Biomedical subjects

K Wesnes

Publications and source records attributed to K Wesnes.

At least 19 recordsLinked to original sources

PubMed2007

Effects of TC-1734 (AZD3480), a selective neuronal nicotinic receptor agonist, on cognitive performance and the EEG of young healthy male volunteers.

OBJECTIVES: The aim of this study was to get insight into the central effects of TC-1734 (renamed AZD3480), a selective agonist at the neuronal nicotinic receptor of the alpha4beta2 subtype. MATERIALS AND METHODS: Electroencephalography (EEG) techniques and computerized cognitive tests were performed in young, healthy male volunteers during two double-blind and placebo-controlled studies: a rising single dose crossover study (from 2 to 320 mg) and a rising repeated dose study with a parallel group design (50, 100, and 200 mg). RESULTS: In contrast to acute administration, administration of AZD3480 over 10 days produced statistically significant enhancement of several cognitive measures (attention and episodic memory) compared to placebo. Regarding EEG data, AZD3480 showed acceleration of the alpha centroid and of the alpha peak in the single-dose study. This EEG profile of the acceleration type was confirmed in the repeated dose study on both day 1 and day 10, with the greatest effect observed with the highest dose. The EEG pattern shown for AZD3480 was consistent with that previously described with other drugs known to improve attention and vigilance (including nicotine). In addition, subjects dosed with AZD3480 showed a statistically significant increase in mismatch negativity (MMN) amplitude at 50 and 200 mg while reducing MMN latency (200 mg only), suggesting an improvement of pre-attentional mechanisms. CONCLUSION: These early data in healthy subjects provide encouragement to consider development of AZD3480 as a novel agent for the treatment of cognitive decline in the elderly, including age-associated memory impairment and/or dementia of the Alzheimer's type.

Administration, Oral↗

PubMed2006

Effect of levodopa on cognitive function in Parkinson's disease with and without dementia and dementia with Lewy bodies.

BACKGROUND: Levodopa (L-dopa) is the gold standard treatment for Parkinson's disease, but a lack of clear efficacy combined with a perceived liability to neuropsychiatric side effects has limited L-dopa use in patients with parkinsonism and dementia. Therefore, the effect of L-dopa on the cognitive profile of dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD) is unclear. AIM: To ascertain the acute and long-term effects of L-dopa on aspects of attention and cognition in patients with DLB and PDD, and to compare these with the effects in Parkinson's disease. METHOD: Baseline cognitive and motor function was assessed off L-dopa in patients with Parkinson's disease (n = 22), PDD (n = 27) and DLB (n = 11) using standard "bedside" measures and a computerised programme detecting reaction times and accuracy. All patients then underwent an acute L-dopa challenge with subsequent subjective and objective analysis of alertness, verbal recall, reaction times and accuracy. The same parameters were measured after 3 months on L-dopa to assess the prolonged effect. RESULTS: Acute L-dopa challenge considerably improved motor function and subjective alertness in all patients without compromising either reaction times or accuracy, but increased fluctuations were noted in both groups with dementia. Neuropsychiatric scores improved in patients with Parkinson's disease both with and without dementia on L-dopa at 3 months. Although patients with Parkinson's disease also had better mean global cognitive function at this time, mean verbal attention and memory deteriorated, and patients with PDD had slower reaction times in some tests. No patient had a marked deterioration over this time. Patients with DLB did not experience any adverse cognitive or neuropsychiatric effects after 3 months of L-dopa treatment. CONCLUSION: The use of L-dopa in patients with parkinsonism with dementia does not adversely affect cognitive function.

Aged↗

PubMed2006

Adjunct armodafinil improves wakefulness and memory in obstructive sleep apnea/hypopnea syndrome.

OBJECTIVE: Armodafinil is the R-enantiomer of racemic modafinil and has a significantly longer half-life than the S-enantiomer. This study evaluated armodafinil 150 mg/day as an adjunct treatment for residual excessive sleepiness in patients with obstructive sleep apnea/hypopnea syndrome (OSA/HS) who were otherwise well controlled with nasal continuous positive airway pressure (nCPAP). We assessed the ability of armodafinil to improve wakefulness and cognition and reduce fatigue in this population. METHODS: In this 12-week, randomized, double-blind study, patients (n=259) received armodafinil (150 mg) or placebo once daily. Efficacy assessments at baseline and weeks 4, 8, and 12 included the Maintenance of Wakefulness Test (MWT), Clinical Global Impression of Change (CGI-C), Cognitive Drug Research battery, Epworth Sleepiness Scale, and Brief Fatigue Inventory. RESULTS: At final visit, mean (SD) MWT sleep latency increased from baseline by 2.3 (7.8) min with armodafinil and decreased by 1.3 (7.1) min in the placebo group (P=0.0003). Armodafinil improved clinical condition (CGI-C, 71% vs. 53% for armodafinil and placebo, respectively; P=0.0069). Armodafinil significantly improved episodic secondary memory (P=0.0102) and patient-estimated wakefulness (P<0.01) and reduced fatigue (P<0.05) compared with placebo. Armodafinil did not adversely affect nCPAP use. The most common adverse event associated with armodafinil was headache. Sleep macroarchitecture was not altered by armodafinil. CONCLUSION: Adjunct treatment with armodafinil significantly improved alertness, overall clinical condition, and long-term memory. Armodafinil also reduced fatigue and the impact of sleepiness on daily activities in patients with OSA/HS who have residual excessive sleepiness notwithstanding regular use of nCPAP. Armodafinil was well tolerated.

Adjuvants, Pharmaceutic↗

PubMed2006

Attentional deficits affect activities of daily living in dementia-associated with Parkinson's disease.

OBJECTIVE: To investigate the effects of attentional deficits on activities of daily living (ADL) in patients with dementia associated with Parkinson's disease (PDD). METHOD: 461 patients were assessed neuropsychologically. Factor analyses were used to differentiate attention from other cognitive functions and to differentiate different aspects of ADL functions. The effects of the attentional measure on ADL were examined using sequential multiple regression, controlling for age, sex, education, severity of motor symptoms and other cognitive functions. RESULTS: Three cognitive factors were identified, with one factor emerging as a measure of vigilance and focused attention. This factor predicted different aspects of ADL status even after controlling for motor functions and other cognitive factors. The attention factor was the single strongest cognitive predictor of ADL status, matching the strength of the effects of motor functions on ADL status. CONCLUSION: Impaired attention is an important determinant of ADL functions in patients with PDD.

Activities of Daily Living↗

PubMed2005

Effect of 902 MHz mobile phone transmission on cognitive function in children.

We examine whether a standard mobile exposure at 902 MHz has a significant effect on cognitive function in 18 children 10-12 years of age. These were in a single group in which each child was given a single training session and then three test sessions in a randomized, three-way crossover design, using the cognitive drug research (CDR) cognitive assessment system. Exposures were 0, 0.025, or 0.25 W from a standard Nokia 3110 mobile phone handset mounted on a plastic headset in normal use position. The results of testing showed that the baseline (0 W) performance for the reaction time measurements was considerably slower than for the comparable measures in adult. There was a tendency for reaction time to be shorter during exposure to radiation than in the sham (baseline) condition, an effect that was most marked for simple reaction time. However, no effects reached statistical significance after Bonferroni correction. Therefore, we conclude that this study on 18 children did not replicate our earlier finding in adults that exposure to microwave radiation was associated with a reduction in reaction time. It should be noted that the present study investigated the effects of radiation from a GSM handset, whereas in our previous study the effect on reaction time was observed only with a more powerful analogue handset.

Body Burden↗

PubMed2003

Carotid endarterectomy improves cognitive function in patients with exhausted cerebrovascular reserve.

OBJECTIVE: To investigate changes in cognitive function following carotid endarterectomy (CEA). DESIGN: Prospective study with controls. METHODS: CEA patients (n=159) were compared to a urology surgery control group (n=20). In CEA patients cerebrovascular reserve (CVR) was measured preoperatively. During surgery emboli and blood flow velocity in the middle cerebral artery were measured by transcranial Doppler (TCD) and cerebral oxygen saturation (CsO2) by near infrared spectroscopy. Cognitive function was measured preoperatively and at 5 days and 8 weeks postoperatively using a standardised computer battery of tests. RESULTS: Only 8% of patients had normal CVR bilaterally. The median number of emboli during CEA was 12 (range 0-181). On carotid clamping, TCD velocity fell a median of 41% and cerebral oxygen saturation by 5%. Attention deteriorated compared to controls 5 days following CEA (p=0.003) and this deterioration was related to the rise in TCD velocity on declamping (r=-0.3, p=0.002). Median attention reaction times improved significantly by 8 weeks (p=0.001) especially in patients' with severely impaired CVR before surgery (p=0.02). CONCLUSIONS: Attention improved at 2 months following CEA in patients with impaired CVR. CEA may offer more than reduced stroke risk to patients with impaired CVR.

Aged↗

PubMed2001

Cerebral injury during cardiopulmonary bypass: emboli impair memory.

OBJECTIVES: Cognitive deficits occur in up to 80% of patients after cardiac surgery. We investigated the influence of cerebral perfusion and embolization during cardiopulmonary bypass on cognitive function and recovery. METHODS: Cerebrovascular reactivity was measured in 70 patients before coronary operations in which nonpulsatile bypass was used. Throughout the operations, middle cerebral artery flow velocity and embolization were recorded by transcranial Doppler and regional oxygen saturation was recorded by near-infrared spectroscopy. Cognitive function was measured by a computerized battery of tests before the operation and 1 week, 2 months, and 6 months after surgery. Elderly patients undergoing urologic surgery served as controls. RESULTS: Cerebrovascular reactivity was impaired preoperatively in 49 patients. Median (interquartile range) regional cerebral oxygen saturation fell during bypass by 10% (6%-15%), indicating increased oxygen extraction, whereas mean middle cerebral flow velocity increased significantly by a median of 6 cm/s (both P <.0001, Wilcoxon), suggesting increased arterial tone. More than 200 emboli were detected in 40 patients, mainly on aortic clamping and release, when bypass was initiated, and during defibrillation. Cognitive function deteriorated more in patients having cardiopulmonary bypass than in control patients having urologic operations but recovered in most tests by 2 months. Measures of cerebral perfusion (poor cerebrovascular reactivity, low arterial pressures, and flow velocity in the middle cerebral artery) predicted poor attention at 1 week (r = 0.3, P <.01, Spearman). Emboli were associated with memory loss (r = 0.3, P <.02, Spearman). CONCLUSIONS: Cognitive deficits were common after cardiopulmonary bypass. Occult cerebrovascular disease was more severe than expected and predisposed to attention difficulties, whereas emboli caused memory deficits. We believe this to be the first report of differing cognitive effects from emboli and hypoperfusion.

Aged↗

PubMed2000

Dose-dependent effects of flumazenil on cognition, mood, and cardio-respiratory physiology in healthy volunteers.

OBJECTIVES: To assess the possible effects of flumazenil on cognitive processing, physiology, and mood. Design A double-blind, placebo controlled, four-way cross-over study, using healthy volunteers. METHODS: On each of 4 separate visits, 16 participants received 0.5 mg, 2.5 mg, 5.0 mg of flumazenil, or normal saline. They then performed a computerised test battery assessing cognitive function. Measures of pulse rate, arterial oxygen saturation and mean arterial pressure were also taken. Finally, participants completed visual analogue scales assessing their subjective mood state. RESULTS: The majority of cognitive tasks showed dose-dependent declines in performance. Mean arterial pressure was significantly reduced, as was pulse rate. Subjective alertness showed a similar decline. CONCLUSIONS: Flumazenil has been clinically described as an agent with few intrinsic properties, whose primary effect lies in its ability to reverse benzodiazepine-induced states. This study has shown that flumazenil does possess intrinsic activity which have a significant effect on cognition, cardiovascular physiology and mood. Clinicians need to be aware of these effects.

Adult↗

PubMed2000

Efficacy of rivastigmine in dementia with Lewy bodies: a randomised, double-blind, placebo-controlled international study.

BACKGROUND: Dementia with Lewy bodies is a common form of dementia in the elderly, characterised clinically by fluctuating cognitive impairment, attention deficits, visual hallucinations, parkinsonism, and other neuropsychiatric features. Neuroleptic medication can provoke severe sensitivity reactions in patients with dementia of this type. Many deficits in cholinergic neurotransmission are seen in the brain of patients with Lewy-body dementia; therefore, drugs enhancing central cholinergic function represent a rationally-based therapeutic approach to this disorder. Rivastigmine, a cholinesterase inhibitor, was tested in a group of clinically characterised patients with Lewy-body dementia. METHODS: A placebo-controlled, double-blind, multicentre study was done in 120 patients with Lewy-body dementia from the UK, Spain, and Italy. Individuals were given up to 12 mg rivastigmine daily or placebo for 20 weeks, followed by 3 weeks rest. Assessment by means of the neuropsychiatric inventory was made at baseline, and again at weeks 12, 20, and 23. A computerised cognitive assessment system and neuropsychological tests were also used, and patients underwent close medical and laboratory safety analysis. FINDINGS: Patients taking rivastigmine were significantly less apathetic and anxious, and had fewer delusions and hallucinations while on treatment than controls. Almost twice as many patients on rivastigmine (37, 63%), than on placebo (18, 30%), showed at least a 30% improvement from baseline. In the computerised cognitive assessment system and the neuropsychological tests, patients were significantly faster and better than those on placebo, particularly on tasks with a substantial attentional component. Both predefined primary efficacy measures differed significantly between rivastigmine and placebo. After drug discontinuation differences between rivastigmine and placebo tended to disappear. Known adverse events of cholinesterase inhibitors (nausea, vomiting, anorexia) were seen more frequently with rivastigmine than with placebo, but safety and tolerability of the drug in these mostly multimorbid patients were judged acceptable. INTERPRETATION: Rivastigmine 6-12 mg daily produces statistically and clinically significant behavioural effects in patients with Lewy-body dementia, and seems safe and well tolerated if titrated individually.

Aged↗

PubMed2000

Quantifying fluctuation in dementia with Lewy bodies, Alzheimer's disease, and vascular dementia.

BACKGROUND: Case reports and clinical observations suggest that fluctuating cognition (FC) is common in the major dementias, particularly dementia with Lewy bodies (DLB), where it is one of three core clinical diagnostic features. OBJECTIVES: To examine the frequency, characteristics, and diagnostic utility of FC in dementia using clinical, attentional, and EEG markers. METHOD: - A total of 155 subjects (61 with AD, 37 with DLB, 22 with vascular dementia [VaD], 35 elderly controls) received clinical evaluation for FC using a semiquantified measure applied by experienced clinicians and 90-second cognitive choice reaction time (CRT) and vigilance reaction time (VIGRT) trials. Forty subjects also received an evaluation of mean EEG frequency across 90 seconds. RESULTS: Patients with DLB had a greater prevalence and severity of FC than did patients with AD or VaD rated using clinical, attentional, and EEG measures. The 90-second cognitive and EEG trials demonstrated that FC occurs on a second-to-second basis in patients with DLB. Patients with VaD had a higher prevalence of FC than did those with AD, although the profile of FC was different from that expressed by DLB cases. Optimal cutoff values on the clinical scale achieved good discrimination between the dementia groups (sensitivity 81%, specificity 92%, DLB versus AD; sensitivity 81%, specificity 82%, DLB versus VaD; sensitivity 64%, specificity 77%, VaD versus AD). CONCLUSION: Standardized assessment methods demonstrate that FC is significantly more common and severe in DLB than in other major dementias. The periodicity of FC is different in DLB and VaD cases, with important implications for the underlying causal mechanisms and for differential diagnosis.

Aged↗

PubMed2000

The cognitive and psychomotor effects of morphine in healthy subjects: a randomized controlled trial of repeated (four) oral doses of dextropropoxyphene, morphine, lorazepam and placebo.

Ten healthy subjects (four male) of mean age 31 years (range 25-40) took part in a randomized double-blind four-way crossover study to examine the cognitive and psychomotor effects of repeated oral doses of dextropropoxyphene and morphine. Four treatments were compared: dextropropoxyphene napsylate 100 mg, morphine sulphate 10 mg, lorazepam 0.5 mg and placebo. Four doses of each drug were given at 4-h intervals to each subject on four separate study days at least 1 week apart. Cognitive function was assessed using choice reaction time, number vigilance, memory scanning, immediate and delayed word recall, word recognition, picture recognition, critical flicker fusion threshold (CFFT) and subjective measures of alertness, calmness and contentment. Lorazepam impaired the speed of responding on all tasks in which speed was recorded (except digit vigilance) and increased subjective ratings of calmness. Morphine had one major effect, which was to increase the accuracy of responding on the choice reaction time task, at every assessment. Morphine produced some sporadic effects in other tests and an increase in subjective calmness. Dextropropoxyphene impaired performance on choice reaction time and picture recognition. These data show that oral morphine may enhance performance in some measures of cognitive function, whereas dextropropoxyphene (in usual therapeutic doses) seems more likely to cause impairment. Neither opioid has substantial effects on cognition and psychomotor function compared with lorazepam.

Adult↗

PubMed2000

Cognitive performance in hypertensive and normotensive older subjects.

Longitudinal studies suggest that hypertension in midlife is associated with cognitive impairment in later life. Cross-sectional studies are difficult to interpret because blood pressure can change with onset of dementia and the inclusion of subjects on treatment and with hypertensive end-organ damage can make analysis difficult. We examined cognitive performance in hypertensive and normotensive subjects without dementia or stroke >/=70 years of age. Cognitive performance was determined with the use of a computerized assessment battery in 107 untreated hypertensives (55 women, age 76+/-4 years, blood pressure, 164+/-9/89+/-7; range, 138 to 179/68 to 99 mm Hg) and 116 normotensives (51 female, age 76+/-4 years, 131+/-10/74+/-7; 108 to 149/60 to 89 mm Hg). Older subjects with hypertension were significantly slower in all tests (reaction time, milliseconds; simple, 346+/-100 versus 318+/-56, P<0.05; memory scanning, 867+/-243 versus 789+/-159, P<0.01; immediate word recognition, 947+/-261 versus 886+/-192, P<0.05; and delayed word recognition, 937+/-230 versus 856+/-184, P<0.05; picture recognition, 952+/-184 versus 894+/-137, P<0.01; spatial memory, 1390+/-439 versus 1258+/-394, P<0.01; excepting choice reaction time, 510+/-75 versus 498+/-72, P=0.08). Accuracy was also impaired in tests of number vigilance, 99.2+/-2.5% versus 99.9+/-0.9, P<0.01; delayed word recognition, 83.5+/-16 versus 87.9+/-9.8, P<0.01; and spatial memory 64+/-32 versus 79+/-20, P<0.001. Hypertension in older subjects is associated with impaired cognition in a broad range of areas in the absence of clinically evident target organ damage.

Aged↗

PubMed2000

The Clinician Assessment of Fluctuation and the One Day Fluctuation Assessment Scale. Two methods to assess fluctuating confusion in dementia.

BACKGROUND: The identification of fluctuating confusion is central to improving the differential diagnosis of the common dementias. AIMS: To determine the value of two rating scales to measure fluctuating confusion. METHOD: The agreement between the clinician-rated scale and the scale completed by a non-clinician was determined. Correlations between the two scales were calculated; variability in attention was calculated on a computerised cognitive assessment and variability in delta rhythm on an electroencephalogram (EEG). RESULTS: The Clinician Assessment of Fluctuation and the computerised cognitive assessment were completed for 155 patients (61 Alzheimer's disease, 37 dementia with Lewy bodies, 22 vascular dementia, 35 elderly controls). A subgroup (n = 40) received a further evaluation using the One Day Fluctuation Assessment Scale and an EEG. The two scales correlated significantly with each other, and with the neuropsychological and electrophysiological measures of fluctuation. CONCLUSIONS: Both scales are useful instruments for the clinical assessment of fluctuation in dementia.

Aged↗

PubMed1999

Cognitive properties of sedation agents: comparison of the effects of nitrous oxide and midazolam on memory and mood.

OBJECTIVES: To compare the effects of nitrous oxide and midazolam on cognition and mood. DESIGN: A three-way, counterbalanced, cross-over study, using patients receiving conscious sedation for routine dental treatment. METHODS: On each of three separate visits, patients performed a computerised test battery to determine baseline cognitive performance. Then, following administration of either midazolam, nitrous oxide, or no drug, patients re-performed the test battery. Finally, patients completed visual analogue scales assessing their subjective mood state. RESULTS: Relative to baseline performance, midazolam administration produced significantly slower reaction times compared with nitrous oxide and no-drug conditions. Furthermore, patients receiving midazolam were impaired in accuracy relative to the other conditions on many of the cognitive tasks, particularly those assessing the recall of information. Patient performance in nitrous oxide and control conditions did not significantly differ. These results could not be explained by differences in mood between the conditions, as subjective mood ratings during midazolam or nitrous oxide administration were very similar. CONCLUSIONS: It is important for clinicians to be aware that peri-operative recall of information is reduced in patients who have undergone midazolam sedation. This is an advantage for patients who are anxious, and do not wish to be aware of the operative treatment being performed. However, as the cognitive impairment is enduring, an adult escort and written post-operative instructions should be mandatory for midazolam sedation patients. In contrast, the use of nitrous oxide sedation does not significantly impair higher cognitive tasks and thus patients receiving nitrous oxide sedation can resume normal activities in the post-operative period.

Adolescent↗

PubMed1999

Cognitive performance, hyperoxia, and heart rate following oxygen administration in healthy young adults.

It was recently established that supplemental oxygen administration significantly enhances memory formation in healthy young adults. In the present study, a double-blind, placebo-controled design was employed to assess the cognitive and physiological effects of subjects' inspiration of oxygen or air (control) prior to undergoing simple memory and reaction-time tasks. Arterial blood oxygen saturation and heart rate were monitored during each of six phases of the experiment, corresponding to baseline, gas inhalation, word presentation, reaction time, distractor and word recall, respectively. The results confirm that oxygen administration significantly enhances cognitive performance above that seen in the air inhalation condition. Subjects who received oxygen recalled more words and had faster reaction times. Moreover, compared to participants who inhaled air, they exhibited significant hyperoxia during gas administration, word presentation, and the reaction-time task, but not at other phases of the experiment. Compared to baseline, heart rate was significantly elevated during the word presentation, reaction-time, and distractor tasks in both the air and oxygen groups. In the oxygen group, significant correlations were found between changes in oxygen saturation and cognitive performance. In the air group, greater changes in heart rate were associated with more improved cognitive performance. These results are discussed in the context of cognitive demand and metabolic supply. It is suggested that under periods of cognitive demand a number of physiological responses are brought into play that serve to increase the delivery of metabolic substrates to active neural tissue. These mechanisms can be supplemented by increased availability of circulating blood oxygen, resulting in an augmentation of cognitive performance. Heart rate reactivity and the capacity for increased blood oxygen appear to be important physiological individual differences mediating these phenomena.

Adult↗

PubMed1999

Effect of a 915-MHz simulated mobile phone signal on cognitive function in man.

PURPOSE: To examine whether a simulated mobile telephone transmission at 915 MHz has an effect on cognitive function in man. MATERIALS AND METHODS: Thirty-six subjects in two groups were each given two training sessions and then three test sessions in a randomized three-way cross-over design. About 1 W mean power at 915 MHz from a quarter-wave antenna mounted on a physical copy of an analogue phone, as a sine wave, or modulated at 217 Hz with 12.5% duty cycle, or no power, was applied to the left squamous temple region of the subjects while they undertook a series of cognitive function tests lasting approximately 25-30 min. The second group was investigated for sleep, consumption of alcohol and beverages, and any other substances that might affect performance. RESULTS: In both groups, the only test affected was the choice reaction time and this showed as an increase in speed (a decrease in reaction time). There were no changes in word, number or picture recall, or in spatial memory. While an effect of visit-order was evident suggesting a learning effect of repeat tests, the design of the study allowed for this. Additionally, there was no systematic error introduced as a result of consumption of substances or sleep time. CONCLUSIONS: There was evidence of an increase in responsiveness, strongly in the analogue and less in the digital simulation, in choice reaction time. This could be associated with an effect on the angular gyrus that acts as an interface between the visual and speech centres and which lies directly under and on the same side as the antenna. Such an effect could be consistent with mild localized heating, or possibly a non-thermal response, which is nevertheless power-dependent.

Absorption↗

PubMed1999

A comparison of the effects of olanzapine, haloperidol and placebo on cognitive and psychomotor functions in healthy elderly volunteers.

The cognitive and psychomotor effects of olanzapine (3 mg) were compared with haloperidol (3 mg) and placebo in a double-blind, cross-over study. Fourteen healthy elderly volunteers (>65 years) were randomized to receive once daily medication for 4 days with a 16-day interval between treatment periods. Assessments of attention, memory and motor control were made prior to dosing on each day, at 2, 4, 6 and 8 h after dosing on days 1 and 4, and at 24 and 48 h following the last dose. On day 1, detectable impairment was observed at all time points in both groups. On day 4, haloperidol treated subjects showed increased impairment compared with day 1 and this was sustained throughout the 48 h of testing. Olanzapine treated subjects showed reduced day 4 deficit (compared with day 1), with no significant difference from placebo beyond 6 h post dose. These results suggest that both haloperidol and olanzapine have a measurable initial effect on cognitive and psychomotor function in elderly volunteers. However, acute effects associated with olanzapine decrease with repeated dosing and show substantial adaptation within 4 days. In contrast, effects seen with haloperidol are sustained and increase with repeated dosing over the same period.

Aged↗

PubMed1998

Scopolamine-induced cognitive impairment as a predictor of cognitive decline in healthy elderly volunteers: a 6-year follow-up.

OBJECTIVE: To determine if scopolamine-induced cognitive impairment in healthy elderly people predicts cognitive decline 6 years later. DESIGN: Prospective cohort study. SETTING: Elderly care research unit. PARTICIPANTS: Healthy elderly people who were part of a volunteer panel of research subjects. INTERVENTIONS: Scopolamine 0.2 mg administered subcutaneously at baseline. MAIN OUTCOME MEASURES: Cognitive drug research computerized cognitive testing battery pre- and post-scopolamine, with repeat testing over 6 years later. MAIN RESULTS: 16/24 subjects were retested. Although marked decrements in cognitive functioning were seen with scopolamine, there was little change in performance over 6 years, and no significant association was seen between scopolamine-induced decrement and change over time. CONCLUSIONS: The scopolamine challenge test is not likely to play a role in the preclinical diagnosis of Alzheimer's disease.

Aged↗