Search PubMed⌕ Search

Biomedical subjects

Keith Wesnes

Publications and source records attributed to Keith Wesnes.

At least 19 recordsLinked to original sources
PubMed2006

Effects of donepezil on central processing speed and attentional measures in Parkinson's disease with dementia and dementia with Lewy bodies.

BACKGROUND: We examined attention-enhancing effects of the cholinesterase inhibitor donepezil in Dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD) by means of open label study. METHODS: 22 DLBs and 23 PDDs were assessed over 20 weeks using the Cognitive Drug Research Computerized Attentional Tasks. We examined how much closer our patients moved towards being normal for their age by comparing them to a non-demented elderly control sample (n = 183, aged 71-75 years). RESULTS: Donepezil treatment improved power of attention, continuity of attention and reaction time variability. The deficit in responses was moved towards normal by 38 and 56% for power of attention and 22 and 10% for continuity of attention in PDD and DLB, respectively. CONCLUSIONS: Improvements in attention were found with donepezil in PDD and DLB.

Aged↗
PubMed2005

Apolipoprotein E epsilon4 allele and lorazepam effects on memory in high-functioning older adults.

CONTEXT: The apolipoprotein E (APOE) epsilon4 allele has been implicated as a significant risk factor in the development of late-onset Alzheimer disease, but the evidence of cognitive sequelae in healthy individuals has been mixed. OBJECTIVE: To determine if the APOE epsilon4 allele increases susceptibility to lorazepam-induced verbal learning impairment in nondemented older adults. DESIGN: A placebo-controlled crossover design. SETTING: A community-based sample of subjects. PARTICIPANTS: Sixty-four cognitively intact and highly educated (>12 years) adults. Twenty-four subjects (mean age, 66.3 years) were carriers of an APOE epsilon4 allele (epsilon4 positive) and 40 (mean age, 66.0 years) were not (epsilon4 negative). INTERVENTIONS: All subjects received a single oral dose of placebo and lorazepam (0.5 and 1.0 mg) 1 week apart. MAIN OUTCOME MEASURE: We used the Buschke Selective Reminding Test to assess verbal learning during a 5-hour period after placebo or lorazepam administration. RESULTS: We found a time-related, dose-dependent effect of lorazepam, with long-term recall generally decreasing with higher doses of lorazepam at up to 2.5 hours. At 5 hours, the epsilon4-negative group showed significant improvement in long-term memory, but the epsilon4-positive group demonstrated a persistent deficit. Subsequent analysis revealed that the poor performance at 5 hours was found in an epsilon4-positive subgroup with lower baseline performance. CONCLUSIONS: In cognitively intact, older adults, the effect of the APOE epsilon4 allele is not necessarily seen in the immediate response to benzodiazepine challenge. Rather, the APOE epsilon4 allele appears to affect the carrier's ability to recover from a cognitive challenge in a normal fashion, at least in a subgroup of subjects with relatively low baseline performance. This suggests that although carrying an APOE epsilon4 allele increases the risk for cognitive toxic effects, allele status alone is not a sufficient predictor of such effects. Studying the response to and the recovery from cognitive challenges may provide insights into the role of the APOE epsilon4 allele and its interaction with other factors in the development of Alzheimer disease and other age-related cognitive problems.

Aged↗
PubMed2005

A review of cognitive impairment and cerebral metabolite abnormalities in patients with hepatitis C infection.

Numerous studies have reported associations between chronic hepatitis C virus (HCV) infection and fatigue, depression and impairments in health-related quality of life, which are independent of the severity of liver disease. Although there are a large number of potential explanations for these symptoms, including a history of substance abuse and associated personality types, or the effect of the diagnosis of HCV infection itself, there has been recent interest in the possibility of a biological effect of HCV infection on cerebral function. There is emerging evidence of mild, but significant neurocognitive impairment in HCV infection, which cannot be wholly attributed to substance abuse, co-existent depression or hepatic encephalopathy. Impairments are predominantly in the domains of attention, concentration and information processing speed. Furthermore, in-vivo cerebral magnetic resonance spectroscopy studies in patients with hepatitis C and normal liver function have reported elevations in cerebral choline-containing compounds and reductions in N-acetyl aspartate, suggesting that a biological mechanism may underlie the cognitive findings. The recent detection of HCV genetic sequences in post-mortem brain tissue raises the intriguing possibility that HCV infection of the central nervous system may be related to the reported neuropsychological symptoms and cognitive impairment.

Brain↗
PubMed2005

Assessment of cognitive function of the elderly population: effects of darifenacin.

PURPOSE: Overactive bladder is common in the elderly population, which is susceptible to cognitive disorders and drug induced cognitive impairment. Existing overactive bladder treatments may cause adverse events, such as cognitive impairment, due to antagonism of the M1 receptor in the central nervous system. In this study we evaluated the effect of darifenacin, an M3 selective antagonist, on cognitive function in elderly volunteers without clinical dementia. MATERIALS AND METHODS: This double-blind, 3-period crossover study randomized 129 volunteers 65 years or older with no/mild cognitive impairment to receive 3 of 5 treatments, namely darifenacin controlled release (3.75, 7.5 or 15 mg once daily), darifenacin immediate-release (5 mg 3 times daily) or matching placebo for 14 days. Each treatment period was separated by 7 days of washout. Cognitive function tests were completed at baseline and at treatment end. RESULTS: For the primary end points of memory scanning sensitivity, speed of choice reaction time and word recognition sensitivity, there were no statistically significant differences for darifenacin vs placebo. There were no statistically significant differences in secondary variables except memory scanning speed, which increased in all groups relative to baseline, but improvement was greater with placebo than with 3.75 mg darifenacin. Darifenacin treatment was not associated with changes in alertness, contentment or calmness, which are likely to be clinically relevant. Darifenacin was well tolerated. CONCLUSIONS: : In elderly volunteers 2 weeks of treatment with darifenacin had no effect on cognitive function compared with baseline and it was not significantly different from placebo. This may be related to its M3 receptor selectivity with negligible M1 receptor antagonism.

Aged↗
PubMed2005

Association between mild vascular cognitive impairment and impaired activities of daily living in older stroke survivors without dementia.

OBJECTIVES: To determine the relationship between mild vascular cognitive impairment (mVCI) and functional disability in older stroke survivors without dementia. DESIGN: Cohort study. SETTING: Stroke patients from representative hospital-based stroke registers. PARTICIPANTS: Three hundred thirty-nine stroke survivors without dementia, aged 75 and older. MEASUREMENTS: Neuropsychological assessments were completed 3 months poststroke. Activities of daily living (ADLs) were evaluated using the Bristol scale. Operationalized criteria, including cognitive impairment no dementia (CIND), were applied for mVCI. RESULTS: Significant impairments of ADLs were evident in mVCI (CIND vs no CIND; basic care: z=3.2; P=.001, intermediate care: z=3.6; P<.001, complex management: z=4.5; P<.001) but varied according to the profile of cognitive impairments. Patients with attentional or global impairments had more severe functional disability than patients with isolated memory deficits, with an intermediate level of dysfunction in patients with executive impairments. CONCLUSION: The findings emphasize the importance of identifying early cognitive impairments to optimize rehabilitation, care planning, and secondary prevention of dementia in stroke patients.

Activities of Daily Living↗
PubMed2005

Early onset effects of galantamine treatment on attention in patients with Alzheimer's disease.

INTRODUCTION: Exploratory pilot studies and knowledge of its mode of action suggested that galantamine, a cholinesterase inhibitor and modulator of nicotinic receptors, can improve attention. This study was designed to test the effects of galantamine on attention in patients with mild-to-moderate Alzheimer's disease (AD) and to see how changes in attention affected their caregivers. METHODS: This was an open-label, multicentre study. Patients received galantamine (up to 24 mg/day) for 12 weeks. Attention was assessed after 1, 4, 8 and 12 weeks using computerized tests including Choice Reaction Time (CRT), and caregiver, physician and patient ratings. RESULTS: Data were available from 373 patients (mean age 75 years, mean baseline MMSE score 21). Attention as measured by CRT improved significantly from baseline to study endpoint (p < 0.001), improvements were observed after 1 week and statistical significance was maintained from 8 weeks. Physicians rated 67% of patients as globally improved and 5% as worsened. Caregivers reported improved attention in 57% of patients and worsening in 6%; 62% of patients considered they had improved and 3% considered themselves to be worse. Caregiver stress, time spent caring for patients and patients' interactions with others all improved from baseline to endpoint. Galantamine was generally well tolerated; the most common adverse events were gastrointestinal. CONCLUSION: Previous controlled trials have demonstrated that galantamine has a positive effect on cognition, activities of daily living, behaviour and global condition, but this is the first study to suggest that galantamine may specifically improve attention (according to both objective and subjective measures) in patients with AD. These effects may be a consequence of galantamine's potentiating action at nicotinic receptors.

Adult↗
PubMed2004

White matter hyperintensities are associated with impairment of memory, attention, and global cognitive performance in older stroke patients.

BACKGROUND: The importance of white matter hyperintensities (WMH) for cognitive performance in older stroke patients is largely unknown. We hypothesized that processing speed and executive dysfunction will be associated with frontal WMH whereas impaired memory will be associated with temporal WMH. METHODS: Neuropsychological assessments using the Cambridge Cognitive Examination (CAMCOG) and the Cognitive Drug Research (CDR) were completed for 96 stroke survivors aged older than 75 and 23 age-matched controls. Magnetic resonance imaging whole-brain axial FLAIR images were undertaken to visualize WMH and an automated threshold technique was used to determine their volume. RESULTS: In comparison to controls, the stroke patients had significantly greater volume of WMH in all key areas. Within the stroke group, a consistent pattern of significant association was identified between total and frontal WHM volumes and attention and processing speed tasks (eg, choice reaction time [right: R=0.24 P=0.02; left: R=0.26, P=0.01]), but not with executive function. There were significant associations between memory and temporal WMH volumes (right: R=0.27, P=0.008; left: R=0.20, P=0.047). CONCLUSIONS: In older stroke patients, cognitive processing speed and performance on measures of attention are significantly associated with WMH volume, particularly in the frontal lobe regions, whereas memory impairment is associated with the volume of temporal lobe WMH.

Aged↗
PubMed2004

Effects of acute lorazepam administration on aminergic activity in normal elderly subjects: relationship to performance effects and apolipoprotein genotype.

The effects of acute lorazepam challenges on plasma (p) HVA, MHPG, and 5-HIAA, and their relationship to drug-induced cognitive and motor deficits and the apolipoprotein (APOE)-epsilon4 allele were examined. Eighteen healthy elderly (8 epsilon4 carriers) received placebo or acute oral lorazepam doses (0.5 mg or 1 mg) in random sequence, 1-week apart. Cognitive assessment and plasma levels of pHVA, pMHPG, and p5-HIAA were determined at baseline and at 1, 2.5, and 5 h postchallenge. There was no drug-to-placebo difference in monoamine levels and no consistent relationship between changes in monoamine levels and cognitive performance, regardless of epsilon4 status. However, the 1.0 mg dose increased p5-HIAA in epsilon4 carriers, whereas it caused a reduction in noncarriers. Higher baseline pMHPG and p5-HIAA levels were associated with better baseline memory. The epsilon4 allele may modulate the effect of lorazepam on p5-HIAA, but further studies are needed to confirm this finding and elucidate its possible significance.

Aged↗
PubMed2004

Increased anticholinergic challenge-induced memory impairment associated with the APOE-epsilon4 allele in the elderly: a controlled pilot study.

The degree to which elderly adults experience cognitive impairments from centrally acting anticholinergic drugs is variable, but the cause of this variability is unknown. The present study examined the epsilon4 allele as a possible modulator of the effects of trihexyphenidyl hydrochloride (Artane( trade mark )), an anticholinergic drug, on memory functioning. Of the 24 cognitively intact, elderly participants (age range 62-76), 12 who possessed the epsilon4 allele, participated in a double-blind, randomized, placebo-controlled, crossover, three-way study. All participants were tested after receiving a single oral dose of trihexyphenidyl (1 or 2 mg) or placebo, with a 7-day washout period between sessions. Memory and psychomotor tests were administered at baseline, and at 1, 2.5, and 5 h post-treatment. Results showed that participants with the epsilon4 allele demonstrated significant impairments in delayed recall after both 1 and 2 mg doses of trihexyphenidyl while the non-epsilon4 group did not. Additionally, while acute administration of the 2 mg dose significantly impaired total recall in both epsilon4 and non-epsilon4 carriers, the epsilon4 carriers showed a more persistent impairment. These findings held when participants with the epsilon2 allele were excluded from the analyses. The epsilon4 groups did not differ with respect to psychomotor performance or plasma drug levels. These results provide evidence suggesting that the epsilon4 allele plays a significant role in increasing cognitive sensitivity to trihexyphenidyl and that a temporal component of memory consolidation may be especially vulnerable. A larger study is warranted to confirm these preliminary findings.

Aged↗
PubMed2003

Mild cognitive impairment and vascular cognitive impairment in stroke patients.

In 150 older stroke patients (>75) without dementia, the proportion of people meeting different criteria for early cognitive impairment varied from 17% to 23% depending upon the individual criteria used. Given this large disparity, prospective studies to clarify the utility of different criteria as a predictor of subsequent dementia are a priority.

Aged↗
PubMed2003

Effects of hypertension on attention, memory, and executive function in older adults.

Hypertension is associated with impairments in cognitive function in older adults, but the nature and extent of these deficits are unclear. Brief cognitive measures lack sensitivity, whereas comprehensive assessments produce numerous variables that are difficult to interpret. The authors performed a principal-components analysis using a computerized cognitive assessment battery and neuropsychological measures of executive function in 506 hypertensive and normotensive older participants. Composite factor scores were used to reanalyze data from 223 untreated participants without vascular complications. The hypertensive group had deficits in Speed of Cognition, Episodic and Working Memory, and Executive Function but not Continuity of Attention. Using composite scores simplified data interpretation and suggested differential effects of hypertension on cognitive performance not clearly evident in individual test results.

Aged↗
PubMed2003

Aromas of rosemary and lavender essential oils differentially affect cognition and mood in healthy adults.

This study was designed to assess the olfactory impact of the essential oils of lavender (Lavandula angustifolia) and rosemary (Rosmarlnus officinalis) on cognitive performance and mood in healthy volunteers. One hundred and forty-four participants were randomly assigned to one of three independent groups, and subsequently performed the Cognitive Drug Research (CDR) computerized cognitive assessment battery in a cubicle containing either one of the two odors or no odor (control). Visual analogue mood questionnaires were completed prior to exposure to the odor, and subsequently after completion of the test battery. The participants were deceived as to the genuine aim of the study until the completion of testing to prevent expectancy effects from possibly influencing the data. The outcome variables from the nine tasks that constitute the CDR core battery feed into six factors that represent different aspects of cognitive functioning. Analysis of performance revealed that lavender produced a significant decrement in performance of working memory, and impaired reaction times for both memory and attention based tasks compared to controls. In contrast, rosemary produced a significant enhancement of performance for overall quality of memory and secondary memory factors, but also produced an impairment of speed of memory compared to controls. With regard to mood, comparisons of the change in ratings from baseline to post-test revealed that following the completion of the cognitive assessment battery, both the control and lavender groups were significantly less alert than the rosemary condition; however, the control group was significantly less content than both rosemary and lavender conditions. These findings indicate that the olfactory properties of these essential oils can produce objective effects on cognitive performance, as well as subjective effects on mood.

Adult↗
PubMed2003

Regulation of attention and response to therapy in dementia by butyrylcholinesterase.

OBJECTIVES: To determine the response of patients with different butyrylcholinesterase genotypes to therapy, and the influence of butyrylcholinesterase on cognition. Acetylcholine plays a key role in attention and memory and reduced cortical acetylcholine is associated with the severity of dementia. Inhibitors of the enzyme acetylcholinesterase are an effective dementia treatment, though the role of the related enzyme butyrylcholinesterase is less well understood. METHODS: We examined the response of a cohort of dementia patients enrolled in a trial of a cholinesterase inhibitor who had been genotyped at the butyrylcholinesterase locus. Additionally a prospectively assessed cohort of dementia patients was genotyped and rate of cognitive decline examined, along with baseline cognitive performance in a group of elderly non-demented individuals. We identified that the presence of reduced-activity butyrylcholinesterase variants correlates with preserved attentional performance and reduced rate of cognitive decline. During cholinesterase inhibitor therapy, patients with normal butyrylcholinesterase show improved attention, though patients carrying reduced-activity enzyme do not, possibly due to being at ceiling performance. Butyrylcholinesterase did not however affect attentional performance in non-demented individuals with mild cognitive impairment. CONCLUSIONS: These findings indicate that the butyrylcholinesterase enzyme is a major regulator of attention especially in cholinergic deficiency states through its ability to hydrolyse acetylcholine. Pharmacologic manipulation of this enzyme may be a viable strategy in dementia treatment and, with butyrylcholinesterase genotyping, may provide pharmacogenomic treatment of dementia.

Acetylcholine↗
PubMed2002

Apolipoprotein E epsilon 4 and short-term recovery from predominantly mild brain injury.

OBJECTIVE: To determine whether APOE genotype explained variability in short-term recovery from predominantly mild traumatic brain injury (TBI). METHODS: A total of 87 adult patients presenting with mild or moderate TBI to a shock trauma center were enrolled prospectively. A battery of 13 neuropsychological tests was administered twice, at approximately 3 and 6 weeks after injury. Eighty of 87 patients were successfully genotyped for APOE using a buccal swab technique. RESULTS: Ninety percent of study patients had mild TBI (Glasgow Coma Scale score of 13 to 15); 18 (22.5%) had one APOE epsilon 4 and none had two epsilon 4 alleles. After adjusting for potential confounders, patients positive for the APOE epsilon 4 allele had lower mean scores on 12 of 13 neuropsychological outcomes at visit 1 compared with APOE epsilon 4-negative patients. Two of the differences were significant (grooved pegboard test, p = 0.005; paced auditory serial addition task 2.8-second trial, p = 0.004). At visit 2, APOE epsilon 4-positive patients had lower adjusted mean scores on 11 of the 13 neuropsychological outcomes. None of the differences was significant. CONCLUSIONS: APOE genotype may influence the severity of the acute injury. However, with no consistent pattern to the recovery curves, it is not clear if APOE genotype influences the rate of recovery.

Adolescent↗
PubMed2002

Assessing cognitive function in clinical trials: latest developments and future directions.

Properly developed automated test systems are of value for assessing changes in cognitive function in clinical trials. Besides the other advantages that automation brings to trials, such as increased reliability and utility, it is shown that such systems are also more sensitive to change in cognitive function than traditional nonautomated procedures. Data from a variety of topical areas in drug development are presented to illustrate the added value such techniques have brought. The latest developments in automation include remote testing via the Internet and telephone.

Attention↗
PubMed2002

The acute nootropic effects of Ginkgo biloba in healthy older human subjects: a preliminary investigation.

Ginkgo biloba has been shown to have chronic memory enhancing effects in healthy subjects and patients with dementia. There is limited research on the acute nootropic effects of Ginkgo biloba in humans. The current study aimed to examine the acute effects of Ginkgo biloba (120 mg) on memory functioning in healthy older volunteers using the cognitive drug research (CDR) battery of memory tests and the Rey auditory verbal learning task (AVLT). The study was a double-blind placebo-controlled design, with each participant tested under both placebo and Ginkgo biloba treatment conditions. Testing was conducted pre- and 90 min post-drug administration for each treatment condition. Treatment conditions were separated by a 7 day wash out period. No acute effects of Ginkgo biloba were found for any of the memory tests examined. The findings suggest that 120 mg of Ginkgo biloba has no acute nootropic effects in healthy older humans.

Aged↗