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Roy W Jones

Publications and source records attributed to Roy W Jones.

10 recordsLinked to original sources
PubMed2004

A multinational, randomised, 12-week study comparing the effects of donepezil and galantamine in patients with mild to moderate Alzheimer's disease.

OBJECTIVES: To compare directly, in the same patient cohort, the ease of use and tolerability of donepezil and galantamine in the treatment of Alzheimer's disease (AD), and investigate the effects of both treatments on cognition and activities of daily living (ADL). METHODS: Patients with mild to moderate AD from 14 European centres were randomised to receive open-label donepezil (up to 10 mg once daily) or galantamine (up to 12 mg twice daily) for 12 weeks, according to the approved product labelling. Physicians and caregivers completed questionnaires rating satisfaction with treatment/ease of use in daily practice. Secondary assessments were the ADAS-cog, the MMSE, and the DAD scale to assess ADL. Tolerability was evaluated by reporting adverse events (AEs). RESULTS: Both physicians and caregivers reported significantly greater overall satisfaction/ease of use for donepezil (n = 64) compared with galantamine (n = 56) at weeks 4, 12, and endpoint (week 12 LOCF; all p-values <0.05). Significantly greater improvements in cognition were also observed for donepezil versus galantamine on the ADAS-cog at Week 12 and endpoint (p-values <0.05). ADL improved significantly in the donepezil group compared with the galantamine group at weeks 4, 12, and endpoint (p-values <0.05). Most AEs were mild to moderate, however, 46% galantamine-treated patients reported gastrointestinal AEs vs 25% donepezil patients. CONCLUSIONS: Physician and caregiver ease of use/satisfaction scores, and assessments of cognition and ADL, showed significant benefits for donepezil compared with galantamine in this direct comparative trial. Both treatments were well tolerated, with more gastrointestinal AEs reported for galantamine vs donepezil.

Activities of Daily Living↗
PubMed2004

A category-specific advantage for numbers in verbal short-term memory: evidence from semantic dementia.

This study explored possible reasons for the striking difference between digit span and word span in patients with semantic dementia. Immediate serial recall (ISR) of number and non-number words was examined in four patients. For every case, the recall of single-digit numbers was normal whereas the recall of non-number words was impaired relative to controls. This difference extended to multi-digit numbers, and remained even when frequency, imageability, word length, set size and size of semantic category were matched for the numbers and words. The advantage for number words also applied to the patients' reading performance. Previous studies have suggested that semantic memory plays a critical role in verbal short-term memory (STM) and reading: patients with semantic dementia show superior recall and reading of words that are still relatively well known compared to previously known but now semantically degraded words. Additional assessments suggested that this semantic locus was the basis of the patients' category-specific advantage for numbers. Comprehension was considerably better for number than non-number words. Number knowledge may be relatively preserved in semantic dementia because the cortical atrophy underlying the condition typically spares the areas of the parietal lobes thought to be crucial in numerical cognition but involves the inferolateral temporal-lobes known to support general conceptual knowledge.

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PubMed2004

Deficient acquisition and consolidation: intertrial free recall performance in Alzheimer's disease and mild cognitive impairment.

Abstract Previous research demonstrates that dementia of the Alzheimer type (DAT) is characterised by deficits of episodic memory, especially in the acquisition of new material. As well as this deficit in acquisition, some researchers have also argued for a deficit in consolidation in DAT. We examined acquisition and consolidation by measuring the intertrial gained and lost access in DAT, Mild Cognitive Impairment (MCI) and controls. We report findings from a study of clinical data based on assessment of patients using three free recall trials of a word list. We found that both DAT and MCI groups showed a deficit in acquisition and consolidation of items between trials relative to controls. Moreover, the DAT group was significantly impaired relative to the MCI group for both acquisition and consolidation. Correlations within each group showed that there were strong relationships between intertrial measures and standard measures of memory function. Importantly in no group was there a significant correlation between our measures of acquisition and consolidation: we argue that these measures reflect different underlying processes, and the failure to consolidate in DATand MCI is not related to the deficit in acquisition. Finally, we showed strong correlations between our measure and dementia severity, suggesting that acquisition and consolidation both get worse as the dementia progresses.

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PubMed2004

Deficits for semantics and the irregular past tense: a causal relationship?

The regular and irregular past tense has become a focus for recent debates about the structure of the language processing system, asking whether language functions are subserved by different neural and functional mechanisms or whether all processes can be accommodated within a single unified system. A critical claim of leading single mechanism accounts is that the relationship between an irregular stem and its past tense form is primarily semantic and not morphological in nature. This predicts an obligatory relationship between semantic performance and access to the irregular past tense, such that a semantic deficit necessarily leads to impairments on the irregulars. We tested this claim in a series of studies probing the comprehension and production of regular and irregular past tense forms in four semantic dementia patients, all of whom had profound semantic deficits. In two elicitation tasks and one auditory priming study, we found that three out of the four patients did not have a deficit for the irregular past tense, in spite of their semantic deficits. This argues against the view that the relationship between irregular past tense forms and their stems is primarily semantic, and more generally against the single system claim that morphological structure can be captured solely based on phonological and semantic relationships.

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PubMed2004

Cost effectiveness of memantine in Alzheimer's disease: an analysis based on a probabilistic Markov model from a UK perspective.

BACKGROUND: Clinical trials with memantine, an uncompetitive moderate-affinity NMDA antagonist, have shown improved clinical outcomes, increased independence and a trend towards delayed institutionalisation in patients with moderately severe-to-severe Alzheimer's disease. In a randomised double-blind, placebo-controlled, 28-week study conducted in the US, reductions in resource utilisation and total healthcare costs were noted with memantine relative to placebo. While these findings suggest that, compared with placebo, memantine provides cost savings, further analyses may help to quantify potential economic gains over a longer treatment period. OBJECTIVE: To evaluate the cost effectiveness of memantine therapy compared with no pharmacological treatment in patients with moderately severe-to-severe Alzheimer's disease over a 2-year period. METHODS: A Markov model was constructed to simulate patient progression through a series of health states related to severity, dependency (determined by patient scores on the Alzheimer's Disease Cooperative Study-Activities of Daily Living [ADCS-ADL] inventory and residential status ('institutionalisation') with a time horizon of 2 years (each 6-month Markov cycle was repeated four times). Transition probabilities from one health state to another 6 months later were mainly derived from a 28-week, randomised, double-blind, placebo-controlled clinical trial. Inputs related to epidemiological and cost data were derived from a UK longitudinal epidemiological study, while data on quality-adjusted life-years (QALYs) were derived from a Danish longitudinal study. To ensure conservative estimates from the model, the base case analysis assumed drug effectiveness was limited to 12 months. Monte Carlo simulations were performed for each state parameter following definition of a priori distributions for the main variables of the model. Sensitivity analyses included worst case scenario in which memantine was effective for 6 months and one-way sensitivity analyses on key parameters. Finally, a subgroup analysis was performed to determine which patients were most likely to benefit from memantine. Informal care was not included in this model as the costs were considered from National Health Service and Personal Social Services perspective. RESULTS: The base case analysis found that, compared with no treatment, memantine was associated with lower costs and greater clinical effectiveness in terms of years of independence, years in the community and QALYs. Sensitivity analyses supported these findings. For each category of Alzheimer's disease patient examined, treatment with memantine was a cost-effective strategy. The greatest economic gain of memantine treatment was in independent patients with a Mini-Mental State Examination score of > or =10. CONCLUSION: This model suggests that memantine treatment is cost effective and provides cost savings compared with no pharmacological treatment. These benefits appear to result from prolonged patient independence and delayed institutionalisation for moderately severe and severe Alzheimer's disease patients on memantine compared with no pharmacological treatment.

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PubMed2003

Have cholinergic therapies reached their clinical boundary in Alzheimer's disease?

The cholinergic hypothesis suggests that Alzheimer's disease (AD) results from a selective loss in cholinergic neurons with decreased acetylcholine levels. Treatments that increase the level of acetylcholine would be expected to provide clinical benefit. Clinical trials of dietary precursors of acetylcholine and muscarinic receptor agonists have been unsuccessful. Further research is needed to confirm whether nicotine or nicotinic agonists are of value. The most successful approach has been to increase acetylcholine levels by inhibiting cholinesterase function. A number of cholinesterase inhibitors (ChEI) show clinical efficacy including phyostigmine but it is poorly tolerated. Tacrine, the first ChEI to be licensed for AD, needs frequent administration and causes a specific reversible hepatotoxicity. Three ChEI, donepezil, rivastigmine and galantamine are widely available. They are effective in mild to moderate (and possibly severe) AD. Tolerability is improved by slow dose titration and there are a significant number of non-responders. Donepezil appears to be effective, the simplest to use and the best tolerated. Rivastigmine is effective but less well tolerated: galantamine is also very effective with intermediate tolerability. Although there are pharmacological differences between the three compounds, it remains uncertain whether these are clinically relevant. There are still unanswered questions. It is difficult to predict who will respond to the drugs and it is unclear how long treatment benefits last. At present there are little data to support the suggestion of activity beyond symptomatic benefit. Trials are also being conducted in Mild Cognitive Impairment, other dementias and other conditions where cognitive impairment is a problem.

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PubMed2002

Retrieval-induced forgetting in Alzheimer's disease.

It is claimed that Alzheimer's disease (AD) patients show reduced inhibitory processing and this has been put forward as a reason why AD patients make intrusion errors at recall. However, the evidence to date has been equivocal, because non-inhibitory mechanisms can account for the pattern of findings. Recently, however, a paradigm has been developed that is claimed to give a purer measure of inhibitory processing in episodic memory, the retrieval-induced forgetting (RIF) paradigm [Inhibitory Processes in Attention, Memory and Language, Academic Press, San Diego, 1994, p. 265; J. Exp. Psychol.: Learning, Memory Cognition 20 (1994) 1063; Psychol. Rev. 102 (1995) 68]. Thus, we were interested whether AD patients would show a deficit in inhibitory processing using this procedure. Participants studied lists of category cue-exemplar pairs (e.g. fruit-orange) then practised retrieval for a subset of items from a subset of categories before taking a final memory test for all studied items. As in previous work, inhibition was measured as the difference between final memory performance for unpractised items from practised categories, and unpractised items from unpractised categories. The results show that AD patients showed normal levels of inhibition with both tests of cued recall and category generation (CG). This suggests that a deficit in inhibitory processes during retrieval is not behind the high levels of intrusion errors made in recall in AD.

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PubMedDate not supplied

Enhancement of antibody responses to influenza vaccination in the elderly following a cognitive-behavioural stress management intervention.

BACKGROUND: Previous research has demonstrated that the psychological morbidity experienced by informal caregivers is associated with increased vulnerability to infectious diseases, in particular influenza. A pragmatic trial was conducted to examine whether a stress management intervention (SMI) could reduce psychological morbidity and enhance the antibody response to influenza vaccination in the elderly, and whether changes in immune response of SMI participants were associated with hypothalamic-pituitary-adrenal (HPA) axis activity. METHODS: Forty-three elderly spousal carers of dementia patients and 27 non-carer controls were recruited. Sixteen carers were allocated to an 8-week SMI or a non-intervention condition (n = 27). The non-carers formed a no treatment, 'normal' comparison group. At the end of the SMI or its equivalent time period, all participants received an influenza vaccination. IgG antibody titres to the vaccine were measured 0, 2, 4 and 6 weeks post-vaccine. RESULTS: There was evidence of elevated distress in both carer groups compared with non-carer controls throughout the SMI period, but no between-group differences in salivary cortisol. Immune responses to the vaccine revealed that 50% of SMI carers, 7% of non-intervention carers and 29% of non-carer controls produced a four-fold increase in antibody titre. CONCLUSIONS: The immune response to influenza vaccination appears amenable to improvement through stress management, although the mechanisms underlying this effect remain unclear.

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PubMedDate not supplied

The dementias.

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Activities of Daily Living↗