4.37 to -1.29, P=0.0003) at 28 weeks and for memantine (30mg/day) at 6 weeks (MD: -3.04. 95% CI -5.68 to -0.40, P=0.02). Effects on Activities of Daily living (ADL) were difficult to interpret. One study provided data using a non-validated scale for measuring five simple instrumental tasks under the guidance of an investigator. When pooled with another study the analysis gave statistically significant results in favour of memantine for 30 mg/day at 6 weeks (SMD: -1.36 95% CI -1.77 to -0.96, P=0.0003). Mood and behaviour: One trial provided data on memantine 30 mg/day at 6 weeks using the NOSIE scale. The OC analysis found statistically significant differences in favour of treatment (MD: 23.30 95% CI 17.83 to 28.77, P<0.00001). Global scales: The analysis revealed a statistically significant difference in favour of memantine (20mg/day ) at 6 weeks (MD: -12.30 95% CI -16.90 to -7.70, P<0.00001). Similar results were found for larger doses (memantine 30 mg/day) at 6 weeks in a pooled meta-analysis of two other studies (WMD: -10.77 95% CI -13.46 to -8.09, P<0.00001). With regard to the Global Impression of Change three studies found statistically significant results in favour of 10, 20 and 30 mg/day of memantine compared with placebo at 6 or 12 weeks. There was a benefit in favour of memantine (20 mg/day) compared with placebo at 6 weeks, for the numbers improved ( 24/41 compared with 11/41)(OR, 3.85, 95% CI 1.52 to 9.75, P=0.004), in favour of memantine (30 mg/day) compared with placebo at 6 weeks, for the numbers improved ( 20/30 compared with 8/29)(OR, 5.25, 95% CI 1.72 to 15.98, P=0.004) and in favour of memantine (10 mg/day) compared with placebo at 12 weeks, for the numbers improved ( 60/82 compared with 38/84)(OR, 3.30, 95% CI 1.72 to 6.33, P=0.0003). In general memantine seemed to be well tolerated. There was no statistically significant difference between memantine and placebo for the three studies that reported adverse events. There were some data on specific adverse events. In one study the incidence of restlessness by the end of the treatment at 6 weeks was statistically significantly lower in the placebo group than in the group taking memantine 30 mg/day (15/30 compared with 2/29) (OR 13.50, 95% CI 2.71 to 67.19, P=0.001). The number of dropouts was similar in treatment and placebo groups at 6 or 28 weeks time for memantine 20 mg/day and at 6 weeks for memantine 30 mg/day. REVIEWER'S CONCLUSIONS: Memantine is a safe drug and may be useful for treating Alzheimer's, vascular,and mixed dementia of all severities. Most of the trials so far reported have been small and not long enough to detect clinically important benefits. However there is a possible benefit on cognition and global measures, and an early improvement in behaviour in people with dementia. More studies are needed.

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PubMed1989

Development of infant reaching in the dark to luminous objects and 'invisible sounds'.

Two studies were conducted to investigate the existence of an unusual U-shaped developmental function described by Wishart et al (1978) for human infants reaching towards invisible sounds. In study 1, 2-7 month olds were presented with four conditions: (i) an invisible auditory stimulus alone, (ii) a glowing visual stimulus alone, (iii) auditory and visual stimuli on the same side (ie combined), and (iv) auditory and visual stimuli on opposite sides (ie in conflict). Study 2 was designed to examine the effects of practice and possible associations made when using the 'combined conflict' paradigm. Infants of 5 and 7 months of age were given five trials with the auditory stimulus, with or without prior visual experience, and five trials with the visual stimulus, with the position of the stimulus varied on each trial. Stimuli were presented individually at the midline, and +/- 30 and +/- 60 degrees from the midline. In both studies testing was conducted in complete darkness. Results indicated that the auditory-alone condition was slower to elicit a reach from the infants, relative to the visual-alone one, and reaches were least frequent to the auditory target. No U-shaped function was obtained, and reaching for auditory targets occurred later in age than for visual targets, but even at 7 months of age did not occur as often and was achieved by fewer infants. In both studies the quality of the reach was significantly poorer to auditory than to visual targets, but there were some accurate reaches. This research adds to our understanding of the development of auditory-manual coordination in sighted infants and is relevant to theories of auditory localization, visually guided reaching, and programming for the blind.

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