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Biomedical subjects

Keith Wesnes

Publications and source records attributed to Keith Wesnes.

25 records · Page 2Linked to original sources

A pharmacokinetic and pharmacodynamic drug interaction study of acamprosate and naltrexone.

Acamprosate and naltrexone have each demonstrated safety and efficacy for alcohol dependence in placebo-controlled clinical trials. There is scientific and clinical interest in evaluating these drugs in combination, given their high tolerability, moderate effect sizes, different pharmacological profiles and potentially different effects on drinking outcomes. Thus, this is the first human pharmacokinetic and pharmacodynamic drug interaction study of acamprosate and naltrexone. Twenty-four normal, healthy adult volunteers participated in a double-blind, multiple dose, within subjects, randomized, 3-way crossover drug interaction study of the standard therapeutic dose of acamprosate (2 g/d) and the standard therapeutic dose of naltrexone (50 mg/d), given alone and in combination, with seven days per treatment condition and seven days washout between treatments. Blood samples were collected on a standardized schedule for pharmacokinetic analysis of naltrexone, 6-beta-naltrexol, and acamprosate. A computerized assessment system evaluated potential drug effects on cognitive functioning. Coadministration of acamprosate with naltrexone significantly increased the rate and extent of absorption of acamprosate, as indicated by an average 33% increase in acamprosate maximum plasma concentration, 33% reduction in time to maximum plasma concentration, and 25% increase in area under the plasma concentration-time curve. Acamprosate did not affect the pharmacokinetic parameters of naltrexone or 6-beta-naltrexol. A complete absence of negative interactions on measures of safety and cognitive function supports the absence of a contraindication to co-administration of acamprosate and naltrexone in clinical practice.

Acamprosate↗

Neuropsychological deficits in older stroke patients.

This paper examines the frequency of CIND, the profile of early cognitive deficits in stroke patients, the differences in the profile of cognitive impairment in people with CIND and those with vascular dementia, and the MRI associations of CIND in older stroke patients.

Aged↗

Cognitive associations of subcortical white matter lesions in older people.

Hyperintense lesions (HL), as visualized on T2-weighted or FLAIR MRI, are a common finding in older people, but their clinical significance and influence on cognitive function remain to be clarified. We investigated the relationship between HL in deep white and gray matter structures and cognition in older subjects. We recruited 154 nondemented (Mini-Mental State Examination > 24) subjects (79 males) over the age of 70 from primary care (103 subjects with mild hypertension and 51 normotensive subjects). All subjects underwent FLAIR and proton density and T2-weighted axial 1.5-tesla MRI scans (slice thickness: 5 mm). The scans were rated for the presence and distribution of HL in the subcortical gray matter (caudate, putamen, globus pallidus, thalamus) and associated white matter tracts (internal/external capsule). Subjects (n = 149) underwent a comprehensive cognitive assessment involving tests of attention, processing speed, episodic memory, working memory, and executive function. Partial correlations (correcting for age, systolic blood pressure, and New Adult Reading Test [NART] score) were performed to investigate the relationship between cognition and white matter change. HL were found in 49% of subjects. HL in both the gray (thalamus and caudate) and white matter were significantly associated with impaired cognitive function in tasks involving processing speed and/or executive function, but showed no associations with episodic or working memory. HL in both subcortical gray matter structures and associated fiber tracts correlate with impairments in attention, executive function and processing, and memory retrieval speed in nondemented older community-dwelling subjects. Such lesions may be an important cause of age-related attentional and executive dysfunction in the elderly, as well as temporal lobe and hippocampal changes that have previously been reported to be associated with impairments to the ability to actually store and retrieve information from memory.

Aged↗

The effect of glucose administration and the emotional content of words on heart rate and memory.

The effects of glucose administration and emotionality of target material on heart rate and memory were examined in a double-blind, placebo-controlled, balanced crossover study. Memory for neutral and emotional words was tested in 20 young adults following a glucose drink and a placebo. Heart rate and blood glucose were also measured. Emotional words were recalled and recognized better than neutral words in both drink conditions but there was no direct effect of drink type on memory. During the neutral word memory tasks, similar heart rate deceleration was observed in both drink conditions. However, during the processing of emotional material, heart rates were lowered in the placebo condition and relatively increased in the glucose condition. These results further differentiate the physiological responses involved during memory for affective and neutral material.

Adult↗

Reliable diagnoses of dementia by the naive credal classifier inferred from incomplete cognitive data.

Dementia is a serious personal, medical and social problem. Recent research indicates early and accurate diagnoses as the key to effectively cope with it. No definitive cure is available but in some cases when the impairment is still mild the disease can be contained. This paper describes a diagnostic tool that jointly uses the naive credal classifier and the most widely used computerized system of cognitive tests in dementia research, the Cognitive Drug Research system. The naive credal classifier extends the discrete naive Bayes classifier to imprecise probabilities. The naive credal classifier models both prior ignorance and ignorance about the likelihood by sets of probability distributions. This is a new way to deal with small and incomplete datasets that departs significantly from most established classification methods. In the empirical study presented here, the naive credal classifier provides reliability and unmatched predictive performance. It delivers up to 95% correct predictions while being very robust with respect to the partial ignorance due to the largely incomplete data. The diagnostic tool also proves to be very effective in discriminating between Alzheimer's disease and dementia with Lewy bodies.

Alzheimer Disease↗